Tibetan medicine "RNSP" in treatment of Alzheimer disease.

PubMed

Shi, Jing-Ming; He, Xue; Lian, Hui-Juan; Yuan, Dong-Ya; Hu, Qun-Ying; Sun, Zheng-Qi; Li, Yan-Song; Zeng, Yu-Wen

2015-01-01

Alzheimer disease (Alzheimer Disease, AD) is one of the most common type in senile dementia. Its main pathological features were that a large number of senile plaques gathered in brain extracellular and tangles fibrosis appeared in nerve cells. Currently, the pathogenesis of AD is still uncertain, and scale investigation and combined brain CT, MRI data were analyzed mainly for clinical diagnosis. Mitigation and improvement of the nervous system activity to interfere with the subsequent behavior of the patients are the main methods for treatment. In clinical no drug can really prevent and cure AD. From the view point of Tibetan medicine studies, Tibetan medicine RNSP has effect on improving memory and repairing the neurons in the brain. In this study, we combined the characteristics of AD pathology, pathogenesis, diagnosis and treatment methods to explore the feasibility of Tibetan medicine RNSP for the treatment of AD to provide new ideas for the diagnosis and treatment of AD.

Angiolymphoid hyperplasia with eosinophilia versus Kimura's disease: a case report and a clinical and histopathological comparison*

PubMed Central

de Bastos, Julien Totti; da Rocha, Camila Roos Mariano; Silva, Priscila Mara Chaves e; de Freitas, Bruno Messias Pires; Cassia, Flávia de Freire; Avelleira, João Carlos Regazzi

2017-01-01

Angiolymphoid hyperplasia with eosinophilia is a rare and benign vascular tumor whose etiology remains uncertain. It clinically presents itself by angiomatous papules or nodules located on the head and neck. Many controversies in the literature are found in relation to angiolymphoid hyperplasia with eosinophilia and Kimura's disease - its main differential diagnosis - due to their clinical and histopathological similarities. However, currently, most studies agree that they are distinct diseases. The present case illustrates a characteristic description of angiolymphoid hyperplasia with eosinophilia and also highlights the main differences with Kimura's disease. PMID:29186256

Anxiety associated with diagnostic uncertainty in early pregnancy.

PubMed

Richardson, A; Raine-Fenning, N; Deb, S; Campbell, B; Vedhara, K

2017-08-01

To determine anxiety levels of women presenting to an early pregnancy assessment unit (EPAU) with abdominal pain and/or vaginal bleeding and to assess how these levels change over time and according to ultrasonographic diagnosis. We undertook a prospective cohort study in an EPAU in a large UK teaching hospital. Women with abdominal pain and/or vaginal bleeding in early pregnancy (< 12 weeks' gestation) presenting for the first time were eligible for inclusion in the study. State anxiety levels were assessed using the standardized short form of Spielberger's state-trait anxiety inventory (STAI) on three occasions (before, immediately after and 48-72 hours after an ultrasound scan). Scores were correlated with ultrasonographic diagnosis. The diagnosis was either certain or uncertain. Certain diagnoses were either positive, i.e. a viable intrauterine pregnancy (IUP), or negative, i.e. a non-viable IUP or ectopic pregnancy. Uncertain diagnoses included pregnancy of unknown location and pregnancy of uncertain viability. Statistical analysis involved mixed ANOVAs and the post-hoc Tukey-Kramer test. A total of 160 women were included in the study. Anxiety levels decreased over time for women with a certain diagnosis (n = 128), even when negative (n = 64), and increased over time for women with an uncertain diagnosis (n = 32). Before the ultrasound examination, anxiety levels were high (STAI value, 21.96 ± 1.11) and there was no significant difference between the five groups. Immediately after the ultrasound examination, anxiety levels were lower in the viable IUP group (n = 64; 7.75 ± 1.13) than in any other group. The difference between the five groups was significant (P < 0.005). After 48-72 hours, women with a certain diagnosis had significantly lower anxiety levels than had those with an uncertain diagnosis (10.77 ± 4.30 vs 22.94 ± 1.65; P < 0.005). The experience of abdominal pain and/or vaginal bleeding in early pregnancy is highly anxiogenic. Following an ultrasound examination, the certainty of the diagnosis affects anxiety levels more than does the positive or negative connotations associated with the diagnosis per se. Healthcare providers should be aware of this when communicating uncertain diagnoses. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

The value of electrocardiography for differential diagnosis in wide QRS complex tachycardia.

PubMed

Sousa, Pedro A; Pereira, Salomé; Candeias, Rui; de Jesus, Ilídio

2014-03-01

Correct diagnosis in wide QRS complex tachycardia remains a challenge. Differential diagnosis between ventricular and supraventricular tachycardia has important therapeutic and prognostic implications, and although data from clinical history and physical examination may suggest a particular origin, it is the 12-lead surface electrocardiogram that usually enables this differentiation. Since 1978, various electrocardiographic criteria have been proposed for the differential diagnosis of wide complex tachycardias, particularly the presence of atrioventricular dissociation, and the axis, duration and morphology of QRS complexes. Despite the wide variety of criteria, diagnosis is still often difficult, and errors can have serious consequences. To reduce such errors, several differential diagnosis algorithms have been proposed since 1991. However, in a small percentage of wide QRS tachycardias the diagnosis remains uncertain and in these the wisest decision is to treat them as ventricular tachycardias. The authors' objective was to review the main electrocardiographic criteria and differential diagnosis algorithms of wide QRS tachycardia. Copyright © 2012 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Use of electronic health records to ascertain, validate and phenotype acute myocardial infarction: A systematic review and recommendations.

PubMed

Rubbo, Bruna; Fitzpatrick, Natalie K; Denaxas, Spiros; Daskalopoulou, Marina; Yu, Ning; Patel, Riyaz S; Hemingway, Harry

2015-01-01

Electronic health records (EHRs) offer the opportunity to ascertain clinical outcomes at large scale and low cost, thus facilitating cohort studies, quality of care research and clinical trials. For acute myocardial infarction (AMI) the extent to which different EHR sources are accessible and accurate remains uncertain. Using MEDLINE and EMBASE we identified thirty three studies, reporting a total of 128658 patients, published between January 2000 and July 2014 that permitted assessment of the validity of AMI diagnosis drawn from EHR sources against a reference such as manual chart review. In contrast to clinical practice, only one study used EHR-derived markers of myocardial necrosis to identify possible AMI cases, none used electrocardiogram findings and one used symptoms in the form of free text combined with coded diagnosis. The remaining studies relied mostly on coded diagnosis. Thirty one studies reported positive predictive value (PPV)≥ 70% between AMI diagnosis from both secondary care and primary care EHRs and the reference. Among fifteen studies reporting EHR-derived AMI phenotypes, three cross-referenced ST-segment elevation AMI diagnosis (PPV range 71-100%), two non-ST-segment elevation AMI (PPV 91.0, 92.1%), three non-fatal AMI (PPV range 82-92.2%) and six fatal AMI (PPV range 64-91.7%). Clinical coding of EHR-derived AMI diagnosis in primary care and secondary care was found to be accurate in different clinical settings and for different phenotypes. However, markers of myocardial necrosis, ECG and symptoms, the cornerstones of a clinical diagnosis, are underutilised and remain a challenge to retrieve from EHRs. Copyright © 2015. Published by Elsevier Ireland Ltd.

Nasal potential difference outcomes support diagnostic decisions in cystic fibrosis.

PubMed

Tridello, Gloria; Menin, Laura; Pintani, Emily; Bergamini, Gabriella; Assael, Baroukh Maurice; Melotti, Paola

2016-09-01

When cystic fibrosis (CF) is suspected Nasal Potential Difference (NPD) measurements are proposed to support controversial diagnosis: we investigated appropriate outcomes at the CF Centre of Verona. NPD were measured in 196 subjects: 50 non-CF, 65 classical CF (the reference group) and 81 with uncertain CF (case group). Discriminating power was determined by comparison between several outcomes from the CF reference group versus non-CF: basal, amiloride, 0Cl, isoproterenol, ATP, Delta-amiloride, Delta-0Cl, Delta-isoproterenol, Delta-ATP, Delta-isoproterenol+Delta-0Cl, Wilschanski Index (WI) and Sermet score (SS). The most appropriate cut-off values for variables with the best discriminating power were then applied to the case group. Descriptive statistics, logistic regression models and ROC curve analysis were applied. WI and SS were the most powerful in discriminating CF from non-CF subjects. In the reference group sensitivity of the 0.82 WI cut-off was 98%, specificity 96%; both sensitivity and specificity of the -0.44 SS cut-off value were 100%. For the case group, WI and SS were, respectively, consistent with CF diagnosis in 94% and 92% of the cases. Formulae have the highest discriminating power and can support the diagnosis in uncertain cases; they should be utilized for standardized interpretation of NPD for diagnosis and possibly for clinical research. Copyright © 2016. Published by Elsevier B.V.

Cryptogenic stroke. A non-diagnosis.

PubMed

Gutiérrez-Zúñiga, Raquel; Fuentes, Blanca; Díez-Tejedor, Exuperio

2018-04-30

The term cryptogenic stroke refers to a stroke for which there is no specific attributable cause after a comprehensive evaluation. However, there are differences between the diagnostic criteria of etiological classifications used in clinical practice. An improvement in diagnostic tools such advances in monitoring for atrial fibrillation, advances in vascular imaging and evidence regarding the implication of patent foramen oval on the risk of stroke specially in young patients are reducing the proportion of stroke patients without etiological diagnosis. We carried out a critical review of the current concept of cryptogenic stroke, as a non-diagnosis, avoiding the simplification of it and reviewing the different entities that could fall under this diagnosis and reviewing the different entities that could fall under this diagnosis; and therefore avoid the same treatment for differents entities with uncertains results. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

Teicoplanin allergy - an emerging problem in the anaesthetic allergy clinic.

PubMed

Savic, L C; Garcez, T; Hopkins, P M; Harper, N J N; Savic, S

2015-10-01

Anaphylaxis to teicoplanin appears to be extremely rare, with only one confirmed case report worldwide. Two anaesthetic allergy clinics in the UK have received a number of suspected cases referred for investigation, and we present here the first case series of teicoplanin allergy. We investigated 20 cases of suspected teicoplanin allergy, identified from the two clinics over a period of two years. We devised a set of five criteria to categorize the certainty of their diagnosis. These included: (1) reaction within 15 min of administration of teicoplanin, (2) ≥2 features of anaphylaxis present, (3) positive skin testing or challenge testing, (4) raised serum mast cell tryptase (MCT), (5) alternative diagnosis excluded. Based on these criteria we defined the likelihood of IgE-mediated allergy to teicoplanin as: definite-met all criteria; probable-met criteria 1.2 and 5, plus 3 or 4; uncertain-met criteria 1.2 and 5; excluded- any others. We identified 7 'definite', 7 'probable' and 2 'uncertain' cases of teicoplanin allergy. Four cases were excluded. IgE-mediated anaphylaxis to teicoplanin appears to be more common than previously thought. This is true even if only definitive cases are considered. Investigation of teicoplanin allergy is hampered by the lack of standardized skin test concentrations. In some cases, there was a severe clinical reaction, but without any skin test evidence of histamine release. The mechanism of reaction in these cases is not known and requires further study. © The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Oral Lichen Planus: An Update on Etiology, Pathogenesis, Clinical Presentation, Diagnosis and Management

PubMed Central

Gupta, Sonia; Jawanda, Manveen Kaur

2015-01-01

The mouth is a mirror of health or disease, a sentinel or early warning system. The oral cavity might well be thought as a window to the body because oral manifestations accompany many systemic diseases. In many instances, oral involvement precedes the appearance of other symptoms or lesions at other locations. Oral lichen planus (OLP) is a chronic mucocutaneous disorder of stratified squamous epithelium of uncertain etiology that affects oral and genital mucous membranes, skin, nails, and scalp. LP is estimated to affect 0.5% to 2.0% of the general population. This disease has most often been reported in middle-aged patients with 30-60 years of age and is more common in females than in males. The disease seems to be mediated by an antigen-specific mechanism, activating cytotoxic T cells, and non-specific mechanisms like mast cell degranulation and matrix metalloproteinase activation. A proper understanding of the pathogenesis, clinical presentation, diagnosis of the disease becomes important for providing the right treatment. This article discusses the prevalence, etiology, clinical features, oral manifestations, diagnosis, complications and treatment of oral LP. PMID:26120146

Early diagnosis in glaucoma.

PubMed

Garway-Heath, David F

2008-01-01

This chapter reviews the evidence for the clinical application of vision function tests and imaging devices to identify early glaucoma, and sets out a scheme for the appropriate use and interpretation of test results in screening/case-finding and clinic settings. In early glaucoma, signs may be equivocal and the diagnosis is often uncertain. Either structural damage or vision function loss may be the first sign of glaucoma; neither one is consistently apparent before the other. Quantitative tests of visual function and measurements of optic-nerve head and retinal nerve fiber layer anatomy are useful to either raise or lower the probability that glaucoma is present. The posttest probability for glaucoma may be calculated from the pretest probability and the likelihood ratio of the diagnostic criterion, and the output of several diagnostic devices may be combined to achieve a final probability. However, clinicians need to understand how these diagnostic devices make their measurements, so that the validity of each test result can be adequately assessed. Only then should the result be used, together with the patient history and clinical examination, to derive a diagnosis.

Plasma cell gingivitis - A rare case related to Colocasia (arbi) leaves.

PubMed

Bali, Deepika; Gill, Sanjeet; Bali, Amit

2012-09-01

Plasma cell gingivitis is an uncommon inflammatory condition of uncertain etiology often flavoured chewing gum, spices, foods, candies, or dentifrices. The diagnosis of plasma cell gingivitis is based on comprehensive history taking, clinical examination, and appropriate diagnostic tests. Here we are presenting a rare case of plasma cell gingivitis caused by consumption of colocasia (arbi) leaves. Colocasia is a kind of vegetable, very commonly consumed in the regions of North India.

Diagnostic value of chest radiographs in bedridden patients suspected of having pneumonia.

PubMed

Esayag, Yaacov; Nikitin, Irina; Bar-Ziv, Jacob; Cytter, Ruth; Hadas-Halpern, Irith; Zalut, Todd; Yinnon, Amos M

2010-01-01

To assess the diagnostic value of the chest radiograph for the diagnosis of pneumonia in bedridden patients, using non-contrast-enhanced high-resolution chest computed tomography (CT) as the gold standard. We prospectively evaluated bedridden patients hospitalized with moderate to high clinical probability of pneumonia. Chest radiographs were interpreted in a blinded fashion by 3 observers and classified as definite, normal, or uncertain for pneumonia. Chest CT was obtained within 12 hours of chest radiograph. We applied Bayesian analysis to assess the accuracy of chest radiograph in the diagnosis of pneumonia. In a 5-month period, 58 patients were evaluated, 31 (53%) were female. Their chest radiographs were interpreted as negative, uncertain, or positive for pneumonia in 31 (53%), 15 (26%), and 12 (21%) patients, respectively, while CT confirmed pneumonia in 11 (35%), 10 (67%), and in 10 (83%). The sensitivity of the chest radiograph to diagnose pneumonia was 65%, the specificity was 93%, the positive and negative predictive values were, respectively, 83% and 65%, while the overall accuracy was 69% (95% confidence interval, 50%-79%). In bedridden patients with suspected pneumonia, a normal chest radiograph does not rule out the diagnosis, hence, a chest CT scan might provide valuable diagnostic information. Copyright 2010 Elsevier Inc. All rights reserved.

ACCF/ASE/AHA/ASNC/HFSA/HRS/SCAI/SCCM/SCCT/SCMR 2011 Appropriate Use Criteria for Echocardiography. A Report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, American Society of Echocardiography, American Heart Association, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Critical Care Medicine, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance American College of Chest Physicians.

PubMed

Douglas, Pamela S; Garcia, Mario J; Haines, David E; Lai, Wyman W; Manning, Warren J; Patel, Ayan R; Picard, Michael H; Polk, Donna M; Ragosta, Michael; Parker Ward, R; Weiner, Rory B

2011-03-01

The American College of Cardiology Foundation (ACCF), in partnership with the American Society of Echocardiography (ASE) and along with key specialty and subspecialty societies, conducted a review of common clinical scenarios where echocardiography is frequently considered. This document combines and updates the original transthoracic and transesophageal echocardiography appropriateness criteria published in 2007 (1) and the original stress echocardiography appropriateness criteria published in 2008 (2). This revision reflects new clinical data, reflects changes in test utilization patterns,and clarifies echocardiography use where omissions or lack of clarity existed in the original criteria.The indications (clinical scenarios)were derived from common applications or anticipated uses, as well as from current clinical practice guidelines and results of studies examining the implementation of the original appropriate use criteria (AUC).The 202 indications in this document were developed by a diverse writing group and scored by a separate independent technical panel on a scale of 1 to 9,to designate appropriate use(median 7 to 9), uncertain use(median 4 to 6), and inappropriate use (median 1 to 3). Ninety-seven indications were rated as appropriate, 34 were rated as uncertain, and 71 were rated as inappropriate. In general,the use of echocardiography for initial diagnosis when there is a change in clinical status or when the results of the echocardiogram are anticipated to change patient management were rated appropriate. Routine testing when there was no change in clinical status or when results of testing were unlikely to modify management were more likely to be inappropriate than appropriate/uncertain.The AUC for echocardiography have the potential to impact physician decision making,healthcare delivery, and reimbursement policy. Furthermore,recognition of uncertain clinical scenarios facilitates identification of areas that would benefit from future research.

Refining diagnosis of Parkinson's disease with deep learning-based interpretation of dopamine transporter imaging.

PubMed

Choi, Hongyoon; Ha, Seunggyun; Im, Hyung Jun; Paek, Sun Ha; Lee, Dong Soo

2017-01-01

Dopaminergic degeneration is a pathologic hallmark of Parkinson's disease (PD), which can be assessed by dopamine transporter imaging such as FP-CIT SPECT. Until now, imaging has been routinely interpreted by human though it can show interobserver variability and result in inconsistent diagnosis. In this study, we developed a deep learning-based FP-CIT SPECT interpretation system to refine the imaging diagnosis of Parkinson's disease. This system trained by SPECT images of PD patients and normal controls shows high classification accuracy comparable with the experts' evaluation referring quantification results. Its high accuracy was validated in an independent cohort composed of patients with PD and nonparkinsonian tremor. In addition, we showed that some patients clinically diagnosed as PD who have scans without evidence of dopaminergic deficit (SWEDD), an atypical subgroup of PD, could be reclassified by our automated system. Our results suggested that the deep learning-based model could accurately interpret FP-CIT SPECT and overcome variability of human evaluation. It could help imaging diagnosis of patients with uncertain Parkinsonism and provide objective patient group classification, particularly for SWEDD, in further clinical studies.

[Functional neuroimaging in the diagnosis of patients with Parkinsonism: Update and recommendations for clinical use].

PubMed

Arbizu, J; Luquin, M R; Abella, J; de la Fuente-Fernández, R; Fernandez-Torrón, R; García-Solís, D; Garrastachu, P; Jiménez-Hoyuela, J M; Llaneza, M; Lomeña, F; Lorenzo-Bosquet, C; Martí, M J; Martinez-Castrillo, J C; Mir, P; Mitjavila, M; Ruiz-Martínez, J; Vela, L

2014-01-01

Functional Neuroimaging has been traditionally used in research for patients with different Parkinsonian syndromes. However, the emergence of commercial radiotracers together with the availability of single photon emission computed tomography (SPECT) and, more recently, positron emission tomography (PET) have made them available for clinical practice. Particularly, the development of clinical evidence achieved by functional neuroimaging techniques over the past two decades have motivated a progressive inclusion of several biomarkers in the clinical diagnostic criteria for neurodegenerative diseases that occur with Parkinsonism. However, the wide range of radiotracers designed to assess the involvement of different pathways in the neurodegenerative process underlying Parkinsonian syndromes (dopaminergic nigrostriatal pathway integrity, basal ganglia and cortical neuronal activity, myocardial sympathetic innervation), and the different neuroimaging techniques currently available (scintigraphy, SPECT and PET), have generated some controversy concerning the best neuroimaging test that should be indicated for the differential diagnosis of Parkinsonism. In this article, a panel of nuclear medicine and neurology experts has evaluated the functional neuroimaging techniques emphazising practical considerations related to the diagnosis of patients with uncertain origin parkinsonism and the assessment Parkinson's disease progression. Copyright © 2014 Elsevier España, S.L. and SEMNIM. All rights reserved.

Diagnoses behind patients with hard-to-classify tremor and normal DaT-SPECT: a clinical follow up study.

PubMed

Menéndez-González, Manuel; Tavares, Francisco; Zeidan, Nahla; Salas-Pacheco, José M; Arias-Carrión, Oscar

2014-01-01

The [(123)I]ioflupane-a dopamine transporter radioligand-SPECT (DaT-SPECT) has proven to be useful in the differential diagnosis of tremor. Here, we investigate the diagnoses behind patients with hard-to-classify tremor and normal DaT-SPECT. Therefore, 30 patients with tremor and normal DaT-SPECT were followed up for 2 years. In 18 cases we were able to make a diagnosis. The residual 12 patients underwent a second DaT-SPECT, were then followed for additional 12 months and thereafter the diagnosis was reconsidered again. The final diagnoses included cases of essential tremor, dystonic tremor, multisystem atrophy, vascular parkinsonism, progressive supranuclear palsy, corticobasal degeneration, fragile X-associated tremor ataxia syndrome, psychogenic parkinsonism, iatrogenic parkinsonism and Parkinson's disease. However, for 6 patients the diagnosis remained uncertain. Larger series are needed to better establish the relative frequency of the different conditions behind these cases.

Plasma cell gingivitis - A rare case related to Colocasia (arbi) leaves

PubMed Central

Bali, Deepika; Gill, Sanjeet; Bali, Amit

2012-01-01

Plasma cell gingivitis is an uncommon inflammatory condition of uncertain etiology often flavoured chewing gum, spices, foods, candies, or dentifrices. The diagnosis of plasma cell gingivitis is based on comprehensive history taking, clinical examination, and appropriate diagnostic tests. Here we are presenting a rare case of plasma cell gingivitis caused by consumption of colocasia (arbi) leaves. Colocasia is a kind of vegetable, very commonly consumed in the regions of North India. PMID:23230358

[Smooth muscle tumor of uncertain malignant potential (STUMP)--clinico-pathomorphological analysis of the cases and literature review].

PubMed

Dańska-Bidzińska, Anna; Bakuła-Zalewska, Elwira; Nasierowska-Guttmejer, Anna; Kowalewska, Magdalena; Barnaś, Edyta; Sobiczewski, Piotr; Bidziński, Mariusz

2012-06-01

This retrospective study was designed to evaluate the clinical and pathological features and outcomes of patients diagnosed with uterine smooth muscle tumor of uncertain malignant potential (STUMP). Ten patients diagnosed with uterine STUMP and seen between 2008 and 2011 at the Memorial Cancer Center--Institute of Oncology in Warsaw were identified using the institution databases. Variables of interest included histopathological details, age at diagnosis, types of treatment and recurrence rate. The mean age at diagnosis was 41 years (range 25-56 years). The mean follow-up time was 16 months (range 4-29 months). Diameter of the tumors ranged from 3 to 29 cm. Uterine bleeding was the second most frequent symptom observed in this cohort In three cases conservative procedure was performed, whereas in other patients hysterectomy was performed. No recurrence was observed during the follow-up period. In all tumors mitoses were less than 10 per 10/hpf, atypia of middle or severe type, and in 3 cases necrosis was observed. In half of the tumors expression of TP53 was found, and value of MIB 1 was estimated at 2-35%. STUMP should be diagnosed by experienced pathologists due to the fact that they are often misdiagnosed as leiomyosarcomas. Clinical behavior of these tumors allows to consider a conservative management in patients wishing to preserve fertility

Pulmonary Paragonimiasis: The Detection of a Worm Migration Track as a Diagnostic Clue for Uncertain Eosinophilic Pleural Effusion.

PubMed

Akaba, Tomohiro; Takeyama, Kiyoshi; Toriyama, Midori; Kubo, Ayako; Mizobuchi, Rie; Yamada, Takeshi; Tagaya, Etsuko; Kondo, Mitsuko; Sakai, Shuji; Tamaoki, Jun

2016-01-01

A 38-year-old woman with sustained right chest pain was referred to our hospital. She showed pleural effusion and peripheral blood eosinophilia. Thoracentesis revealed eosinophilic pleural effusion in which the smear, culture and cytological examinations were all negative. Although she had no notable dietary history, chest CT revealed linear opacities, which suggested the migration tracks of paragonimiasis. The diagnosis was confirmed using enzyme-linked immunosorbent assays, which showed elevated Paragonimus westermani and Paragonimus miyazakii antibody levels. After the initiation of praziquantel therapy, all clinical findings were promptly improved. The detection of a migration track may therefore be useful in the diagnosis of paragonimiasis.

Melioidosis: evolving concepts in epidemiology, pathogenesis, and treatment.

PubMed

Currie, Bart J

2015-02-01

Infection with Burkholderia pseudomallei can result in asymptomatic seroconversion, a single skin lesion that may or may not heal spontaneously, a pneumonia which can be subacute or chronic and mimic tuberculosis or rapidly progressive resulting in fatal overwhelming sepsis. Latency with subsequent activation of disease is well recognized, but very uncommon. Melioidosis also has a myriad of other clinical presentations and diagnosis is often delayed because of this and because of difficulties with laboratory diagnosis and lack of recognition outside melioidosis-endemic regions. The perception of B. pseudomallei as a top tier biothreat agent has driven large funding for research, yet resources for diagnosis and therapy of melioidosis in many endemic locations remain extremely limited, with mortality as high as 50% in comparison to around 10% in regions where state-of-the-art intensive care therapy for sepsis is available. Fatal melioidosis is extremely unlikely from natural infection in a healthy person, provided the diagnosis is made early, ceftazidime or meropenem is commenced and intensive care therapy is available. While biothreat research is directed toward potential aerosol exposure to B. pseudomallei, the overall proportion of melioidosis cases resulting from inhalation rather than from percutaneous inoculation remains entirely uncertain, although the epidemiology supports a shift to inhalation during severe weather events such as cyclones and typhoons. What makes B. pseudomallei such a dangerous organism for patients with diabetes and other selective risk factors remains unclear, but microbial genome-wide association studies linking clinical aspects of melioidosis cases to nonubiquitous or polymorphic B. pseudomallei genes or genomic islands are beginning to uncover specific virulence signatures. Finally, what also remains uncertain is the global phylogeography of B. pseudomallei and whether melioidosis is spreading beyond historical locations or is just being unmasked in Africa and the Americas by better recognition and increased surveillance. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Identification of a Novel PMS2 Alteration c.505C>G (R169G) In Trans with a PMS2 Pathogenic Mutation in a Patient with Constitutional Mismatch Repair Deficiency

PubMed Central

Mork, Maureen E.; Borras, Ester; Taggart, Melissa W.; Cuddy, Amanda; Bannon, Sarah A.; You, Y. Nancy; Lynch, Patrick M.; Ramirez, Pedro T.; Rodriguez-Bigas, Miguel A.; Vilar, Eduardo

2016-01-01

Constitutional mismatch repair deficiency syndrome (CMMRD) is a rare autosomal recessive predisposition to colorectal polyposis and other malignancies, often childhood-onset, that is caused by biallelic inheritance of mutations in the same mismatch repair gene. Here, we describe a patient with a clinical diagnosis of CMMRD based on colorectal polyposis and young-onset endometrial cancer who was identified to have two alterations in trans in PMS2: one known pathogenic mutation (c.1831insA; p.Ile611Asnfs*2) and one novel variant of uncertain significance (c.505C>G; p.Arg169Glu), a missense alteration. We describe the clinical and molecular features in the patient harboring this novel alteration c.505C>G, who meets clinical criteria for CMMRD and exhibits molecular evidence supporting a diagnosis of CMMRD. Although experimental validation is needed to confirm its pathogenicity, PMS2 c.505C>G likely has functional consequences that contributes to our patient's phenotype based on the patient's clinical presentation, tumor studies, and bioinformatics analysis. PMID:27017610

Identification of a novel PMS2 alteration c.505C>G (R169G) in trans with a PMS2 pathogenic mutation in a patient with constitutional mismatch repair deficiency.

PubMed

Mork, Maureen E; Borras, Ester; Taggart, Melissa W; Cuddy, Amanda; Bannon, Sarah A; You, Y Nancy; Lynch, Patrick M; Ramirez, Pedro T; Rodriguez-Bigas, Miguel A; Vilar, Eduardo

2016-10-01

Constitutional mismatch repair deficiency syndrome (CMMRD) is a rare autosomal recessive predisposition to colorectal polyposis and other malignancies, often childhood-onset, that is caused by biallelic inheritance of mutations in the same mismatch repair gene. Here, we describe a patient with a clinical diagnosis of CMMRD based on colorectal polyposis and young-onset endometrial cancer who was identified to have two alterations in trans in PMS2: one known pathogenic mutation (c.1831insA; p.Ile611Asnfs*2) and one novel variant of uncertain significance (c.505C>G; p.Arg169Glu), a missense alteration. We describe the clinical and molecular features in the patient harboring this novel alteration c.505C>G, who meets clinical criteria for CMMRD and exhibits molecular evidence supporting a diagnosis of CMMRD. Although experimental validation is needed to confirm its pathogenicity, PMS2 c.505C>G likely has functional consequences that contributes to our patient's phenotype based on the patient's clinical presentation, tumor studies, and bioinformatics analysis.

Physician decision-making in the management of work related upper extremity injuries.

PubMed

Szekeres, Mike; Macdermid, Joy C; Katchky, Adam; Grewal, Ruby

2018-05-22

Physicians working in a tertiary care injured worker clinic are faced with clinical decision-making that must balance the needs of patients and society in managing complex clinical problems that are complicated by the work-workplace context. The purpose of this study is to describe and characterize the decision-making process of upper extremity specialized surgeons when managing injured workers within a specialized worker's compensation clinic. Surgeons were interviewed in a semi-structured manner. Following each interview, the surgeon was also observed in a clinic visit during a new patient assessment, allowing observation of the interactional patterns between surgeon and patient, and comparison of the process described in the interview to what actually occurred during clinic visits. The primary central theme emerging from the surgeon interviews and the clinical observation was the focus on the importance of comprehensive assessment to make the first critical decision: an accurate diagnosis. Two subthemes were also found. The first of these involved the decision whether to proceed to management strategies or to continue with further investigation if the correct diagnosis is uncertain. Once the central theme of diagnosis was achieved, a second subtheme was highlighted; selecting appropriate management options, given the complexities of managing the injured worker, the workplace, and the compensation board. This study illustrates that upper extremity surgeons rely on their training and experience with upper extremity conditions to follow a sequential but iterative decision-making process to provide a more definitive diagnosis and treatment plan for workers with injuries that are often complex. The surgeons are challenged by the context which takes them out of their familiar zone of typical clinical practice to deal with the interactions between the injury, worker, work, workplace and insurer.

Soft-Tissue Infections and Their Imaging Mimics: From Cellulitis to Necrotizing Fasciitis.

PubMed

Hayeri, Mohammad Reza; Ziai, Pouya; Shehata, Monda L; Teytelboym, Oleg M; Huang, Brady K

2016-10-01

Infection of the musculoskeletal system can be associated with high mortality and morbidity if not promptly and accurately diagnosed. These infections are generally diagnosed and managed clinically; however, clinical and laboratory findings sometimes lack sensitivity and specificity, and a definite diagnosis may not be possible. In uncertain situations, imaging is frequently performed to confirm the diagnosis, evaluate the extent of the disease, and aid in treatment planning. In particular, cross-sectional imaging, including computed tomography and magnetic resonance imaging, provides detailed anatomic information in the evaluation of soft tissues due to their inherent high spatial and contrast resolution. Imaging findings of soft-tissue infections can be nonspecific and can have different appearances depending on the depth and anatomic extent of tissue involvement. Although many imaging features of infectious disease can overlap with noninfectious processes, imaging can help establish the diagnosis when combined with the clinical history and laboratory findings. Radiologists should be familiar with the spectrum of imaging findings of soft-tissue infections to better aid the referring physician in managing these patients. The aim of this article is to review the spectrum of soft-tissue infections using a systematic anatomic compartment approach. We discuss the clinical features of soft-tissue infections, their imaging findings with emphasis on cross-sectional imaging, their potential mimics, and clinical management. © RSNA, 2016.

Burning mouth syndrome: an enigmatic disorder.

PubMed

Javali, M A

2013-01-01

Burning mouth syndrome (BMS) is a chronic oral pain or burning sensation affecting the oral mucosa, often unaccompanied by mucosal lesions or other evident clinical signs. It is observed principally in middle-aged patients and postmenopausal women and may be accompanied by xerostomia and altered taste. Burning mouth syndrome is characterized by an intense burning or stinging sensation, preferably on the tongue or in other areas of mouth. This disorder is one of the most common, encountered in the clinical practice. This condition is probably of multifactorial origin; however the exact underlying etiology remains uncertain. This article discusses several aspects of BMS, updates current knowledge about the etiopathogenesis and describes the clinical features as well as the diagnosis and management of BMS patients.

Diagnosis, follow-up and treatment of cystic fibrosis-related liver disease.

PubMed

van de Peppel, Ivo P; Bertolini, Anna; Jonker, Johan W; Bodewes, Frank A J A; Verkade, Henkjan J

2017-11-01

To provide an insight and overview of the challenges in the diagnosis, follow-up and treatment of cystic fibrosis-related liver disease (CFLD). The variable pathophysiology of CFLD complicates its diagnosis and treatment. A 'gold standard' for CFLD diagnosis is lacking. Over the past years, new techniques to diagnose features of CFLD, such as transient elastography, have been investigated. Although most of these tests confirm cystic fibrosis-related liver involvement (CFLI), they are, however, not suitable to distinguish various phenotypical presentations or predict progression to clinically relevant cirrhosis or portal hypertension. A combined initiative from the European and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition has been started, aimed to obtain consensus on CFLD criteria and definitions. Currently, only ursodeoxycholic acid is used in CFLD treatment, although it has not been convincingly demonstrated to change the natural course of the disease. Drugs that directly target cystic fibrosis transmembrane conductance regulator protein dysfunction show promising results; however, more long-term follow-up and validation studies are needed. CFLD is an umbrella term referring to a wide variety of liver manifestations with variable clinical needs and consequences. CFLD with portal hypertension is the most severe form of CFLD due to its significant implications on morbidity and mortality. The clinical relevance of other CFLI is uncertain. Consensus on CFLD definitions is essential to validate new diagnostic tools and therapeutic outcome measures.

Importance of spontaneous nystagmus detection in the differential diagnosis of acute vertigo.

PubMed

Pavlin-Premrl, Davor; Waterston, John; McGuigan, Sean; Infeld, Bernard; Sultana, Ron; O'Sullivan, Richard; Gerraty, Richard P

2015-03-01

Vertigo is a common cause of emergency department attendance. Detection of spontaneous nystagmus may be a useful sign in distinguishing vestibular neuritis from other vestibular diagnoses. We aimed to assess the contribution of spontaneous nystagmus in the diagnosis of acute vertigo. We enrolled consecutive consenting patients arriving at a single emergency department with acute vertigo. There was no declared protocol for the emergency department staff. A standardized history and examination was conducted by the investigators. Observation for spontaneous nystagmus, its response to visual fixation, and testing the vestibulo-ocular reflex with the horizontal head impulse test were the chief examination components. MRI was obtained within 24 hours. Clinical criteria and MRI were used to reach the final diagnosis. The investigators' physical findings and final neurological diagnosis were compared with the initial emergency department examination findings and the referral diagnosis. There were 28 patients, 15 with vestibular neuritis, six with benign paroxysmal positional vertigo, one with stroke, suspected clinically, and three with migraine. In three the diagnosis remained uncertain. Spontaneous nystagmus was seen in all 15 patients with vestibular neuritis, fixation-suppressed in eight of 11 tested for this. The head impulse test was positive in 12 of 15 with vestibular neuritis. The emergency department referral diagnosis was correct in six of 23 patients. The ability to detect spontaneous nystagmus is useful in vestibular diagnosis, both in support of a diagnosis of vestibular neuritis and in avoiding false positive diagnoses of benign paroxysmal positional vertigo. Copyright © 2014 Elsevier Ltd. All rights reserved.

Usher syndrome: an effective sequencing approach to establish a genetic and clinical diagnosis.

PubMed

Lenarduzzi, S; Vozzi, D; Morgan, A; Rubinato, E; D'Eustacchio, A; Osland, T M; Rossi, C; Graziano, C; Castorina, P; Ambrosetti, U; Morgutti, M; Girotto, G

2015-02-01

Usher syndrome is an autosomal recessive disorder characterized by retinitis pigmentosa, sensorineural hearing loss and, in some cases, vestibular dysfunction. The disorder is clinically and genetically heterogeneous and, to date, mutations in 11 genes have been described. This finding makes difficult to get a precise molecular diagnosis and offer patients accurate genetic counselling. To overcome this problem and to increase our knowledge of the molecular basis of Usher syndrome, we designed a targeted resequencing custom panel. In a first validation step a series of 16 Italian patients with known molecular diagnosis were analysed and 31 out of 32 alleles were detected (97% of accuracy). After this step, 31 patients without a molecular diagnosis were enrolled in the study. Three out of them with an uncertain Usher diagnosis were excluded. One causative allele was detected in 24 out 28 patients (86%) while the presence of both causative alleles characterized 19 patients out 28 (68%). Sixteen novel and 27 known alleles were found in the following genes: USH2A (50%), MYO7A (7%), CDH23 (11%), PCDH15 (7%) and USH1G (2%). Overall, on the 44 patients the protocol was able to characterize 74 alleles out of 88 (84%). These results suggest that our panel is an effective approach for the genetic diagnosis of Usher syndrome leading to: 1) an accurate molecular diagnosis, 2) better genetic counselling, 3) more precise molecular epidemiology data fundamental for future interventional plans. Copyright © 2014 Elsevier B.V. All rights reserved.

Broad Ligament Perivascular Epithelioid Cell Tumor (PEComa) of Uncertain Malignant Potential.

PubMed

Mathew, Mary; Nayal, Bhavna; Rao, Lakshmi; Nagel, Bhawna

2016-01-01

PEComas are uncommon mesenchymal tumors often involving the pelvic organs. They have an unpredictable behavior. Accurate diagnosis and long-term follow-up is therefore essential in these patients. We report this case of PEComa of uncertain malignant potential in an unusual location with excellent prognosis.

Practical approach to hip pain.

PubMed

Karrasch, Christopher; Lynch, Scott

2014-07-01

Hip pain is a common complaint among patients presenting to outpatient clinics. Stratifying patients based on age, acuity, and location of pain (extra-articular vs intra-articular) can help to aid in appropriate imaging and timely referral to an orthopedic surgeon. A thorough history and an organized physical examination combined with radiographs are usually sufficient to diagnose most hip complaints. If the diagnosis remains uncertain, magnetic resonance imaging, usually with intra-articular gadolinium, is the imaging modality of choice in diagnosing both intra-articular and extra-articular pathologies. Copyright © 2014 Elsevier Inc. All rights reserved.

Bacterial Meningitis in the Infant

PubMed Central

Ku, Lawrence C.; Boggess, Kim A.

2014-01-01

SYNOPSIS Neonatal bacterial meningitis is an uncommon but devastating infection. Although the incidence and mortality have declined over the last several decades, morbidity among survivors remains high. The types and distribution of causative pathogens are related to birth gestational age, postnatal age, and geographic region. Confirming the diagnosis of meningitis can be difficult. Clinical signs are often subtle, and the lumbar puncture is frequently deferred in clinically unstable infants. When obtained, confirmatory testing with cerebrospinal fluid (CSF) culture is often compromised by antepartum or postnatal antibiotic exposure. While blood cultures and CSF parameters may be helpful in cases where the diagnosis is uncertain, bacterial meningitis occurs in infants without bacteremia and with normal CSF parameters. Newer tests such as the polymerase chain reaction are promising but require further study. Prompt treatment with appropriate antibiotics is essential to optimize outcomes. Successful efforts to prevent meningitis in infants have included the use of intrapartum antibiotic prophylaxis against Group B Streptococcus (GBS). Clinical trials investigating the use of a GBS vaccine for the prevention of neonatal GBS disease are ongoing. PMID:25677995

Adenomyosis: a life-cycle approach.

PubMed

Benagiano, Giuseppe; Brosens, Ivo; Habiba, Marwan

2015-03-01

The life-cycle approach to endometriosis highlighted unexpected features of the condition; the same approach was therefore applied to gain insight into the clinical features of adenomyosis and to draw a comparison with endometriosis. This is possible today thanks to new imaging techniques enabling non-invasive diagnosis of adenomyosis. The specificity and sensitivity of magnetic resonance imaging and transvaginal ultrasound remain uncertain. Unlike endometriosis, little information is available on the presence of classic adenomyosis in adolescents, except for rare cystic forms that may not represent the true disease. Adenomyosis is most likely to affect adult women, although most reported incidences are still based on post-hysterectomy studies, and are affected by diligence in histopathologic diagnosis and the adopted cut-off point. The traditionally accepted associations of adult adenomyosis, such as multiparity, a link to infertility and its effect on pregnancy are uncertain. Active adenomyosis has been found in pre- and peri-menopausal women and in postmenopausal women receiving tamoxifen. In conclusion, major diagnostic limitations and the systematic bias of hysterectomy make it difficult to draw firm conclusions from existing evidence. In addition, no information is available on the natural history of adenomyosis and no study has systematically evaluated its existence in adolescents. Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Sarcoidosis onset simulating a unique hepatic metastasis.

PubMed

Diéguez Castillo, Carmelo; Martín-Lagos Maldonado, Alicia; Ríos Pelegrina, Rosa María; Díaz Alcázar, María Del Mar; Roa Colomo, Amparo; Ruiz Escolano, Elena

2018-06-22

Sarcoidosis is a systemic granulomatous disease with an uncertain etiology, characterized by the production of non-necrotizing granulomas. The most frequent presentation is pulmonary and mediastinal, although it might affect any other organ. Hepatic alterations occur in 50 to 65% of the cases. Nevertheless, it is commonly subclinical or detected during a study of the alteration of liver enzymes. It is very unusual that disease onset occurs as an isolated hepatic tumor. A hepatic biopsy is usually required to confirm the diagnosis. A differential diagnosis must be established via any hepatic granulomatous disease, infectious or autoimmune disease as well as the exclusion of malignancy. We present a clinical case of a female diagnosed with an isolated hepatic sarcoidosis that simulated a unique hepatic metastatic lesion. The hepatic biopsy was diagnostic.

Clinically actionable mutation profiles in patients with cancer identified by whole-genome sequencing

PubMed Central

Mizani, Tuba; Hamblin, Angela; Parton, Marina; Orosz, Zsolt; Athanasou, Nick; Hassan, Bass; Flanagan, Adrienne M.; Ahmed, Ahmed; Winter, Stuart; Harris, Adrian; Popitsch, Niko; Church, David; Taylor, Jenny C.

2018-01-01

Next-generation sequencing (NGS) efforts have established catalogs of mutations relevant to cancer development. However, the clinical utility of this information remains largely unexplored. Here, we present the results of the first eight patients recruited into a clinical whole-genome sequencing (WGS) program in the United Kingdom. We performed PCR-free WGS of fresh frozen tumors and germline DNA at 75× and 30×, respectively, using the HiSeq2500 HTv4. Subtracted tumor VCFs and paired germlines were subjected to comprehensive analysis of coding and noncoding regions, integration of germline with somatically acquired variants, and global mutation signatures and pathway analyses. Results were classified into tiers and presented to a multidisciplinary tumor board. WGS results helped to clarify an uncertain histopathological diagnosis in one case, led to informed or supported prognosis in two cases, leading to de-escalation of therapy in one, and indicated potential treatments in all eight. Overall 26 different tier 1 potentially clinically actionable findings were identified using WGS compared with six SNVs/indels using routine targeted NGS. These initial results demonstrate the potential of WGS to inform future diagnosis, prognosis, and treatment choice in cancer and justify the systematic evaluation of the clinical utility of WGS in larger cohorts of patients with cancer. PMID:29610388

Recommendations regarding the genetic and immunological study of reproductive dysfunction.

PubMed

Alonso-Cerezo, María Concepción; Calero Ruiz, Mercedes; Chantada-Abal, Venancio; de la Fuente-Hernández, Luis Alfonso; García-Cobaleda, Inmaculada; García-Ochoa, Carlos; García-Sagredo, José Miguel; Nuñez, Rocío; Oliva, Rafael; Orera-Clemente, María; Pintado-Vera, David; Sanchez-Ramon, Silvia

2018-04-19

In this article several members of diverse scientific associations and reproduction experts from Spain have updated different genetic and immunological procedure recommendations in couples affected by reproductive dysfunction with the goal of providing a set of useful guidelines for the clinic. The laboratory test has been considered as highly recommendable for making clinical decisions when the result of the diagnostic test is relevant, moderately recommendable when the results are of limited evidence because they are inconsistent, and low when the benefit of the test is uncertain. It is expected that these recommendations will provide some useful guidelines for the diagnosis, prognosis and treatment of couples presenting reproductive dysfunction. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

[Diagnostic difficulties in a case of constricted tubular visual field].

PubMed

Dogaru, Oana-Mihaela; Rusu, Monica; Hâncu, Dacia; Horvath, Kárin

2013-01-01

In the paper below we present the clinical case of a 48 year old female with various symptoms associated with functional visual disturbance -constricted tubular visual fields, wich lasts from 6 years; the extensive clinical and paraclinical ophthalmological investigations ruled out the presence of an organic disorder. In the present, we suspect a diagnosis of hysteria, still uncertain, wich represented over time a big challenge in psychology and ophthalmology. The mechanisms and reasons for hysteria are still not clear and it could represent a fascinating research theme. The tunnel, spiral or star-shaped visual fields are specific findings in hysteria for patients who present visual disturbance. The question of whether or not a patient with hysterical visual impairment can or cannot "see" is still unresolved.

FDG-PET improves accuracy in distinguishing frontotemporal dementia and Alzheimer's disease.

PubMed

Foster, Norman L; Heidebrink, Judith L; Clark, Christopher M; Jagust, William J; Arnold, Steven E; Barbas, Nancy R; DeCarli, Charles S; Turner, R Scott; Koeppe, Robert A; Higdon, Roger; Minoshima, Satoshi

2007-10-01

Distinguishing Alzheimer's disease (AD) and frontotemporal dementia (FTD) currently relies on a clinical history and examination, but positron emission tomography with [(18)F] fluorodeoxyglucose (FDG-PET) shows different patterns of hypometabolism in these disorders that might aid differential diagnosis. Six dementia experts with variable FDG-PET experience made independent, forced choice, diagnostic decisions in 45 patients with pathologically confirmed AD (n = 31) or FTD (n = 14) using five separate methods: (1) review of clinical summaries, (2) a diagnostic checklist alone, (3) summary and checklist, (4) transaxial FDG-PET scans and (5) FDG-PET stereotactic surface projection (SSP) metabolic and statistical maps. In addition, we evaluated the effect of the sequential review of a clinical summary followed by SSP. Visual interpretation of SSP images was superior to clinical assessment and had the best inter-rater reliability (mean kappa = 0.78) and diagnostic accuracy (89.6%). It also had the highest specificity (97.6%) and sensitivity (86%), and positive likelihood ratio for FTD (36.5). The addition of FDG-PET to clinical summaries increased diagnostic accuracy and confidence for both AD and FTD. It was particularly helpful when raters were uncertain in their clinical diagnosis. Visual interpretation of FDG-PET after brief training is more reliable and accurate in distinguishing FTD from AD than clinical methods alone. FDG-PET adds important information that appropriately increases diagnostic confidence, even among experienced dementia specialists.

Occupational Asthma in Antibiotic Manufacturing Workers: Case Reports and Systematic Review

PubMed Central

Díaz Angulo, Sara; Szram, Joanna; Welch, Jenny; Cannon, Julie; Cullinan, Paul

2011-01-01

Background. The risks of occupational asthma (OA) from antibiotics are uncertain. We report 4 new cases and a systematic review of the literature. Methods. Cases were identified through a specialist clinic, each underwent specific provocation testing (SPT). We subsequently reviewed the published literature. Results. The patients were employed in the manufacture of antibiotics; penicillins were implicated in three cases, in the fourth erythromycin, not previously reported to cause OA. In two, there was evidence of specific IgE sensitisation. At SPT each developed a late asthmatic reaction and increased bronchial hyperresponsiveness. 36 case reports have been previously published, 26 (citing penicillins or cephalosporins). Seven cross-sectional workplace-based surveys found prevalences of 5–8%. Conclusions. OA in antibiotic manufacturers may be more common than is generally recognised. Its pathogenesis remains unclear; immunological tests are of uncertain value and potential cases require confirmation with SPT. Further study of its frequency, mechanisms, and diagnosis is required. PMID:21603168

Spine lesion analysis in 3D CT data - Reporting on research progress

NASA Astrophysics Data System (ADS)

Jan, Jiri; Chmelik, Jiri; Jakubicek, Roman; Ourednicek, Petr; Amadori, Elena; Gavelli, Giampaolo

2018-04-01

The contribution describes progress in the long-term project concerning automatic diagnosis of spine bone lesions. There are two difficult problems: segmenting reliably possibly severely deformed vertebrae in the spine and then detect, segment and classify the lesions that are often hardly visible thus making even the medical expert decisions highly uncertain, with a large inter-expert variety. New approaches are described enabling to solve both problems with a success rate acceptable for clinical testing, at the same time speeding up the process substantially compared to the previous stage. The results are compared with previously published achievements.

Sepsis and identification of reliable biomarkers for postoperative period prognosis.

PubMed

Siloşi, Cristian Adrian; Siloşi, Isabela; Pădureanu, Vlad; Bogdan, Maria; Mogoantă, Stelian Ştefăniţă; Ciurea, Marius Eugen; Cojocaru, Manole; Boldeanu, Lidia; Avrămescu, Carmen Silvia; Boldeanu, Mihail Virgil; Popa, Dragoş George

2018-01-01

Sepsis is currently defined as the presence of organ dysfunction occurring as the result of a disturbed host response to a serious infection. Sepsis is one of the most common diseases, which cause mortality and a considerable absorber of healthcare resources. Despite progress in technology and improving knowledge of pathophysiology, the disease mechanism is still poorly understood. At present, diagnosis is based on non-specific physiological criteria and on the late identification of the pathogen. For these reasons, the diagnosis may be uncertain, treatment delayed or an immunomodulatory therapy cannot be established. An early and reliable diagnosis is essential to achieve better outcomes on disease progression. The host response to infection involves hundreds of many mediators of which have been proposed as biomarkers. There is a need for new diagnostic approaches for sepsis, new sepsis biomarkers that can aid in diagnosis, therapeutic decision and monitoring of the response to therapy. The differentiation of sepsis from non-infectious systemic inflammatory response syndrome is difficult, and the search for a highly accurate biomarker of sepsis has become one important objective of the medicine. The goal of our review is to summarize the recent advances on the most commonly studied serum biomarkers, evaluated in clinical and experimental studies, for early diagnosis of sepsis and their informative value in diagnosis, prognosis, or response to therapy. In this context, we have tracked the clinical utility of measuring serum biomarkers, such as procalcitonin, pro- and anti-inflammatory cytokines, C-reactive protein, leptin and their combinations. Currently, has not been identified an ideal biomarker to aid in the diagnosis of sepsis. It is hoped that the discovery of new serum markers, as well as their combinations, will serve for the diagnosis and prognosis of sepsis.

Clinical Amyloid Imaging.

PubMed

Mallik, Atul; Drzezga, Alex; Minoshima, Satoshi

2017-01-01

Amyloid plaques, along with neurofibrillary tangles, are a neuropathologic hallmark of Alzheimer disease (AD). Recently, amyloid PET radiotracers have been developed and approved for clinical use in the evaluation of suspected neurodegenerative disorders. In both research and clinical settings, amyloid PET imaging has provided important diagnostic and prognostic information for the management of patients with possible AD, mild cognitive impairment (MCI), and other challenging diagnostic presentations. Although the overall impact of amyloid imaging is still being evaluated, the Society of Nuclear Medicine and Molecular Imaging and Alzheimer's Association Amyloid Imaging Task Force have created appropriate use criteria for the standard clinical use of amyloid PET imaging. By the appropriate use criteria, amyloid imaging is appropriate for patients with (1) persistent or unexplained MCI, (2) AD as a possible but still uncertain diagnosis after expert evaluation and (3) atypically early-age-onset progressive dementia. To better understand the clinical and economic effect of amyloid imaging, the Imaging Dementia-Evidence for Amyloid Scanning (IDEAS) study is an ongoing large multicenter study in the United States, which is evaluating how amyloid imaging affects diagnosis, management, and outcomes for cognitively impaired patients who cannot be completely evaluated by clinical assessment alone. Multiple other large-scale studies are evaluating the prognostic role of amyloid PET imaging for predicting MCI progression to AD in general and high-risk populations. At the same time, amyloid imaging is an important tool for evaluating potential disease-modifying therapies for AD. Overall, the increased use of amyloid PET imaging has led to a better understanding of the strengths and limitations of this imaging modality and how it may best be used with other clinical, molecular, and imaging assessment techniques for the diagnosis and management of neurodegenerative disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

[Significance of PSMA imaging in prostate cancer].

PubMed

Gasch, C; Düwel, C; Kopka, K; Kratochwil, C; Vinsensia, M; Eiber, M; Maurer, T; Haberkorn, U; Hadaschik, B; Giesel, F L

2017-01-01

Prostate cancer (PCa) is one of the most common malignancies of men in developed countries. To improve clinical diagnostics of PCa, 68 Ga-PSMA-11 was recently introduced as a new PET tracer. 68 Ga-PSMA-11 is able to specifically bind to the prostate-specific membrane antigen (PSMA), which is upregulated on the surface of prostate cancer cells in most patients. To analyse the current significance of 68 Ga-PSMA-11 PET imaging in prostate cancer in relation to staging of men with initial diagnosis, biochemical recurrence and metastatic disease. Retrospective analysis of current literature (PubMed search) regarding 68 Ga-PSMA-11 PET diagnostics in primary staging, in biochemical recurrence and in metastasized disease. Compared to conventional imaging, 68 Ga-PSMA-11 PET/CT reaches a higher sensitivity with an excellent specificity in the clinical diagnosis of primary staging as well as staging for recurrence and advanced, metastasized disease. In biochemical recurrence, 68 Ga-PSMA-11 PET/CT shows significantly higher detection rates in comparison to choline PET/CT, especially in patients with low PSA values. In the clinical diagnosis of recurrent disease, therapy concepts were changed in more than a quarter of the patients due to the use of 68 Ga-PSMA-11 PET/CT. The significance of staging with 68 Ga-PSMA-11 PET/CT in advanced metastasized patients remains uncertain. Due to the excellent results of 68 Ga-PSMA-11 PET imaging, even in patients with slightly elevated PSA levels, it will continue to play an important role in clinical diagnostics of prostate cancer and, thus, its clinical utilization will become more widely spread.

Histopathologic evaluation of atypical neurofibromatous tumors and their transformation into malignant peripheral nerve sheath tumor in patients with neurofibromatosis 1-a consensus overview.

PubMed

Miettinen, Markku M; Antonescu, Cristina R; Fletcher, Christopher D M; Kim, Aerang; Lazar, Alexander J; Quezado, Martha M; Reilly, Karlyne M; Stemmer-Rachamimov, Anat; Stewart, Douglas R; Viskochil, David; Widemann, Brigitte; Perry, Arie

2017-09-01

Patients with neurofibromatosis 1 (NF1) develop multiple neurofibromas, with 8% to 15% of patients experiencing malignant peripheral nerve sheath tumor (MPNST) during their lifetime. Prediction of transformation, typically from plexiform neurofibroma, is clinically and histologically challenging. In this overview, after a consensus meeting in October 2016, we outline the histopathologic features and molecular mechanisms involved in the malignant transformation of neurofibromas. Nuclear atypia alone is generally insignificant. However, with atypia, loss of neurofibroma architecture, high cellularity, and/or mitotic activity >1/50 but <3/10 high-power fields, the findings are worrisome for malignancy. We propose the term "atypical neurofibromatous neoplasms of uncertain biologic potential (ANNUBP)" for lesions displaying at least 2 of these features. This diagnosis should prompt additional sampling, clinical correlation, and possibly, expert pathology consultation. Currently, such tumors are diagnosed inconsistently as atypical neurofibroma or low-grade MPNST. Most MPNSTs arising from neurofibromas are high-grade sarcomas and pose little diagnostic difficulty, although rare nonnecrotic tumors with 3-9 mitoses/10 high-power fields can be recognized as low-grade variants. Although neurofibromas contain numerous S100 protein/SOX10-positive Schwann cells and CD34-positive fibroblasts, both components are reduced or absent in MPNST. Loss of p16/CDKN2A expression, elevated Ki67 labeling, and extensive nuclear p53 positivity are also features of MPNST that can to some degree already occur in atypical neurofibromatous neoplasms of uncertain biologic potential. Complete loss of trimethylated histone 3 lysine 27 expression is potentially more reliable, being immunohistochemically detectable in about half of MPNSTs. Correlated clinicopathological, radiologic, and genetic studies should increase our understanding of malignant transformation in neurofibromas, hopefully improving diagnosis and treatment soon. Published by Elsevier Inc.

The clinical significance of occult gynecologic primary tumours in metastatic cancer.

PubMed

Hannouf, M B; Winquist, E; Mahmud, S M; Brackstone, M; Sarma, S; Rodrigues, G; Rogan, P K; Hoch, J S; Zaric, G S

2017-10-01

We estimated the frequency of occult gynecologic primary tumours (gpts) in patients with metastatic cancer from an uncertain primary and evaluated the effect on disease management and overall survival (os). We used Manitoba administrative health databases to identify all patients initially diagnosed with metastatic cancer during 2002-2011. We defined patients as having an "occult" primary tumour if the primary was classified at least 6 months after the initial diagnosis. Otherwise, we considered patients to have "obvious" primaries. We then compared clinicopathologic and treatment characteristics and 2-year os for women with occult and with obvious gpts. We used Cox regression adjustment and propensity score methods to assess the effect on os of having an occult gpt. Among the 5953 patients diagnosed with metastatic cancer, occult primary tumours were more common in women ( n = 285 of 2552, 11.2%) than in men ( n = 244 of 3401, 7.2%). In women, gpts were the most frequent occult primary tumours ( n = 55 of 285, 19.3%). Compared with their counterparts having obvious gpts, women with occult gpts ( n = 55) presented with similar histologic and metastatic patterns but received fewer gynecologic diagnostic examinations during diagnostic work-up. Women with occult gpts were less likely to undergo surgery, waited longer for radiotherapy, and received a lesser variety of chemotherapeutic agents. Having an occult compared with an obvious gpt was associated with decreased os (hazard ratio: 1.62; 95% confidence interval: 1.2 to 2.35). Similar results were observed in adjusted analyses. In women with metastatic cancer from an uncertain primary, gpts constitute the largest clinical entity. Accurate diagnosis of occult gpts early in the course of metastatic cancer might lead to more effective treatment decisions and improved survival outcomes.

The clinical significance of occult gynecologic primary tumours in metastatic cancer

PubMed Central

Hannouf, M.B.; Winquist, E.; Mahmud, S.M.; Brackstone, M.; Sarma, S.; Rodrigues, G.; Rogan, P.K.; Hoch, J.S.; Zaric, G.S.

2017-01-01

Objective We estimated the frequency of occult gynecologic primary tumours (gpts) in patients with metastatic cancer from an uncertain primary and evaluated the effect on disease management and overall survival (os). Methods We used Manitoba administrative health databases to identify all patients initially diagnosed with metastatic cancer during 2002–2011. We defined patients as having an “occult” primary tumour if the primary was classified at least 6 months after the initial diagnosis. Otherwise, we considered patients to have “obvious” primaries. We then compared clinicopathologic and treatment characteristics and 2-year os for women with occult and with obvious gpts. We used Cox regression adjustment and propensity score methods to assess the effect on os of having an occult gpt. Results Among the 5953 patients diagnosed with metastatic cancer, occult primary tumours were more common in women (n = 285 of 2552, 11.2%) than in men (n = 244 of 3401, 7.2%). In women, gpts were the most frequent occult primary tumours (n = 55 of 285, 19.3%). Compared with their counterparts having obvious gpts, women with occult gpts (n = 55) presented with similar histologic and metastatic patterns but received fewer gynecologic diagnostic examinations during diagnostic work-up. Women with occult gpts were less likely to undergo surgery, waited longer for radiotherapy, and received a lesser variety of chemotherapeutic agents. Having an occult compared with an obvious gpt was associated with decreased os (hazard ratio: 1.62; 95% confidence interval: 1.2 to 2.35). Similar results were observed in adjusted analyses. Conclusions In women with metastatic cancer from an uncertain primary, gpts constitute the largest clinical entity. Accurate diagnosis of occult gpts early in the course of metastatic cancer might lead to more effective treatment decisions and improved survival outcomes. PMID:29089807

Diagnosis of Wilson disease in young children: molecular genetic testing and a paradigm shift from the laboratory diagnosis.

PubMed

Seo, Jeong Kee

2012-12-01

Wilson disease (WD) is an autosomal recessive disorder of copper metabolism that results in accumulation of copper primarily in the liver, brain and cornea. Mutations in the WD gene, ATP7B, cause failure of copper excretion from hepatocyte into bile and a defective synthesis of ceruloplasmin. More than 500 mutations are now recognized, scattered throughout the ATP7B gene. Since WD has protean clinical presentations, awareness of WD in clinical practice is important for the early diagnosis and prevention of accumulated copper toxicity. Molecular genetic testing is playing an increasingly important role in the diagnosis of WD in uncertain cases and family screening. Siblings should be screened for WD once an index case has been diagnosed. Discrimination of heterozygotes from asymptomatic patients is essential to avoid inappropriate lifelong therapy for heterozygotes. Genetic testing, either by haplotype analysis or by mutation analysis, is the only definite solution for differentiating heterozygote carriers from affected asymptomatic patients. Routine genetic testing, because of the multitude of documented mutations, has been thought to be impractical until recently. However, genetic testing is now being more actively applied to the diagnosis of WD, particularly in young children in whom conventional biochemical diagnosis has much limitation and only genetic testing is able to confirm WD. Because advancement of modern biochemical technology now allows more rapid, easier, and less expensive mutation detection, direct DNA sequencing could be actively considered as the primary mode of diagnostic investigation rather than a supplementary test to the conventional biochemical tests. This review will focus on the recent advancement of molecular genetics and genetic diagnosis of WD in very young children on the basis of research data of the Seoul National University Children's Hospital and recent literature.

Lymphoproliferative disorders in patients with chronic myeloproliferative neoplasms: A systematic review.

PubMed

Marchetti, Monia; Carobbio, Alessandra; Capitoni, Enrica; Barbui, Tiziano

2018-05-01

Patients with a Ph-negative myeloproliferative neoplasm (MPN) may harbor or develop lymphoproliferative disorders (LPD), however, the clinical and molecular determinants of MPN and LPD co-occurrence are still uncertain. To systematically pool the available knowledge, we conducted a scoping review of literature published since January 2005 and analyzed single-patient clinical data from 50 papers reporting 214 individuals harboring both MPN and LPD. Patients had been diagnosed essential thrombocythemia (44%), polycythemia vera (29%), or myelofibrosis (23%) at a median age of 67 years (26-94): half of them incurred a LPD after a median of 72 months from MPN diagnosis, while in 20% the LPD diagnosis was antecedent or synchronous. Patients mainly incurred indolent LPD, particularly chronic lymphocytic leukemia (CLL), while aggressive lymphomas and multiple myeloma were a relevant portion of the LPDs occurring in the follow-up of MPN. CLL was preferentially diagnosed in PV patients and was associated with a very high male-to-female ratio, as well as an older age at MPN diagnosis. On converse, multiple myeloma was rarely reported in PV patients and was preferentially diagnosed in female patients not harboring the JAK2 V617F mutation. Based on the 46 cases reporting follow-up data, median survival after MPN diagnosis was 96 months. This thorough review of published evidence confirms that LPD are relevant clinical events in the history of MPN patients. Controlled studies are needed to better refine individuals at higher risk of developing LPD, to support surveillance programs and to avoid therapies possibly favoring LPD. © 2018 Wiley Periodicals, Inc.

Recommendations for the use of microarrays in prenatal diagnosis.

PubMed

Suela, Javier; López-Expósito, Isabel; Querejeta, María Eugenia; Martorell, Rosa; Cuatrecasas, Esther; Armengol, Lluis; Antolín, Eugenia; Domínguez Garrido, Elena; Trujillo-Tiebas, María José; Rosell, Jordi; García Planells, Javier; Cigudosa, Juan Cruz

2017-04-07

Microarray technology, recently implemented in international prenatal diagnosis systems, has become one of the main techniques in this field in terms of detection rate and objectivity of the results. This guideline attempts to provide background information on this technology, including technical and diagnostic aspects to be considered. Specifically, this guideline defines: the different prenatal sample types to be used, as well as their characteristics (chorionic villi samples, amniotic fluid, fetal cord blood or miscarriage tissue material); variant reporting policies (including variants of uncertain significance) to be considered in informed consents and prenatal microarray reports; microarray limitations inherent to the technique and which must be taken into account when recommending microarray testing for diagnosis; a detailed clinical algorithm recommending the use of microarray testing and its introduction into routine clinical practice within the context of other genetic tests, including pregnancies in families with a genetic history or specific syndrome suspicion, first trimester increased nuchal translucency or second trimester heart malformation and ultrasound findings not related to a known or specific syndrome. This guideline has been coordinated by the Spanish Association for Prenatal Diagnosis (AEDP, «Asociación Española de Diagnóstico Prenatal»), the Spanish Human Genetics Association (AEGH, «Asociación Española de Genética Humana») and the Spanish Society of Clinical Genetics and Dysmorphology (SEGCyD, «Sociedad Española de Genética Clínica y Dismorfología»). Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Dendritic cell and histiocytic neoplasms: biology, diagnosis, and treatment.

PubMed

Dalia, Samir; Shao, Haipeng; Sagatys, Elizabeth; Cualing, Hernani; Sokol, Lubomir

2014-10-01

Dendritic and histiocytic cell neoplasms are rare malignancies that make up less than 1% of all neoplasms arising in lymph nodes or soft tissues. These disorders have distinctive disease biology, clinical presentations, pathology, and unique treatment options. Morphology and immunohistochemistry evaluation by a hematopathologist remains key for differentiating between these neoplasms. In this review, we describe tumor biology, clinical features, pathology, and treatment of follicular dendritic cell sarcoma, interdigitating dendritic cell sarcoma, indeterminate dendritic cell sarcoma, histiocytic sarcoma, fibroblastic reticular cell tumors, and disseminated juvenile xanthogranuloma. A literature search for articles published between 1990 and 2013 was undertaken. Articles are reviewed and salient findings are systematically described. Patients with dendritic cell and histiocytic neoplasms have distinct but variable clinical presentations; however, because many tumors have recently been recognized, their true incidence is uncertain. Although the clinical features can present in many organs, most occur in the lymph nodes or skin. Most cases are unifocal and solitary presentations have good prognoses with surgical resection. The role of adjuvant therapy in these disorders remains unclear. In cases with disseminated disease, prognosis is poor and data on treatment options are limited, although chemotherapy and referral to a tertiary care center should be considered. Excisional biopsy is the preferred method of specimen collection for tissue diagnosis, and immunohistochemistry is the most important diagnostic method for differentiating these disorders from other entities. Dendritic cell and histiocytic cell neoplasms are rare hematological disorders with variable clinical presentations and prognoses. Immunohistochemistry remains important for diagnosis. Larger pooled analyses or clinical trials are needed to better understand optimal treatment options in these rare disorders. Whenever possible, patients should be referred to a tertiary care center for disease management.

Identifying Model-Based Reconfiguration Goals through Functional Deficiencies

NASA Technical Reports Server (NTRS)

Benazera, Emmanuel; Trave-Massuyes, Louise

2004-01-01

Model-based diagnosis is now advanced to the point autonomous systems face some uncertain and faulty situations with success. The next step toward more autonomy is to have the system recovering itself after faults occur, a process known as model-based reconfiguration. After faults occur, given a prediction of the nominal behavior of the system and the result of the diagnosis operation, this paper details how to automatically determine the functional deficiencies of the system. These deficiencies are characterized in the case of uncertain state estimates. A methodology is then presented to determine the reconfiguration goals based on the deficiencies. Finally, a recovery process interleaves planning and model predictive control to restore the functionalities in prioritized order.

Postmortem audit in a paediatric cardiology unit.

PubMed Central

Russell, G A; Berry, P J

1989-01-01

Postmortem examinations performed on 76 children with a clinical diagnosis of congenital heart disease were reviewed retrospectively and compared with the findings before death. Both operated and unoperated cases were studied over a three year period. Despite intensive investigation during life, there was a high rate of unsuspected abnormalities at necropsy (80%): 29 cases had undiagnosed additional cardiac anomalies or surgical flaws, which contributed to death in 13 cases. Defects in surgery were uncommon but permitted modification in surgical technique to avoid recurrence. Myocardial necrosis and pulmonary foreign body embolism were common findings, the importance of which is uncertain and requires further study for their prevention. Even in the most thoroughly investigated cases postmortem examination has a high yield of clinically important pathology which is undetected during life. Images PMID:2794078

Differential diagnosis between tuberculous spondylodiscitis and pyogenic spontaneous spondylodiscitis: a multicenter descriptive and comparative study.

PubMed

Yoon, Young K; Jo, Yu M; Kwon, Hyun H; Yoon, Hee J; Lee, Eun J; Park, So Y; Park, Seong Y; Choo, Eun J; Ryu, Seong Y; Lee, Mi S; Yang, Kyung S; Kim, Shin W

2015-08-01

Although tuberculous and pyogenic spondylodiscitis are common causes of spinal infections, their protean manifestation complicates differential diagnosis. The clinical, laboratory, and radiologic characteristics of tuberculous and pyogenic spontaneous spondylodiscitis were compared in this study. This multicenter retrospective study was conducted in 11 teaching hospitals in the Republic of Korea from January 2011 to December 2013. Study subjects included adult patients (≥18 years) diagnosed with tuberculous (n=60) or pyogenic (n=117) spontaneous spondylodiscitis. Risk factors for tuberculous spondylodiscitis were determined, and their predictive performance was evaluated. Multivariate logistic regression analysis was performed to determine predictors independently associated with tuberculous spondylodiscitis. Receiver-operating characteristic curve analysis using the presence or absence of risk factors was used to generate a risk index to identify patients with increased probability of tuberculous spondylodiscitis. Of 177 patients, multivariate logistic regression analysis showed that patients with tuberculous spondylodiscitis (n=60) were more frequently women, with increased nonlumbar spinal involvement and associated non-spinal lesions, delayed diagnosis, higher serum albumin levels, reduced white blood cell counts, and lower C-reactive protein and procalcitonin levels. Among 117 patients with pyogenic spondylodiscitis, the most frequent causative microorganism was Staphylococcus aureus (64.1%). The mean diagnostic delay was significantly shorter, which may reflect higher clinical expression leading to earlier diagnosis. A combination of clinical data and biomarkers had better predictive value for differential diagnosis compared with biomarkers alone, with an area under the curve of 0.93, and sensitivity, specificity, and positive and negative predictive values of 95.0%, 79.5%, 70.4%, and 96.9%, respectively. This study provides guidance for clinicians to predict the causative organisms of spondylodiscitis in uncertain situations and before culture or pathologic examinations. Clinical data and single biomarkers combined can be useful for differential diagnoses between tuberculous and pyogenic spondylodiscitis. Copyright © 2015. Published by Elsevier Inc.

Diagnostic and therapeutic value of laparoscopy for small bowel blunt injuries: A case report.

PubMed

Addeo, Pietro; Calabrese, Daniela Paola

2011-01-01

Small bowel injuries after blunt abdominal trauma represent both a diagnostic and a therapeutic challenge. Early diagnosis and prompt treatment are necessary in order to avoid a dangerous diagnostic delay. Laparoscopy can represent a diagnostic and therapeutic tool in patients with uncertain clinical symptoms. We report the case of a 25-year-old man, haemodynamically stable, admitted for acute abdominal pain a few hours after a physical assault. Giving the persistence of the abdominal pain and the presence of free fluids at the computed tomography examination, an exploratory laparoscopy was performed. At the laparoscopic exploration, an isolated small bowel perforation was found, 60 cm distal from the ligament of Treitz. The injury was repaired by laparoscopic suturing and the patient was discharged home at postoperative day 3 after an uneventful postoperative course. Laparoscopy represents a valuable tool for patients with small bowel blunt injuries allowing a timely diagnosis and a prompt treatment.

Determinants of parental decision to abort or continue after non-aneuploid ultrasound-detected fetal abnormalities.

PubMed

Pryde, P G; Isada, N B; Hallak, M; Johnson, M P; Odgers, A E; Evans, M I

1992-07-01

This study evaluated factors influencing the decision to abort after abnormalities in the karyotypically normal fetus were found through ultrasonography. We reviewed all pregnancies complicated by ultrasound-detected abnormalities managed on our service from April 1990 through August 1991 (N = 262). Cases with associated karyotypic abnormalities were excluded (N = 35), as were cases diagnosed after the legal gestational age limit for abortion (N = 68). The remaining 159 cases were stratified into prognosis groups of "severe," "uncertain," and "mild." The prognostic severity of the ultrasound abnormality strongly correlated with the decision to abort (P less than .0001). Rates of termination were 0, 12, and 66% in the "mild," "uncertain," and "severe" groups, respectively. The patients' age, gravidity, and parity, and the fetal gestational age at diagnosis did not differ significantly between the groups. 1) In non-aneuploid pregnancies with an ultrasound diagnosis of fetal abnormality, the major predictor of the decision to abort was the severity of fetal prognosis. 2) The gestational age at diagnosis was not an important variable in the decision to abort for fetal structural abnormalities. 3) Parents who had fetuses with abnormalities associated with uncertain prognoses usually opted to continue the pregnancy. This appeared to be particularly true for defects that were potentially correctable in utero or by neonatal intervention (even if investigational).

Risk factors for the development of invasive cancer in unresected ductal carcinoma in situ.

PubMed

Maxwell, Anthony J; Clements, Karen; Hilton, Bridget; Dodwell, David J; Evans, Andrew; Kearins, Olive; Pinder, Sarah E; Thomas, Jeremy; Wallis, Matthew G; Thompson, Alastair M

2018-04-01

The natural history of ductal carcinoma in situ (DCIS) remains uncertain. The risk factors for the development of invasive cancer in unresected DCIS are unclear. Women diagnosed with DCIS on needle biopsy after 1997 who did not undergo surgical resection for ≥1 year after diagnosis were identified by breast centres and the cancer registry and outcomes were reviewed. Eighty-nine women with DCIS diagnosed 1998-2010 were identified. The median age at diagnosis was 75 (range 44-94) years with median follow-up (diagnosis to death, invasive disease or last review) of 59 (12-180) months. Twenty-nine women (33%) developed invasive breast cancer after a median interval of 45 (12-144) months. 14/29 (48%) with high grade, 10/31 (32%) with intermediate grade and 3/17 (18%) with low grade DCIS developed invasive cancer after median intervals of 38, 60 and 51 months. The cumulative incidence of invasion was significantly higher in high grade DCIS than other grades (p = .0016, log-rank test). Invasion was more frequent in lesions with calcification as the predominant feature (23/50 v. 5/25; p = .042) and in younger women (p = .0002). Endocrine therapy was associated with a lower rate of invasive breast cancer (p = .048). High cytonuclear grade, mammographic microcalcification, young age and lack of endocrine therapy were risk factors for DCIS progression to invasive cancer. Surgical excision of high grade DCIS remains the treatment of choice. Given the uncertain long-term natural history of non-high grade DCIS, the option of active surveillance of women with this condition should be offered within a clinical trial. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

Accuracy of dengue clinical diagnosis with and without NS1 antigen rapid test: Comparison between human and Bayesian network model decision.

PubMed

Sa-Ngamuang, Chaitawat; Haddawy, Peter; Luvira, Viravarn; Piyaphanee, Watcharapong; Iamsirithaworn, Sopon; Lawpoolsri, Saranath

2018-06-18

Differentiating dengue patients from other acute febrile illness patients is a great challenge among physicians. Several dengue diagnosis methods are recommended by WHO. The application of specific laboratory tests is still limited due to high cost, lack of equipment, and uncertain validity. Therefore, clinical diagnosis remains a common practice especially in resource limited settings. Bayesian networks have been shown to be a useful tool for diagnostic decision support. This study aimed to construct Bayesian network models using basic demographic, clinical, and laboratory profiles of acute febrile illness patients to diagnose dengue. Data of 397 acute undifferentiated febrile illness patients who visited the fever clinic of the Bangkok Hospital for Tropical Diseases, Thailand, were used for model construction and validation. The two best final models were selected: one with and one without NS1 rapid test result. The diagnostic accuracy of the models was compared with that of physicians on the same set of patients. The Bayesian network models provided good diagnostic accuracy of dengue infection, with ROC AUC of 0.80 and 0.75 for models with and without NS1 rapid test result, respectively. The models had approximately 80% specificity and 70% sensitivity, similar to the diagnostic accuracy of the hospital's fellows in infectious disease. Including information on NS1 rapid test improved the specificity, but reduced the sensitivity, both in model and physician diagnoses. The Bayesian network model developed in this study could be useful to assist physicians in diagnosing dengue, particularly in regions where experienced physicians and laboratory confirmation tests are limited.

N-terminal pro-brain natriuretic peptide and high-sensitivity troponin in the evaluation of acute chest pain of uncertain etiology. A PITAGORAS substudy.

PubMed

Sanchis, Juan; Bardají, Alfredo; Bosch, Xavier; Loma-Osorio, Pablo; Marín, Francisco; Sánchez, Pedro L; Calvo, Francisco; Avanzas, Pablo; Hernández, Carolina; Serrano, Silvia; Carratalá, Arturo; Barrabés, José A

2013-07-01

High-sensitivity troponin assays have improved the diagnosis of acute coronary syndrome in patients presenting with chest pain and normal troponin levels as measured by conventional assays. Our aim was to investigate whether N-terminal pro-brain natriuretic peptide provides additional information to troponin determination in these patients. A total of 398 patients, included in the PITAGORAS study, presenting to the emergency department with chest pain and normal troponin levels as measured by conventional assay in 2 serial samples (on arrival and 6 h to 8h later) were studied. The samples were also analyzed in a central laboratory for high-sensitivity troponin T (both samples) and for N-terminal pro-brain natriuretic peptide (second sample). The endpoints were diagnosis of acute coronary syndrome and the composite endpoint of in-hospital revascularization or a 30-day cardiac event. Acute coronary syndrome was adjudicated to 79 patients (20%) and the composite endpoint to 59 (15%). When the N-terminal pro-brain natriuretic peptide quartile increased, the diagnosis of acute coronary syndrome also increased (12%, 16%, 23% and 29%; P=.01), as did the risk of the composite endpoint (6%, 13%, 16% and 24%; P=.004). N-terminal pro-brain natriuretic peptide elevation (>125ng/L) was associated with both endpoints (relative risk= 2.0; 95% confidence interval, 1.2-3.3; P=.02; relative risk=2.4; 95% confidence interval, 1.4-4.2; P=.004). However, in the multivariable models adjusted by clinical and electrocardiographic data, a predictive value was found for high-sensitivity T troponin but not for N-terminal pro-brain natriuretic peptide. In low-risk patients with chest pain of uncertain etiology evaluated using high-sensitivity T troponin, N-terminal pro-brain natriuretic peptide does not contribute additional predictive value to diagnosis or the prediction of short-term outcomes. Copyright © 2012 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

KBG syndrome involving a single-nucleotide duplication in ANKRD11

PubMed Central

Kleyner, Robert; Malcolmson, Janet; Tegay, David; Ward, Kenneth; Maughan, Annette; Maughan, Glenn; Nelson, Lesa; Wang, Kai; Robison, Reid; Lyon, Gholson J.

2016-01-01

KBG syndrome is a rare autosomal dominant genetic condition characterized by neurological involvement and distinct facial, hand, and skeletal features. More than 70 cases have been reported; however, it is likely that KBG syndrome is underdiagnosed because of lack of comprehensive characterization of the heterogeneous phenotypic features. We describe the clinical manifestations in a male currently 13 years of age, who exhibited symptoms including epilepsy, severe developmental delay, distinct facial features, and hand anomalies, without a positive genetic diagnosis. Subsequent exome sequencing identified a novel de novo heterozygous single base pair duplication (c.6015dupA) in ANKRD11, which was validated by Sanger sequencing. This single-nucleotide duplication is predicted to lead to a premature stop codon and loss of function in ANKRD11, thereby implicating it as contributing to the proband's symptoms and yielding a molecular diagnosis of KBG syndrome. Before molecular diagnosis, this syndrome was not recognized in the proband, as several key features of the disorder were mild and were not recognized by clinicians, further supporting the concept of variable expressivity in many disorders. Although a diagnosis of cerebral folate deficiency has also been given, its significance for the proband's condition remains uncertain. PMID:27900361

Gestational Trophoblastic Disease: A Multimodality Imaging Approach with Impact on Diagnosis and Management

PubMed Central

Ramani, Subhash; Thakur, Meenkashi

2014-01-01

Gestational trophoblastic disease is a condition of uncertain etiology, comprised of hydatiform mole (complete and partial), invasive mole, choriocarcinoma, and placental site trophoblastic tumor. It arises from abnormal proliferation of trophoblastic tissue. Early diagnosis of gestational trophoblastic disease and its potential complications is important for timely and successful management of the condition with preservation of fertility. Initial diagnosis is based on a multimodality approach: encompassing clinical features, serial quantitative β-hCG titers, and pelvic ultrasonography. Pelvic magnetic resonance imaging (MRI) is sometimes used as a problem-solving tool to assess the depth of myometrial invasion and extrauterine disease spread in equivocal and complicated cases. Chest radiography, body computed tomography (CT), and brain MRI have been recommended as investigative tools for overall disease staging. Angiography has a role in management of disease complications and metastases. Efficacy of PET (positron emission tomography) and PET/CT in the evaluation of recurrent or metastatic disease has not been adequately investigated yet. This paper discusses the imaging features of gestational trophoblastic disease on various imaging modalities and the role of different imaging techniques in the diagnosis and management of this entity. PMID:25126425

Canine blastomycosis in Wisconsin: a survey of small-animal veterinary practices.

PubMed

Anderson, Jennifer L; Dieckman, Jordan L; Reed, Kurt D; Meece, Jennifer K

2014-10-01

The disease burden and impact of canine blastomycosis in Wisconsin is uncertain. We surveyed small-animal veterinary practices to obtain estimates of disease incidence, determine patient outcomes, and investigate variation in diagnostic and treatment strategies used by veterinarians. Veterinarians representing small-animal practices in Wisconsin were contacted by mail with the option to complete a paper or online questionnaire. Questionnaires were returned from 68 of 443 veterinary practices (15%) that estimated diagnosing 239 cases of canine blastomycosis annually, with an overall mortality of 36%. Annual incidence rates of canine blastomycosis were calculated for 43 individual veterinary clinics and differed significantly between clinics in endemic and nonendemic counties (P = 0.01), with the mean in endemic counties being 204/100,000/yr and nonendemic counties being 72/100,000/yr. Veterinarians reported an increase in canine blastomycosis cases from April through August. A wide variety of methods were used for diagnosis, ranging from clinical signs alone to antigen testing and "in-house" cytology. Of note, fungal culture was used rarely for diagnosis. In addition, veterinarians at these 68 clinics estimated diagnosing 36 cases of feline blastomycosis annually. The incidence of canine blastomycosis is high but quite variable among veterinary practices in Wisconsin. Diagnosis is based frequently on clinical signs exclusively due, in part, to the perceived high cost of laboratory tests. Similarly, the mortality associated with blastomycosis is likely negatively impacted because some dog owners defer therapy due to the cost of antifungal drugs. © The Author 2014. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Technological innovations in the development of cardiovascular clinical information systems.

PubMed

Hsieh, Nan-Chen; Chang, Chung-Yi; Lee, Kuo-Chen; Chen, Jeen-Chen; Chan, Chien-Hui

2012-04-01

Recent studies have shown that computerized clinical case management and decision support systems can be used to assist surgeons in the diagnosis of disease, optimize surgical operation, aid in drug therapy and decrease the cost of medical treatment. Therefore, medical informatics has become an extensive field of research and many of these approaches have demonstrated potential value for improving medical quality. The aim of this study was to develop a web-based cardiovascular clinical information system (CIS) based on innovative techniques, such as electronic medical records, electronic registries and automatic feature surveillance schemes, to provide effective tools and support for clinical care, decision-making, biomedical research and training activities. The CIS developed for this study contained monitoring, surveillance and model construction functions. The monitoring layer function provided a visual user interface. At the surveillance and model construction layers, we explored the application of model construction and intelligent prognosis to aid in making preoperative and postoperative predictions. With the use of the CIS, surgeons can provide reasonable conclusions and explanations in uncertain environments.

Sensor fault diagnosis of singular delayed LPV systems with inexact parameters: an uncertain system approach

NASA Astrophysics Data System (ADS)

Hassanabadi, Amir Hossein; Shafiee, Masoud; Puig, Vicenc

2018-01-01

In this paper, sensor fault diagnosis of a singular delayed linear parameter varying (LPV) system is considered. In the considered system, the model matrices are dependent on some parameters which are real-time measurable. The case of inexact parameter measurements is considered which is close to real situations. Fault diagnosis in this system is achieved via fault estimation. For this purpose, an augmented system is created by including sensor faults as additional system states. Then, an unknown input observer (UIO) is designed which estimates both the system states and the faults in the presence of measurement noise, disturbances and uncertainty induced by inexact measured parameters. Error dynamics and the original system constitute an uncertain system due to inconsistencies between real and measured values of the parameters. Then, the robust estimation of the system states and the faults are achieved with H∞ performance and formulated with a set of linear matrix inequalities (LMIs). The designed UIO is also applicable for fault diagnosis of singular delayed LPV systems with unmeasurable scheduling variables. The efficiency of the proposed approach is illustrated with an example.

Inflammatory Myofibroblastic Tumor Mimicking Apical Periodontitis.

PubMed

Adachi, Makoto; Kiho, Kazuki; Sekine, Genta; Ohta, Takahisa; Matsubara, Makoto; Yoshida, Takakazu; Katsumata, Akitoshi; Tanuma, Jun-ichi; Sumitomo, Shinichiro

2015-12-01

Inflammatory myofibroblastic tumors (IMTs) are rare. IMTs of the head and neck occur in all age groups, from neonates to old age, with the highest incidence occurring in childhood and early adulthood. An IMT has been defined as a histologically distinctive lesion of uncertain behavior. This article describes an unusual case of IMT mimicking apical periodontitis in the mandible of a 42-year-old man. At first presentation, the patient showed spontaneous pain and percussion pain at teeth #28 to 30, which continued after initial endodontic treatment. Panoramic radiography revealed a radiolucent lesion at the site. Cone-beam computed tomographic imaging showed osteolytic lesions, suggesting an aggressive neoplasm requiring incisional biopsy. Histopathological examination indicated an IMT. The lesion was removed en bloc under general anesthesia, and the patient manifested no clinical evidence of recurrence for 24 months. Lesions of nonendodontic origin should be included in the differential diagnosis of apical periodontitis. Every available diagnostic tool should be used to confirm the diagnosis. Cone-beam computed tomographic imaging is very helpful for differential diagnosis in IMTs mimicking apical periodontitis. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Overview of recent trends in diagnosis and management of leptomeningeal multiple myeloma.

PubMed

Yellu, Mahender R; Engel, Jessica M; Ghose, Abhimanyu; Onitilo, Adedayo A

2016-03-01

Neurological complications related to multiple myeloma (MM) are not uncommon; however, direct involvement of the central nervous system (CNS) is extremely rare and represents a diagnostic and therapeutic challenge. Significant survival difference has been noted with the introduction of novel therapy in patients with MM, but their effect on the incidence and their use for management of leptomeningeal myeloma (LMM) is uncertain. Analysis of published data demonstrates its recent increased incidence, median time to CNS presentation, and slight improvement in median survival after diagnosis of LMM. Less common MM isotypes have been overrepresented in LMM. CNS relapse occurred mostly in patients with Durie-Salmon stage III MM. Despite treatments, standard or experimental, the survival rates of LMM remain dismal. Monitoring high risk patients closely, even after achieving complete remission, may be useful in early detection of LMM. As we gain better understanding of LMM, we recommend that future research and clinical care focus on earlier diagnosis and development of more efficient CNS-directed therapy to improve survival in this patient population. Copyright © 2014 John Wiley & Sons, Ltd.

Misdiagnosis of primary immune thrombocytopenia and frequency of bleeding: lessons from the McMaster ITP Registry

PubMed Central

Nazy, Ishac; Clare, Rumi; Jaffer, Anushka M.; Aubie, Brandon; Li, Na; Kelton, John G.

2017-01-01

Nonspecific diagnostic criteria and uncertain estimates of severe bleeding events are fundamental gaps in knowledge of primary immune thrombocytopenia (ITP). To address these issues, we created the McMaster ITP Registry. In this report, we describe the methodology of the registry, the process for arriving at the diagnosis, and the frequency of bleeding. Consecutive patients with platelets <150 × 109/L from a tertiary hematology clinic in Canada were eligible. Patients completed a panel of investigations and were managed per clinical need. Two hematologists initially determined the cause of the thrombocytopenia using standard criteria and reevaluated the diagnosis over time, which was adjudicated at regular team meetings. Bleeding was graded from 0 (none) to 2 (severe) prospectively using an ITP-specific tool. Data were validated by duplicate chart review and source verification. Between 2010 and 2016, 614 patients were enrolled. Median follow-up for patients with >1 visit was 1.7 years (interquartile range, 0.8-3.4). At registration, 295 patients were initially diagnosed with primary ITP; of those, 36 (12.2%) were reclassified as having a different diagnosis during follow-up. At registration, 319 patients were initially diagnosed with another thrombocytopenic condition; of those, 10 (3.1%) were ultimately reclassified as having primary ITP. Of 269 patients with a final diagnosis of primary ITP, 56.5% (95% confidence interval [CI], 50.4-62.5] experienced grade 2 bleeding at 1 or more anatomical site, and 2.2% (95% CI, 0.8-4.8) had intracranial hemorrhage. Nearly 1 in 7 patients with primary ITP were misdiagnosed. Grade 2 bleeding was common. Registry data can help improve the clinical and laboratory classification of patients with ITP. PMID:29296891

The cystic dilation of ventriculus terminalis with neurological symptoms: Three case reports and a literature review.

PubMed

Lotfinia, Iraj; Mahdkhah, Ata

2018-05-23

The ventriculus terminalis (VT) is a very small ependymal-lined residual lumen in the conus medullaris. It is normally present in all subjects during fetal development. VT in adults appears as an unusual pathology with an uncertain pathogenesis. In this paper, we described three case reports of symptomatic fifth ventricle cystic dilations. All of them were female and their mean age was 59 years. We treated them surgically and all three patients were improved based on clinical and imaging assessments. Our cases suggested that surgical decompression was a safe and effective treatment in symptomatic patients and the neurosurgeons should be aware of such rare situations. A complete list of differential diagnosis about other cystic dilations of the conus medullaris should be emphasized to select the correct clinical approach.

Peripheral cemento-ossifying fibroma: A case report with review of literature

PubMed Central

Mishra, Amit Kumar; Maru, Rahul; Dhodapkar, Shrikant Vishnuprasad; Jaiswal, Gagan; Kumar, Rajesh; Punjabi, Heena

2013-01-01

Peripheral cemento-ossifying fibroma (PCOF) is a rare osteogenic neoplasm that ordinarily presents as an epulis-like growth. This is of a reactive rather than neoplastic nature and its pathogenesis is uncertain. PCOF predominantly affects adolescent and young adults with greatest prevalence around 28 years. We report here a rare clinical case of PCOF of the mandible, 1 cm mesiodistally and 1.5 cm occluso-gingivally in diameter, which caused difficulty in eating and speech, in a 42-year-old female patient. She was asymptomatic for 1 year and on follow-up for 6 mo post surgically showed gingival health and normal radioopacity of bone without any recurrence. Clinical, radiographic and histological characteristics are discussed and recommendations regarding differential diagnosis, treatment and follow up are provided. The controversial varied nomenclature and possible etiopathogenesis of PCOF are emphasized. PMID:24303483

Peripheral cemento-ossifying fibroma: A case report with review of literature.

PubMed

Mishra, Amit Kumar; Maru, Rahul; Dhodapkar, Shrikant Vishnuprasad; Jaiswal, Gagan; Kumar, Rajesh; Punjabi, Heena

2013-06-16

Peripheral cemento-ossifying fibroma (PCOF) is a rare osteogenic neoplasm that ordinarily presents as an epulis-like growth. This is of a reactive rather than neoplastic nature and its pathogenesis is uncertain. PCOF predominantly affects adolescent and young adults with greatest prevalence around 28 years. We report here a rare clinical case of PCOF of the mandible, 1 cm mesiodistally and 1.5 cm occluso-gingivally in diameter, which caused difficulty in eating and speech, in a 42-year-old female patient. She was asymptomatic for 1 year and on follow-up for 6 mo post surgically showed gingival health and normal radioopacity of bone without any recurrence. Clinical, radiographic and histological characteristics are discussed and recommendations regarding differential diagnosis, treatment and follow up are provided. The controversial varied nomenclature and possible etiopathogenesis of PCOF are emphasized.

The frequency of CSF oligoclonal banding in multiple sclerosis increases with latitude.

PubMed

Lechner-Scott, J; Spencer, B; de Malmanche, T; Attia, J; Fitzgerald, M; Trojano, M; Grand'Maison, F; Gomez, J Antonio C; Izquierdo, G; Duquette, P; Girard, M; Grammond, P; Oreja-Guevara, C; Hupperts, R; Bergamaschi, R; Boz, C; Giuliani, G; van Pesch, V; Iuliano, G; Fiol, M; Cristiano, E; Verheul, F; Saladino, M Laura; Slee, M; Barnett, M; Deri, N; Flechter, S; Vella, N; Shaw, C; Herbert, J; Moore, F; Petkovska-Boskova, T; Jokubaitis, V; Butzkueven, H

2012-07-01

With the advent of MRI scanning, the value of lumbar puncture to assess oligoclonal band (OCB) status-for the diagnosis of multiple sclerosis (MS) is increasingly uncertain. One major issue is that the reported frequency of cerebrospinal fluid (CSF)-restricted oligoclonal banding for the diagnosis of MS varies considerably in different studies. In addition, the relationship between OCB positivity and disease outcome remains uncertain, as reported studies are generally too small to assess comparative disability outcomes with sufficient power. In order to further investigate variation of OCB positivity in patients with MS, we utilized MSBase, a longitudinal, Web-based collaborative MS outcomes registry following clinical cohorts in several continents and latitudes. We also assessed whether OCB positivity affects long-term disability outcome. A total of 13,242 patient records were obtained from 37 MS specialist centres in 19 different countries. OCB status was documented in 4481 (34%) patients and 80% of these were OCB positive. The presence of OCB was associated with degree of latitude (p = 0.02). Furthermore, the outcome of patients negative for CSF-specific OCB was significantly better in comparison to the OCB positive patients, as assessed by Expanded Disability Status Scale change (p < 0.001). The results of this study indicate that latitude could explain some of the inconsistencies in OCB status reported in different populations. The study confirms that OCB positivity in MS is associated with a worse long-term prognosis.

Granulomatous lobular mastitis: difficulty of diagnosis.

PubMed

Kanazawa, S; Nagae, T; Fukuda, K; Katsu, I; Mukai, N; Sugihara, Y; Otani, H; Higami, Y; Tsunoda, T

2000-02-01

We report a case of a rare inflammatory disease, granulomatous lobular mastitis. Two weeks prior to admission the patient, a 43 year-old woman, (gravida 1, para 1) had noticed a left breast mass associated with tenderness. Palpation, gross inspection, and clinical examination, as well as the rapid growth of the mass lesion led us to believe that it was highly suspicious of malignant neoplasm. Mammography, ultrasonography, and computed tomography did not differentiate it from a malignant neoplasm. Aspiration cytology revealed an inflammatory lesion with a few clusters of epithelial cells it was diagnosed as borderline malignancy(class III) by a prudent pathologist, and thus mastectomy was performed. However, the final histologi-cal diagnosis was granulomatous lobular mastitis with no evidence of malignancy. As the clinical manifestations of granulomatous mastitis are similar to those of mammary carcinoma and, as it is an inflammatory lesion of uncertain etiology and pathogenesis, it has often been mistaken clinically for carcinoma and treated as such. Our review of the literature indicated that granulomatous mastitis most often occurs in young patients with a history of childbirth or oral contraceptive usage. Recurrence was documented in 38% of patients, and, accordingly long-term follow-up by aspiration cytology, complete resection, and adequate drug treatment with corticosteroids are recommended.

The liquid biopsy: a tool for a combined diagnostic and theranostic approach for care of a patient with late-stage lung carcinoma presenting with bilateral ocular metastases.

PubMed

Bouhlel, Linda; Hofman, Véronique; Maschi, Célia; Ilié, Marius; Allégra, Maryline; Marquette, Charles-Hugo; Audigier-Valette, Clarisse; Thariat, Juliette; Hofman, Paul

2017-12-01

Liquid biopsies (LB) are used routinely in clinical practice in two situations for late stage non-small-cell lung cancer (NSCLC) patients, (i) at the initial diagnosis when looking for activating mutations in EGFR in the absence of analyzable tissue DNA and, (ii) during tumor progression on a tyrosine kinase inhibitor treatment to look for the resistance mutation T790M in EGFR. LB is not presently recommended in daily practice for the diagnosis of NSCLC. Areas covered: We report the diagnosis of a NSCLC in a patient with bilateral ocular metastases after detection of a deletion in exon 19 of EGFR when using plasma DNA. Without histological analysis, the origin of the primary ocular metastasis was uncertain. In this context, a LB showing an activating mutation in EGFR and circulating tumor cells positive for TTF1 led to the diagnosis of NSCLC and targeted therapy. Expert commentary: When no tumor tissue sample is available a LB can be used to diagnose for metastatic NSCLC, when a mutation in EGFR is identified. While a tissue biopsy is the gold standard approach for the diagnosis of a NSCLC and for identification of activating mutations, LB can exceptionally provide both a diagnosis of the primitive tumor and indicate appropriate therapy based on a molecular analysis.

Rationale and design of three observational, prospective cohort studies including biobanking to evaluate and improve diagnostics, management strategies and risk stratification in venous thromboembolism: the VTEval Project

PubMed Central

Frank, Bernd; Ariza, Liana; Lamparter, Heidrun; Grossmann, Vera; Prochaska, Jürgen H; Ullmann, Alexander; Kindler, Florentina; Weisser, Gerhard; Walter, Ulrich; Lackner, Karl J; Espinola-Klein, Christine; Münzel, Thomas; Konstantinides, Stavros V; Wild, Philipp S

2015-01-01

Introduction Venous thromboembolism (VTE) with its two manifestations deep vein thrombosis (DVT) and pulmonary embolism (PE) is a major public health problem. The VTEval Project aims to investigate numerous research questions on diagnosis, clinical management, treatment and prognosis of VTE, which have remained uncertain to date. Methods and analysis The VTEval Project consists of three observational, prospective cohort studies on VTE comprising cohorts of individuals with a clinical suspicion of acute PE (with or without DVT), with a clinical suspicion of acute DVT (without symptomatic PE) and with an incidental diagnosis of VTE (PE or DVT). The VTEval Project expects to enrol a total of approximately 2000 individuals with subsequent active and passive follow-up investigations over a time period of 5 years per participant. Time points for active follow-up investigations are at months 3, 6, 12, 24 and 36 after diagnosis (depending on the disease cohort); passive follow-up investigations via registry offices and the cancer registry are performed 48 and 60 months after diagnosis for all participants. Primary short-term outcome is defined by overall mortality (PE-related death and all other causes of death), primary long-term outcome by symptomatic VTE (PE-related death, recurrence of non-fatal PE or DVT). The VTEval Project includes three ‘all-comer’ studies and involves the standardised acquisition of high-quality data, covering the systematic assessment of VTE including symptoms, risk profile, psychosocial, environmental and lifestyle factors as well as clinical and subclinical disease, and it builds up a large state-of-the-art biorepository containing various materials from serial blood samplings. Ethics and dissemination The VTEval Project has been approved by the local data safety commissioner and the responsible ethics committee (reference no. 837.320.12 (8421-F)). Trial results will be published in peer-reviewed journals and presented at national and international scientific meetings. Trial registration number NCT02156401. PMID:26133379

Guidelines for the clinical management and follow-up of infants with inconclusive cystic fibrosis diagnosis through newborn screening.

PubMed

Sermet-Gaudelus, I; Brouard, J; Audrézet, M-P; Couderc Kohen, L; Weiss, L; Wizla, N; Vrielynck, S; LLerena, K; Le Bourgeois, M; Deneuville, E; Remus, N; Nguyen-Khoa, T; Raynal, C; Roussey, M; Girodon, E

2017-12-01

Neonatal screening for cystic fibrosis (CF) can detect infants with elevated immunoreactive trypsinogen (IRT) levels and inconclusive sweat tests and/or CFTR DNA results. These cases of uncertain diagnosis are defined by (1) either the presence of at most one CF-associated cystic fibrosis transmembrane conductance regulator (CFTR) mutation with sweat chloride values between 30 and 59mmol/L or (2) two CFTR mutations with at least one of unknown pathogenic potential and a sweat chloride concentration below 60mmol/L. This encompasses various clinical situations whose progression cannot be predicted. In these cases, a sweat chloride test has to be repeated at 12 months, and if possible at 6 and 24 months of life along with extended CFTR sequencing to detect rare mutations. When the diagnosis is not definite, CFTR functional explorations may provide a better understanding of CFTR dysfunction. The initial evaluation of these infants must be conducted in dedicated CF reference centers and should include bacteriological sputum analysis, chest radiology, and fecal elastase assay. The primary care physicians in charge of these patients should be familiar with the current management of CF and should work in collaboration with CF centers. A follow-up should be performed in a CF reference center at 3, 6, and 12 months of life and every year thereafter. Any symptom indicative of CF requires immediate reevaluation of the diagnosis. These guidelines were established by the "neonatal screening and difficult diagnoses" working group of the French CF society. Their objective is to standardize the management of infants with unclear diagnosis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

When doctors disagree: a qualitative study of doctors’ and parents’ views on the risks of childhood food allergy

PubMed Central

Hu, Wendy; Grbich, Carol; Kemp, Andrew

2008-01-01

Abstract Objective  To examine the views of doctors which underpin clinical practice variation concerning an uncertain health risk, and the views of parents who had sought advice from these doctors, using the example of childhood food allergy. Study design  Qualitative study involving in‐depth interviews and participant observation over 16 months. Focus groups and consultation audio‐recordings provided corroborative data. Setting  Three specialist allergy clinics located in one metropolitan area. Participants  Eighteen medical specialists and trainees in allergy, and 85 parents (from 69 families) with food allergic children. Results  Doctors expressed a spectrum of views. The most divergent views were characterized by: scientific scepticism rather than precaution in response to uncertainty; emphasis on quantifiable physical evidence rather than parental histories; professional roles as providers of physical diagnosis and treatment rather than of information and advocacy; libertarian rather than communitarian perspectives on responsibility for risk; and values about allergy as a disease and normal childhood. Parents held a similar, but less divergent range of views. The majority of parents preferred more moderate doctors’ views, with 43% (30 of 69) of families expressing their dissatisfaction by seeking another specialist opinion. Many were confused by variation in doctors’ opinions, preferring relationships with doctors that recognized their concerns, addressed their information needs, and confirmed that they were managing their child’s allergy appropriately. Conclusions  In uncertain clinical situations, parents do not expect absolute certainty from doctors; inflexible certainty may not allow parental preferences to be acknowledged or accommodated, and is associated with the seeking of second opinions. PMID:18816318

Updates on Aspergillus, Pneumocystis and other opportunistic pulmonary mycoses.

PubMed

Curbelo, Jose; Galván, Jose María; Aspa, Javier

2015-12-01

Mycoses are serious diseases with potentially fatal outcome. The introduction of immunosuppressive treatments and life support techniques has led to a growing prevalence of different degrees of immunosuppression. Compromised immune response is the primary risk factor for the development of opportunistic mycoses. Early diagnosis and treatment are crucial for improving prognosis. However, isolation in cultures or identification using antigen detection techniques cannot distinguish between colonization and invasive infection, and the clinical status of the patient often prevents biopsy sampling. Clinicians thus find themselves in an uncertain position, requiring them to quickly recognize clinical and radiological signs and interpret microbiological results in context. The aim of this review is to provide a general overview of the profile of patients susceptible to these infections, the role of the immune system and, in more detail, the major diagnostic developments that have gained most acceptance and recognition among the scientific community. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

Morton's metatarsalgia: sonographic findings and correlated histopathology.

PubMed

Read, J W; Noakes, J B; Kerr, D; Crichton, K J; Slater, H K; Bonar, F

1999-03-01

The results of 79 high resolution ultrasound examinations of the forefoot that were performed for suspected Morton's metatarsalgia were retrospectively assessed. Scans were only obtained if the pain was poorly localized or if there were atypical features that made the clinical diagnosis uncertain. Ultrasound detected 92 hypoechoic intermetatarsal web space masses in 63 patients. Surgery was performed on 23 web spaces in 22 patients where the response to nonsurgical management had been poor. The surgical specimens were retrieved and reviewed by a pathologist in 21 cases. The histopathology in 20 of 21 operated cases was that of Morton's neuroma; however, prominent mucoid degeneration was also found to involve the adjacent loose fibroadipose tissues in 19 of 20 neuroma specimens. Ultrasound was sensitive in the detection of web space abnormality (sensitivity, 0.95), but could not clearly separate Morton's neuroma from associated mass-like mucoid degeneration in the adjacent loose connective tissues. The implications of these observations for both diagnosis and treatment are discussed.

Subungual Ewing sarcoma/PNET tumor family of the great toe: a case report

PubMed Central

Binesh, Fariba; Sobhanardekani, Mohammad; Zare, Saeedeh; Behniafard, Nasim

2016-01-01

Ewing’s sarcoma is seen mainly in patients less than 18. This aggressive tumor generally affects the axial skeleton and only rarely involves the acral regions. Ewing’s sarcoma in the foot is inordinately scarce. Clinical features are uncertain and can imitate other common diseases. This paper presents a case of 62-year-old malewith complaints of pain and swelling of the subungual area of his right great toe. The lesion was excised, and histopathological diagnosis of Ewing’s sarcoma was made. Histopathological examination, supported by immunochemical methods, remains the mainstay of diagnosis. Surgical ablation along with chemotherapy is the therapy of choice. To our knowledge, this is the first report of Ewing’s sarcoma involving the nail bed of the great toe without bone erosion. The key messages of this case report is “Subungual Ewing sarcoma is a rare case, and Ewing’s sarcoma must be kept in mind for acral lesions, especially in the adult population.” PMID:27279998

Conidial heads (Fruiting Bodies) as a hallmark for histopathological diagnosis of angioinvasive aspergillosis

PubMed Central

Lanzarin, Luciana Depiere; Mariano, Livia Caroline Barbosa; Macedo, Maria Cristina Martins de Almeida; Batista, Marjorie Vieira

2015-01-01

Aspergillosis is a mycosis that afflicts immunocompetent and immunocompromised hosts; among the former it exhibits different clinical pictures, and among the latter the infection renders an invasive form of the disease. The histologic diagnosis of invasive aspergillosis is somewhat challenging mostly because of some morphological similarities between other fungi. However, when present, the conidial heads are pathognomonic of aspergillosis. The authors present the case of a 68-year-old woman who was submitted to autologous hematopoietic stem cell transplantation in the pursuit of multiple myeloma treatment. The post-transplantation period was troublesome with the development of severe neutropenia, human respiratory syncytial virus pneumonia, and disseminated aspergillosis, which was suspected because of a positive serum galactomannan antigen determination, and resulted in a fatal outcome. The autopsy findings showed diffuse alveolar damage associated with angioinvasive pulmonary aspergillosis with numerous hyphae and conidial heads in the lung parenchyma histology. The authors call attention to the aid of autopsy in confirming the diagnosis of this deep mycosis, since only the research of the galactomannan antigen may be insufficient and uncertain due to its specificity and of the possibility of false-positive results. PMID:26894041

Different Treatment Stages in Medical Diagnosis using Fuzzy Membership Matrix

NASA Astrophysics Data System (ADS)

Sundaresan, T.; Sheeja, G.; Govindarajan, A.

2018-04-01

The field of medicine is the most important and developing area of applications of fuzzy set theory. The nature of medical documentation and uncertain information gathered in the use of fuzzy triangular matrix. In this paper, procedures are presented for medical diagnosis and treatment-stages, patient and drug is constructed in fuzzy membership matrix. Examples are given to verify the proposed approach.

Multiple Sub-Epidermal Calcified Nodule Mimicking Eruptive Xanthoma: A Case Report and Review of the Literature

PubMed Central

Ozuguz, Pinar; Balta, Ilknur; Bozkurt, Ozlem; Unverdi, Hatice; Dostbil, Ahmet

2013-01-01

Sub-epidermal calcified nodule (SCN) is an uncommon form of idiopathic calcinosis. It usually occurs in children, particularly in the head and neck region, presenting as a solitary, painless, yellow-white nodule with papillomatous features. These lesions occur twice as common in males compared with females. The pathogenesis is uncertain, but the clinical and histological features of this lesion are distinctive. We report a case of 22-year-old man with multiple nodules bilaterally located on the dorsum of hands simulating eruptive xanthoma. Histopathological examination of one of the excised lesion confirmed the diagnosis showing epidermal and sub-epidermal deposition of calcium. This paper presents a review of the literature and adds a new case of SCN. PMID:24082201

Urinary Biomarkers of Brain Diseases

PubMed Central

An, Manxia; Gao, Youhe

2016-01-01

Biomarkers are the measurable changes associated with a physiological or pathophysiological process. Unlike blood, urine is not subject to homeostatic mechanisms. Therefore, greater fluctuations could occur in urine than in blood, better reflecting the changes in human body. The roadmap of urine biomarker era was proposed. Although urine analysis has been attempted for clinical diagnosis, and urine has been monitored during the progression of many diseases, particularly urinary system diseases, whether urine can reflect brain disease status remains uncertain. As some biomarkers of brain diseases can be detected in the body fluids such as cerebrospinal fluid and blood, there is a possibility that urine also contain biomarkers of brain diseases. This review summarizes the clues of brain diseases reflected in the urine proteome and metabolome. PMID:26751805

The use of contrasted transvaginal sonography in the diagnosis of gynecologic diseases: a preliminary study.

PubMed

Testa, Antonia Carla; Ferrandina, Gabriella; Fruscella, Erika; Van Holsbeke, Caroline; Ferrazzi, Enrico; Leone, Francesco P G; Arduini, Domenico; Exacoustos, Caterina; Bokor, Daniela; Scambia, Giovanni; Timmerman, Dirk

2005-09-01

The purpose of this study was to evaluate the efficacy of a new contrast-dedicated ultrasound technology, contrast-tuned imaging (CnTI), implemented on an endovaginal probe and using the second-generation contrast agent SonoVue (Bracco International BV, Amsterdam, the Netherlands), compared with the standard ultrasound examination in different gynecologic diseases. Eighty-nine patients were enrolled in the study in 4 different clinical centers. The study included 40 patients with uncertain pelvic adnexal masses, 10 patients with pelvic masses indicative of recurrences of gynecologic tumors, 26 patients with uterine pathologic features, and 13 patients with cervical lesions. Application of CnTI technology after the SonoVue injection gave a picture of the intralesional microvascularization dramatically different from that obtained during color Doppler examination. Of the 40 pelvic masses, 15 (37.5%) were considered benign and 25 (62.5%) were considered malignant at B-mode and color Doppler examinations. Contrast-enhanced sonography showed no intralesional contrast perfusion in 11 (73%) of 15 cases, and all these were benign at final diagnosis. Of the 4 (27%) cases that had perfusion, 2 were malignant. Conversely, of the 25 cases with positive findings at color Doppler examination and therefore expected to show the appearance of contrast tissue-filling morphologic characteristics, 13 (52%) were malignant at final diagnosis. For evaluation of uterine pathologic features, the CnTI-SonoVue technology did not appear to be superior to the B-mode and color Doppler examinations; however, for the evaluation of cervical cancer, CnTI-SonoVue technology revealed a better definition of the margins of the neoplastic lesions in 4 (40%) of 10 cases. In the evaluation of uncertain pelvic masses, the CnTI technology led to an improvement in the ability of the practitioner to differentiate benign from malignant adnexal lesions.

[MRI and CT-scan in presumed benign ovarian tumors].

PubMed

Thomassin-Naggara, I; Bazot, M

2013-12-01

Radiological examinations are required for the assessment of complex or indeterminate ovarian masses, mainly using MRI and CT-scan. MRI provides better tissue characterization than Doppler ultrasound or CT-scan (LE2). Pelvic MRI is recommended in case of an indeterminate or complex ovarian ultrasonographic mass (grade B). The protocol of a pelvic MRI should include morphological T1 and T2 sequences (grade B). In case of solid portion, perfusion and diffusion sequences are recommended (grade C). In case of doubt about the diagnosis of ovarian origin, pelvic MRI is preferred over the CT-scan (grade C). MRI is the technique of choice for the difference between functional and organic ovarian lesion diagnosis (grade C). It can be useful in case of clinical diagnostic uncertainty between polycystic ovary syndrome and ovarian hyperstimulation and multilocular ovarian tumor syndrome (grade C). No MRI classification for ovarian masses is currently validated. The establishment of a presumption of risk of malignancy is required in a MRI report of adnexal mass with if possible a guidance on the histological diagnosis. In the absence of clinical or sonographic diagnosis, pelvic CT-scan is recommended in the context of acute painful pelvic mass in non-pregnant patients (grade C). It specifies the anomalies and allows the differential diagnosis with digestive and urinary diseases (LE4). Given the lack of data in the literature, the precautionary principle must be applied to the realization of a pelvic MRI in a pregnant patient. A risk-benefit balance should be evaluated case by case by the clinician and the radiologist and information should be given to the patient. In an emergency situation during pregnancy, pelvic MRI is an alternative to CT-scan for the exploration of acute pelvic pain in case of uncertain sonographic diagnosis (grade C). Copyright © 2013. Published by Elsevier Masson SAS.

Contemporary treatment principles for early rheumatoid arthritis: a consensus statement.

PubMed

Kiely, Patrick D W; Brown, Andrew K; Edwards, Christopher J; O'Reilly, David T; Ostör, Andrew J K; Quinn, Mark; Taggart, Allister; Taylor, Peter C; Wakefield, Richard J; Conaghan, Philip G

2009-07-01

RA has a substantial impact on both patients and healthcare systems. Our objective is to advance the understanding of modern management principles in light of recent evidence concerning the condition's diagnosis and treatment. A group of practicing UK rheumatologists formulated contemporary management principles and clinical practice recommendations concerning both diagnosis and treatment. Areas of clinical uncertainty were documented, leading to research recommendations. A fundamental concept governing treatment of RA is minimization of cumulative inflammation, referred to as the inflammation-time area under the curve (AUC). To achieve this, four core principles of management were identified: (i) detect and refer patients early, even if the diagnosis is uncertain: patients should be referred at the first suspicion of persistent inflammatory polyarthritis and rheumatology departments should provide rapid access to a diagnostic and prognostic service; (ii) treat RA immediately: optimizing outcomes with conventional DMARDs and biologics requires that effective treatment be started early-ideally within 3 months of symptom onset; (iii) tight control of inflammation in RA improves outcome: frequent assessments and an objective protocol should be used to make treatment changes that maintain low-disease activity/remission at an agreed target; (iv) consider the risk-benefit ratio and tailor treatment to each patient: differing patient, disease and drug characteristics require long-term monitoring of risks and benefits with adaptations of treatments to suit individual circumstances. These principles focus on effective control of the inflammatory process in RA, but optimal uptake may require changes in service provision to accommodate appropriate care pathways.

An efficient sampling algorithm for uncertain abnormal data detection in biomedical image processing and disease prediction.

PubMed

Liu, Fei; Zhang, Xi; Jia, Yan

2015-01-01

In this paper, we propose a computer information processing algorithm that can be used for biomedical image processing and disease prediction. A biomedical image is considered a data object in a multi-dimensional space. Each dimension is a feature that can be used for disease diagnosis. We introduce a new concept of the top (k1,k2) outlier. It can be used to detect abnormal data objects in the multi-dimensional space. This technique focuses on uncertain space, where each data object has several possible instances with distinct probabilities. We design an efficient sampling algorithm for the top (k1,k2) outlier in uncertain space. Some improvement techniques are used for acceleration. Experiments show our methods' high accuracy and high efficiency.

Diagnosis and Treatment of Alcoholic Hepatitis: A Systematic Review

PubMed Central

Singal, Ashwani K; Kodali, Sudha; Vucovich, Lee A; Darley-Usmar, Victor; Schiano, Thomas D

2016-01-01

Alcoholic hepatitis occurs in about one third of individuals reporting long term heavy alcohol use. It is associated with high short-term mortality, economic burden, and hospital resources utilization. We performed this systematic review to a) describe clinical characteristics and genomics associated with the risk of alcoholic hepatitis; b) discuss role and limitations of liver biopsy and prognostic scoring systems; c) summarize evidence regarding the currently available therapies including liver transplantation; and d) outline emerging therapies with areas of unmet need. Literature search was performed for studies published in English language (January 1971 through - March 2016). Following search engines were used: Pubmed, Elsevier Embase, PsychINFO, and Cochrane Library. For the treatment section, only randomized controlled studies were included for this review. A total of 138 studies (59 randomized, 22 systematic reviews or meta-analyses, 7 surveys or guidelines, 7 population based, and 43 prospective cohort) were cited. There are over 325,000 annual admissions with alcoholic hepatitis contributing to about 0.8% of all hospitalizations in the US. Liver biopsy may be required in about 25–30% cases for uncertain clinical diagnosis. Corticosteroids with or without N-acetylcysteine remains the only available therapy for severe episode. Data are emerging on the role of liver transplantation as salvage therapy for select patients. Abstinence remains the most important factor impacting long-term prognosis. Results from the ongoing clinical trials within the National institute on Alcohol Abuse and Alcoholism funded consortia are awaited for more effective and safer therapies. Alcoholic hepatitis is a potentially lethal condition with a significant short-term mortality. A high index of suspicion is required. There remains an unmet need for non-invasive biomarkers for diagnosis, and predicting prognosis and response to therapy. PMID:27254289

Cannabis sativa allergy: looking through the fog.

PubMed

Decuyper, I I; Van Gasse, A L; Cop, N; Sabato, V; Faber, M A; Mertens, C; Bridts, C H; Hagendorens, M M; De Clerck, L; Rihs, H P; Ebo, D G

2017-02-01

IgE-mediated Cannabis (C. sativa, marihuana) allergy seems to be on the rise. Both active and passive exposure to cannabis allergens may trigger a C. sativa sensitization and/or allergy. The clinical presentation of a C. sativa allergy varies from mild to life-threatening reactions and often seems to depend on the route of exposure. In addition, sensitization to cannabis allergens can result in various cross-allergies, mostly for plant foods. This clinical entity, designated as the 'cannabis-fruit/vegetable syndrome', might also imply cross-reactivity with tobacco, natural latex and plant-food-derived alcoholic beverages. Hitherto, these cross-allergies are predominantly reported in Europe and appear mainly to rely upon cross-reactivity between nonspecific lipid transfer proteins or thaumatin-like proteins present in C. sativa and their homologues, ubiquitously distributed throughout plant kingdom. At present, diagnosis of cannabis-related allergies predominantly rests upon a thorough history completed with skin testing using native extracts from crushed buds and leaves. However, quantification of specific IgE antibodies and basophil activation tests can also be helpful to establish correct diagnosis. In the absence of a cure, treatment comprises absolute avoidance measures. Whether avoidance of further use will halt the extension of related cross-allergies remains uncertain. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Hepatic perivascular epithelioid cell tumor

PubMed Central

Tang, Da; Wang, Jianmin; Tian, Yuepeng; Li, Qiuguo; Yan, Haixiong; Wang, Biao; Xiong, Li; Li, Qinglong

2016-01-01

Abstract Rational: Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal neoplasm which expresses both myogenic and melanocytic markers. PEComas are found in a variety locations in the body, but up to now only approximately 30 cases about hepatic perivascular epithelioid cell tumor are reported in English language worldwide. Patient concerns: A 32-year-old woman was admitted in our hospital with intermittent right upper quadrant pain for 1 month and recent (1 day) progressive deterioration. Diagnoses: Based on the results of the laboratory examinations and the findings of the computed tomography, the diagnosis of hepatic hamartoma or the hepatocecullar carcinoma with hemorrhage was made. Interventions: The patient underwent a segmentectomy of the liver, and the finally diagnosis of hepatic PEComa was made with immunohistochemical confirmation with HMB-45 and SMA. Outcomes: There is no clinical or radiographic evidence of recurrence 9 months after surgery. Lessons: This kind of tumor is extremely rare and the natural history of PEComa is uncertain, as the treatment protocol for hepatic PEComa has not reached a consensus. But the main treatment of the disease may be surgical resection. Only after long term follow-up can we know whether the tumor is benign or malignant. It appears that longer clinical follow-up is necessary in all patients with hepatic PEComas. PMID:28002331

[Clinicopathological features of uterine neoplasms with perivascular epithelioid cell differentiation].

PubMed

Lu, Hai-zhen; Zhang, Hong-tu; Liu, Xiu-yun; Xue, Xin-hua; Xie, Yong-qiang; Liu, Shang-mei; Su, Qin

2009-03-01

To study the neoplasm with perivascular epithelioid cell differentiation (PEComa) with respect to their morphologic, immunohistochemical and clinical phenotypes. Three PEComas were included in this study, one located at the left uterine horn, and two presented as a mass in the uterine corpus. The tumors were examined by histopathology and immunohistochemistry. The lesions were composed of spindle, blunt epithelioid cells, with foci of, or scattered, cells showing adipose differentiation in two cases. The myomelanocytic differentiation was demonstrated, proving the diagnosis as PEComa. Mild nuclear atypia and focal necrosis was observed in one lesion, and the rest two showed malignant morphologic phenotypes including moderate nuclear atypia and coagulative necrosis. The mitotic and Ki67-labelling indices ranged from 0.5/10 HPF to 14/10 HPF and 0.6% to 7.0%, respectively. All of the three patients remain alive. Malignant nature of the two lesions with worrisome morphology was confirmed by occurrence of metastases after hysterectomy. PEComa is a rare tumor, occurring preferentially in the uterus. It is regarded as a tumor with uncertain malignant potential, but a minority of them shows malignant clinical behaviors. Some pathologic parameters including large tumor size, sheet-like necrosis, marked nuclear atypia, elevated mitotic index (> or = 10/10 HPF), aberrant mitotic figure and vascular invasion may help to establish a diagnosis of malignant PEComa.

Hepatic perivascular epithelioid cell tumor: Case report and brief literature review.

PubMed

Tang, Da; Wang, Jianmin; Tian, Yuepeng; Li, Qiuguo; Yan, Haixiong; Wang, Biao; Xiong, Li; Li, Qinglong

2016-12-01

Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal neoplasm which expresses both myogenic and melanocytic markers. PEComas are found in a variety locations in the body, but up to now only approximately 30 cases about hepatic perivascular epithelioid cell tumor are reported in English language worldwide. A 32-year-old woman was admitted in our hospital with intermittent right upper quadrant pain for 1 month and recent (1 day) progressive deterioration. Based on the results of the laboratory examinations and the findings of the computed tomography, the diagnosis of hepatic hamartoma or the hepatocecullar carcinoma with hemorrhage was made. The patient underwent a segmentectomy of the liver, and the finally diagnosis of hepatic PEComa was made with immunohistochemical confirmation with HMB-45 and SMA. There is no clinical or radiographic evidence of recurrence 9 months after surgery. This kind of tumor is extremely rare and the natural history of PEComa is uncertain, as the treatment protocol for hepatic PEComa has not reached a consensus. But the main treatment of the disease may be surgical resection. Only after long term follow-up can we know whether the tumor is benign or malignant. It appears that longer clinical follow-up is necessary in all patients with hepatic PEComas.

Clinical utility of FDG-PET for the differential diagnosis among the main forms of dementia.

PubMed

Nestor, Peter J; Altomare, Daniele; Festari, Cristina; Drzezga, Alexander; Rivolta, Jasmine; Walker, Zuzana; Bouwman, Femke; Orini, Stefania; Law, Ian; Agosta, Federica; Arbizu, Javier; Boccardi, Marina; Nobili, Flavio; Frisoni, Giovanni Battista

2018-05-07

To assess the clinical utility of FDG-PET as a diagnostic aid for differentiating Alzheimer's disease (AD; both typical and atypical forms), dementia with Lewy bodies (DLB), frontotemporal lobar degeneration (FTLD), vascular dementia (VaD) and non-degenerative pseudodementia. A comprehensive literature search was conducted using the PICO model to extract evidence from relevant studies. An expert panel then voted on six different diagnostic scenarios using the Delphi method. The level of empirical study evidence for the use of FDG-PET was considered good for the discrimination of DLB and AD; fair for discriminating FTLD from AD; poor for atypical AD; and lacking for discriminating DLB from FTLD, AD from VaD, and for pseudodementia. Delphi voting led to consensus in all scenarios within two iterations. Panellists supported the use of FDG-PET for all PICOs-including those where study evidence was poor or lacking-based on its negative predictive value and on the assistance it provides when typical patterns of hypometabolism for a given diagnosis are observed. Although there is an overall lack of evidence on which to base strong recommendations, it was generally concluded that FDG-PET has a diagnostic role in all scenarios. Prospective studies targeting diagnostically uncertain patients for assessing the added value of FDG-PET would be highly desirable.

Management of post-neurosurgical meningitis: narrative review.

PubMed

Hussein, K; Bitterman, R; Shofty, B; Paul, M; Neuberger, A

2017-09-01

Infections complicating neurosurgery pose unacceptable mortality and morbidity. To summarize what is known about the epidemiology, diagnosis and treatment of post-neurosurgical meningitis (PNM). PubMed, references of identified studies and reviews, and personal experience when evidence was lacking. The incidence and pathogen distribution of PNM is highly variable. A shift towards Gram-negative bacteria has been observed with use of antibiotic prophylaxis and antibiotic-coated devices directed mainly against Gram-positive bacteria. However, knowledge of the local epidemiology is necessary to treat PNM. The diagnosis of PNM is difficult because, unlike community-acquired meningitis, symptoms are less specific; patients are ill at baseline and many neurosurgical conditions mimic meningitis and cause cerebrospinal fluid (CSF) abnormalities. Pivotal CSF findings for diagnosis of PNM are the CSF glucose, CSF lactate and Gram stain. CSF leucocyte counts are not specific in PNM. Current diagnostic capabilities leave a non-negligible category of patients with microbiologically negative, uncertain diagnosis of PNM. There is no high-quality evidence on several cardinal issues in PNM management, including the effectiveness of intraventricular or intrathecal (IV/IT) antibiotics, effectiveness of dual antibiotic therapy for multidrug-resistant Gram-negative bacteria; clinical benefit of routine therapeutic drug monitoring; and safest timing of shunt replacement. Some data point to a potential benefit of IV/IT antibiotic treatment, mainly for PNM caused by carbapenem-resistant Gram-negative bacteria. Carbapenem-colistin combination therapy is suggested for PNM caused by carbapenem-resistant Gram-negative bacteria with a carbapenem MIC ≤8 mg/L. Guiding the optimal management of PNM will necessitate collaborative multicentre efforts and unique study designs. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Tumor Marker Usage and Medical Care Costs Among Older Early-Stage Breast Cancer Survivors

PubMed Central

Ramsey, Scott D.; Henry, N. Lynn; Gralow, Julie R.; Mirick, Dana K.; Barlow, William; Etzioni, Ruth; Mummy, David; Thariani, Rahber; Veenstra, David L.

2015-01-01

Purpose Although American Society of Clinical Oncology guidelines discourage the use of tumor marker assessment for routine surveillance in nonmetastatic breast cancer, their use in practice is uncertain. Our objective was to determine use of tumor marker tests such as carcinoembryonic antigen and CA 15-3/CA 27.29 and associated Medicare costs in early-stage breast cancer survivors. Methods By using Surveillance, Epidemiology, and End Results-Medicare records for patients diagnosed with early-stage breast cancer between 2001 and 2007, tumor marker usage within 2 years after diagnosis was identified by billing codes. Logistic regression models were used to identify clinical and demographic factors associated with use of tumor markers. To determine impact on costs of care, we used multivariable regression, controlling for other factors known to influence total medical costs. Results We identified 39,650 eligible patients. Of these, 16,653 (42%) received at least one tumor marker assessment, averaging 5.7 tests over 2 years, with rates of use per person increasing over time. Factors significantly associated with use included age at diagnosis, diagnosis year, stage at diagnosis, race/ethnicity, geographic region, and urban/rural status. Rates of advanced imaging, but not biopsies, were significantly higher in the assessment group. Medical costs for patients who received at least one test were approximately 29% greater than costs for those who did not, adjusting for other factors. Conclusion Breast cancer tumor markers are frequently used among women with early-stage disease and are associated with an increase in both diagnostic procedures and total cost of care. A better understanding of factors driving the use of and the potential benefits and harms of surveillance-based tumor marker testing is needed. PMID:25332254

[A stereotypical clinical presentation of childhood linear purpura of the arms: Analysis of six cases].

PubMed

Hosteing, S; Uthurriague, C; Boralevi, F; Mazereeuw-Hautier, J

2017-01-01

Among causes of childhood purpura, other- or self-induced mechanical purpura, such as factitious purpura, needs to be considered. This cause is unfamiliar to pediatricians, usually compromising early diagnosis. We report on the cases of six children, seen between 1998 and 2014 at the Toulouse and Bordeaux Departments of Dermatology, presenting with a stereotypical linear purpura on the arms. All were females, aged 6-14 years. One patient had a psychiatric history, whereas the others were undergoing a stressful time period. All had several relapses and diagnosis was delayed in all. The patients presented with multiple oval or square purpuric macules, forming a discontinuous linear band. Some patients reported functional discomfort such as pain or pruritus. Lesions were always located on the arms and sometimes on other areas of the body. Biological assessments were normal and there was no vasculitis at skin histology. We retained the diagnosis of induced mechanical purpura. Psychological support was offered to four patients. One of them declared that the lesions were induced by classmates using suction. Another child declared that she caused the lesions herself, without explaining the mechanism. Outcome was favorable in five children (one was lost to follow-up), 1-4 years after diagnosis. In conclusion, induced mechanical purpura in children, although rarely described in the medical literature, must be kept in mind. Investigations should be carried out in cases with uncertain diagnosis. Underlying psychological distress should be sought. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Sensor Data Fusion with Z-Numbers and Its Application in Fault Diagnosis

PubMed Central

Jiang, Wen; Xie, Chunhe; Zhuang, Miaoyan; Shou, Yehang; Tang, Yongchuan

2016-01-01

Sensor data fusion technology is widely employed in fault diagnosis. The information in a sensor data fusion system is characterized by not only fuzziness, but also partial reliability. Uncertain information of sensors, including randomness, fuzziness, etc., has been extensively studied recently. However, the reliability of a sensor is often overlooked or cannot be analyzed adequately. A Z-number, Z = (A, B), can represent the fuzziness and the reliability of information simultaneously, where the first component A represents a fuzzy restriction on the values of uncertain variables and the second component B is a measure of the reliability of A. In order to model and process the uncertainties in a sensor data fusion system reasonably, in this paper, a novel method combining the Z-number and Dempster–Shafer (D-S) evidence theory is proposed, where the Z-number is used to model the fuzziness and reliability of the sensor data and the D-S evidence theory is used to fuse the uncertain information of Z-numbers. The main advantages of the proposed method are that it provides a more robust measure of reliability to the sensor data, and the complementary information of multi-sensors reduces the uncertainty of the fault recognition, thus enhancing the reliability of fault detection. PMID:27649193

Dynamic Uncertain Causality Graph for Knowledge Representation and Probabilistic Reasoning: Directed Cyclic Graph and Joint Probability Distribution.

PubMed

Zhang, Qin

2015-07-01

Probabilistic graphical models (PGMs) such as Bayesian network (BN) have been widely applied in uncertain causality representation and probabilistic reasoning. Dynamic uncertain causality graph (DUCG) is a newly presented model of PGMs, which can be applied to fault diagnosis of large and complex industrial systems, disease diagnosis, and so on. The basic methodology of DUCG has been previously presented, in which only the directed acyclic graph (DAG) was addressed. However, the mathematical meaning of DUCG was not discussed. In this paper, the DUCG with directed cyclic graphs (DCGs) is addressed. In contrast, BN does not allow DCGs, as otherwise the conditional independence will not be satisfied. The inference algorithm for the DUCG with DCGs is presented, which not only extends the capabilities of DUCG from DAGs to DCGs but also enables users to decompose a large and complex DUCG into a set of small, simple sub-DUCGs, so that a large and complex knowledge base can be easily constructed, understood, and maintained. The basic mathematical definition of a complete DUCG with or without DCGs is proved to be a joint probability distribution (JPD) over a set of random variables. The incomplete DUCG as a part of a complete DUCG may represent a part of JPD. Examples are provided to illustrate the methodology.

Communicating Uncertain News in Cancer Consultations.

PubMed

Alby, Francesca; Zucchermaglio, Cristina; Fatigante, Marilena

2017-12-01

In cancer communication, most of the literature is in the realm of delivering bad news while much less attention has been given to the communication of uncertain news around the diagnosis and the possible outcomes of the illness. Drawing on video-recorded cancer consultations collected in two Italian hospitals, this article analyzes three communication practices used by oncologists to interactionally manage the uncertainty during the visit: alternating between uncertain bad news and certain good news, anticipating scenarios, and guessing test results. Both diagnostic and personal uncertainties are not hidden to the patient, yet they are reduced through these practices. Such communication practices are present in 32 % of the visits in the data set, indicating that the interactional management of uncertainty is a relevant phenomenon in oncological encounters. Further studies are needed to improve both its understanding and its teaching.

Rationale and design of three observational, prospective cohort studies including biobanking to evaluate and improve diagnostics, management strategies and risk stratification in venous thromboembolism: the VTEval Project.

PubMed

Frank, Bernd; Ariza, Liana; Lamparter, Heidrun; Grossmann, Vera; Prochaska, Jürgen H; Ullmann, Alexander; Kindler, Florentina; Weisser, Gerhard; Walter, Ulrich; Lackner, Karl J; Espinola-Klein, Christine; Münzel, Thomas; Konstantinides, Stavros V; Wild, Philipp S

2015-07-01

Venous thromboembolism (VTE) with its two manifestations deep vein thrombosis (DVT) and pulmonary embolism (PE) is a major public health problem. The VTEval Project aims to investigate numerous research questions on diagnosis, clinical management, treatment and prognosis of VTE, which have remained uncertain to date. The VTEval Project consists of three observational, prospective cohort studies on VTE comprising cohorts of individuals with a clinical suspicion of acute PE (with or without DVT), with a clinical suspicion of acute DVT (without symptomatic PE) and with an incidental diagnosis of VTE (PE or DVT). The VTEval Project expects to enrol a total of approximately 2000 individuals with subsequent active and passive follow-up investigations over a time period of 5 years per participant. Time points for active follow-up investigations are at months 3, 6, 12, 24 and 36 after diagnosis (depending on the disease cohort); passive follow-up investigations via registry offices and the cancer registry are performed 48 and 60 months after diagnosis for all participants. Primary short-term outcome is defined by overall mortality (PE-related death and all other causes of death), primary long-term outcome by symptomatic VTE (PE-related death, recurrence of non-fatal PE or DVT). The VTEval Project includes three 'all-comer' studies and involves the standardised acquisition of high-quality data, covering the systematic assessment of VTE including symptoms, risk profile, psychosocial, environmental and lifestyle factors as well as clinical and subclinical disease, and it builds up a large state-of-the-art biorepository containing various materials from serial blood samplings. The VTEval Project has been approved by the local data safety commissioner and the responsible ethics committee (reference no. 837.320.12 (8421-F)). Trial results will be published in peer-reviewed journals and presented at national and international scientific meetings. NCT02156401. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Pancreatic head excavation for tissue diagnosis may reduce unnecessary pancreaticoduodenectomies in the setting of chronic pancreatitis.

PubMed

Fancellu, Alessandro; Ginesu, Giorgio C; Feo, Claudio F; Cossu, Maria L; Puledda, Marco; Pinna, Antonio; Porcu, Alberto

2017-06-01

The necessity to obtain a tissue diagnosis of cancer prior to pancreatic surgery still remains an open debate. In fact, a non-negligible percentage of patients undergoing pancreaticoduodenectomy (PD) for suspected cancer has a benign lesion at final histology. We describe an approach for patients with diagnostic uncertainty between cancer and chronic pancreatitis, with the aim of minimizing the incidence of PD for suspicious malignancy finally diagnosed as benign disease. Eighty-eight patients (85.4%) with a clinicoradiological picture highly suggestive for malignancy received formal PD (group 1). Fifteen patients (14.6%) in whom preoperative diagnosis was uncertain between pancreatic cancer and chronic pancreatitis underwent pancreatic head excavation (PHEX) for intraoperative tissue diagnosis (group 2): those diagnosed as having cancer received PD, whereas those with chronic pancreatitis received pancreaticojejunostomy (PJ). No patient received PD for benign disease. All patients in group 1 had adenocarcinoma on final histology. Eight patients of group 2 (53.3%) received PD after intraoperative diagnosis of cancer, whereas 7 (46.7%) received PJ because no malignancy was found at introperative frozen sections. No signs of cancer were encountered in patients receiving PHEX and PJ after a median follow-up of 42 months. Overall survival did not differ between patients receiving PD for cancer in the group 1 and those receiving PD for cancer after PHEX in the group 2 (P=0.509). Although the described technique has been used in a very selected group of patients, our results suggest that PHEX for tissue diagnosis may reduce rates of unnecessary PD, when the preoperative diagnosis is uncertain between cancer and chronic pancreatitis.

Idiopathic Granulomatous Mastitis

PubMed Central

Al-Jarrah, Adil; Taranikanti, Varna; Lakhtakia, Ritu; Al-Jabri, Asma; Sawhney, Sukhpal

2013-01-01

Objectives: Idiopathic granulomatous mastitis (IGM) is a rare benign disorder of the breast whose aetiology is controversial, and is often misdiagnosed clinically and radiologically as mammary malignancy; as a result, it may be incorrectly treated. Although no standard treatment is available for this chronic disease, surgery with or without corticosteroids has been tried with controversial results. This study discusses the clinical presentation, diagnosis, management, recurrence, and follow-up data of IGM with a review of relevant literature. Methods: From 2009–2012, the Breast Unit at Sultan Qaboos University Hospital, Oman, conducted a clinical study on 20 patients with breast lumps. Their clinical and radiological examinations were indeterminate, and a diagnosis of granulomatous mastitis was established only by histopathology. Results: The majority of the patients were cases of unknown aetiology, who presented with a unilateral breast mass. A few patients had a mass with an abscess, along with axillary lymphadenopathy. A total of 4 patients were suspected of malignancy using radiology. In all patients, sterilised pus was sent for culture and sensitivity. Microscopy showed the characteristic pattern of granulomatous inflammation. All patients were treated with antibiotics for 6 weeks, and the mean follow-up period was 15 months (11–33 months). All patients had complete remission with no further recurrence. Conclusion: This single largest study of cases of IGM in Oman highlights the pitfalls in diagnosing this non-neoplastic disease of unknown aetiology and uncertain pathogenesis. It emphasises IGM’s excellent response to antibiotics, which is crucial, as IGM is a disease which is notoriously difficult and controversial to treat. PMID:23862029

Impact of forced vital capacity loss on survival after the onset of chronic lung allograft dysfunction.

PubMed

Todd, Jamie L; Jain, Rahil; Pavlisko, Elizabeth N; Finlen Copeland, C Ashley; Reynolds, John M; Snyder, Laurie D; Palmer, Scott M

2014-01-15

Emerging evidence suggests a restrictive phenotype of chronic lung allograft dysfunction (CLAD) exists; however, the optimal approach to its diagnosis and clinical significance is uncertain. To evaluate the hypothesis that spirometric indices more suggestive of a restrictive ventilatory defect, such as loss of FVC, identify patients with distinct clinical, radiographic, and pathologic features, including worse survival. Retrospective, single-center analysis of 566 consecutive first bilateral lung recipients transplanted over a 12-year period. A total of 216 patients developed CLAD during follow-up. CLAD was categorized at its onset into discrete physiologic groups based on spirometric criteria. Imaging and histologic studies were reviewed when available. Survival after CLAD diagnosis was assessed using Kaplan-Meier and Cox proportional hazards models. Among patients with CLAD, 30% demonstrated an FVC decrement at its onset. These patients were more likely to be female, have radiographic alveolar or interstitial changes, and histologic findings of interstitial fibrosis. Patients with FVC decline at CLAD onset had significantly worse survival after CLAD when compared with those with preserved FVC (P < 0.0001; 3-yr survival estimates 9% vs. 48%, respectively). The deleterious impact of CLAD accompanied by FVC loss on post-CLAD survival persisted in a multivariable model including baseline demographic and clinical factors (P < 0.0001; adjusted hazard ratio, 2.73; 95% confidence interval, 1.86-4.04). At CLAD onset, a subset of patients demonstrating physiology more suggestive of restriction experience worse clinical outcomes. Further study of the biologic mechanisms underlying CLAD phenotypes is critical to improving long-term survival after lung transplantation.

[Solitary rectal ulcer syndrome: report of 7 cases at the Salvador +Zubirán National Institute of Nutrition, from 1980 to 1992].

PubMed

Rodríguez Leal, G A; Jiménez Torres, R; Lome, C; Pérez Alvarado, N; Muñoz Fernández, L; Vargas Rodríguez, A

1993-01-01

Solitary rectal ulcer syndrome (SRUS) is an unusual disorder which is seldom seen in our hospital. Considerable uncertainly remains concerning the cause, natural history, and management of this condition. During 1980-1992 period, 7 patients were seen at the Instituto Nacional de la Nutrición and the diagnosis was established on histological, sigmoidoscopic and clinical grounds. Most of the patients suffered rectal bleeding, abdominal pain, straining at defecation, tenemus and rectal mucus discharge. Laboratory results were non specific. Eighty-five percent has macroscopic ulcerations and these were found within 5.2 cm of the anal margin and usually situated anteriorly. Neither medical nor local surgical treatment consistently achieved relief of symptoms or healing of the lesion.

Available Evidence of Association between Zika Virus and Microcephaly

PubMed Central

Wu, Jing; Huang, Da-Yong; Ma, Jun-Tao; Ma, Ying-Hua; Hu, Yi-Fei

2016-01-01

Objective: To clarify the possible association between the Zika virus (ZIKV) and microcephaly and understand where we are in terms of research and the debate on the causation between mild maternal clinical features and severe fetal microcephaly. Data Sources: We did a comprehensive literature review with the keywords “zika” and/or “microcephaly” from inception to May 27, 2016, with PubMed. Study Selection: Studies were included and analyzed if they met all of the following criteria: “probable or confirmed infant microcephaly” and “probable or confirmed ZIKV infection among mothers or infants”. Results: We emphasize the diagnosis of ZIKV infection, including maternal clinical manifestations, maternal and fetal laboratory confirmation, and possible autopsy if need. Other confounders that may lead to microcephaly should be excluded from the study. We presented the results from clinical manifestations of ZIKV infection, testing methods evolving but the mechanism of microcephaly uncertain, flexible definition challenging the diagnosis of microcephaly, and limited causal reference on pregnant women. We made analog comparison of severe acute respiratory syndrome and chikungunya virus in terms of DNA mutation and global movement to provide further research recommendation. The chance of catch-up growth may decrease the number of pervious “diagnosed” microcephaly. Conclusions: There are some evidence available through mice models and direct isolation of ZIKV in affected pregnancies on kindly causal relationship but not convincible enough. We analyzed and presented the weakness or limitation of published reports with the desire to shed light to further study directions. PMID:27647195

Integration of an EEG biomarker with a clinician's ADHD evaluation

PubMed Central

Snyder, Steven M; Rugino, Thomas A; Hornig, Mady; Stein, Mark A

2015-01-01

Background This study is the first to evaluate an assessment aid for attention-deficit/hyperactivity disorder (ADHD) according to both Class-I evidence standards of American Academy of Neurology and De Novo requirements of US Food and Drug Administration. The assessment aid involves a method to integrate an electroencephalographic (EEG) biomarker, theta/beta ratio (TBR), with a clinician's ADHD evaluation. The integration method is intended as a step to help improve certainty with criterion E (i.e., whether symptoms are better explained by another condition). Methods To evaluate the assessment aid, investigators conducted a prospective, triple-blinded, 13-site, clinical cohort study. Comprehensive clinical evaluation data were obtained from 275 children and adolescents presenting with attentional and behavioral concerns. A qualified clinician at each site performed differential diagnosis. EEG was collected by separate teams. The reference standard was consensus diagnosis by an independent, multidisciplinary team (psychiatrist, psychologist, and neurodevelopmental pediatrician), which is well-suited to evaluate criterion E in a complex clinical population. Results Of 209 patients meeting ADHD criteria per a site clinician's judgment, 93 were separately found by the multidisciplinary team to be less likely to meet criterion E, implying possible overdiagnosis by clinicians in 34% of the total clinical sample (93/275). Of those 93, 91% were also identified by EEG, showing a relatively lower TBR (85/93). Further, the integration method was in 97% agreement with the multidisciplinary team in the resolution of a clinician's uncertain cases (35/36). TBR showed statistical power specific to supporting certainty of criterion E per the multidisciplinary team (Cohen's d, 1.53). Patients with relatively lower TBR were more likely to have other conditions that could affect criterion E certainty (10 significant results; P ≤ 0.05). Integration of this information with a clinician's ADHD evaluation could help improve diagnostic accuracy from 61% to 88%. Conclusions The EEG-based assessment aid may help improve accuracy of ADHD diagnosis by supporting greater criterion E certainty. PMID:25798338

A comparative study of South Asian and non-Asian referrals to an eating disorders service in Leicester, UK.

PubMed

Abbas, S; Damani, S; Malik, I; Button, E; Aldridge, S; Palmer, R L

2010-01-01

Literature on eating disorders (EDs) among South Asian people in Britain is limited. In an extension of an earlier study, referrals to the Leicester Adult Eating Disorders Service were examined between 1991 and 2005. All South-Asians presenting to the service were compared on age, gender and diagnosis with non-Asians. Female Asian patients diagnosed as bulimia nervosa and ED not otherwise specified were compared on a larger number of variables with the same number of non-Asian patients matched for diagnosis. As there were only six Asian patients with anorexia nervosa they were excluded from this comparison. Only 4.5% of female patients were Asian, as opposed to 13.8% of the local young female population in the most recent UK census. Overall, Asian women were significantly younger than the non-Asians but did not differ significantly with regard to clinical features or treatment variables. Asians are under-represented amongst women presenting to the service. The explanation for this remains uncertain. Overall, Asian sufferers who reach secondary specialist services closely resemble non-Asian patients.

The role of orbital ultrasonography in distinguishing papilledema from pseudopapilledema

PubMed Central

Carter, S B; Pistilli, M; Livingston, K G; Gold, D R; Volpe, N J; Shindler, K S; Liu, G T; Tamhankar, M A

2014-01-01

Purpose To determine the sensitivity and specificity of orbital ultrasonography in distinguishing papilledema from pseudopapilledema in adult patients. Methods The records of all adult patients referred to the neuro-ophthalmology service who underwent orbital ultrasonography for the evaluation of suspected papilledema were reviewed. The details of history, ophthalmologic examination, and results of ancillary testing including orbital ultrasonography, MRI, and lumbar puncture were recorded. Results of orbital ultrasonography were correlated with the final diagnosis of papilledema or pseudopapilledema on the basis of the clinical impression of the neuro-ophthalmologist. Ultrasound was considered positive when the optic nerve sheath diameter was ≥3.3 mm along with a positive 30° test. Results The sensitivity of orbital ultrasonography for detection of papilledema was 90% (CI: 80.2–99.3%) and the specificity in detecting pseudopapilledema was 79% (CI: 67.7–90.7%). Conclusions Orbital ultrasonography is a rapid and noninvasive test that is highly sensitive, but less specific in differentiating papilledema from pseudopapilledema in adult patients, and can be useful in guiding further management of patients in whom the diagnosis is initially uncertain. PMID:25190532

Dengue in the elderly: a review.

PubMed

Lin, Ray Junhao; Lee, Tau Hong; Leo, Yee Sin

2017-08-01

Changing dengue epidemiological trends have resulted in a shift in the disease burden to the adult population. Older adults suffer from poorer outcomes as compared to their younger counterparts, making clinical management of this sub-population particularly challenging. Areas covered: We present a review of the current literature on the changing epidemiology of dengue in the elderly, the atypical features of the clinical disease in this population with emphasis on severe disease presentations and challenges in the current management strategies. Expert commentary: Dengue in the elderly is an increasingly important yet greatly understudied area. There is an urgent need to refine the current diagnostic criteria to improve diagnosis, classification of disease severity and identify individuals in this population who are likely to progress to severe disease. Management strategies in this population would have to be adjusted to account for the increased number of co-morbidities. The role of the available dengue vaccines in this group is uncertain, and more studies into their safety and efficacy are critically needed.

A novel mitochondrial DNA deletion in a patient with Pearson syndrome and neonatal diabetes mellitus provides insight into disease etiology, severity and progression.

PubMed

Chen, Xin-Yu; Zhao, Si-Yu; Wang, Yan; Wang, Dong; Dong, Chang-Hu; Yang, Ying; Wang, Zhi-Hua; Wu, Yuan-Ming

2016-07-01

Pearson syndrome (PS) is a rare, mitochondrial DNA (mtDNA) deletion disorder mainly affecting hematopoietic system and exocrine pancreas in early infancy, which is characterized by multi-organ involvement, variable manifestations and poor prognosis. Since the clinical complexity and uncertain outcome of PS, the ability to early diagnose and anticipate disease progression is of great clinical importance. We described a patient with severe anemia and hyperglycinemia at birth was diagnosed with neonatal diabetes mellitus, and later with PS. Genetic testing revealed that a novel mtDNA deletion existed in various non-invasive tissues from the patient. The disease course was monitored by mtDNA deletion heteroplasmy and mtDNA/nucleus DNA genome ratio in different tissues and at different time points, showing a potential genotype-phenotype correlation. Our findings suggest that for patient suspected for PS, it may be therapeutically important to first perform detailed mtDNA analysis on non-invasive tissues at the initial diagnosis and during disease progression.

[Constitutional syndrome: clinical entity or a mixed bag].

PubMed

Suárez-Ortega, Saturnino; Puente-Fernández, Alicia; Santana-Baez, Sergio; Godoy-Díaz, Davinia; Serrano-Fuentes, Miriam; Sanz-Peláez, Oscar

2013-01-01

Fatigue, anorexia and involuntary weight loss have been included under the term constitutional syndrome. These manifestations accompany many diseases in which the diagnosis is made by specific symptoms and signs. However, these events are generally the main reason for consultation and the patient does not report other specific data. This forces us to rigorously investigate the possible causes of the disorder. Usually, three manifestations coexist: asthenia, anorexia and weight loss, but sometimes the patient has only one or two of them. The causes of constitutional symptoms are varied and can be divided into three groups: psychiatric diseases, neoplasms and non-neoplastic diseases. The etiological identification is usually done with a simple protocol, which rules out malignancy; the rest of the cases of uncertain etiology are subject to evolution. The constitutional syndrome correlates well with good prognosis or medical functional processes. Although no clinical guidelines have been developed, score scales may help for the etiological assessment. Given the myriad of different causes of the constitutional syndrome, the treatment of this illness depends primarily on the etiology.

Avoiding misdiagnosing neuroblastoma as Wilms tumor.

PubMed

Dickson, Paxton V; Sims, Thomas L; Streck, Christian J; McCarville, M Beth; Santana, Victor M; McGregor, Lisa M; Furman, Wayne L; Davidoff, Andrew M

2008-06-01

Although occasionally difficult, distinguishing abdominal neuroblastoma (NBL) from Wilms tumor (WT) at presentation is important, as surgical management differs significantly. We reviewed our 20-year experience (1987-2006) treating patients with NBL, focusing on those with an initial diagnosis of WT, to determine presenting features that would have suggested the correct preoperative diagnosis. Retrospective case cohort study reviewing charts and imaging of patients with NBL initially diagnosed clinically with WT. Preoperative symptoms, laboratory studies, and imaging were evaluated. Similar variables were assessed in the 20 patients with WT most recently treated at our institution. Nine patients with NBL were identified as those who had an exploratory laparotomy with a preoperative diagnosis of WT; 8 underwent nephrectomy at exploration. Children with NBL had symptoms such as fever and weight loss at presentation (67%) more often than patients with WT (20%). Preoperative computed tomography demonstrated intratumoral calcifications, vascular encasement, or both in 78% of patients with NBL but were never seen in WT patients. Of interest, preoperative urinary catecholamines were elevated in 5 patients ultimately diagnosed with NBL. Although NBL can be mistaken for WT at presentation, the presence of constitutional symptoms, or intratumoral calcification or vascular encasement on preoperative imaging should heighten suspicion for NBL. In addition, laboratory evaluation, including urinary catecholamines, should be completed before surgery when the etiology of an abdominal tumor is uncertain.

Evaluation of Adult Acute Scrotum in the Emergency Room: Clinical Characteristics, Diagnosis, Management, and Costs.

PubMed

Lorenzo, Laura; Rogel, Ramon; Sanchez-Gonzalez, Jose V; Perez-Ardavin, Javier; Moreno, Elena; Lujan, Saturnino; Broseta, Enrique; Boronat, Francisco

2016-08-01

To evaluate the clinic characteristics, diagnosis, management, and costs of the adult acute scrotum in the emergency room (ER). Acute scrotum is a syndrome characterized by intense, acute scrotal pain that may be accompanied by other symptoms. It is usual in children and commonly found as well in adults, with different causal pathologies between these groups. Between November 2013 and September 2014, 669 cases of adult acute scrotum who presented to our ER were prospectively analyzed. Patients under 15 years of age were excluded. Patient age, reason for consultation, investigations performed, final diagnosis, management, and costs were evaluated. For the statistical analysis, the Mann-Whitney, Kruskal-Wallis U, and chi-square tests were used. A total of 669 cases of acute scrotum were analyzed. The mean age at presentation was 40.2 ± 17.3 years. The most presented diagnoses were orchiepididymitis (28.7%), epididymitis (28.4%), symptoms of uncertain etiology (25.1%), and orchitis (10.3%). Diagnostic tests were carried out in 57.8% of cases. Most cases were treated as outpatients (94.2%), with 5.83% admitted and 1% undergoing surgical treatment. Overall, 13.3% of patients represented to the ER. Abnormal results in blood and urine tests were more common among older patients and infectious pathologies. The average cost generated by an acute scrotum ER consult was 195.03€. Infectious pathologies are the most common causes of acute scrotum at ER. Abnormal blood and urine tests are unusual and are more common in older patients and infectious pathologies. Copyright © 2016 Elsevier Inc. All rights reserved.

Diagnosis of nosocomial pneumonia in intubated, intensive care unit patients.

PubMed

Salata, R A; Lederman, M M; Shlaes, D M; Jacobs, M R; Eckstein, E; Tweardy, D; Toossi, Z; Chmielewski, R; Marino, J; King, C H

1987-02-01

The clinical distinction between bacterial colonization of the tracheobronchial tree and nosocomial pneumonia is difficult, especially in intubated patients. We studied 51 intubated, intensive care unit patients prospectively by serial examinations of tracheal aspirates for elastin fibers, graded Gram's stains, and quantitative bacterial cultures in conjunction with clinical and radiologic observations in an attempt to develop criteria for the early detection of pulmonary infection. Patients with infection had new or progressive pulmonary infiltrates plus 1 of the following: positive blood culture results, radiographic evidence of cavitation, or histologic evidence of pneumonia, or 2 or more of the following: new fever, new leukocytosis, or grossly purulent tracheal aspirates. Twenty-one patients developed infection, 22 remained colonized, and 8 had an uncertain status. Infiltrates developed in 34 patients (21 infected, 8 colonized, 5 uncertain status). Gram-negative bacilli were most commonly isolated and were more frequent in infected patients (81 versus 47%, p less than 0.05); Pseudomonas aeruginosa and Serratia marcescens were most often associated with infection. No differences were observed between infected and colonized patients in demographic features, smoking history, underlying disease, previous antibiotic therapy, days in hospital before intubation, preexisting pneumonia upon intubation, or highest temperature or leukocyte count during course. By univariate analysis, infected patients had a longer duration of intubation (p less than 0.05), higher Gram's stain grading for neutrophils (p less than 0.05) or bacteria (p less than 0.005), higher bacterial colony counts (p less than 0.05), and more frequent detection of elastin fibers in tracheal aspirates (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Long-Term Outcome of Low-Energy Extracorporeal Shock Wave Therapy for Plantar Fasciitis: Comparative Analysis According to Ultrasonographic Findings

PubMed Central

Park, Jong-Wan; Yoon, Kyungjae; Chun, Kwang-Soo; Lee, Joon-Youn; Park, Hee-Jin; Lee, So-Yeon

2014-01-01

Objective To investigate the long-term effect of low-energy extracorporeal shock wave therapy (ESWT) for plantar fasciitis (PF) according to ultrasonography (US) findings. Methods Thirty feet of 25 patients with clinical diagnosis of PF were enrolled and divided into two groups (Apparent-US and Uncertain-US) according to US findings, such as plantar fascia thickening or hypoechogenicity. Inclusion criteria were symptom duration >6 months and a fair or poor grade in Roles-Maudsley score (RMS). ESWT (0.10 mJ/mm2, 600 shocks) was given once a week for 6 weeks. Numeric rating scale (NRS) and RMS were evaluated prior to each ESWT session, at short-term follow-up (one week after all ESWT sessions) and long-term follow-up telephone interview (mean 24 months after ESWT). Good and excellent grade in RMS were considered as treatment success. Results Repeated measure ANOVA demonstrated that NRS significantly decreased with time after ESWT up to the long-term follow-up (time effect, p<0.001) without group-time interaction (p=0.641), indicating that ESWT equally decreased pain in both groups. Overall success rate was 63.3% (short-term follow-up) and 80.0% (long-term follow-up). In comparative analysis between groups, success rate of Apparent-US and Uncertain-US at short-term follow-up was 61.9% and 66.7%, respectively, and 85.7% and 66.7%, respectively, at long-term follow-up. Conclusion If other causes of heel pain are ruled out through meticulous physical examination and ultrasonography, low-energy ESWT in PF seems to be beneficial regardless of US findings. In terms of success rate, however, long-term outcome of Apparent-US appears to be superior to Uncertain-US. PMID:25229032

Interobserver agreement for post mortem renal histopathology and diagnosis of acute tubular necrosis in critically ill patients.

PubMed

Glassford, Neil J; Skene, Alison; Guardiola, Maria B; Chan, Matthew J; Bagshaw, Sean M; Bellomo, Rinaldo; Solez, Kim

2017-12-01

The renal histopathology of critically ill patients dying with acute kidney injury (AKI) in intensive care units of high income countries remains uncertain. Retrospective observational assessment of interobserver agreement in the reporting of renal post mortem histopathology, and the ability of pathologists blinded to the clinical context to independently identify the presence of pre-mortem AKI from digital images of histological sections from 34 critically ill patients dying in teaching hospitals in Australia and Canada. We identified a heterogeneous cohort with a median age of 65 years (interquartile range [IQR], 56.5-77), APACHE II score of 27 (IQR, 19-33), and sepsis as the most common admission diagnosis (12/34; 35%). The most common proximate causes of death were cardiovascular (19/34; 56%) and respiratory (7/34; 21%) failure. AKI was common, with 23 patients (68%) developing RIFLE-F AKI, and 21 patients (62%) receiving renal replacement therapy. Structured reporting for tubular inflammation showed excellent agreement (kappa = 1), but no other subdomain demonstrated better than moderate agreement (kappa < 0.6). Only fair agreement (55.9% of cases; kappa = 0.23) was demonstrated on the diagnosis of moderate to severe acute tubular necrosis (ATN). Pathologist A predicted RIFLE-I or worse AKI with the diagnosis of ATN, with an overall accuracy of 61.8%; pathologist B predicted AKI with an accuracy of 35.3%. Post mortem assessment of the renal histopathology in critically ill patients is neither robust nor reproducible; independent pathologists agree poorly on the diagnosis of ATN, and their structural assessment appears dissociated from ante-mortem renal function.

Sociocultural Context of Suicidal Behaviour in the Sundarban Region of India

PubMed Central

Chowdhury, A. N.; Banerjee, S.; Brahma, A.; Hazra, A.; Weiss, M. G.

2013-01-01

The role of mental illness in nonfatal deliberate self-harm (DSH) is controversial, especially in Asian countries. This prospective study examined the role of psychiatric disorders, underlying social and situational problems, and triggers of DSH in a sample of 89 patients hospitalised in primary care hospitals of the Sundarban Delta, India. Data were collected by using a specially designed DSH register, Explanatory Model Interview Catalogue (EMIC), and clinical interview. Psychiatric diagnosis was made following the DSM-IV guidelines. The majority of subjects were young females (74.2%) and married (65.2%). Most of them (69.7%) were uncertain about their “intention to die,” and pesticide poisoning was the commonest method (95.5%). Significant male-female differences were found with respect to education level, occupation, and venue of the DSH attempt. Typical stressors were conflict with spouse, guardians, or in-laws, extramarital affairs, chronic physical illness, and failed love affairs. The major depressive disorder (14.6%) was the commonest psychiatric diagnosis followed by adjustment disorder (6.7%); however 60.7% of the cases had no psychiatric illness. Stressful life situations coupled with easy access to lethal pesticides stood as the risk factor. The sociocultural dynamics behind suicidal behaviour and community-specific social stressors merit detailed assessment and timely psychosocial intervention. These findings will be helpful to design community-based mental health clinical services and community action in the region. PMID:24286067

Cross-Sectional Imaging in a Case of Adventitial Cystic Disease of the Popliteal Artery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ricci, Paolo; Panzetti, Claudio; Mastantuono, Marco

1999-01-15

Adventitial cystic disease of the popliteal artery is an unusual condition of uncertain etiology, in which a mucin-containing cyst forms in the wall of the artery and produces lower extremity claudication, typically in young and middle-aged men. A diagnosis of adventitial cystic disease of the popliteal artery was made preoperatively in a 47-year-old man by means of several imaging modalities, including angiography, magnetic resonance imaging, and ultrasound. The pathological findings confirmed the suggested diagnosis.

Validation of specific inhalation challenge for the diagnosis of occupational asthma due to persulphate salts

PubMed Central

Munoz, X; Cruz, M; Orriols, R; Torres, F; Espuga, M; Morell, F

2004-01-01

Background: The significant value of tests used to certify the diagnosis of occupational asthma due to persulphate salts remains uncertain. Aims: To validate the specific inhalation challenge (SIC) test for the diagnosis of occupational asthma. Methods: Eight patients with occupational asthma due to persulphate salts, eight patients with bronchial asthma who were never exposed to persulphate salts, and ten healthy subjects were studied. Clinical history taking, spirometry, bronchial challenge with methacholine, skin prick testing to common inhalant allergens and persulphate salts, total IgE levels, and SIC to potassium persulphate were carried out in all subjects. The SIC used increasing concentrations of potassium persulphate (5, 10, 15, and 30 g) mixed with 150 g of lactose. Patients tipped the mixture from one tray to another at a distance of 30 cm from the face for 10 minutes in a challenge booth. Results: The SIC was positive in all subjects with persulphate induced asthma and in one patient with bronchial asthma who had never been exposed to persulphate salts. Sensitivity was 100% (95% CI 67.6 to 100) and specificity was 87.5% (95% CI 52.9–97.8) when patients with occupational asthma due to persulphate salts were compared with those with bronchial asthma never exposed to persulphate salts. Conclusions: SIC to persulphate salts performed according to the protocol described appears to be useful for the diagnosis of occupational asthma secondary to inhalation of this substance. PMID:15377773

Consideration of a new definition of clinically relevant myocardial infarction after coronary revascularization: an expert consensus document from the Society for Cardiovascular Angiography and Interventions (SCAI).

PubMed

Moussa, Issam D; Klein, Lloyd W; Shah, Binita; Mehran, Roxana; Mack, Michael J; Brilakis, Emmanouil S; Reilly, John P; Zoghbi, Gilbert; Holper, Elizabeth; Stone, Gregg W

2014-01-01

Numerous definitions have been proposed for the diagnosis of myocardial infarction (MI) after coronary revascularization. The universal definition for MI designates post procedural biomarker thresholds for defining percutaneous coronary intervention (PCI)-related MI (type 4a) and coronary artery bypass grafting (CABG)-related MI (type 5) which are of uncertain prognostic importance. In addition, for both MI types cTn is recommended as the biomarker of choice, the prognostic significance of which is less well validated than CK-MB. Widespread adoption of a MI definition not clearly linked to subsequent adverse events such as mortality or heart failure may have serious consequences for the appropriate assessment of devices and therapies, may affect clinical care pathways, and may result in misinterpretation of physician competence. Rather than employing an MI definition sensitive for small degrees of myonecrosis (the occurrence of which, based on contemporary large-scale studies, are unlikely to have important clinical consequences), it is instead recommended that a threshold level of biomarker elevation which has been strongly linked to subsequent adverse events in clinical studies be used to define a "clinically relevant MI." The present document introduces a new definition for "clinically relevant MI" after coronary revascularization (PCI or CABG) which is applicable for use in clinical trials, patient care, and quality outcomes assessment. Copyright © 2013 Wiley Periodicals, Inc.

Managing Severe Community-Acquired Pneumonia Due to Community Methicillin-Resistant Staphylococcus aureus (MRSA).

PubMed

Kwong, Jason C; Chua, Kyra; Charles, Patrick G P

2012-06-01

Community-associated methicillin-resistant Staphylococcus aureus (MRSA) is a rare, but significant cause of community-acquired pneumonia (CAP). A number of virulence determinants have been implicated in the development of severe community MRSA pneumonia, characterized by multilobar cavitating necrosis in patients without usual risk-factors for pneumonia. Optimal management is uncertain, and is extrapolated from anecdotal experiences with small case series, randomized studies of hospital-acquired pneumonia, and laboratory investigations using in vitro experiments and animal models of MRSA pneumonia. Adequate clinical suspicion, early diagnosis and administration of appropriate antibiotics are necessary for best patient outcomes, although some patients will still do badly even with early anti-MRSA therapy. Vancomycin or linezolid have been recommended as first-line therapy, possibly in combination with other antibiotics. Newer antibiotics such as ceftaroline are still being evaluated.

Urinary Biomarkers of Brain Diseases.

PubMed

An, Manxia; Gao, Youhe

2015-12-01

Biomarkers are the measurable changes associated with a physiological or pathophysiological process. Unlike blood, urine is not subject to homeostatic mechanisms. Therefore, greater fluctuations could occur in urine than in blood, better reflecting the changes in human body. The roadmap of urine biomarker era was proposed. Although urine analysis has been attempted for clinical diagnosis, and urine has been monitored during the progression of many diseases, particularly urinary system diseases, whether urine can reflect brain disease status remains uncertain. As some biomarkers of brain diseases can be detected in the body fluids such as cerebrospinal fluid and blood, there is a possibility that urine also contain biomarkers of brain diseases. This review summarizes the clues of brain diseases reflected in the urine proteome and metabolome. Copyright © 2016 The Authors. Production and hosting by Elsevier Ltd.. All rights reserved.

Spontaneous pneumomediastinum after bench press training.

PubMed

Nishino, Tomoya

2017-04-01

Spontaneous pneumomediastinum is often associated with asthma and mainly affects adolescent males with a tall, thin body habitus. A 17-year-old man complained of chest and pharyngeal pain after bench press training and spontaneous pneumomediastinum was diagnosed. It should be considered in the differential diagnosis of chest pain of uncertain cause.

Dyspnoea at Term in an Obese Mother

PubMed Central

O'Dwyer, Vicky; O'Brien, Yvonne; Farah, Nadine; Turner, Michael J.

2011-01-01

Peripartum cardiomyopathy is a serious, potentially life-threatening heart disease of uncertain aetiology in previously healthy women. We report a morbidly obese woman who presented with peripartum shortness of breath. We discuss the differential diagnosis of dyspnoea in pregnancy and highlight the complexity of care of the morbidly obese woman. PMID:22567503

Multigene panel next generation sequencing in a patient with cherry red macular spot: Identification of two novel mutations in NEU1 gene causing sialidosis type I associated with mild to unspecific biochemical and enzymatic findings.

PubMed

Mütze, Ulrike; Bürger, Friederike; Hoffmann, Jessica; Tegetmeyer, Helmut; Heichel, Jens; Nickel, Petra; Lemke, Johannes R; Syrbe, Steffen; Beblo, Skadi

2017-03-01

Lysosomal storage diseases (LSD) often manifest with cherry red macular spots. Diagnosis is based on clinical features and specific biochemical and enzymatic patterns. In uncertain cases, genetic testing with next generation sequencing can establish a diagnosis, especially in milder or atypical phenotypes. We report on the diagnostic work-up in a boy with sialidosis type I, presenting initially with marked cherry red macular spots but non-specific urinary oligosaccharide patterns and unusually mild excretion of bound sialic acid. Biochemical, enzymatic and genetic tests were performed in the patient. The clinical and electrophysiological data was reviewed and a genotype-phenotype analysis was performed. In addition a systematic literature review was carried out. Cherry red macular spots were first noted at 6 years of age after routine screening myopia. Physical examination, psychometric testing, laboratory investigations as well as cerebral MRI were unremarkable at 9 years of age. So far no clinical myoclonic seizures occurred, but EEG displays generalized epileptic discharges and visual evoked potentials are prolonged bilaterally. Urine thin layer chromatography showed an oligosaccharide pattern compatible with different LSD including sialidosis, galactosialidosis, GM1 gangliosidosis or mucopolysaccharidosis type IV B. Urinary bound sialic acid excretion was mildly elevated in spontaneous and 24 h urine samples. In cultured fibroblasts, α-sialidase activity was markedly decreased to < 1%; however, bound and free sialic acid were within normal range. Diagnosis was eventually established by multigene panel next generation sequencing of genes associated to LSD, identifying two novel, compound heterozygous variants in NEU1 gene (c.699C > A, p.S233R in exon 4 and c.803A > G; p.Y268C in Exon 5 in NEU1 transcript NM_000434.3), leading to amino acid changes predicted to impair protein function. Sialidosis should be suspected in patients with cherry red macular spots, even with non-significant urinary sialic acid excretion. Multigene panel next generation sequencing can establish a definite diagnosis, allowing for counseling of the patient and family.

Clinical Utility of Magnetic Resonance Imaging (MRI) and Ultrasonography (US) for Diagnosis of Polycystic Ovary Syndrome (PCOS) in Adolescent Girls

PubMed Central

Kenigsberg, Lisa E; Agarwal, Chhavi; Sin, Sanghun; Shifteh, Keivan; Isasi, Carmen R; Crespi, Rebecca; Ivanova, Janeta; Coupey, Susan M; Heptulla, Rubina A; Arens, Raanan

2015-01-01

Objectives Evaluate ovarian morphology using 3-dimensional MRI in adolescent girls with and without PCOS. Compare the utility of MRI versus ultrasonography (US) for diagnosis of PCOS Design Cross-sectional Setting Urban academic tertiary-care children’s hospital Patients Thirty-nine adolescent girls with untreated PCOS and 22 age/BMI-matched controls. Intervention MRI and/or transvaginal/transabdominal US Main Outcome Measure Ovarian volume (OV); follicle number per section (FNPS); correlation between OV on MRI and US; proportion of subjects with features of polycystic ovaries on MRI and US. Results MRI demonstrated larger OV and higher FNPS in subjects with PCOS compared to controls. Within the PCOS group, median OV was 11.9 (7.7) cm3 by MRI, compared with 8.8 (7.8) cm3 by US. Correlation coefficient between OV by MRI and US was 0.701. Due to poor resolution, FNPS could not be determined by US or compared with MRI. ROC curve analysis for MRI demonstrated that increasing volume cut-offs for polycystic ovaries from 10cm3 to 14cm3, increased specificity from 77% to 95%. For FNPS on MRI, specificity increased from 82% to 98% by increasing cut-offs from ≥12 to ≥17. Using Rotterdam cut-offs, 91% of subjects with PCOS met polycystic ovary criteria on MRI, while only 52% met criteria by US. Conclusions US measures smaller OV than MRI, cannot accurately detect follicle number, and is a poor imaging modality for characterizing polycystic ovaries in adolescents with suspected PCOS. For adolescents in whom diagnosis of PCOS remains uncertain after clinical and laboratory evaluation, MRI should be considered as a diagnostic imaging modality. PMID:26354095

Clinical utility of magnetic resonance imaging and ultrasonography for diagnosis of polycystic ovary syndrome in adolescent girls.

PubMed

Kenigsberg, Lisa E; Agarwal, Chhavi; Sin, Sanghun; Shifteh, Keivan; Isasi, Carmen R; Crespi, Rebecca; Ivanova, Janeta; Coupey, Susan M; Heptulla, Rubina A; Arens, Raanan

2015-11-01

To evaluate ovarian morphology using three-dimensional magnetic resonance imaging (MRI) in adolescent girls with and without polycystic ovary syndrome (PCOS). Also compare the utility of MRI versus ultrasonography (US) for diagnosis of PCOS. Cross-sectional study. Urban academic tertiary-care children's hospital. Thirty-nine adolescent girls with untreated PCOS and 22 age/body mass index (BMI)-matched controls. Magnetic resonance imaging and/or transvaginal/transabdominal US. Ovarian volume (OV); follicle number per section (FNPS); correlation between OV on MRI and US; proportion of subjects with features of polycystic ovaries (PCOs) on MRI and US. Magnetic resonance imaging demonstrated larger OV and higher FNPS in subjects with PCOS compared with controls. Within the PCOS group, median OV was 11.9 (7.7) cm(3) by MRI compared with 8.8 (7.8) cm(3) by US. Correlation coefficient between OV by MRI and US was 0.701. Due to poor resolution, FNPS could not be determined by US or compared with MRI. The receiver operating characteristic curve analysis for MRI demonstrated that increasing volume cutoffs for PCOs from 10-14 cm(3) increased specificity from 77%-95%. For FNPS on MRI, specificity increased from 82%-98% by increasing cutoffs from ≥ 12 to ≥ 17. Using Rotterdam cutoffs, 91% of subjects with PCOS met PCO criteria on MRI, whereas only 52% met criteria by US. Ultrasonography measures smaller OV than MRI, cannot accurately detect follicle number, and is a poor imaging modality for characterizing PCOs in adolescents with suspected PCOS. For adolescents in whom diagnosis of PCOS remains uncertain after clinical and laboratory evaluation, MRI should be considered as a diagnostic imaging modality. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Acute Otitis Media in Children.

PubMed

Leung, Alexander K C; Wong, Alex H C

2017-01-01

Acute otitis media is a common childhood infection. Prompt diagnosis and appropriate treatment are very important. To review in depth the epidemiology, pathophysiology, clinical manifestations, diagnosis, complications and particularly treatment of acute otitis media in children. A PubMed search was completed in Clinical Queries using the key term "acute otitis media". Patents were searched using the key term "acute otitis media" from www.google.com/patents, http://espacenet.com, and www.freepatentsonline.com. Acute otitis media affects over 80% of children before their third birthday and 30 to 45% of these children have suffered two or more episodes. Streptococcus pneumoniae, nontypable Haemophilus influenzae, and Moraxella catarrhalis are the most frequently isolated middle-ear pathogens. The diagnosis is based on acute onset of symptoms such as otalgia and fever, middle ear inflammation such as erythema of the tympanic membrane, and middle ear effusion. The choice of treatment method depends on the age of the child, laterality, and the severity of the disease. Recent patents related to the management of acute otitis media are also retrieved and discussed. Antimicrobial treatment is recommended for all children less than two years of age, as well as in children ≥ two years of age who have a temperature ≥ 39oC; are toxic looking; have otalgia > 48 hours; have bilateral otitis media or otorrhea; have craniofacial abnormalities; are immunocompromised; or have uncertain access to follow-up. Amoxicillin is the drug of choice. Observation without antibiotic is an option in immunocompetent children ≥ two years of age who have an acute uncomplicated otitis media and non-severe illness if appropriate follow-up can be arranged. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Diagnosis, treatment, and prevention of Lyme disease in children.

PubMed

Eppes, Stephen C

2003-01-01

The approaches to diagnosing and treating Lyme disease (LD) have been improved and refined as a result of basic and clinical research, and considerable practical experience. In addition, there have been recent studies that have allowed improvements in the ability to prevent infection with Borrelia burgdorferi. This paper will review the relevant literature and address recent developments in the diagnosis, treatment, and prevention of LD. Issues specifically related to the management of children will be identified. Controversies regarding treatment approaches will be examined in some detail. Understanding the clinical manifestations, or stage, of LD is crucial when approaching both diagnosis and treatment. Early localized disease is best diagnosed by recognizing the characteristic skin lesion, erythema migrans. Early disease will frequently, but not always, be accompanied by a detectable antibody response, particularly IgM antibody to the spirochete. Late disease, chiefly arthritis, is generally associated with high levels of IgG antibody. Western blot technology allows confirmation of enzyme immunoassay results and is especially useful when the latter is in the low or equivocal range. Early localized disease responds well to oral antibacterial therapy. Early disseminated disease, often associated with neurologic findings, may require parenteral therapy. The arthritis associated with LD frequently responds to oral antibacterials, but some refractory cases may require intravenous therapy, and occasionally surgery. Doxycycline is the oral antibacterial of choice, while amoxicillin and cefuroxime axetil are alternatives that may be preferred in young children. Owing to its long half-life and once daily dose administration, intravenous ceftriaxone has become the accepted standard for parenteral therapy. Tick avoidance has long been the mainstay for preventing LD. Antibacterial prophylaxis, using doxycycline, for tick bites has been shown to be an effective approach to prevention, but its relevance to pediatrics is uncertain. Vaccines designed to prevent infection have also been developed.

Implications of sperm banking for health-related quality of life up to 1 year after cancer diagnosis

PubMed Central

Pacey, A; Merrick, H; Arden-Close, E; Morris, K; Rowe, R; Stark, D; Eiser, C

2013-01-01

Background: Sperm banking is recommended for all men diagnosed with cancer where treatment is associated with risk of long-term gonadatoxicity, to offer the opportunity of fatherhood and improved quality of life. However, uptake of sperm banking is lower than expected and little is known about why men refuse. Our aims were to determine: (i) demographic and medical variables associated with decisions about banking and (ii) differences in quality of life between bankers and non-bankers at diagnosis (Time 1 (T1)) and 1 year later (Time 2 (T2)). Methods: Questionnaires were completed by 91 men (response rate=86.67%) at T1 and 78 (85.71% response rate) at T2. Results: In all, 44 (56.41%) banked sperm. They were younger and less likely to have children than non-bankers. In a subset of men who were not sure if they wanted children in the future (n=36), 24 banked sperm. Among this group, those who banked were younger, more satisfied with clinic appointments and less worried about the health of future children. At T2, there were no differences in quality of life between bankers and non-bankers. Conclusion: For those who are uncertain about future reproductive plans, decisions depend on their health on diagnosis and satisfaction with clinic care. We conclude that extra care should be taken in counselling younger men who may have given little consideration to future parenting. Results support previous findings that the role of the doctor is vital in facilitating decisions, especially for those who are undecided about whether they wanted children in the future or not. PMID:23470465

The diagnostic management of upper extremity deep vein thrombosis: A review of the literature.

PubMed

Kraaijpoel, Noémie; van Es, Nick; Porreca, Ettore; Büller, Harry R; Di Nisio, Marcello

2017-08-01

Upper extremity deep vein thrombosis (UEDVT) accounts for 4% to 10% of all cases of deep vein thrombosis. UEDVT may present with localized pain, erythema, and swelling of the arm, but may also be detected incidentally by diagnostic imaging tests performed for other reasons. Prompt and accurate diagnosis is crucial to prevent pulmonary embolism and long-term complications as the post-thrombotic syndrome of the arm. Unlike the diagnostic management of deep vein thrombosis (DVT) of the lower extremities, which is well established, the work-up of patients with clinically suspected UEDVT remains uncertain with limited evidence from studies of small size and poor methodological quality. Currently, only one prospective study evaluated the use of an algorithm, similar to the one used for DVT of the lower extremities, for the diagnostic workup of clinically suspected UEDVT. The algorithm combined clinical probability assessment, D-dimer testing and ultrasonography and appeared to safely and effectively exclude UEDVT. However, before recommending its use in routine clinical practice, external validation of this strategy and improvements of the efficiency are needed, especially in high-risk subgroups in whom the performance of the algorithm appeared to be suboptimal, such as hospitalized or cancer patients. In this review, we critically assess the accuracy and efficacy of current diagnostic tools and provide clinical guidance for the diagnostic management of clinically suspected UEDVT. Copyright © 2017 Elsevier Ltd. All rights reserved.

Acute penile trauma and associated morbidity: 9-year experience at a tertiary care center.

PubMed

Phillips, Elizabeth A; Esposito, Anthony J; Munarriz, Ricardo

2015-05-01

Penile fracture is an uncommon urologic emergency, defined as traumatic rupture of the tunica albuginea of the corpus cavernosum. It occurs mainly in young adults during sexual activity. In the United States, urethral injury is associated with 10-38% of all penile fractures. Diagnosis can be made clinically with the classic triad of an audible crack, detumescence, and appearance of hematoma. We sought to identify characteristics associated with true penile fracture vs. other diagnoses, and determine associated morbidity and risk factors for complications. Retrospective operative chart review identified 39 patients (mean age 39.4 years) with clinical features of penile fracture presenting to Boston Medical Center from June 2004 to May 2013. Average time from injury to presentation was 76 h (range 0.5 h-9 days) and the mechanism of injury was coital in 32 (82%) patients. Thirty-two patients (82%) had confirmed penile fracture, 7 (18%) had isolated vascular injury. Of confirmed fractures, 4 (13%) had bilateral corporal injury and associated urethral injury. Imaging was utilized in a total of 21 cases, penoscrotal ultrasound (US) in 17 cases, retrograde urethrogram (RUG) in 3 cases, and magnetic resonance imaging (MRI) in 1 case. Penile exploration was carried out via degloving (n = 5, 13%) or penoscrotal (n = 34, 87%) incisions. At follow-up, six patients (15%) had complications: 2 wound infections, 2 new-onset erectile dysfunction (ED), 1 urethral stricture, 1 fistula and 1 wound dehiscence. Urethral injury increased the risk of post-operative complications (p = 0.015). Penile fracture is primarily a clinical diagnosis, however imaging may be helpful if diagnosis is uncertain. Urethral injury should be suspected in cases of bilateral corporal injury and may be associated with increased morbidity. Surgical approach does not affect morbidity, but may facilitate surgical repair. © 2015 American Society of Andrology and European Academy of Andrology.

123I-FP-CIT SPECT imaging in early diagnosis of dementia in patients with and without a vascular component

PubMed Central

Garriga, Marina; Milà, Marta; Mir, Manzoor; Al-Baradie, Raid; Huertas, Sonia; Castejon, Cesar; Casas, Laura; Badenes, Dolors; Giménez, Nuria; Font, M. Angels; Gonzalez, Jose M.; Ysamat, Maria; Aguilar, Miguel; Slevin, Mark; Krupinski, Jerzy

2015-01-01

Alzheimer’s disease (AD) and vascular dementia (VaD) are the most common cause of dementia. Cerebral ischemia is a major risk factor for development of dementia. 123I-FP-CIT SPECT (DaTScan) is a complementary tool in the differential diagnoses of patients with incomplete or uncertain Parkinsonism. Additional application of DaTScan enables the categorization of Parkinsonian disease with dementia (PDD), and its differentiation from pure AD, and may further contribute to change the therapeutic decision. The aim of this study was to analyze the vascular contribution towards dementia and mild cognitive impairment (MCI). We evaluated the utility of DaTScan for the early diagnosis of dementia in patients with and without a clinical vascular component, and the association between neuropsychological function, vascular component and dopaminergic function on DaTScan. One-hundred and five patients with MCI or the initial phases of dementia were studied prospectively. We developed an initial assessment using neurologic examination, blood tests, cognitive function tests, structural neuroimaging and DaTScan. The vascular component was later quantified in two ways: clinically, according to the Framingham Risk Score (FRS) and by structural neuroimaging using Wahlund Scale Total Score (WSTS). Early diagnosis of dementia was associated with an abnormal DaTScan. A significant association was found between a high WSTS and an abnormal DaTScan (p < 0.01). Mixed AD was the group with the highest vascular component, followed by the VaD group, while MCI and pure AD showed similar WSTS. No significant associations were found between neuropsychological impairment and DaTScan independently of associated vascular component. DaTScan seems to be a good tool to discriminate, in a first clinical assessment, patients with MCI from those with established dementia. There was bigger general vascular affectation observable in MRI or CT in patients with abnormal dopaminergic uptake seen on DaTScan. PMID:26190980

The sensitivity in the IR spectrum of the intact and pathological tissues by laser biophotometry.

PubMed

Ravariu, Cristian; Bondarciuc, Ala

2014-03-01

In this paper, we use the laser biophotometry for in vivo investigations, searching the most sensitive interactions of the near-infrared spectrum with different tissues. The experimental methods are based on the average reflection coefficient (ARC) measurements. For healthy persons, ARC is the average of five values provided by the biophotometer. The probe is applied on dry skin with minimum pilosity, in five regions: left-right shank, left-right forearm, and epigastrium. For the pathological tissues, the emitting terminal is moved over the suspected area, controlling the reflection coefficient level, till a minimum value occurs, as ARC-Pathological. Then, the probe is moved on the symmetrical healthy region of the body to read the complementary coefficient from intact tissue, ARC-Intact, from the same patient. The experimental results show an ARC range between 67 and 59 mW for intact tissues and a lower range, up to 58-42 mW, for pathological tissues. The method is efficient only in those pathological processes accompanied by variable skin depigmentation, water retention, inflammation, thrombosis, or swelling. Frequently, the ARC ranges are overlapping for some diseases. This induces uncertain diagnosis. Therefore, a statistical algorithm is adopted for a differential diagnosis. The laser biophotometry provides a quantitative biometric parameter, ARC, suitable for fast diagnosis in the internal and emergency medicine. These laser biophotometry measurements are representatives for the Romanian clinical trials.

Accessible Modelling of Complexity in Health (AMoCH) and associated data flows: asthma as an exemplar.

PubMed

Liyanage, Harshana; Luzi, Daniela; De Lusignan, Simon; Pecoraro, Fabrizio; McNulty, Richard; Tamburis, Oscar; Krause, Paul; Rigby, Michael; Blair, Mitch

2016-04-18

Background Modelling is an important part of information science. Models are abstractions of reality. We use models in the following contexts: (1) to describe the data and information flows in clinical practice to information scientists, (2) to compare health systems and care pathways, (3) to understand how clinical cases are recorded in record systems and (4) to model health care business models.Asthma is an important condition associated with a substantial mortality and morbidity. However, there are difficulties in determining who has the condition, making both its incidence and prevalence uncertain.Objective To demonstrate an approach for modelling complexity in health using asthma prevalence and incidence as an exemplar.Method The four steps in our process are:1. Drawing a rich picture, following Checkland's soft systems methodology;2. Constructing data flow diagrams (DFDs);3. Creating Unified Modelling Language (UML) use case diagrams to describe the interaction of the key actors with the system;4. Activity diagrams, either UML activity diagram or business process modelling notation diagram.Results Our rich picture flagged the complexity of factors that might impact on asthma diagnosis. There was consensus that the principle issue was that there were undiagnosed and misdiagnosed cases as well as correctly diagnosed. Genetic predisposition to atopy; exposure to environmental triggers; impact of respiratory health on earnings or ability to attend education or participate in sport, charities, pressure groups and the pharmaceutical industry all increased the likelihood of a diagnosis of asthma. Stigma and some factors within the health system diminished the likelihood of a diagnosis. The DFDs and other elements focused on better case finding.Conclusions This approach flagged the factors that might impact on the reported prevalence or incidence of asthma. The models suggested that applying selection criteria may improve the specificity of new or confirmed diagnosis.

Inactivation of DNA mismatch repair by variants of uncertain significance in the PMS2 gene.

PubMed

Drost, Mark; Koppejan, Hester; de Wind, Niels

2013-11-01

Lynch syndrome (LS) is a common cancer predisposition caused by an inactivating mutation in one of four DNA mismatch repair (MMR) genes. Frequently a variant of uncertain significance (VUS), rather than an obviously pathogenic mutation, is identified in one of these genes. The inability to define pathogenicity of such variants precludes targeted healthcare. Here, we have modified a cell-free assay to test VUS in the MMR gene PMS2 for functional activity. We have analyzed nearly all VUS in PMS2 found thus far and describe loss of MMR activity for five, suggesting the applicability of the assay for diagnosis of LS. © 2013 WILEY PERIODICALS, INC.

Neural basis of uncertain cue processing in trait anxiety.

PubMed

Zhang, Meng; Ma, Chao; Luo, Yanyan; Li, Ji; Li, Qingwei; Liu, Yijun; Ding, Cody; Qiu, Jiang

2016-02-19

Individuals with high trait anxiety form a non-clinical group with a predisposition for an anxiety-related bias in emotional and cognitive processing that is considered by some to be a prerequisite for psychiatric disorders. Anxious individuals tend to experience more worry under uncertainty, and processing uncertain information is an important, but often overlooked factor in anxiety. So, we decided to explore the brain correlates of processing uncertain information in individuals with high trait anxiety using the learn-test paradigm. Behaviorally, the percentages on memory test and the likelihood ratios of identifying novel stimuli under uncertainty were similar to the certain fear condition, but different from the certain neutral condition. The brain results showed that the visual cortex, bilateral fusiform gyrus, and right parahippocampal gyrus were active during the processing of uncertain cues. Moreover, we found that trait anxiety was positively correlated with the BOLD signal of the right parahippocampal gyrus during the processing of uncertain cues. No significant results were found in the amygdala during uncertain cue processing. These results suggest that memory retrieval is associated with uncertain cue processing, which is underpinned by over-activation of the right parahippocampal gyrus, in individuals with high trait anxiety.

Venous outflow obstruction and portopulmonary hypertension after orthotopic liver transplantation

PubMed Central

Aguirre-Avalos, Guadalupe; Covarrubias-Velasco, Marco Antonio; Rojas-Sánchez, Antonio Gerardo

2013-01-01

Patient: Female, 54 Final Diagnosis: Suprahepatic inferior vena cava anastomosis stricture Symptoms: Ascites • fatigue • lower limb edema • hepatomegaly Medication: — Clinical Procedure: — Specialty: Transplantology • Critical Care Medicine Objective: Unusual clinical course Background: Suprahepatic inferior vena cava anastomosis stricture is an unusual vascular complication after orthotopic liver transplantation with the “piggyback” technique. Clinical manifestations are dependent upon the severity of the stenosis. Portopulmonary hypertension after orthotopic liver transplantation is a complication that carries high mortality due to cardiopulmonary dysfunction. The pathogenesis of pulmonary vascular disorders after orthotopic liver transplantation remains uncertain. Case Report: We report a case of acute right heart pressure overload after surgical correction of the suprahepatic inferior vena cava anastomotic stricture in a 54-year-old woman who had preexisting pulmonary arterial hypertension associated with portal hypertension after orthotopic liver transplantation. Twenty months posttransplantation, she developed fatigue and progressive ascites. On admission, the patient had hepatomegaly, ascites, and lower limb edema. Symptoms in the patient developed gradually over time. Conclusions: Recurrent portal hypertension by vascular complications is a cause of pulmonary arterial hypertension after orthotopic liver transplantation. Clinical manifestations of suprahepatic inferior vena cava anastomotic stenosis are dependent upon their severity. Sildenafil is an effective drug for treatment of pulmonary arterial hyper-tension after portal hypertension by vascular complications. PMID:24046802

Diagnostic criteria for Patulous Eustachian Tube: A proposal by the Japan Otological Society.

PubMed

Kobayashi, Toshimitsu; Morita, Masahiro; Yoshioka, Satoshi; Mizuta, Kunihiro; Ohta, Shigeto; Kikuchi, Toshiaki; Hayashi, Tatsuya; Kaneko, Akihiro; Yamaguchi, Nobumasa; Hashimoto, Sho; Kojima, Hiromi; Murakami, Shingo; Takahashi, Haruo

2018-02-01

Patulous Eustachian Tube (PET) is of increasing importance in otology. However, despite the abundance of diseases requiring a differential diagnosis from PET, such as superior semicircular canal dehiscence syndrome, perilymphatic fistula, acute low-tone sensorineural hearing loss, etc., there are currently no established diagnostic criteria for PET. In view of these circumstances, the Japan Otological Society (JOS) Eustachian Tube Committee proposed the diagnostic criteria for Patulous Eustachian Tube in 2012, in order to promote clinical research on PET. A revision was made in 2016, maintaining the original concept that the criteria should be very simple, avoid any contamination of "Definite PET" with uncertain cases. Moreover, it was also intended to minimize the number of cases that could be accidentally excluded even in the presence of some suspected findings ("Possible PET"). The criteria can be used by all otolaryngologists even without using the Eustachian tube function test apparatus. However, the use of such an apparatus may increase the chances of detecting "Definite PET". The algorithm for the diagnosis of PET using the criteria has also been described. The JOS diagnostic criteria for Patulous Eustachian Tube will further promote international scientific communication on PET. Copyright © 2017 Elsevier B.V. All rights reserved.

ACCF/ACR/AIUM/ASE/ASN/ICAVL/SCAI/SCCT/SIR/SVM/SVS 2012 Appropriate Use Criteria for Peripheral Vascular Ultrasound and Physiological Testing Part I: Arterial Ultrasound and Physiological Testing

PubMed Central

Mohler, Emile R.; Gornik, Heather L.; Gerhard-Herman, Marie; Misra, Sanjay; Olin, Jeffrey W.; Zierler, R. Eugene; Wolk, Michael J.; Mohler, Emile R.; Dixon, Bradley S.; Driver, Vickie R.; Fail, Peter S.; Fazel, Reza; Findeiss, Laura; Fuchs, Richard; Gillespie, John; Hughes, Joseph P.; Jaigobin, Cheryl; Leers, Steven A.; Moore, Colleen; Pellerito, John S.; Robbin, Michelle L.; Shugart, Rita E.; Weaver, Fred A.; White, Christopher J.; Yevzlin, Alexander S.; Wolk, Michael J.; Bailey, Steven R.; Douglas, Pamela S.; Hendel, Robert C.; Kramer, Christopher M.; Min, James K.; Patel, Manesh R.; Shaw, Leslee; Stainback, Raymond F.; Allen, Joseph M.

2015-01-01

The American College of Cardiology Foundation (ACCF), in partnership with key specialty and subspecialty societies, conducted a review of common clinical scenarios where noninvasive vascular testing (ultrasound and physiological testing) is frequently considered. The indications (clinical scenarios) were derived from common applications or anticipated uses, as well as from current clinical practice guidelines and results of studies examining the implementation of the original appropriate use criteria (AUC). The 159 indications in this document were developed by a diverse writing group and scored by a separate independent technical panel on a scale of 1 to 9, to designate appropriate use (median 7 to 9), uncertain use (median 4 to 6), and inappropriate use (median 1 to 3). A total of 255 indications (with the inclusion of surveillance timeframes) were rated. One hundred and seventeen indications were rated as appropriate, 84 were rated as uncertain, and 54 were rated as inappropriate. The AUC for peripheral vascular disease have the potential to impact physician decision making, healthcare delivery, and reimbursement policy. Furthermore, recognition of uncertain clinical scenarios facilitates identification of areas that would benefit from future research. PMID:22694840

The unique value of cardiovascular magnetic resonance in patients with suspected acute coronary syndrome and culprit-free coronary angiograms.

PubMed

Panovský, Roman; Borová, Júlia; Pleva, Martin; Feitová, Věra; Novotný, Petr; Kincl, Vladimír; Holeček, Tomáš; Meluzín, Jaroslav; Sochor, Ondřej; Štěpánová, Radka

2017-06-28

Patients with chest pain, elevated troponin, and unobstructed coronary disease present a clinical dilemma. The purpose of this study was to investigate the incremental diagnostic value of cardiovascular magnetic resonance (CMR) in a cohort of patients with suspected acute coronary syndrome (ACS) and unobstructed coronary arteries. Data files of patients meeting the inclusion criteria in two cardiology centres were searched and analysed. The inclusion criteria included: 1) thoracic pain suspected with ACS; 2) a significant increase in the high-sensitive Troponin T value; 3) ECG changes; 4) coronary arteries without any significant stenosis; 5) a CMR examination included in the diagnostic process; 6) an uncertain diagnosis before the CMR exam; and 7) the absence of known CMR and contrast media contraindications. Special attention was paid to the benefits of CMR in determining the final diagnosis. In total, 136 patients who underwent coronary angiography for chest pain were analysed. The most frequent underlying causes were myocarditis (38%) and perimyocarditis (18%), followed by angiographically unrecognised acute myocardial infarction (18%) and Takotsubo cardiomyopathy (15%). The final diagnosis remained unclear in 6% of the patients. The contribution of CMR in determining the final diagnosis determination was crucial in 57% of the patients. In another 35% of the patients, CMR confirmed the suspicion and, only 8% of the CMR examinations did not help at all and had no influence on diagnosis or treatment. CMR provided a powerful incremental diagnostic value in the cohort of patients with suspected ACS and unobstructed coronary arteries. CMR is highly recommended to be incorporated as an inalienable part of the diagnostic algorithms in these patients.

Pregnant patients' risk perception of prenatal test results with uncertain fetal clinical significance: ultrasound versus advanced genetic testing.

PubMed

Richards, Elliott G; Sangi-Haghpeykar, Haleh; McGuire, Amy L; Van den Veyver, Ignatia B; Fruhman, Gary

2015-12-01

A common concern of utilizing prenatal advanced genetic testing is that a result of uncertain clinical significance will increase patient anxiety. However, prenatal ultrasound may also yield findings of uncertain significance, such as 'soft markers' for fetal aneuploidy, or findings with variable prognosis, such as mild ventriculomegaly. In this study we compared risk perception following uncertain test results from each modality. A single survey with repeated measures design was administered to 133 pregnant women. It included 'intolerance of uncertainty' questions, two hypothetical scenarios involving prenatal ultrasound or advanced genetic testing, and response questions. The primary outcome was risk perception score. Risk perception did not vary significantly between ultrasound and genetic scenarios (p = 0.17). The genetic scenario scored a higher accuracy (p = 0.04) but lower sense of empowerment (p = 0.01). Furthermore, patients were more likely to seek additional testing after an ultrasound than after genetic testing (p = 0.05). There were no differences in other secondary outcomes including perception of life-altering consequences and hypothetical worry, anxiety, confusion, or medical care decisions. Our data suggest that uncertain findings on prenatal genetic testing do not elicit a higher perception of risk or anxiety when compared to ultrasound findings of comparable uncertainty. © 2015 John Wiley & Sons, Ltd. © 2015 John Wiley & Sons, Ltd.

Uptake, Results, and Outcomes of Germline Multiple-Gene Sequencing After Diagnosis of Breast Cancer.

PubMed

Kurian, Allison W; Ward, Kevin C; Hamilton, Ann S; Deapen, Dennis M; Abrahamse, Paul; Bondarenko, Irina; Li, Yun; Hawley, Sarah T; Morrow, Monica; Jagsi, Reshma; Katz, Steven J

2018-05-10

Low-cost sequencing of multiple genes is increasingly available for cancer risk assessment. Little is known about uptake or outcomes of multiple-gene sequencing after breast cancer diagnosis in community practice. To examine the effect of multiple-gene sequencing on the experience and treatment outcomes for patients with breast cancer. For this population-based retrospective cohort study, patients with breast cancer diagnosed from January 2013 to December 2015 and accrued from SEER registries across Georgia and in Los Angeles, California, were surveyed (n = 5080, response rate = 70%). Responses were merged with SEER data and results of clinical genetic tests, either BRCA1 and BRCA2 (BRCA1/2) sequencing only or including additional other genes (multiple-gene sequencing), provided by 4 laboratories. Type of testing (multiple-gene sequencing vs BRCA1/2-only sequencing), test results (negative, variant of unknown significance, or pathogenic variant), patient experiences with testing (timing of testing, who discussed results), and treatment (strength of patient consideration of, and surgeon recommendation for, prophylactic mastectomy), and prophylactic mastectomy receipt. We defined a patient subgroup with higher pretest risk of carrying a pathogenic variant according to practice guidelines. Among 5026 patients (mean [SD] age, 59.9 [10.7]), 1316 (26.2%) were linked to genetic results from any laboratory. Multiple-gene sequencing increasingly replaced BRCA1/2-only testing over time: in 2013, the rate of multiple-gene sequencing was 25.6% and BRCA1/2-only testing, 74.4%;in 2015 the rate of multiple-gene sequencing was 66.5% and BRCA1/2-only testing, 33.5%. Multiple-gene sequencing was more often ordered by genetic counselors (multiple-gene sequencing, 25.5% and BRCA1/2-only testing, 15.3%) and delayed until after surgery (multiple-gene sequencing, 32.5% and BRCA1/2-only testing, 19.9%). Multiple-gene sequencing substantially increased rate of detection of any pathogenic variant (multiple-gene sequencing: higher-risk patients, 12%; average-risk patients, 4.2% and BRCA1/2-only testing: higher-risk patients, 7.8%; average-risk patients, 2.2%) and variants of uncertain significance, especially in minorities (multiple-gene sequencing: white patients, 23.7%; black patients, 44.5%; and Asian patients, 50.9% and BRCA1/2-only testing: white patients, 2.2%; black patients, 5.6%; and Asian patients, 0%). Multiple-gene sequencing was not associated with an increase in the rate of prophylactic mastectomy use, which was highest with pathogenic variants in BRCA1/2 (BRCA1/2, 79.0%; other pathogenic variant, 37.6%; variant of uncertain significance, 30.2%; negative, 35.3%). Multiple-gene sequencing rapidly replaced BRCA1/2-only testing for patients with breast cancer in the community and enabled 2-fold higher detection of clinically relevant pathogenic variants without an associated increase in prophylactic mastectomy. However, important targets for improvement in the clinical utility of multiple-gene sequencing include postsurgical delay and racial/ethnic disparity in variants of uncertain significance.

A statistical method for lung tumor segmentation uncertainty in PET images based on user inference.

PubMed

Zheng, Chaojie; Wang, Xiuying; Feng, Dagan

2015-01-01

PET has been widely accepted as an effective imaging modality for lung tumor diagnosis and treatment. However, standard criteria for delineating tumor boundary from PET are yet to develop largely due to relatively low quality of PET images, uncertain tumor boundary definition, and variety of tumor characteristics. In this paper, we propose a statistical solution to segmentation uncertainty on the basis of user inference. We firstly define the uncertainty segmentation band on the basis of segmentation probability map constructed from Random Walks (RW) algorithm; and then based on the extracted features of the user inference, we use Principle Component Analysis (PCA) to formulate the statistical model for labeling the uncertainty band. We validated our method on 10 lung PET-CT phantom studies from the public RIDER collections [1] and 16 clinical PET studies where tumors were manually delineated by two experienced radiologists. The methods were validated using Dice similarity coefficient (DSC) to measure the spatial volume overlap. Our method achieved an average DSC of 0.878 ± 0.078 on phantom studies and 0.835 ± 0.039 on clinical studies.

Fascial preadipocytes: another missing piece of the puzzle to understand fibromyalgia?

PubMed

Bordoni, Bruno; Marelli, Fabiola; Morabito, Bruno; Cavallaro, Francesca; Lintonbon, David

2018-01-01

Fibromyalgia (FM) syndrome is a chronic condition causing pain, affecting approximately 0.5%-6% of the developed countries' population, and on average, 2% of the worldwide population. Despite the large amount of scientific literature available, the FM etiology is still uncertain. The diagnosis is based on the clinical presentation and the severity of the symptomatology. Several studies pointed out pathological alterations within the central nervous system, suggesting that FM could originate from a central sensitization of the pain processing centers. Research supports the thesis of a peripheral neuropathic component, with the finding of axonal damages. The fibromyalgia patient has many myofascial system abnormalities, such as pain and fatigue, impairing the symptomatic profile. This paper revises the myopathic compensations, highlighting the possible role of the fascia in generating symptoms, being aware of the new information about the fascia's activity in stimulating inflammation and fat cell production.

Diagnostic instruments for behavioural addiction: an overview

PubMed Central

Albrecht, Ulrike; Kirschner, Nina Ellen; Grüsser, Sabine M.

2007-01-01

In non-substance-related addiction, the so-called behavioural addiction, no external psychotropic substances are consumed. The psychotropic effect consists of the body’s own biochemical processes induced only by excessive activities. Until recently, knowledge was limited with respect to clinically relevant excessive reward-seeking behaviour, such as pathological gambling, excessive shopping and working which meet diagnostic criteria of dependent behaviour. To date, there is no consistent concept for diagnosis and treatment of excessive reward-seeking behaviour, and its classification is uncertain. Therefore, a clear conceptualization of the so-called behavioural addictions is of great importance. The use of adequate diagnostic instruments is necessary for successful therapeutical implications. This article provides an overview of the current popular diagnostic instruments assessing the different forms of behavioural addiction. Especially in certain areas there are only few valid and reliable instruments available to assess excessive rewarding behaviours that fulfill the criteria of addiction. PMID:19742294

A retrospective cohort study of patients treated with anti-tuberculous therapy for presumed ocular tuberculosis.

PubMed

Damato, Erika Marie; Dawson, Sarah; Liu, Xiaoxuan; Mukherjee, Chandoshi; Horsburgh, John; Denniston, Alastair K; Moran, Edward; Dedicoat, Martin; Murray, Philip Ian

2017-12-04

Uveitis involving the posterior segment is a significant and potentially blinding condition. The diagnosis and treatment of patients with uveitis associated with tuberculosis remains controversial, and commonly, patients are systemically well. Use of the interferon-gamma release assays has added to the controversy, as the significance of a positive test may be uncertain. We aim to report the outcomes of anti-tuberculous treatment in a cohort of patients treated in Birmingham, for presumed "ocular tuberculosis", based on clinical findings, systemic assessment and specific testing for tuberculosis. We found that in our cohort of 41 patients treated between 2010 and 2014, the majority achieved disease-free remission, even in cases where anti-tuberculous treatment was delayed. Despite controversy, this study strongly supports the use of anti-tuberculous therapy in such patients and highlights the need for formal prospective trials and treatment protocols.

Evaluation of musculoskeletal sepsis with indium-111 white blood cell imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ouzounian, T.J.; Thompson, L.; Grogan, T.J.

The detection of musculoskeletal sepsis, especially following joint replacement, continues to be a challenging problem. Often, even with invasive diagnostic evaluation, the diagnosis of infection remains uncertain. This is a report on the first 55 Indium-111 white blood cell (WBC) images performed in 39 patients for the evaluation of musculoskeletal sepsis. There were 40 negative and 15 positive Indium-111 WBC images. These were correlated with operative culture and tissue pathology, aspiration culture, and clinical findings. Thirty-eight images were performed for the evaluation of possible total joint sepsis (8 positive and 30 negative images); 17 for the evaluation of nonarthroplasty-related musculoskeletalmore » sepsis (7 positive and 10 negative images). Overall, there were 13 true-positive, 39 true-negative, two false-positive, and one false-negative images. Indium-111 WBC imaging is a sensitive and specific means of evaluating musculoskeletal sepsis, especially following total joint replacement.« less

Expert opinion: diagnosis and treatment of proximal hamstring tendinopathy.

PubMed

Lempainen, Lasse; Johansson, Kristian; Banke, Ingo J; Ranne, Juha; Mäkelä, Keijo; Sarimo, Janne; Niemi, Pekka; Orava, Sakari

2015-01-01

proximal hamstring tendinopathy (PHT) is a disabilitating disease often causing underperformance in the athletically demanding patients. The main symptom of PHT is lower gluteal pain especially during running or while prolonged sitting. Mainly affecting athletically active individuals, PHT is a considerable challenge for treating health care professionals. this paper aims to concisely present the literature on PHT to guide health care professionals treating these patients and doing research on the subject. we reviewed the literature on PHT through literature search of scientific journal databases. as a tendinopathic pathology, it is a rather recently discovered exertion injury. As with other chronic tendon overuse injuries, current treatment strategies are unspecific with uncertain outcomes due to the unknown etiology of the tendon degeneration. Diagnostic features as well as both operative and non-operative treatments are evaluated from a clinical perspective, providing up to date information for clinicians and sports medicine therapists dealing with hamstring problems. V.

Fascial preadipocytes: another missing piece of the puzzle to understand fibromyalgia?

PubMed Central

Bordoni, Bruno; Marelli, Fabiola; Morabito, Bruno; Cavallaro, Francesca; Lintonbon, David

2018-01-01

Fibromyalgia (FM) syndrome is a chronic condition causing pain, affecting approximately 0.5%–6% of the developed countries’ population, and on average, 2% of the worldwide population. Despite the large amount of scientific literature available, the FM etiology is still uncertain. The diagnosis is based on the clinical presentation and the severity of the symptomatology. Several studies pointed out pathological alterations within the central nervous system, suggesting that FM could originate from a central sensitization of the pain processing centers. Research supports the thesis of a peripheral neuropathic component, with the finding of axonal damages. The fibromyalgia patient has many myofascial system abnormalities, such as pain and fatigue, impairing the symptomatic profile. This paper revises the myopathic compensations, highlighting the possible role of the fascia in generating symptoms, being aware of the new information about the fascia’s activity in stimulating inflammation and fat cell production. PMID:29750060

Intestinal "bioavailability" of solutes and water: we know how but not why.

PubMed Central

Charney, A. N.

1996-01-01

Only minimal quantities of ingested and normally secreted solutes and water are excreted in the stool. This near 100% bioavailability means that the diet and kidneys are relatively more important determinants of solute, water and acid-base balance than the intestine. Intestinal bioavailability is based on excess transport capacity under normal conditions and the ability to adapt to altered or abnormal conditions. Indeed, the regulatory system of the intestine is as complex, segmented and multi factorial as in the kidney. Alterations in the rate and intestinal site of absorption reflect this regulation, and the diagnosis and treatment of various clinical abnormalities depend on the integrity of intestinal absorptive processes. However, the basis for this regulation an bioavailability are uncertain. Perhaps they had survival value for mammals, a phylogenic class that faced the twin threats of intestinal pathogens and shortages of solutes and water. PMID:9273987

Stroke and Chronic Kidney Disease: Epidemiology, Pathogenesis, and Management Across Kidney Disease Stages

PubMed Central

Weiner, Daniel E.; Dad, Taimur

2015-01-01

Summary Cerebrovascular disease and stroke are very common at all stages of chronic kidney disease (CKD), likely representing both shared risk factors as well as synergy among risk factors. More subtle ischemic brain lesions may be particularly common in the CKD population, with subtle manifestations including cognitive impairment. For individuals with nondialysis CKD, the prevention, approach to, diagnosis, and management of stroke is similar to the general, non-CKD population. For individuals with end-stage renal disease, far less is known regarding the prevention of stroke. Stroke prophylaxis using warfarin in dialysis patients with atrial fibrillation in particular remains of uncertain benefit. End-stage renal disease patients can be managed aggressively in the setting of acute stroke. Outcomes after stroke at all stages of CKD are poor, and improving these outcomes should be the subject of future clinical trials. PMID:26355250

Surgical implications and variability in the use of the flat epithelial atypia diagnosis on breast biopsy specimens.

PubMed

Samples, Laura S; Rendi, Mara H; Frederick, Paul D; Allison, Kimberly H; Nelson, Heidi D; Morgan, Thomas R; Weaver, Donald L; Elmore, Joann G

2017-08-01

Flat epithelial atypia (FEA) is a relatively new diagnostic term with uncertain clinical significance for surgical management. Any implied risk of invasive breast cancer associated with FEA is contingent upon diagnostic reproducibility, yet little is known regarding its use. Pathologists in the Breast Pathology Study interpreted one of four 60-case test sets, one slide per case, constructed from 240 breast biopsy specimens. An electronic data form with standardized diagnostic categories was used; participants were instructed to indicate all diagnoses present. We assessed participants' use of FEA as a diagnostic term within: 1) each test set; 2) 72 cases classified by reference as benign without FEA; and 3) six cases classified by reference as FEA. 115 pathologists participated, providing 6900 total independent assessments. Notation of FEA ranged from 0% to 35% of the cases interpreted, with most pathologists noting FEA on 4 or more test cases. At least one participant noted FEA in 34 of the 72 benign non-FEA cases. For the 6 reference FEA cases, participant agreement with the case reference FEA diagnosis ranged from 17% to 52%; diagnoses noted by participating pathologists for these FEA cases included columnar cell hyperplasia, usual ductal hyperplasia, atypical lobular hyperplasia, and atypical ductal hyperplasia. We observed wide variation in the diagnosis of FEA among U.S. pathologists. This suggests that perceptions of diagnostic criteria and any implied risk associated with FEA may also vary. Surgical excision following a core biopsy diagnosis of FEA should be reconsidered and studied further. Copyright © 2017 Elsevier Ltd. All rights reserved.

Recent advances in biosensor development for the detection of cancer biomarkers.

PubMed

Jayanthi, V S P K Sankara Aditya; Das, Asim Bikas; Saxena, Urmila

2017-05-15

Cancer is the second largest disease throughout the world with an increasing mortality rate over the past few years. The patient's survival rate is uncertain due to the limitations of cancer diagnosis and therapy. Early diagnosis of cancer is decisive for its successful treatment. A biomarker-based cancer diagnosis may significantly improve the early diagnosis and subsequent treatment. Biosensors play a crucial role in the detection of biomarkers as they are easy to use, portable, and can do analysis in real time. This review describes various biosensors designed for detecting nucleic acid and protein-based cancer biomarkers for cancer diagnosis. It mainly lays emphasis on different approaches to use electrochemical, optical, and mass-based transduction systems in cancer biomarker detection. It also highlights the analytical performances of various biosensor designs concerning cancer biomarkers in detail. Copyright © 2016 Elsevier B.V. All rights reserved.

Examination of the Clinicopathologic Continuum of Alzheimer Disease in the Autopsy Cohort of the National Alzheimer Coordinating Center

PubMed Central

Serrano-Pozo, Alberto; Qian, Jing; Monsell, Sarah E.; Frosch, Matthew P.; Betensky, Rebecca A.; Hyman, Bradley T.

2014-01-01

To test the hypothesis that Alzheimer disease (AD) is a clinical and pathologic continuum between normal aging and end-stage dementia, we selected a convenience sample of subjects from the National Alzheimer Coordinating Center 2005 to 2012 autopsy cohort (n = 2,083) with the last clinical evaluation within 2 years before autopsy and no other primary neuropathologic diagnosis. Demographic and neuropathologic characteristics were correlated with the Clinical Dementia Rating–Sum of Boxes in the 835 subjects meeting these criteria. Both neuritic plaques and neurofibrillary tangles independently predicted Clinical Dementia Rating–Sum of Boxes. Severe small-vessel disease, severe amyloid angiopathy, and hippocampal sclerosis were also independently associated with the degree of cognitive impairment. By contrast, education was a strong independent protective factor against cognitive deficits. The cause of mild to moderate dementia remained uncertain in 14% of the patients. Inverse probability weighting suggests the generalizability of these results to nonautopsied cohorts. These data indicate that plaques and tangles independently contribute to cognitive impairment, that concurrent vascular disease strongly correlates with cognitive dysfunction even in a sample selected to represent the AD pathologic continuum, and that education further modifies clinical expression. Thus, multiple concomitant etiologies of brain damage and premorbid characteristics contribute to the uncertainty of AD clinicopathologic correlations based only on tangles and plaques. PMID:24226270

Examination of the clinicopathologic continuum of Alzheimer disease in the autopsy cohort of the National Alzheimer Coordinating Center.

PubMed

Serrano-Pozo, Alberto; Qian, Jing; Monsell, Sarah E; Frosch, Matthew P; Betensky, Rebecca A; Hyman, Bradley T

2013-12-01

To test the hypothesis that Alzheimer disease (AD) is a clinical and pathologic continuum between normal aging and end-stage dementia, we selected a convenience sample of subjects from the National Alzheimer Coordinating Center 2005 to 2012 autopsy cohort (n = 2,083) with the last clinical evaluation within 2 years before autopsy and no other primary neuropathologic diagnosis. Demographic and neuropathologic characteristics were correlated with the Clinical Dementia Rating-Sum of Boxes in the 835 subjects meeting these criteria. Both neuritic plaques and neurofibrillary tangles independently predicted Clinical Dementia Rating-Sum of Boxes. Severe small-vessel disease, severe amyloid angiopathy, and hippocampal sclerosis were also independently associated with the degree of cognitive impairment. By contrast, education was a strong independent protective factor against cognitive deficits. The cause of mild to moderate dementia remained uncertain in 14% of the patients. Inverse probability weighting suggests the generalizability of these results to nonautopsied cohorts. These data indicate that plaques and tangles independently contribute to cognitive impairment, that concurrent vascular disease strongly correlates with cognitive dysfunction even in a sample selected to represent the AD pathologic continuum, and that education further modifies clinical expression. Thus, multiple concomitant etiologies of brain damage and premorbid characteristics contribute to the uncertainty of AD clinicopathologic correlations based only on tangles and plaques.

Germline BRCA1/BRCA2 mutations among high risk breast cancer patients in Jordan.

PubMed

Abdel-Razeq, Hikmat; Al-Omari, Amal; Zahran, Farah; Arun, Banu

2018-02-06

Breast cancer is the most common malignancy and the leading cause of cancer-related deaths among Jordanian women. With a median age of 50 years at diagnosis, a higher prevalence of hereditary breast cancer may be expected. The objective of this pilot study is to evaluate, for the first time, the contribution of germline mutations in BRCA1/2 to breast cancer among Jordanian patients. Jordanian breast cancer women with a selected high risk profile were invited to participate. Peripheral blood samples were obtained for DNA extraction. A detailed 3-generation family history was also collected. BRCA sequencing was performed at a reference laboratory. Mutations were classified as deleterious, suspected deleterious, variant of uncertain significance or favor polymorphisms. Patients' medical records were reviewed for extraction of clinical and tumor pathology data. One hundred patients were enrolled to the study. Median age was 40 (22-75) years. In total, 20 patients had deleterious and 7 suspected deleterious mutations in BRCA1 or BRCA2 genes. Seven variants of uncertain significance were also detected. After excluding patients tested subsequent to the index case in their families, highest mutation rates were observed among triple negatives (9/16, 56.3%) especially among those with positive family history of breast and/or ovarian cancer (9/13, 69.2%), patients with bilateral or second primary breast cancer (10/15, 66.7%) and those with family history of male breast cancer (2/5, 40.0%). BRCA1/2 mutations are not uncommon among selected Jordanian females with breast cancer. The contribution of these findings to much younger age at diagnosis is debatable. Although small, our selected patient cohort shows an important incidence of deleterious and suspected deleterious BRCA1/2 mutations suggesting that genetic testing should be offered to patients with certain high risk features.

Spinal epidural angiolipomas: Clinical characteristics, management and outcomes

PubMed Central

Bouali, Sofiene; Maatar, Nidhal; Bouhoula, Asma; Abderrahmen, Khansa; Said, Imed Ben; Boubaker, Adnen; Kallel, Jalel; Jemel, Hafedh

2016-01-01

Purpose: The spinal epidural angiolipomas are rare expansive processes made of mature lipomatous and angiomatous elements. They often have a benign character. Their etiology, pathogenesis remains uncertain, and it is a cause of spinal cord compression. The magnetic resonance imaging is the most important neuroradiological examination. Histological examination is the only examination to confirm the diagnosis. Surgery is the treatment of choice. Methods: A retrospective study of all patients operated on for a spinal epidural angiolipoma at the Department of Neurosurgery at the National Institute of Neurology of Tunis between January 2000 and December 2014 (15 years) was performed. The aim of this study is to describe the clinical, radiological, histological characteristics and the treatment of this tumor. Results: A total of nine patients were operated from January 01, 2000 to November 30, 2014. The average age of our patients was 51 years with ages that ranged from 29 to 65 with a male predominance. The period between onset of symptoms and diagnosis ranged from 24 months with an average 12 months. Posterior localization of the tumor was seen in all patients. Surgical resection was performed for all cases. The postoperative course has been satisfactory, with a complete recovery of neurological functions in all patients. Conclusions: The spinal epidural angiolipomas is rare expansive process causing spinal cord compression. Treatment is exclusively surgical resection. The functional outcome of spinal epidural angiolipomas is particularly favorable with a complete neurological recovery is if the patient was quickly operated. PMID:27695535

Spinal epidural angiolipomas: Clinical characteristics, management and outcomes.

PubMed

Bouali, Sofiene; Maatar, Nidhal; Bouhoula, Asma; Abderrahmen, Khansa; Said, Imed Ben; Boubaker, Adnen; Kallel, Jalel; Jemel, Hafedh

2016-01-01

The spinal epidural angiolipomas are rare expansive processes made of mature lipomatous and angiomatous elements. They often have a benign character. Their etiology, pathogenesis remains uncertain, and it is a cause of spinal cord compression. The magnetic resonance imaging is the most important neuroradiological examination. Histological examination is the only examination to confirm the diagnosis. Surgery is the treatment of choice. A retrospective study of all patients operated on for a spinal epidural angiolipoma at the Department of Neurosurgery at the National Institute of Neurology of Tunis between January 2000 and December 2014 (15 years) was performed. The aim of this study is to describe the clinical, radiological, histological characteristics and the treatment of this tumor. A total of nine patients were operated from January 01, 2000 to November 30, 2014. The average age of our patients was 51 years with ages that ranged from 29 to 65 with a male predominance. The period between onset of symptoms and diagnosis ranged from 24 months with an average 12 months. Posterior localization of the tumor was seen in all patients. Surgical resection was performed for all cases. The postoperative course has been satisfactory, with a complete recovery of neurological functions in all patients. The spinal epidural angiolipomas is rare expansive process causing spinal cord compression. Treatment is exclusively surgical resection. The functional outcome of spinal epidural angiolipomas is particularly favorable with a complete neurological recovery is if the patient was quickly operated.

Soft-Tissue Sarcomas of the Abdomen and Pelvis: Radiologic-Pathologic Features, Part 2-Uncommon Sarcomas.

PubMed

Levy, Angela D; Manning, Maria A; Miettinen, Markku M

2017-01-01

Soft-tissue sarcomas occurring in the abdomen and pelvis are an uncommon but important group of malignancies. Recent changes to the World Health Organization classification of soft-tissue tumors include the movement of gastrointestinal stromal tumors (GISTs) into the soft-tissue tumor classification. GIST is the most common intraperitoneal sarcoma. Liposarcoma is the most common retroperitoneal sarcoma, and leiomyosarcoma is the second most common. GIST, liposarcoma, and leiomyosarcoma account for the majority of sarcomas encountered in the abdomen and pelvis and are discussed in part 1 of this article. Undifferentiated pleomorphic sarcoma (previously called malignant fibrous histiocytoma), dermatofibrosarcoma protuberans, solitary fibrous tumor, malignant peripheral nerve sheath tumor, rhabdomyosarcoma, extraskeletal chondro-osseous sarcomas, vascular sarcomas, and sarcomas of uncertain differentiation uncommonly arise in the abdomen and pelvis and the abdominal wall. Although these lesions are rare sarcomas and their imaging features overlap, familiarity with the locations where they occur and their imaging features is important so they can be diagnosed accurately. The anatomic location and clinical history are important factors in the differential diagnosis of these lesions because metastasis, more-common sarcomas, borderline fibroblastic proliferations (such as desmoid tumors), and endometriosis have imaging findings that overlap with those of these uncommon sarcomas. In this article, the clinical, pathologic, and imaging findings of uncommon soft-tissue sarcomas of the abdomen and pelvis and the abdominal wall are reviewed, with an emphasis on their differential diagnosis.

Soft-Tissue Sarcomas of the Abdomen and Pelvis: Radiologic-Pathologic Features, Part 2—Uncommon Sarcomas

PubMed Central

Manning, Maria A.; Miettinen, Markku M.

2017-01-01

Soft-tissue sarcomas occurring in the abdomen and pelvis are an uncommon but important group of malignancies. Recent changes to the World Health Organization classification of soft-tissue tumors include the movement of gastrointestinal stromal tumors (GISTs) into the soft-tissue tumor classification. GIST is the most common intraperitoneal sarcoma. Liposarcoma is the most common retroperitoneal sarcoma, and leiomyosarcoma is the second most common. GIST, liposarcoma, and leiomyosarcoma account for the majority of sarcomas encountered in the abdomen and pelvis and are discussed in part 1 of this article. Undifferentiated pleomorphic sarcoma (previously called malignant fibrous histiocytoma), dermatofibrosarcoma protuberans, solitary fibrous tumor, malignant peripheral nerve sheath tumor, rhabdomyosarcoma, extraskeletal chondro-osseous sarcomas, vascular sarcomas, and sarcomas of uncertain differentiation uncommonly arise in the abdomen and pelvis and the abdominal wall. Although these lesions are rare sarcomas and their imaging features overlap, familiarity with the locations where they occur and their imaging features is important so they can be diagnosed accurately. The anatomic location and clinical history are important factors in the differential diagnosis of these lesions because metastasis, more-common sarcomas, borderline fibroblastic proliferations (such as desmoid tumors), and endometriosis have imaging findings that overlap with those of these uncommon sarcomas. In this article, the clinical, pathologic, and imaging findings of uncommon soft-tissue sarcomas of the abdomen and pelvis and the abdominal wall are reviewed, with an emphasis on their differential diagnosis. PMID:28493803

An update on the diagnosis and treatment of chronic idiopathic neutropenia.

PubMed

Dale, David C; Bolyard, Audrey A

2017-01-01

Neutropenia lasting for at least for 3 months and not attributable to drugs or a specific genetic, infectious, inflammatory, autoimmune or malignant cause is called chronic idiopathic neutropenia (CIN). CIN and autoimmune neutropenia (AIN) are very similar and overlapping conditions. The clinical consequences depend upon the severity of neutropenia, but it is not considered a premalignant condition. Long-term observational studies in children indicate that the disease often lasts for 3-5 years in children, then spontaneously remits, but it rarely remits in adult cases. The value of antineutrophil antibody testing in both children and adults is uncertain. Most recent data suggest that CIN and AIN are immune-mediated diseases, but there are no new clinical or genetic tests to aid in diagnosis. Treatment with granulocyte colony stimulating factor (G-CSF) is effective to increase blood neutrophils in almost all cases; this treatment is reserved, however, for patients with both neutropenia and evidence of recurrent fevers, inflammatory symptoms and infections. There is little or no evidence to indicate that G-CSF treatment predisposes to myeloid malignancies in this population. It is important to recognize CIN and AIN, the most common causes of chronic neutropenia in both children and adults. If the neutropenia is not severe, that is more than 0.5 × 10/l, most patients can be observed and not treated prophylactically with antibiotics or a growth factor. When neutropenia is severe, treatment with G-CSF is often beneficial.

An update on the diagnosis and treatment of chronic idiopathic neutropenia

PubMed Central

Dale, David C.; Bolyard, Audrey Anna

2017-01-01

Purpose of Review Neutropenia lasting for at least for 3 months and not attributable to drugs or a specific genetic, infectious, inflammatory, autoimmune or malignant cause is called chronic idiopathic neutropenia. (CIN) CIN and autoimmune neutropenia (AIN) are very similar and overlapping conditions. The clinical consequences depend upon the severity of neutropenia, but it is not considered a premalignant condition. Recent findings Long-term observational studies in children indicate that the disease often lasts for 3 to 5 years in children, then spontaneously remits, but it rarely remits in adult cases. The value of anti-neutrophil antibody testing in both children and adults is uncertain. Most recent data suggest that CIN and AIN are immune mediated diseases, but there are no new clinical or genetic tests to aid in diagnosis. Treatment with granulocyte colony stimulating factor (G-CSF) is effective to increase blood neutrophils in almost all cases; this treatment is reserved, however for patients with both neutropenia and evidence of recurrent fevers, inflammatory symptoms and infections. There is little or no evidence to indicate that G-CSF treatment predisposes to myeloid malignancies in this population. Summary It is important to recognize CIN and AIN, the most common causes of chronic neutropenia in both children and adults. If the neutropenia is not severe, i.e. > 0.5 × 109/L, most patients can be observed and not treated prophylactically with antibiotics or a growth factor. When neutropenia is severe treatment with G-CSF is often beneficial. PMID:27841775

Consideration of a new definition of clinically relevant myocardial infarction after coronary revascularization: an expert consensus document from the Society for Cardiovascular Angiography and Interventions (SCAI).

PubMed

Moussa, Issam D; Klein, Lloyd W; Shah, Binita; Mehran, Roxana; Mack, Michael J; Brilakis, Emmanouil S; Reilly, John P; Zoghbi, Gilbert; Holper, Elizabeth; Stone, Gregg W

2013-10-22

Numerous definitions have been proposed for the diagnosis of myocardial infarction (MI) after coronary revascularization. The universal definition for MI designates post procedural biomarker thresholds for defining percutaneous coronary intervention (PCI)-related MI (type 4a) and coronary artery bypass grafting (CABG)-related MI (type 5), which are of uncertain prognostic importance. In addition, for both the MI types, cTn is recommended as the biomarker of choice, the prognostic significance of which is less well validated than CK-MB. Widespread adoption of a MI definition not clearly linked to subsequent adverse events such as mortality or heart failure may have serious consequences for the appropriate assessment of devices and therapies, may affect clinical care pathways, and may result in misinterpretation of physician competence. Rather than using an MI definition sensitive for small degrees of myonecrosis (the occurrence of which, based on contemporary large-scale studies, are unlikely to have important clinical consequences), it is instead recommended that a threshold level of biomarker elevation which has been strongly linked to subsequent adverse events in clinical studies be used to define a "clinically relevant MI." The present document introduces a new definition for "clinically relevant MI" after coronary revascularization (PCI or CABG), which is applicable for use in clinical trials, patient care, and quality outcomes assessment. Copyright © 2013. Published by Elsevier Inc.

Clinical Characteristics and Outcomes Are Similar in ARDS Diagnosed by Oxygen Saturation/Fio2 Ratio Compared With Pao2/Fio2 Ratio

PubMed Central

Janz, David R.; Shaver, Ciara M.; Bernard, Gordon R.; Bastarache, Julie A.; Ware, Lorraine B.

2015-01-01

BACKGROUND: Oxygen saturation as measured by pulse oximetry/Fio2 (SF) ratio is highly correlated with the Pao2/Fio2 (PF) ratio in patients with ARDS. However, it remains uncertain whether SF ratio can be substituted for PF ratio for diagnosis of ARDS and whether SF ratio might identify patients who are systemically different from patients diagnosed by PF ratio. METHODS: We conducted a secondary analysis of a large observational prospective cohort study. Patients were eligible if they were admitted to the medical ICU and fulfilled the Berlin definition of ARDS with hypoxemia criteria using either the standard PF threshold (PF ratio ≤ 300) or a previously published SF threshold (SF ratio ≤ 315). RESULTS: Of 362 patients with ARDS, 238 (66%) received a diagnosis by PF ratio and 124 (34%) by SF ratio. In a small group of patients who received diagnoses of ARDS by SF ratio who had arterial blood gas measurements on the same day (n = 10), the PF ratio did not meet ARDS criteria. There were no major differences in clinical characteristics or comorbidities between groups with the exception of APACHE (Acute Physiology and Chronic Health Evaluation) II scores, which were higher in the group diagnosed by PF ratio. However, this difference was no longer apparent when arterial blood gas-dependent variables (pH, Pao2) were removed from the APACHE II score. There were also no differences in clinical outcomes including duration of mechanical ventilation (mean, 7 days in both groups; P = .25), duration of ICU stay (mean, 10 days vs 9 days in PF ratio vs SF ratio; P = .26), or hospital mortality (36% in both groups, P = .9). CONCLUSIONS: Patients with ARDS diagnosed by SF ratio have very similar clinical characteristics and outcomes compared with patients diagnosed by PF ratio. These findings suggest that SF ratio could be considered as a diagnostic tool for early enrollment into clinical trials. PMID:26271028

Appropriateness criteria predict outcomes for sinus surgery and may aid in future patient selection.

PubMed

Beswick, Daniel M; Mace, Jess C; Soler, Zachary M; Ayoub, Noel F; Rudmik, Luke; DeConde, Adam S; Smith, Timothy L

2018-05-14

Appropriateness criteria to determine surgical candidacy for chronic rhinosinusitis (CRS) have recently been described. This study stratified patients who underwent endoscopic sinus surgery (ESS) according to these new appropriateness criteria and evaluated postoperative improvements among appropriateness categories. Adult patients with uncomplicated CRS electing ESS were prospectively enrolled in a multi-institutional cohort study between March 2011 and June 2015 to assess outcomes. Subsequently, appropriateness criteria that consider preoperative medical therapy, 22-item SinoNasal Outcome Test (SNOT-22) scores, and Lund-Mackay computed tomography scores were retrospectively applied. A total of 92.6% (436 of 471) were categorized as "appropriate" ESS candidates, 3.8% (18 of 471) as "uncertain," and 3.6% (17 of 471) as "inappropriate." Among uncertain patients, two-thirds (12 of 18) had identifiable reasons for undergoing ESS, most commonly oral corticosteroid intolerance (n = 6). Postoperative follow-up was available for 79% (n = 372). Clinically significant SNOT-22 improvements occurred in both appropriate and uncertain groups (all P < 0.050) but not among the inappropriate group. The inappropriate group reported less mean improvement in SNOT-22 total score compared to appropriate (P = 0.008) and uncertain (P = 0.006) groups. The vast majority of patients (∼93%) who underwent ESS in a multi-institutional research program were identified as appropriate candidates for surgical intervention, as defined by current appropriateness criteria. Valid considerations frequently exist for offering ESS to patients categorized as uncertain. Appropriate and uncertain candidates report similar, clinically significant SNOT-22 improvements following surgery. Patients classified as inappropriate reported significantly less improvement following ESS. Surgical appropriateness criteria may assist in predicting outcomes of ESS. 2b. Laryngoscope, 2018. © 2018 The American Laryngological, Rhinological and Otological Society, Inc.

Use of point-of-care ultrasound to evaluate for penile fracture in a child.

PubMed

Lam, Samuel H F

2015-02-01

Penile fracture is a urologic emergency requiring prompt surgical intervention. Ultrasound may help clarify the diagnosis in cases of uncertain history and physical examination. The author presents a case of suspected pediatric penile fracture, in which point-of-care ultrasound helped to rule out the condition and facilitated disposition of the patient.

Social Communication Disorder outside Autism? A Diagnostic Classification Approach to Delineating Pragmatic Language Impairment, High Functioning Autism and Specific Language Impairment

ERIC Educational Resources Information Center

Gibson, Jenny; Adams, Catherine; Lockton, Elaine; Green, Jonathan

2013-01-01

Background: Developmental disorders of language and communication present considerable diagnostic challenges due to overlapping of symptomatology and uncertain aetiology. We aimed to further elucidate the behavioural and linguistic profile associated with impairments of social communication occurring outside of an autism diagnosis. Methods: Six to…

The genetics of Charcot–Marie–Tooth disease: current trends and future implications for diagnosis and management

PubMed Central

Hoyle, J Chad; Isfort, Michael C; Roggenbuck, Jennifer; Arnold, W David

2015-01-01

Charcot–Marie–Tooth (CMT) disease is the most common hereditary polyneuropathy and is classically associated with an insidious onset of distal predominant motor and sensory loss, muscle wasting, and pes cavus. Other forms of hereditary neuropathy, including sensory predominant or motor predominant forms, are sometimes included in the general classification of CMT, but for the purpose of this review, we will focus primarily on the forms associated with both sensory and motor deficits. CMT has a great deal of genetic heterogeneity, leading to diagnostic considerations that are still rapidly evolving for this disorder. Clinical features, inheritance pattern, gene mutation frequencies, and electrodiagnostic features all are helpful in formulating targeted testing algorithms in practical clinical settings, but these still have shortcomings. Next-generation sequencing (NGS), combined with multigene testing panels, is increasing the sensitivity and efficiency of genetic testing and is quickly overtaking targeted testing strategies. Currently, multigene panel testing and NGS can be considered first-line in many circumstances, although obtaining initial targeted testing for the PMP22 duplication in CMT patients with demyelinating conduction velocities is still a reasonable strategy. As technology improves and cost continues to fall, targeted testing will be completely replaced by multigene NGS panels that can detect the full spectrum of CMT mutations. Nevertheless, clinical acumen is still necessary given the variants of uncertain significance encountered with NGS. Despite the current limitations, the genetic diagnosis of CMT is critical for accurate prognostication, genetic counseling, and in the future, specific targeted therapies. Although whole exome and whole genome sequencing strategies have the power to further elucidate the genetics of CMT, continued technological advances are needed. PMID:26527893

Clinical features of pathologic childhood aerophagia: early recognition and essential diagnostic criteria.

PubMed

Hwang, Jin-Bok; Choi, Won Joung; Kim, Jun Sik; Lee, Sang Yun; Jung, Chul-Ho; Lee, Young Hwan; Kam, Sin

2005-11-01

This study investigated the early recognition and diagnosis of pathologic childhood aerophagia to avoid unnecessary diagnostic approaches and serious complications. Between 1995 and 2003, data from 42 consecutive patients with pathologic childhood aerophagia, aged 2 to 16 years, were reviewed. An esophageal air sign was defined as an abnormal air shadow on the proximal esophagus adjacent to the trachea on a full-inflated chest radiograph. Of the 42 patients, the chief complaints were abdominal distention (52.4%), recurrent abdominal pain syndrome (21.4%), chronic diarrhea (11.9%), acute abdominal pain (7.1%) and others (7.2%). Mean symptom duration before diagnosis was 10.6 months (range, 1 to 60 months), and it exceeded 12 months for 16 (38.1%) patients. The clinical features common to all patients were abdominal distention that increased progressively during the day, increased flatus on sleep, increased bowel sound on auscultation and an air-distended stomach with increased gas in the small and large bowel by radiography. Visible or audible air swallowing (26.2%) and repetitive belching (9.5%) were also noted. Esophageal air sign was observed in 76.2% of the patients and in 9.7% of the controls (P=0.0001). The subgroups of pathologic childhood aerophagia divided by underlying associations were pathologic childhood aerophagia without severe mental retardation (76.2%), which consisted of psychological stresses and uncertain condition, and pathologic childhood aerophagia with severe mental retardation (23.8%). The common manifestations of pathologic childhood aerophagia may be its essential diagnostic criteria, and esophageal air sign may be useful for the early recognition of pathologic childhood aerophagia. Our observations show that the diagnostic clinical profiles suggested by Rome II criteria should be detailed and made clearer if they are to serve as diagnostic criteria for pathologic childhood aerophagia.

Adult-onset hyperinsulinaemic hypoglycaemia in clinical practice: diagnosis, aetiology and management.

PubMed

Challis, Benjamin G; Powlson, Andrew S; Casey, Ruth T; Pearson, Carla; Lam, Brian Y; Ma, Marcella; Pitfield, Deborah; Yeo, Giles S H; Godfrey, Edmund; Cheow, Heok K; Chatterjee, V Krishna; Carroll, Nicholas R; Shaw, Ashley; Buscombe, John R; Simpson, Helen L

2017-10-01

In adults with hyperinsulinaemic hypoglycaemia (HH), in particular those with insulinoma, the optimal diagnostic and management strategies remain uncertain. Here, we sought to characterise the biochemical and radiological assessment, and clinical management of adults with HH at a tertiary centre over a thirteen-year period. Clinical, biochemical, radiological and histological data were reviewed from all confirmed cases of adult-onset hyperinsulinaemic hypoglycaemia at our centre between 2003 and 2016. In a subset of patients with stage I insulinoma, whole-exome sequencing of tumour DNA was performed. Twenty-nine patients were identified (27 insulinoma, including 6 subjects with metastatic disease; 1 pro-insulin/GLP-1 co-secreting tumour; 1 activating glucokinase mutation). In all cases, hypoglycaemia (glucose ≤2.2 mmol/L) was achieved within 48 h of a supervised fast. At fast termination, subjects with stage IV insulinoma had significantly higher insulin, C-peptide and pro-insulin compared to those with insulinoma staged I-IIIB. Preoperative localisation of insulinoma was most successfully achieved with EUS. In two patients with inoperable, metastatic insulinoma, peptide receptor radionuclide therapy (PRRT) with 177 Lu-DOTATATE rapidly restored euglycaemia and lowered fasting insulin. Finally, in a subset of stage I insulinoma, whole-exome sequencing of tumour DNA identified the pathogenic Ying Yang-1 ( YY1 ) somatic mutation (c.C1115G/p.T372R) in one tumour, with all tumours exhibiting a low somatic mutation burden. Our study highlights, in particular, the utility of the 48-h fast in the diagnosis of insulinoma, EUS for tumour localisation and the value of PRRT therapy in the treatment of metastatic disease. © 2017 The authors.

Acute testicular torsion in children: the role of sonography in the diagnostic workup.

PubMed

Gunther, P; Schenk, J P; Wunsch, R; Holland-Cunz, S; Kessler, U; Troger, J; Waag, K L

2006-11-01

Acute testicular torsion in children is an emergency and has to be diagnosed urgently. Doppler sonography is increasingly used in imaging the acute scrotum. Nevertheless, in uncertain cases, surgical exploration is required. In this study, we attempted to define the role of Doppler sonography in the diagnostic workup of the acutely painful scrotum. All patients admitted between 1999 and 2005 with acute scrotal pain were included. After clinical assessment, patients were imaged by Doppler sonography with a ''high-end'' instrument. In cases of absent arterial perfusion of the testis in Doppler sonography, surgical exploration was carried out. Patients with unaffected perfusion were followed clinically by ultrasound for up to 2 years. Sixty-one infants and children aged 1 day to 17 years (median: 7.9 years) were included. In 14 cases, sonography demonstrated absent central perfusion, with abnormal parenchymal echogenicity in six. Absence of venous blood flow together with reduction of central arterial perfusion was found in one infant. In these 15 patients, surgical exploration confirmed testicular torsion. Among the other 46 patients, we found four cases with increased testicular perfusion and 27 with increased perfusion of the epididymis. In one infant, a testicular tumour was found sonographically, and orchiectomy confirmed diagnosis of a teratoma. Follow-up examinations of the conservatively treated patients showed good clinical outcome with physiologic central perfusion as well as normal echogenic pattern of both testes. No case of testicular torsion was missed. By means of Doppler sonography, an unequivocal statement regarding testicular perfusion was possible in all cases. The initial Doppler diagnosis was confirmed by operative evaluation and follow-up ultrasound. Testicular torsion can therefore be excluded by correctly performed ultrasound with modern equipment.

Infliximab for Crohn's disease in the Swiss IBD Cohort Study: clinical management and appropriateness.

PubMed

Juillerat, Pascal; Pittet, Valérie; Vader, John-Paul; Burnand, Bernard; Gonvers, Jean-Jacques; de Saussure, Philippe; Mottet, Christian; Seibold, Frank; Rogler, Gerhard; Sagmeister, Markus; Felley, Christian; Michetti, Pierre; Froehlich, Florian

2010-11-01

Antitumor necrosis factor a agents have significantly improved the management of Crohn's disease (CD), but not all patients benefit from this therapy. We used data from the Swiss Inflammatory Bowel Disease Cohort Study and predefined appropriateness criteria to examine the appropriateness of use of infliximab (IFX) in CD patients. EPACT II (European Panel on the Appropriateness of CD Therapy, 2007; www.epact.ch) appropriateness criteria have been developed using a formal explicit panel process combining evidence from the published literature and expert opinion. Questionnaires relating to EPACT II criteria were used at enrollment and follow-up of all Swiss Inflammatory Bowel Disease Cohort Study patients. A step-by-step analysis of all possible indications for IFX therapy in a given patient allowed identification of the most appropriate indication and final classification in a single appropriateness category (appropriate, uncertain, inappropriate). Eight hundred and twenty-one CD patients were prospectively enrolled between November 2006 and March 2009. IFX was administered to 146 patients (18%) at enrollment and was most frequently used for complex fistulizing disease and for the maintenance of remission induced by biological therapy. IFX therapy was considered appropriate in 44%, uncertain in 44%, and inappropriate in 10% of patients. In this cohort, 9 out of 10 indications for IFX therapy were clinically generally acceptable (appropriate or uncertain) according to EPACT II criteria. Uncertain indications resulted mainly from the current more liberal use of IFX in clinical practice as compared with the EPACT II criteria.

Raising Children Who Soar: A Guide to Healthy Risk-Taking in an Uncertain World

ERIC Educational Resources Information Center

Davis, Susan; Eppler-Wolff, Nancy

2009-01-01

How can we keep children safe in an uncertain world, but also raise them to be confident in taking the healthy, emotional risks necessary to succeed in life? The authors of this unique book--two clinical psychologists, who are also mothers--provide essential guidance for parents and teachers. They explain, step-by-step, how to help children become…

Capsule endoscopy: impact on clinical decision making in patients with suspected small bowel bleeding.

PubMed

Gubler, C; Fox, M; Hengstler, P; Abraham, D; Eigenmann, F; Bauerfeind, P

2007-12-01

Capsule endoscopy is widely used for diagnosis of small-bowel disease; however, the impact of capsule endoscopy on clinical management remains uncertain. We conducted a prospective study of the impact capsule endoscopy on clinical management decisions in 128 patients with suspected small-bowel pathology. Prior to performing each procedure the gastroenterologist predicted the findings of capsule endoscopy and further management based on the clinical history and previous investigations. This prediction was compared with the actual results of capsule endoscopy and the following investigative and therapeutic management. The actual findings of capsule endoscopy and the further management were consistent with clinical prediction in 93/128 patients (73 %) and, irrespective of capsule endoscopy findings, no further procedures were required in 80 % of these patients. In 13 patients (10 %), gastric or colonic pathology was discovered that had not been detected on prior gastroscopy or colonoscopy. Thus, capsule endoscopy findings in the small bowel changed clinical management in 22 patients (17 %). In 4 patients, positive findings on capsule endoscopy that had not been predicted by the examiner prompted referral for abdominal surgery. Conversely, planned surgery was canceled in four other patients. In this series of patients referred for capsule endoscopy, small-bowel findings and appropriate clinical management were predicted on clinical grounds alone in approximately three-quarters of patients. Repetition of standard upper and lower endoscopy may be useful in many patients prior to small-bowel imaging. Referral for capsule endoscopy should take into account whether the findings will impact on clinical management; however, capsule endoscopy is mandatory in patients in whom surgery for small-bowel bleeding is intended.

Breast lesions of uncertain malignant nature and limited metastatic potential: Proposals to improve their recognition and clinical management

PubMed Central

Rakha, Emad A.; Badve, Sunil; Eusebi, Vincenzo; Reis-Filho, Jorge S.; Fox, Stephen B.; Dabbs, David J.; Decker, Thomas; Hodi, Zsolt; Ichihara, Shu; Lee, Andrew HS.; Palacios, José; Richardson, Andrea L.; Vincent-Salomon, Anne; Schmitt, Fernando C.; Tan, Puay-Hoon; Tse, Gary M.; Ellis, Ian O.

2016-01-01

Breast lesions comprise a family of heterogeneous entities with variable patterns of presentation, morphology and clinical behaviour. The majority of breast lesions are traditionally classified into benign and malignant conditions and their behaviour can, in the vast majority of cases, be predicted with a reasonable degree of accuracy. However, there remain lesions which show borderline features and lie in a grey-zone between benign and malignant as their behaviour cannot be predicted reliably. Defined pathological categorisation of such lesions is challenging and for some entities is recognised to be subjective and include a range of diagnoses, and forms of terminology, which may trigger over-treatment or under-treatment. The rarity of these lesions makes acquisition of clinical evidence problematic and limits the development of a sufficient evidence base to support informed decision making by clinicians and patients. Emerging molecular evidence is providing a greater understanding of the biology of these lesions, but this may or may not be reflected in their clinical behaviour. Herein we discuss some breast lesions that are associated with uncertainty regarding classification, behaviour and hence management. These include biologically invasive malignant lesions associated with uncertain metastatic potential such as low-grade adenosquamous carcinoma, low-grade fibromatosis-like spindle cell carcinoma and encapsulated papillary carcinoma. Other lesions remain of uncertain malignant nature such as mammary cylindroma, atypical microglandular adenosis, mammary pleomorphic adenoma and infiltrating epitheliosis. The concept of categories of 1) breast lesions of uncertain malignant nature and 2) breast lesions of limited metastatic potential, are proposed with details of which histological entities could be included in each category, and their management implications are discussed. PMID:26348644

Application of 2011 American College of Cardiology Foundation/American Society of Echocardiography appropriateness use criteria in hospitalized patients referred for transthoracic echocardiography in a community setting.

PubMed

Ballo, Piercarlo; Bandini, Fabrizio; Capecchi, Irene; Chiodi, Leandro; Ferro, Giuseppe; Fortini, Alberto; Giuliani, Gabriele; Landini, Giancarlo; Laureano, Raffaele; Milli, Massimo; Nenci, Gabriele; Pizzarelli, Francesco; Santoro, Giovanni Maria; Vannelli, Pasquale; Cappelletti, Carlo; Zuppiroli, Alfredo

2012-06-01

A recent American College of Cardiology Foundation and American Society of Echocardiography document updated previous appropriate use criteria (AUC) for echocardiography. The aim of this study was to explore the application of the new AUC, and the resulting appropriateness rate, in hospitalized patients referred for transthoracic echocardiography (TTE) in a community setting. A total of 931 consecutive inpatients referred for TTE were prospectively recruited in five community hospitals. Patients were categorized as having appropriate, uncertain, or inappropriate indications for TTE according to the AUC. An additional group of 259 inpatients, discharged without having been referred for TTE, was also considered. In the group referred for TTE, the large majority of indications (98.8%) were classifiable according to the AUC with good interobserver reproducibility. Indications were appropriate in 739 patients (80.3%), of uncertain appropriateness in 46 (5.0%), and inappropriate in 135 (14.7%). Compared with patients with appropriate or uncertain indications, those with inappropriate indications were younger and more often referred by noncardiologists. Most common causes of inappropriate indications were related to the lack of changes in clinical status or to the absence of cardiovascular symptoms and signs. Examinations with appropriate or uncertain indications had an impact on clinical decision making more often than those with inappropriate indications (86.7% vs 14.1%, P < .0001). In the group discharged without having been referred for TTE, TTE might have been appropriate in 16.2% of cases. Clinical application of the new AUC was highly feasible in a community setting. Although inpatient referral for TTE was appropriate in most patients, strategies aimed at implementing these criteria in clinical practice are desirable. Copyright © 2012 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.

Percutaneous transhepatic vs. endoscopic retrograde biliary drainage for suspected malignant hilar obstruction: study protocol for a randomized controlled trial.

PubMed

Al-Kawas, Firas; Aslanian, Harry; Baillie, John; Banovac, Filip; Buscaglia, Jonathan M; Buxbaum, James; Chak, Amitabh; Chong, Bradford; Coté, Gregory A; Draganov, Peter V; Dua, Kulwinder; Durkalski, Valerie; Elmunzer, B Joseph; Foster, Lydia D; Gardner, Timothy B; Geller, Brian S; Jamidar, Priya; Jamil, Laith H; Keswani, Rajesh N; Khashab, Mouen A; Lang, Gabriel D; Law, Ryan; Lichtenstein, David; Lo, Simon K; McCarthy, Sean; Melo, Silvio; Mullady, Daniel; Nieto, Jose; Bayne Selby, J; Singh, Vikesh K; Spitzer, Rebecca L; Strife, Brian; Tarnaksy, Paul; Taylor, Jason R; Tokar, Jeffrey; Wang, Andrew Y; Williams, April; Willingham, Field; Yachimski, Patrick

2018-02-14

The optimal approach to the drainage of malignant obstruction at the liver hilum remains uncertain. We aim to compare percutaneous transhepatic biliary drainage (PTBD) to endoscopic retrograde cholangiography (ERC) as the first intervention in patients with cholestasis due to suspected malignant hilar obstruction (MHO). The INTERCPT trial is a multi-center, comparative effectiveness, randomized, superiority trial of PTBD vs. ERC for decompression of suspected MHO. One hundred and eighty-four eligible patients across medical centers in the United States, who provide informed consent, will be randomly assigned in 1:1 fashion via a web-based electronic randomization system to either ERC or PTBD as the initial drainage and, if indicated, diagnostic procedure. All subsequent clinical interventions, including crossover to the alternative procedure, will be dictated by treating physicians per usual clinical care. Enrolled subjects will be assessed for successful biliary drainage (primary outcome measure), adequate tissue diagnosis, adverse events, the need for additional procedures, hospitalizations, and oncological outcomes over a 6-month follow-up period. Subjects, treating clinicians and outcome assessors will not be blinded. The INTERCPT trial is designed to determine whether PTBD or ERC is the better initial approach when managing a patient with suspected MHO, a common clinical dilemma that has never been investigated in a randomized trial. ClinicalTrials.gov, Identifier: NCT03172832 . Registered on 1 June 2017.

Detection of borreliae in archived sera from patients with clinically suspect Lyme disease.

PubMed

Lee, Sin Hang; Vigliotti, Jessica S; Vigliotti, Veronica S; Jones, William; Shearer, David M

2014-03-11

The diagnoses of Lyme disease based on clinical manifestations, serological findings and detection of infectious agents often contradict each other. We tested 52 blind-coded serum samples, including 20 pre-treatment and 12 post-treatment sera from clinically suspect Lyme disease patients, for the presence of residual Lyme disease infectious agents, using nested PCR amplification of a signature segment of the borrelial 16S ribosomal RNA gene for detection and direct DNA sequencing of the PCR amplicon for molecular validation. These archived sera were split from the samples drawn for the 2-tier serology tests performed by a CDC-approved laboratory, and are used as reference materials for evaluating new diagnostic reagents. Of the 12 post-treatment serum samples, we found DNA evidence of a novel borrelia of uncertain significance in one, which was also positive for the 2-tier serology test. The rest of the post-treatment sera and all 20 control sera were PCR-negative. Of the 20 pre-treatment sera from clinically suspect early Lyme disease patients, we found Borrelia miyamotoi in one which was 2-tier serology-negative, and a Borrelia burgdorferi in two-one negative and one positive for 2-tier serology. We conclude that a sensitive and reliable DNA-based test is needed to support the diagnosis of Lyme disease and Lyme disease-like borreliosis.

Targeted next-generation sequencing makes new molecular diagnoses and expands genotype-phenotype relationship in Ehlers-Danlos syndrome.

PubMed

Weerakkody, Ruwan A; Vandrovcova, Jana; Kanonidou, Christina; Mueller, Michael; Gampawar, Piyush; Ibrahim, Yousef; Norsworthy, Penny; Biggs, Jennifer; Abdullah, Abdulshakur; Ross, David; Black, Holly A; Ferguson, David; Cheshire, Nicholas J; Kazkaz, Hanadi; Grahame, Rodney; Ghali, Neeti; Vandersteen, Anthony; Pope, F Michael; Aitman, Timothy J

2016-11-01

Ehlers-Danlos syndrome (EDS) comprises a group of overlapping hereditary disorders of connective tissue with significant morbidity and mortality, including major vascular complications. We sought to identify the diagnostic utility of a next-generation sequencing (NGS) panel in a mixed EDS cohort. We developed and applied PCR-based NGS assays for targeted, unbiased sequencing of 12 collagen and aortopathy genes to a cohort of 177 unrelated EDS patients. Variants were scored blind to previous genetic testing and then compared with results of previous Sanger sequencing. Twenty-eight pathogenic variants in COL5A1/2, COL3A1, FBN1, and COL1A1 and four likely pathogenic variants in COL1A1, TGFBR1/2, and SMAD3 were identified by the NGS assays. These included all previously detected single-nucleotide and other short pathogenic variants in these genes, and seven newly detected pathogenic or likely pathogenic variants leading to clinically significant diagnostic revisions. Twenty-two variants of uncertain significance were identified, seven of which were in aortopathy genes and required clinical follow-up. Unbiased NGS-based sequencing made new molecular diagnoses outside the expected EDS genotype-phenotype relationship and identified previously undetected clinically actionable variants in aortopathy susceptibility genes. These data may be of value in guiding future clinical pathways for genetic diagnosis in EDS.Genet Med 18 11, 1119-1127.

Clinical germline diagnostic exome sequencing for hereditary cancer: Findings within novel candidate genes are prevalent.

PubMed

Powis, Zöe; Espenschied, Carin R; LaDuca, Holly; Hagman, Kelly D; Paudyal, Tripti; Li, Shuwei; Inaba, Hiroto; Mauer, Ann; Nathanson, Katherine L; Knost, James; Chao, Elizabeth C; Tang, Sha

2018-08-01

Clinical diagnostic exome sequencing (DES) has been effective in diagnosing individuals with suspected genetic conditions; nevertheless little has been described regarding its clinical utility in individuals with a personal and family history of cancer. This study aimed to assess diagnostic yield and clinical characteristics of pediatric and adult patients undergoing germline DES for hereditary cancer. We retrospectively reviewed 2171 patients referred for DES; cases with a personal and/or family history of cancer were further studied. Of 39 cancer patients, relevant alterations were found in eight individuals (21%), including one (3%) positive pathogenic alteration within a characterized gene, two (5%) uncertain findings in characterized genes, and five (13%) alterations in novel candidate genes. Two of the 5 pediatric patients, undergoing testing, (40%) had findings in novel candidate genes, with the remainder being negative. We include brief case studies to illustrate the variety of challenging issues related to these patients. Our observations demonstrate utility of family-based exome sequencing in patients for suspected hereditary cancer, including familial co-segregation analysis, and comprehensive medical review. DES may be particularly useful when traditional approaches do not result in a diagnosis or in families with unique phenotypes. This work also highlights the importance and complexity of analysis of uncharacterized genes in exome sequencing for hereditary cancer. Copyright © 2018 Elsevier Inc. All rights reserved.

From juvenile hyperuricaemia to dysfunctional uromodulin: an ongoing metamorphosis.

PubMed

Venkat-Raman, Gopalakrishnan; Gast, Christine; Marinaki, Anthony; Fairbanks, Lynnette

2016-11-01

Familial juvenile hyperuricaemic nephropathy (FJHN) is a diagnosis that is easily missed. It has taken a long time to clarify the pathophysiology and prevalence of this disease entity which has been shown to be genetically identical to medullary cystic kidney disease (MCKD) type II. The initial suspicion that uric acid was the noxious agent has been replaced by the recognition that a mutant uromodulin (UMOD) is the real culprit-although the exact mechanisms of pathogenicity remain uncertain. The mutation has been traced to the UMOD gene in chromosome 16. The disease is characterised by the classic triad of autosomal dominant inheritance, progressive renal failure beginning in the third to fifth decade of life and gout. Phenotypically similar but genotypically distinct entities have been described over the last 10 years, making a clinical diagnosis difficult. These include mutations in the renin, hepatocyte nuclear factor 1-β and mucin 1 genes. UMOD-associated kidney disease has been proposed as a logical diagnostic label to replace FJHN, but given all these other mutations, an over-arching diagnostic term of 'autosomal dominant tubulointerstitial kidney disease' (ADTKD) has been recently adopted. Allopurinol has been suggested as a therapeutic agent, but unfortunately this was based on non-randomised uncontrolled trials with small patient numbers.

[Triple synchronous primary gynaecological tumours. A case report].

PubMed

Gutiérrez-Palomino, Laura; Romo-de Los Reyes, José María; Pareja-Megía, María Jesús; García-Mejido, José Antonio

2016-01-01

Synchronous multiple primary malignancies in the female genital tract are infrequent. From 50 to 70% of them corresponds to synchronous cancers of the endometrium and ovary. To our knowledge, this is only the third case report in the international literature of three concurrent gynaecological cancers of epithelial origin. A case is presented, as well as a literature review due to the infrequency of its diagnosis and the lack of information on the subject. A 49-year-old woman, with previous gynaecological history of ovarian endometriosis. She underwent a hysterectomy and bilateral oophorectomy, as she had been diagnosed with endometrial hyperplasia with atypia. The final histopathology reported synchronous ovarian, Fallopian tube, and endometrial cancer. An extension study and complete surgical staging was performed, both being negative. She received adjuvant treatment of chemotherapy and radiotherapy. She is currently free of disease. The aetiology is uncertain. There is controversy relating to increased susceptibility of synchronous neoplasms to pelvic endometriosis and inherited genetic syndromes. Its diagnosis needs to differentiate them from metastatic disease. Additionally, they are problematical from a clinical, diagnostic, therapeutic, and prognostic point of view. The presentation of more cases of triple synchronous cancers is necessary for a complete adjuvant and surgical treatment. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

Extraneuraxial Hemangioblastoma: Clinicopathologic Features and Review of the Literature.

PubMed

Bisceglia, Michele; Muscarella, Lucia A; Galliani, Carlos A; Zidar, Nina; Ben-Dor, David; Pasquinelli, Gianandrea; la Torre, Annamaria; Sparaneo, Angelo; Fanburg-Smith, Julie C; Lamovec, Janez; Michal, Michal; Bacchi, Carlos E

2018-05-01

Extraneuraxial hemangioblastoma occurs in nervous paraneuraxial structures, somatic tissues, and visceral organs, as part of von Hippel-Lindau disease (VHLD) or in sporadic cases. The VHL gene plausibly plays a key role in the initiation and tumorigenesis of both central nervous system and extraneuraxial hemangioblastoma, therefore, the underlying molecular and genetic mechanisms of the tumor growth are initially reviewed. The clinical criteria for the diagnosis of VHLD are summarized, with emphasis on the distinction of sporadic hemangioblastoma from the form fruste of VHLD (eg, hemangioblastoma-only VHLD). The world literature on the topic of extraneuraxial hemangioblastomas has been comprehensively reviewed with ∼200 cases reported to date: up to 140 paraneuraxial, mostly of proximal spinal nerve roots, and 65 peripheral, 15 of soft tissue, 6 peripheral nerve, 5 bone, and 39 of internal viscera, including 26 renal and 13 nonrenal. A handful of possible yet uncertain cases from older literature are not included in this review. The clinicopathologic features of extraneuraxial hemangioblastoma are selectively presented by anatomic site of origin, and the differential diagnosis is emphasized in these subsets. Reference is made also to 10 of the authors' personal cases of extraneuraxial hemangioblastomas, which include 4 paraneuraxial and 6 peripheral (2 soft tissue hemangioblastoma and 4 renal).

Placenta accreta: diagnosis, management and the molecular biology of the morbidly adherent placenta.

PubMed

Goh, William A; Zalud, Ivica

2016-01-01

Placenta accreta is now the chief cause of postpartum hemorrhage resulting in maternal and neonatal morbidity. Prenatal diagnosis decreases blood loss at delivery and intra and post-partum complications. Ultrasound is critical for diagnosis and MRI is a complementary tool when the diagnosis is uncertain. Peripartum hysterectomy has been the standard of therapy but conservative management is increasingly being used. The etiology of accreta is due to a deficiency of maternal decidua resulting in placental invasion into the uterine myometrium. The molecular basis for the development of invasive placentation is yet to be elucidated but may involve abnormal paracrine/autocrine signaling between the deficient maternal decidua and the trophoblastic tissue. The interaction of hormones such as Relaxin which is abundant in maternal decidua and insulin-like 4, an insulin-like peptide found in placental trophoblastic tissue may play role in the formation of placenta accreta.

Placenta accreta: Diagnosis, management and the molecular biology of the morbidly adherent placenta

PubMed Central

Goh, William; Zalud, Ivica

2017-01-01

Placenta accreta is now the chief cause of postpartum hemorrhage resulting in maternal and neonatal morbidity. Prenatal diagnosis decreases blood loss at delivery and intra and post-partum complications. Ultrasound is critical for diagnosis and MRI is a complementary tool when the diagnosis is uncertain. Peripartum hysterectomy has been the standard of therapy but conservative management is increasingly being used. The etiology of accreta is due to a deficiency of maternal decidua resulting in placental invasion into the uterine myometrium. The molecular basis for the development of invasive placentation is yet to be elucidated but may involve abnormal paracrine/autocrine signaling between the deficient maternal decidua and the trophoblastic tissue. The interaction of hormones such as Relaxin which is abundant in maternal decidua and INSL4, an insulin like peptide found in placental trophoblastic tissue may play role in the formation of placenta accreta. PMID:26135782

Achieving the Goals of the National HIV/AIDS Strategy: Declining HIV Diagnoses, Improving Clinical Outcomes, and Diminishing Racial/Ethnic Disparities in King County, WA (2004-2013).

PubMed

Golden, Matthew R; Bennett, Amy B; Dombrowski, Julia C; Buskin, Susan E

2016-05-01

The US National HIV/AIDS Strategy defines national objectives related to HIV prevention and care. The extent to which US cities are meeting those objectives is uncertain. We analyzed King County, WA, HIV surveillance data collected between 2004 and 2013. The study population included 9539 persons diagnosed as having and living with HIV infection and 3779 persons with newly diagnosed HIV infection. Between 2004 and 2013, the rate of new HIV diagnosis decreased from 18.4 to 13.2 per 100,000 residents (decline of 28%); AIDS diagnosis rates declined 42% from 12 to 7 per 100,000; and age-adjusted death rates decreased from 27 to 15 per 1000 persons living with HIV/AIDS (decline of 42%; P<0.0001 for all 3 trends). The rate of new HIV diagnosis declined 26% among men who have sex with men (MSM; P=0.0002), with the largest decline occurring in black MSM (44%). Among 8679 individuals with laboratory results reported to National HIV Surveillance System from 2006 through 2013, viral suppression (viral load<200 copies/mL) increased from 45% to 86% (P<0.0001), with all racial/ethnic groups achieving greater than 80% viral suppression in 2013. The rates of new HIV diagnosis, AIDS diagnoses, and mortality in persons living with HIV in King County, WA, have significantly declined over the last decade. These changes have occurred concurrent with a dramatic increase in HIV viral suppression and have affected diverse populations, including MSM and African American MSM. These findings demonstrate substantial local success in achieving the goals of the National HIV/AIDS Strategy.

Introducing malaria rapid diagnostic tests at registered drug shops in Uganda: limitations of diagnostic testing in the reality of diagnosis.

PubMed

Chandler, Clare I R; Hall-Clifford, Rachel; Asaph, Turinde; Pascal, Magnussen; Clarke, Siân; Mbonye, Anthony K

2011-03-01

In Uganda, around two thirds of medicines are procured from the private sector, mostly from drug shops. The introduction of malaria rapid diagnostic tests (RDTs) at drug shops therefore has the potential to make a significant contribution to targeting antimalarial drugs to those with malaria parasites. We undertook formative research in a district in Uganda in preparation for a randomised trial of RDTs in drug shops. In May to July 2009, we interviewed 9 drug shop workers, 5 health workers and 4 district health officials and carried out 10 focus group discussions with a total of 75 community members to investigate the role of drug shops and the potential for implementation of RDTs at these health care outlets. Drug shops were seen to provide an important service to community members, the nature of which is determined by responsiveness to client demands. However, drug shops hold a liminal status: in the eyes of different actors, these outlets are at once a shop and clinic; legitimate and illegitimate; and trusted and distrusted. Malaria treatment was found to be synonymous with diagnosis. Diagnostic testing was deemed useful in theory, and community members were curious about the results, with the expectation that a test would decrease uncertainty and help secure an end to illness. However, whether testing would be sought as a routine step in treatment decisions in practice is uncertain, since the appeal of the tests waned in light of their costs and potential for results to conflict with presumed diagnosis. Interventions that increase awareness of multiple causes and management of malaria-like illness will be needed to support the new rationalisation for malaria treatment represented by parasitological diagnosis. Copyright © 2011 Elsevier Ltd. All rights reserved.

Introducing malaria rapid diagnostic tests at registered drug shops in Uganda: Limitations of diagnostic testing in the reality of diagnosis.

PubMed Central

Hall-Clifford, Rachel; Asaph, Turinde; Magnussen, Pascal; Clarke, Siân; Mbonye, Anthony K

2014-01-01

In Uganda, around two thirds of medicines are procured from the private sector, mostly from drug shops. The introduction of malaria rapid diagnostic tests (RDTs) at drug shops therefore has the potential to make a significant contribution to targeting antimalarial drugs to those with malaria parasites. We undertook formative research in a district in Uganda in preparation for a randomised trial of RDTs in drug shops. In May to July 2009, we interviewed 9 drug shop workers, 5 health workers and 4 district health officials and carried out 10 focus group discussions with a total of 75 community members to investigate the role of drug shops and the potential for implementation of RDTs at these health care outlets. Drug shops were seen to provide an important service to community members, the nature of which is determined by responsiveness to client demands. However, drug shops hold a liminal status: in the eyes of different actors, these outlets are at once a shop and clinic; legitimate and illegitimate; and trusted and distrusted. Malaria treatment was found to be synonymous with diagnosis. Diagnostic testing was deemed useful in theory, and community members were curious about the results, with the expectation that a test would decrease uncertainty and help secure an end to illness. However, whether testing would be sought as a routine step in treatment decisions in practice is uncertain, since the appeal of the tests waned in light of their costs and potential for results to conflict with presumed diagnosis. Interventions that increase awareness of multiple causes and management of malaria-like illness will be needed to support the new rationalisation for malaria treatment represented by parasitological diagnosis. PMID:21349623

Accuracy of ultrasound for the prediction of placenta accreta.

PubMed

Bowman, Zachary S; Eller, Alexandra G; Kennedy, Anne M; Richards, Douglas S; Winter, Thomas C; Woodward, Paula J; Silver, Robert M

2014-08-01

Ultrasound has been reported to be greater than 90% sensitive for the diagnosis of accreta. Prior studies may be subject to bias because of single expert observers, suspicion for accreta, and knowledge of risk factors. We aimed to assess the accuracy of ultrasound for the prediction of accreta. Patients with accreta at a single academic center were matched to patients with placenta previa, but no accreta, by year of delivery. Ultrasound studies with views of the placenta were collected, deidentified, blinded to clinical history, and placed in random sequence. Six investigators prospectively interpreted each study for the presence of accreta and findings reported to be associated with its diagnosis. Sensitivity, specificity, positive predictive, negative predictive value, and accuracy were calculated. Characteristics of accurate findings were compared using univariate and multivariate analyses. Six investigators examined 229 ultrasound studies from 55 patients with accreta and 56 controls for 1374 independent observations. 1205/1374 (87.7% overall, 90% controls, 84.9% cases) studies were given a diagnosis. There were 371 (27.0%) true positives; 81 (5.9%) false positives; 533 (38.8%) true negatives, 220 (16.0%) false negatives, and 169 (12.3%) with uncertain diagnosis. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 53.5%, 88.0%, 82.1%, 64.8%, and 64.8%, respectively. In multivariate analysis, true positives were more likely to have placental lacunae (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.4-1.6), loss of retroplacental clear space (OR, 2.4; 95% CI, 1.1-4.9), or abnormalities on color Doppler (OR, 2.1; 95% CI, 1.8-2.4). Ultrasound for the prediction of placenta accreta may not be as sensitive as previously described. Copyright © 2014 Mosby, Inc. All rights reserved.

Evaluation of low-cost computer monitors for the detection of cervical spine injuries in the emergency room: an observer confidence-based study.

PubMed

Brem, M H; Böhner, C; Brenning, A; Gelse, K; Radkow, T; Blanke, M; Schlechtweg, P M; Neumann, G; Wu, I Y; Bautz, W; Hennig, F F; Richter, H

2006-11-01

To compare the diagnostic value of low-cost computer monitors and a Picture Archiving and Communication System (PACS) workstation for the evaluation of cervical spine fractures in the emergency room. Two groups of readers blinded to the diagnoses (2 radiologists and 3 orthopaedic surgeons) independently assessed-digital radiographs of the cervical spine (anterior-posterior, oblique and trans-oral-dens views). The radiographs of 57 patients who arrived consecutively to the emergency room in 2004 with clinical suspicion of a cervical spine injury were evaluated. The diagnostic values of these radiographs were scored on a 3-point scale (1 = diagnosis not possible/bad image quality, 2 = diagnosis uncertain, 3 = clear diagnosis of fracture or no fracture) on a PACS workstation and on two different liquid crystal display (LCD) personal computer monitors. The images were randomised to avoid memory effects. We used logistic mixed-effects models to determine the possible effects of monitor type on the evaluation of x ray images. To determine the overall effects of monitor type, this variable was used as a fixed effect, and the image number and reader group (radiologist or orthopaedic surgeon) were used as random effects on display quality. Group-specific effects were examined, with the reader group and additional fixed effects as terms. A significance level of 0.05 was established for assessing the contribution of each fixed effect to the model. Overall, the diagnostic score did not differ significantly between standard personal computer monitors and the PACS workstation (both p values were 0.78). Low-cost LCD personal computer monitors may be useful in establishing a diagnosis of cervical spine fractures in the emergency room.

Outcome of breast lesions diagnosed as lesion of uncertain malignant potential (B3) or suspicious of malignancy (B4) on needle core biopsy, including detailed review of epithelial atypia.

PubMed

Rakha, Emad A; Ho, Bernard C; Naik, Veena; Sen, Soumadri; Hamilton, Lisa J; Hodi, Zsolt; Ellis, Ian O; Lee, Andrew H S

2011-03-01

To provide updated evidence of the outcome of breast lesions of uncertain malignant potential (B3) and suspicious of malignancy (B4) diagnosed on needle core biopsy (NCB) and analyse the outcome of the different types of intraductal epithelial atypia. One-hundred and forty-nine B3 and 26 B4 NCBs diagnosed over a 2-year period (2007-2008) were compared with those diagnosed over a previous 2-year period (1998-2000). The proportion of B3 diagnoses increased from 3.1% to 4.5%, and the positive predictive value (PPV) of malignancy of a B3 core decreased from 25% to 10%. Increased diagnosis of radial scar and reductions in the PPV of lobular neoplasia and of atypical intraductal proliferation may explain the reduction in the PPV of the B3 group as a whole. There were no significant changes in the proportion of B4 diagnosis (1.1% and 0.8%) or the PPV of B4 (83% and 88%). Review of cores with intraductal atypia showed a wide range of PPVs, from 100% for suspicious of ductal carcinoma in situ, to 40% for atypical ductal hyperplasia categorized as B3, and 14% for isolated flat epithelial atypia. The study has found a decrease in the PPV for a B3 diagnosis and suggests possible explanations. © 2011 Blackwell Publishing Limited.

The characteristics of patients with uncertain/mild cognitive impairment on the Alzheimer disease assessment scale-cognitive subscale.

PubMed

Pyo, Geunyeong; Elble, Rodger J; Ala, Thomas; Markwell, Stephen J

2006-01-01

The performances of the uncertain/mild cognitive impairment (MCI) patients on the Alzheimer Disease Assessment Scale-Cognitive (ADAS-Cog) subscale were compared with those of normal controls, Alzheimer disease patients with CDR 0.5, and Alzheimer disease patients with CDR 1.0. The Uncertain/MCI group was significantly different from normal controls and Alzheimer disease CDR 0.5 or 1.0 groups on the ADAS-Cog except on a few non-memory subtests. Age was significantly correlated with total error score in the normal group, but there was no significant correlation between age and ADAS-Cog scores in the patient groups. Education was not significantly correlated with the ADAS-Cog scores in any group. Regardless of age and educational level, there were clear differences between the normal group and the Uncertain/MCI group, especially on the total error scores. We found that the total error score of the ADAS-Cog was the most reliable variable in detecting patients with mild cognitive impairment. The present study demonstrated that the ADAS-Cog is a promising tool for detecting and studying patients with mild cognitive impairment. The results also indicated that demographic variables such as age and education do not play a significant role in the diagnosis of mild cognitive impaired patients based on the ADAS-Cog scores.

Appropriate test selection for single-photon emission computed tomography imaging: association with clinical risk, posttest management, and outcomes.

PubMed

Aldweib, Nael; Negishi, Kazuaki; Seicean, Sinziana; Jaber, Wael A; Hachamovitch, Rory; Cerqueira, Manuel; Marwick, Thomas H

2013-09-01

Appropriate use criteria (AUC) for stress single-photon emission computed tomography (SPECT) are only one step in appropriate use of imaging. Other steps include pretest clinical risk evaluation and optimal management responses. We sought to understand the link between AUC, risk evaluation, management, and outcome. We used AUC to classify 1,199 consecutive patients (63.8 ± 12.5 years, 56% male) undergoing SPECT as inappropriate, uncertain, and appropriate. Framingham score for asymptomatic patients and Bethesda angina score for symptomatic patients were used to classify patients into high (≥5%/y), intermediate, and low (≤1%/y) risk. Subsequent patient management was defined as appropriate or inappropriate based on the concordance between management decisions and the SPECT result. Patients were followed up for a median of 4.8 years, and cause of death was obtained from the social security death registry. Overall, 62% of SPECTs were appropriate, 18% inappropriate, and 20% uncertain (only 5 were unclassified). Of 324 low-risk studies, 108 (33%) were inappropriate, compared with 94 (15%) of 621 intermediate-risk and 1 (1%) of 160 high-risk studies (P < .001). There were 79 events, with outcomes of inappropriate patients better than uncertain and appropriate patients. Management was appropriate in 986 (89%), and appropriateness of patient management was unrelated to AUC (P = .65). Pretest clinical risk evaluation may be helpful in appropriateness assessment because very few high-risk patients are inappropriate, but almost half of low-risk patients are inappropriate or uncertain. Appropriate patient management is independent of appropriateness of testing. © 2013.

Pedophilia: a diagnosis in search of a disorder.

PubMed

Malón, Agustin

2012-10-01

This article presents a critical review of the recent controversies concerning the diagnosis of pedophilia in the context of the preparation of the fifth edition of the DSM. The analysis focuses basically on the relationship between pedophilia and the current DSM-IV-TR's definition of mental disorder. Scholars appear not to share numerous basic assumptions ranging from their underlying ideas about what constitutes a mental disorder to the role of psychiatry in modern society, including irreconcilable theories about human sexuality, which interfere with reaching any kind of a consensus as to what the psychiatric status of pedophilia should be. It is questioned if the diagnosis of pedophilia contained in the DSM is more forensic than therapeutic, focusing rather on the dangers inherent in the condition of pedophilia (dangerous dysfunction) than on its negative effects for the subject (harmful dysfunction). The apparent necessity of the diagnosis of pedophilia in the DSM is supported, but the basis for this diagnosis is uncertain.

Accuracy of the initial endoscopic diagnosis in the discrimination of gastric ulcers: is endoscopic follow-up study always needed?

PubMed

Bustamante, Marco; Devesa, Francesc; Borghol, Abdul; Ortuño, Juan; Ferrando, Maria Jose

2002-07-01

Endoscopic follow-up study of gastric ulcers has been recommended routinely because of the possibility that a gastric neoplasm will be missed in the initial endoscopy. Some authors, most of them reporting data from areas of low gastric carcinoma incidence, have questioned this policy because of the low numbers of curable cancers detected and the high cost of such a program. To assess the accuracy of endoscopy diagnosis of gastric ulcers, and to evaluate the efficacy and cost of a gastric ulcer follow-up endoscopic program in an area with an intermediate incidence rate of gastric cancer. A retrospective study was used to identify all the gastroscopies in which a gastric ulcer had been diagnosed during a 6-year period. The endoscopic impression was compared with the histologic diagnosis, sensitivity, specificity, positive and negative predictive values, and the likelihood ratio. Patients who completed a follow-up program also were reviewed. For each neoplasm discovered, the number of endoscopies and global cost were calculated. In the 741 gastroscopies performed, 547 gastric ulcers were diagnosed in 529 patients. Biopsies were taken in 330 patients, in whom 341 gastric ulcers were found. At the index endoscopy, 41 gastric neoplasms (12.4%) were diagnosed. The accuracy of endoscopic malignancy diagnosis was as follows: positive predictive value of 0.68, negative predictive value of 0.98, sensitivity of 0.82, and specificity of 0.95. The likelihood ratio was 16. A total of 117 patients completed the follow-up program. Three new cases of gastric cancer (2.6%) were identified. In these three cases, the initial opinion of the endoscopist was uncertain. In the authors' experience, the cost of each gastric cancer diagnosed has been $4.653 (U.S. dollars). The endoscopic impression correlates with the histologic diagnosis even in a area of intermediate gastric cancer incidence. Endoscopic follow-up study may be restricted to cases of uncertain or malignant endoscopic impression.

Influence of the disease label 'polycystic ovary syndrome' on intention to have an ultrasound and psychosocial outcomes: a randomised online study in young women.

PubMed

Copp, Tessa; McCaffery, Kirsten; Azizi, Lamiae; Doust, Jenny; Mol, Ben W J; Jansen, Jesse

2017-04-01

Does the disease label 'polycystic ovary syndrome' (PCOS) have an impact on desire for medical testing and psychosocial outcomes? When given the disease label PCOS in a hypothetical scenario, participants had higher intention to have an ultrasound, perceived the condition to be more severe and had lower self-esteem than those not given the disease label. Widening diagnostic criteria and improved imaging sensitivity have increased the number of reproductive-aged women diagnosed with PCOS from 4% to 8% to up to 21%. The uncertain clinical benefit of knowing this diagnosis needs to be weighed against the potential for poor psychological outcomes in women labelled with PCOS. This experimental online study randomised 181 young women to receive one of four hypothetical scenarios of a doctor's visit in a 2 (PCOS disease label versus no disease label) x 2 (information about unreliability of ultrasounds in clarifying diagnosis versus no information) design. Participants were university students (mean age: 19.4). After presenting the scenario, intention to have an ultrasound, negative affect, self-esteem, perceived severity of condition, credibility of the doctor and interest in a second opinion were measured. Participants were then presented with a second scenario, where the possibility of PCOS overdiagnosis was mentioned. Change in intention and perceived severity were then measured. Participants given the PCOS label had significantly higher intention to have an ultrasound (mean = 6.62 versus mean = 5.76, P = 0.033, 95% CI(difference) = 0.069-1.599), perceived the condition to be more severe (17.17 versus 15.82, P = 0.019, 95% CI(difference) = 0.229-2.479) and had lower self-esteem (25.86 versus 27.56, P = 0.031, 95% CI(difference) = -3.187 to -0.157). After receiving overdiagnosis information, both intention and perceived severity decreased, regardless of condition (both P < 0.001). This study used hypothetical scenarios; it is likely that for women facing a real diagnosis of PCOS, outcomes would be more affected than in the current study. The hypothetical design, however, allowed the symptoms and risks of PCOS to be held constant across conditions, the impact on intention and psychosocial outcomes directly attributable to the effect of the disease label. These findings demonstrate the potential negative consequences of PCOS labelling. It is crucial we consider the impact of the label before diagnosing more women with PCOS when clinical benefit of this diagnosis is uncertain. This paper was written with support from a NHMRC grant awarded to the Screening and Test Evaluation Program. J.J. is supported by an NHMRC Early Career Fellowship. K.M. is supported by an NHMRC Career Development Fellowship. The authors declare that no competing interests exist. ACTRN12617000111370. 20/01/2017. 01/06/2015. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Deriving the expected utility of a predictive model when the utilities are uncertain.

PubMed

Cooper, Gregory F; Visweswaran, Shyam

2005-01-01

Predictive models are often constructed from clinical databases with the goal of eventually helping make better clinical decisions. Evaluating models using decision theory is therefore natural. When constructing a model using statistical and machine learning methods, however, we are often uncertain about precisely how the model will be used. Thus, decision-independent measures of classification performance, such as the area under an ROC curve, are popular. As a complementary method of evaluation, we investigate techniques for deriving the expected utility of a model under uncertainty about the model's utilities. We demonstrate an example of the application of this approach to the evaluation of two models that diagnose coronary artery disease.

A landscape of germ line mutations in a cohort of inherited bone marrow failure patients.

PubMed

Bluteau, Olivier; Sebert, Marie; Leblanc, Thierry; Peffault de Latour, Régis; Quentin, Samuel; Lainey, Elodie; Hernandez, Lucie; Dalle, Jean-Hugues; Sicre de Fontbrune, Flore; Lengline, Etienne; Itzykson, Raphael; Clappier, Emmanuelle; Boissel, Nicolas; Vasquez, Nadia; Da Costa, Mélanie; Masliah-Planchon, Julien; Cuccuini, Wendy; Raimbault, Anna; De Jaegere, Louis; Adès, Lionel; Fenaux, Pierre; Maury, Sébastien; Schmitt, Claudine; Muller, Marc; Domenech, Carine; Blin, Nicolas; Bruno, Bénédicte; Pellier, Isabelle; Hunault, Mathilde; Blanche, Stéphane; Petit, Arnaud; Leverger, Guy; Michel, Gérard; Bertrand, Yves; Baruchel, André; Socié, Gérard; Soulier, Jean

2018-02-15

Bone marrow (BM) failure (BMF) in children and young adults is often suspected to be inherited, but in many cases diagnosis remains uncertain. We studied a cohort of 179 patients (from 173 families) with BMF of suspected inherited origin but unresolved diagnosis after medical evaluation and Fanconi anemia exclusion. All patients had cytopenias, and 12.0% presented ≥5% BM blast cells. Median age at genetic evaluation was 11 years; 20.7% of patients were aged ≤2 years and 36.9% were ≥18 years. We analyzed genomic DNA from skin fibroblasts using whole-exome sequencing, and were able to assign a causal or likely causal germ line mutation in 86 patients (48.0%), involving a total of 28 genes. These included genes in familial hematopoietic disorders ( GATA2 , RUNX1 ), telomeropathies ( TERC , TERT , RTEL1 ), ribosome disorders ( SBDS , DNAJC21 , RPL5 ), and DNA repair deficiency ( LIG4 ). Many patients had an atypical presentation, and the mutated gene was often not clinically suspected. We also found mutations in genes seldom reported in inherited BMF (IBMF), such as SAMD9 and SAMD9L (N = 16 of the 86 patients, 18.6%), MECOM/EVI1 (N = 6, 7.0%), and ERCC6L2 (N = 7, 8.1%), each of which was associated with a distinct natural history; SAMD9 and SAMD9L patients often experienced transient aplasia and monosomy 7, whereas MECOM patients presented early-onset severe aplastic anemia, and ERCC6L2 patients, mild pancytopenia with myelodysplasia. This study broadens the molecular and clinical portrait of IBMF syndromes and sheds light on newly recognized disease entities. Using a high-throughput sequencing screen to implement precision medicine at diagnosis can improve patient management and family counseling. © 2018 by The American Society of Hematology.

Rationale and Design of the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) Study. Sarcoidosis Protocol.

PubMed

Moller, David R; Koth, Laura L; Maier, Lisa A; Morris, Alison; Drake, Wonder; Rossman, Milton; Leader, Joseph K; Collman, Ronald G; Hamzeh, Nabeel; Sweiss, Nadera J; Zhang, Yingze; O'Neal, Scott; Senior, Robert M; Becich, Michael; Hochheiser, Harry S; Kaminski, Naftali; Wisniewski, Stephen R; Gibson, Kevin F

2015-10-01

Sarcoidosis is a systemic disease characterized by noncaseating granulomatous inflammation with tremendous clinical heterogeneity and uncertain pathobiology and lacking in clinically useful biomarkers. The Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) study is an observational cohort study designed to explore the role of the lung microbiome and genome in these two diseases. This article describes the design and rationale for the GRADS study sarcoidosis protocol. The study addresses the hypothesis that distinct patterns in the lung microbiome are characteristic of sarcoidosis phenotypes and are reflected in changes in systemic inflammatory responses as measured by peripheral blood changes in gene transcription. The goal is to enroll 400 participants, with a minimum of 35 in each of 9 clinical phenotype subgroups prioritized by their clinical relevance to understanding of the pathobiology and clinical heterogeneity of sarcoidosis. Participants with a confirmed diagnosis of sarcoidosis undergo a baseline visit with self-administered questionnaires, chest computed tomography, pulmonary function tests, and blood and urine testing. A research or clinical bronchoscopy with a research bronchoalveolar lavage will be performed to obtain samples for genomic and microbiome analyses. Comparisons will be made by blood genomic analysis and with clinical phenotypic variables. A 6-month follow-up visit is planned to assess each participant's clinical course. By the use of an integrative approach to the analysis of the microbiome and genome in selected clinical phenotypes, the GRADS study is powerfully positioned to inform and direct studies on the pathobiology of sarcoidosis, identify diagnostic or prognostic biomarkers, and provide novel molecular phenotypes that could lead to improved personalized approaches to therapy for sarcoidosis.

Rationale and Design of the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) Study. Sarcoidosis Protocol

PubMed Central

Koth, Laura L.; Maier, Lisa A.; Morris, Alison; Drake, Wonder; Rossman, Milton; Leader, Joseph K.; Collman, Ronald G.; Hamzeh, Nabeel; Sweiss, Nadera J.; Zhang, Yingze; O’Neal, Scott; Senior, Robert M.; Becich, Michael; Hochheiser, Harry S.; Kaminski, Naftali; Wisniewski, Stephen R.; Gibson, Kevin F.

2015-01-01

Sarcoidosis is a systemic disease characterized by noncaseating granulomatous inflammation with tremendous clinical heterogeneity and uncertain pathobiology and lacking in clinically useful biomarkers. The Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) study is an observational cohort study designed to explore the role of the lung microbiome and genome in these two diseases. This article describes the design and rationale for the GRADS study sarcoidosis protocol. The study addresses the hypothesis that distinct patterns in the lung microbiome are characteristic of sarcoidosis phenotypes and are reflected in changes in systemic inflammatory responses as measured by peripheral blood changes in gene transcription. The goal is to enroll 400 participants, with a minimum of 35 in each of 9 clinical phenotype subgroups prioritized by their clinical relevance to understanding of the pathobiology and clinical heterogeneity of sarcoidosis. Participants with a confirmed diagnosis of sarcoidosis undergo a baseline visit with self-administered questionnaires, chest computed tomography, pulmonary function tests, and blood and urine testing. A research or clinical bronchoscopy with a research bronchoalveolar lavage will be performed to obtain samples for genomic and microbiome analyses. Comparisons will be made by blood genomic analysis and with clinical phenotypic variables. A 6-month follow-up visit is planned to assess each participant’s clinical course. By the use of an integrative approach to the analysis of the microbiome and genome in selected clinical phenotypes, the GRADS study is powerfully positioned to inform and direct studies on the pathobiology of sarcoidosis, identify diagnostic or prognostic biomarkers, and provide novel molecular phenotypes that could lead to improved personalized approaches to therapy for sarcoidosis. PMID:26193069

[Perivascular epithelioid cell tumor, not otherwise specified: a clinicopathologic and immunohistochemical analysis of 31 cases].

PubMed

Cai, Jun-Na; Shi, Min; Wang, Jian

2011-04-01

To study the clinicopathologic characteristics of perivascular epithelioid cell tumor (PEComa), not otherwise specified (NOS) and to evaluate the diagnostic criteria for malignancy. The clinical and pathologic features of 31 cases of PEComa-NOS were reviewed. The follow-up data available were analyzed. There were a total of 24 females and 7 males. The age of the patients ranged from 13 to 66 years (mean = 40 years). The site of tumor occurrence included gynecologic organs (n = 12), intraabdominal/peritoneal soft tissue (n = 10), gastrointestinal tract (n = 4), thigh (n = 2), mediastinum (n = 1), left groin (n = 1) and urinary bladder (n = 1). None of the cases was associated with tuberous sclerosis complex. Histologic examination showed that 23 cases (74%) were clear cell sugar tumor-like, 4 cases (13%) were clear cell myomelanocytic tumor-like and 4 cases (13%) were of mixed epithelioid-spindled morphology. According to the classification system proposed by Folpe et al, 19 cases (61%) were classified as malignant, 7 cases (23%) as PEComa of uncertain malignant potential and 5 cases (16%) as benign. The expression rates of HMB45, smooth muscle actin and desmin in tested cases were 100% (31/31), 67% (14/21) and 6/18, respectively. Follow-up data (1 to 56 months) were available in 23 cases (74%). Amongst the 16 cases of malignant PEComa, 7 patients were still alive with no evidence of disease, 6 patients were alive with unresectable or recurrent/metastatic disease and 3 patients died of the disease. The local recurrence and metastasis in those 16 cases were 6 cases and 5 cases, respectively. One of the 4 patients with PEComa of uncertain malignant potential died, while the remaining 3 patients and all of the patients with benign PEComa had an uneventful clinical course. The classification system of PEComas proposed by Folpe et al. is reliable in routine practice. Correlation with the clinical and radiologic findings however is prudent when dealing with core biopsy specimens or sampling from exploration laparotomy. Owing to the histologic heterogeneity of this entity, thorough understanding of the morphologic spectrum is essential in arriving at a correct diagnosis.

Tectal gliomas: assessment of malignant progression, clinical management, and quality of life in a supposedly benign neoplasm.

PubMed

Mohme, Malte; Fritzsche, Friederike S; Mende, Klaus C; Matschke, Jakob; Löbel, Ulrike; Kammler, Gertrud; Westphal, Manfred; Emami, Pedram; Martens, Tobias

2018-06-01

OBJECTIVE Tectal gliomas constitute a rare and inhomogeneous group of lesions with an uncertain clinical course. Because these supposedly benign tumors are frequently followed up by observation over many years, the authors undertook this analysis of their own case series in an effort to demonstrate that the clinical course is highly variable and that there is a potential for a progressive biology. METHODS Clinical data analysis of 23 cases of tectal glioma (involving 9 children and 14 adults) was performed retrospectively. Radiographic data were analyzed longitudinally and MR images were evaluated for tumor volume, contrast enhancement, and growth progression. Quality of life was assessed using the EORTC BN20 and C30 questionnaires during follow-up in a subgroup of patients. RESULTS The patients' mean age at diagnosis was 29.2 years. The main presenting symptom at diagnosis was hydrocephalus (80%). Six patients were treated by primary tumor resection (26.1%), 3 patients underwent biopsy followed by resection (13.1%), and 3 patients underwent biopsy only (13.1%). For additional treatment of hydrocephalus, 14 patients (60.9%) received shunts and/or endoscopic third ventriculostomy. Radiographic tumor progression was observed in 47.9% of the 23 cases. The mean time between diagnosis and growth progression was 51.5 months, and the mean time to contrast enhancement was 69.7 months. Histopathological analysis was obtained in 12 cases (52.2%), resulting in 5 cases of high-grade glioma (3 cases of glioblastoma multiforme [GBM], grade IV, and 2 of anaplastic astrocytoma, grade III), 5 cases of pilocytic astrocytoma, 1 diffuse astrocytoma, and 1 ganglioglioma. Malignant progression was observed in 2 cases, with 1 case progressing from a diffuse astrocytoma (grade II) to a GBM (grade IV) within a period of 13 years. Quality-of-life measurements demonstrated distinct functional deficits compared to a healthy sample as well as glioma control cohorts. CONCLUSIONS Analysis of this case series shows that a major subpopulation of tectal gliomas show progression and malignant transformation in children as well as in adolescents. These tumors therefore cannot be considered inert lesions and require histological confirmation and close follow-up. Quality-of-life questionnaires show that tectal glioma patients might benefit from special psychological support in emotional, social, and cognitive functionality.

Clinical Assessment of Physical Examination Maneuvers for Superior Labral Anterior to Posterior Lesions

PubMed Central

Somerville, Lyndsay E.; Willits, Kevin; Johnson, Andrew M.; Litchfield, Robert; LeBel, Marie-Eve; Moro, Jaydeep; Bryant, Dianne

2017-01-01

Purpose  Shoulder pain and disability pose a diagnostic challenge owing to the numerous etiologies and the potential for multiple disorders to exist simultaneously. The evidence to support the use of clinical tests for superior labral anterior to posterior complex (SLAP) is weak or absent. The purpose of this study is to determine the diagnostic validity of physical examination maneuvers for SLAP lesions by performing a methodologically rigorous, clinically applicable study. Methods  We recruited consecutive new shoulder patients reporting pain and/or disability. The physician took a history and indicated their certainty about each possible diagnosis (“certain the diagnosis is absent/present,” or “uncertain requires further testing”). The clinician performed the physical tests for diagnoses where uncertainty remained. Magnetic resonance imaging arthrogram and arthroscopic examination were the gold standards. We calculated sensitivity, specificity, and likelihood ratios (LRs) and investigated whether combinations of the top tests provided stronger predictions. Results  Ninety-three patients underwent physical examination for SLAP lesions. When using the presence of a SLAP lesion (Types I–V) as disease positive, none of the tests was sensitive (10.3–33.3) although they were moderately specific (61.3–92.6). When disease positive was defined as repaired SLAP lesion (including biceps tenodesis or tenotomy), the sensitivity (10.5–38.7) and specificity (70.6–93.8) of tests improved although not by a substantial amount. None of the tests was found to be clinically useful for predicting repairable SLAP lesions with all LRs close to one. The compression rotation test had the best LR for both definitions of disease (SLAP tear present = 1.8 and SLAP repaired = 1.67). There was no optimal combination of tests for diagnosing repairable SLAP lesions, with at least two tests positive providing the best combination of measurement properties (sensitivity 46.1% and specificity 64.7%). Conclusion  Our study demonstrates that the physical examination tests for SLAP lesions are poor diagnostic indicators of disease. Performing a combination of tests will likely help, although the magnitude of the improvement is minimal. These authors caution clinicians placing confidence in the physical examination tests for SLAP lesions rather we suggest that clinicians rely on diagnostic imaging to confirm this diagnosis. PMID:29018839

Clinical Assessment of Physical Examination Maneuvers for Superior Labral Anterior to Posterior Lesions.

PubMed

Somerville, Lyndsay E; Willits, Kevin; Johnson, Andrew M; Litchfield, Robert; LeBel, Marie-Eve; Moro, Jaydeep; Bryant, Dianne

2017-10-01

Purpose  Shoulder pain and disability pose a diagnostic challenge owing to the numerous etiologies and the potential for multiple disorders to exist simultaneously. The evidence to support the use of clinical tests for superior labral anterior to posterior complex (SLAP) is weak or absent. The purpose of this study is to determine the diagnostic validity of physical examination maneuvers for SLAP lesions by performing a methodologically rigorous, clinically applicable study. Methods  We recruited consecutive new shoulder patients reporting pain and/or disability. The physician took a history and indicated their certainty about each possible diagnosis ("certain the diagnosis is absent/present," or "uncertain requires further testing"). The clinician performed the physical tests for diagnoses where uncertainty remained. Magnetic resonance imaging arthrogram and arthroscopic examination were the gold standards. We calculated sensitivity, specificity, and likelihood ratios (LRs) and investigated whether combinations of the top tests provided stronger predictions. Results  Ninety-three patients underwent physical examination for SLAP lesions. When using the presence of a SLAP lesion (Types I-V) as disease positive, none of the tests was sensitive (10.3-33.3) although they were moderately specific (61.3-92.6). When disease positive was defined as repaired SLAP lesion (including biceps tenodesis or tenotomy), the sensitivity (10.5-38.7) and specificity (70.6-93.8) of tests improved although not by a substantial amount. None of the tests was found to be clinically useful for predicting repairable SLAP lesions with all LRs close to one. The compression rotation test had the best LR for both definitions of disease (SLAP tear present = 1.8 and SLAP repaired = 1.67). There was no optimal combination of tests for diagnosing repairable SLAP lesions, with at least two tests positive providing the best combination of measurement properties (sensitivity 46.1% and specificity 64.7%). Conclusion  Our study demonstrates that the physical examination tests for SLAP lesions are poor diagnostic indicators of disease. Performing a combination of tests will likely help, although the magnitude of the improvement is minimal. These authors caution clinicians placing confidence in the physical examination tests for SLAP lesions rather we suggest that clinicians rely on diagnostic imaging to confirm this diagnosis.

Expert opinion: diagnosis and treatment of proximal hamstring tendinopathy

PubMed Central

Lempainen, Lasse; Johansson, Kristian; Banke, Ingo J.; Ranne, Juha; Mäkelä, Keijo; Sarimo, Janne; Niemi, Pekka; Orava, Sakari

2015-01-01

Summary Background: proximal hamstring tendinopathy (PHT) is a disabilitating disease often causing underperformance in the athletically demanding patients. The main symptom of PHT is lower gluteal pain especially during running or while prolonged sitting. Mainly affecting athletically active individuals, PHT is a considerable challenge for treating health care professionals. Purpose: this paper aims to concisely present the literature on PHT to guide health care professionals treating these patients and doing research on the subject. Methods: we reviewed the literature on PHT through literature search of scientific journal databases. Conclusions: as a tendinopathic pathology, it is a rather recently discovered exertion injury. As with other chronic tendon overuse injuries, current treatment strategies are unspecific with uncertain outcomes due to the unknown etiology of the tendon degeneration. Diagnostic features as well as both operative and non-operative treatments are evaluated from a clinical perspective, providing up to date information for clinicians and sports medicine therapists dealing with hamstring problems. Level of evidence: V. PMID:25878983

Pleomorphic Hyalinizing Angiectatic Tumour: A Rare Case Report and Discussion of Differential Diagnosis.

PubMed

Chalmeti, Ambica; Arakeri, Surekha U; Javalgi, Anita P; Goyal, Shefali

2017-08-01

Pleomorphic Hyalinizing Angiectatic Tumour (PHAT) is one of the rare soft tissue tumour which is non-metastasizing. The origin of this tumour is yet uncertain. It occurs in adults as a slow growing subcutaneous mass mimicking clinically and histologically to various benign and malignant soft tissue tumours such as schwannoma, haemangioma and malignant fibrous histiocytoma. The microscopic features of this tumour include clusters of ectatic, fibrin containing, hyalinized blood vessels with pleomorphic and spindle shaped tumour cells showing intranuclear inclusions, stromal haemosiderin pigment and a variable inflammatory infiltrate. Despite marked pleomorphism, the lesion behaves as a low grade neoplasm, with frequent recurrences, but no metastases. The incidence of this tumour is very rare with less than 100 cases being published. Hence, awareness of this entity is must for proper management of the patient and to avoid misdiagnosis of the lesion. We report a case of pleomorphic hyalinizing angiectatic tumour in a 50-year-old man who presented with a slow growing mass in the left calf region since two years.

Women's experiences receiving abnormal prenatal chromosomal microarray testing results.

PubMed

Bernhardt, Barbara A; Soucier, Danielle; Hanson, Karen; Savage, Melissa S; Jackson, Laird; Wapner, Ronald J

2013-02-01

Genomic microarrays can detect copy-number variants not detectable by conventional cytogenetics. This technology is diffusing rapidly into prenatal settings even though the clinical implications of many copy-number variants are currently unknown. We conducted a qualitative pilot study to explore the experiences of women receiving abnormal results from prenatal microarray testing performed in a research setting. Participants were a subset of women participating in a multicenter prospective study "Prenatal Cytogenetic Diagnosis by Array-based Copy Number Analysis." Telephone interviews were conducted with 23 women receiving abnormal prenatal microarray results. We found that five key elements dominated the experiences of women who had received abnormal prenatal microarray results: an offer too good to pass up, blindsided by the results, uncertainty and unquantifiable risks, need for support, and toxic knowledge. As prenatal microarray testing is increasingly used, uncertain findings will be common, resulting in greater need for careful pre- and posttest counseling, and more education of and resources for providers so they can adequately support the women who are undergoing testing.

Rare case of Takayasu's arteritis associated with Crohn's disease.

PubMed

Kusunoki, Ryusaku; Ishihara, Shunji; Sato, Mariko; Sumita, Yoshiko; Mishima, Yoshiyuki; Okada, Mayumi; Tada, Yasumasa; Oka, Akihiko; Fukuba, Nobuhiko; Oshima, Naoki; Moriyama, Ichiro; Yuki, Takafumi; Sato, Shuichi; Amano, Yuji; Murakawa, Yohko; Kinoshita, Yoshikazu

2011-01-01

Takayasu's arteritis (TA) and Crohn's disease (CD) are chronic inflammatory diseases of uncertain etiology. Although co-existence of these rare diseases is estimated to occur in 1 in 10 billion individuals, a theoretically unexpected association has been reported in several patients and it is suggested that those associations may have been more than an unusual coincidence. Herein, we report a case of TA associated with clinically inactive CD. A Japanese woman was diagnosed with colonic CD at the age of 15, developed aortic valve regurgitation at 19, and then presented with general fatigue, low grade fever, and painful sensations in her left arm at 25. She was diagnosed with TA based on computed tomography scanning and magnetic resonance angiography findings, and treatments with prednisolone and cyclosporine were started. Thereafter, valve replacement and right coronary artery bypass graft surgery were performed. The possible pathophysiological mechanism responsible for concurrent existence of TA and CD may be associated with immune disorders. Early diagnosis of vascular lesions for patients with inflammatory bowel disease is highly encouraged.

The prevalence of mental subnormality*†

PubMed Central

Tizard, J.

1953-01-01

The criteria of mental subnormality are complex, uncertain, and not self-consistent. Confusion arises because of errors of measurement, faulty standardization of tests and measurements, differences in growth patterns, environmental influences, and lack of agreement between the different criteria for diagnosis. Fluctuations in the threshold of community tolerance make the term “mental subnormality” only a relative one, useful mainly for administrative purposes. There is evidence to suggest that mild subnormality is not an irreversible condition. Surveys of prevalence have been of three main sorts: psychometric, clinical, and follow-up. Some of the main findings from each of these are summarized. Since mild subnormality is to a large extent a culturally determined disability, it follows that cultural changes can do much to diminish its occurrence. In particular, better maternal and child health services, more adequate educational provision, social welfare, vocational guidance and training services, and a condition of full employment would together greatly reduce the prevalence of this, the commonest form of mental subnormality. PMID:13106707

Research to knowledge: promoting the training of physician-scientists in the biology of pregnancy.

PubMed

Sadovsky, Yoel; Caughey, Aaron B; DiVito, Michelle; D'Alton, Mary E; Murtha, Amy P

2018-01-01

Common disorders of pregnancy, such as preeclampsia, preterm birth, and fetal growth abnormalities, continue to challenge perinatal biologists seeking insights into disease pathogenesis that will result in better diagnosis, therapy, and disease prevention. These challenges have recently been intensified with discoveries that associate gestational diseases with long-term maternal and neonatal outcomes. Whereas modern high-throughput investigative tools enable scientists and clinicians to noninvasively probe the maternal-fetal genome, epigenome, and other analytes, their implications for clinical medicine remain uncertain. Bridging these knowledge gaps depends on strengthening the existing pool of scientists with expertise in basic, translational, and clinical tools to address pertinent questions in the biology of pregnancy. Although PhD researchers are critical in this quest, physician-scientists would facilitate the inquiry by bringing together clinical challenges and investigative tools, promoting a culture of intellectual curiosity among clinical providers, and helping transform discoveries into relevant knowledge and clinical solutions. Uncertainties related to future administration of health care, federal support for research, attrition of physician-scientists, and an inadequate supply of new scholars may jeopardize our ability to address these challenges. New initiatives are necessary to attract current scholars and future generations of researchers seeking expertise in the scientific method and to support them, through mentorship and guidance, in pursuing a career that combines scientific investigation with clinical medicine. These efforts will promote breadth and depth of inquiry into the biology of pregnancy and enhance the pace of translation of scientific discoveries into better medicine and disease prevention. Copyright © 2017 Elsevier Inc. All rights reserved.

Primary bone marrow oedema syndromes.

PubMed

Patel, Sanjeev

2014-05-01

MRI scanning in patients with rheumatological conditions often shows bone marrow oedema, which can be secondary to inflammatory, degenerative, infective or malignant conditions but can also be primary. The latter condition is of uncertain aetiology and it is also uncertain whether it represents a stage in the progression to osteonecrosis in some patients. Patients with primary bone marrow oedema usually have lower limb pain, commonly the hip, knee, ankle or feet. The diagnosis is one of exclusion with the presence of typical MRI findings. Treatment is usually conservative and includes analgesics and staying off the affected limb. The natural history is that of gradual resolution of symptoms over a number of months. Evidence for medical treatment is limited, but open-label studies suggest bisphosphonates may help in the resolution of pain and improve radiological findings. Surgical decompression is usually used as a last resort.

[Treatment of aerobic vaginitis and clinically uncertain causes of vulvovaginal discomfort].

PubMed

Cepický, P; Malina, J; Kuzelová, M

2003-11-01

The treatment of clinically uncertain conditions of vaginal discomforts with a mixed preparation of nifuratel + nystatin (Macmiror complex) and the relation of uncertain conditions to aerobic vaginitis. A prospective study. Gynecology-Obstetrics Outpatient Department LEVRET Ltd., AescuLab Ltd., Laboratory of Microbiology, Prague. 50 women with vaginal discomfort, causes of which had not been clarified by gynecological examination, determination of pH and the amine test, were examined by vaginal smears using microscopy. The results were evaluated in relation to aerobic vaginitis in a pure form or in combination with other nosological units. The authors also evaluated results of therapy by oral nifuratel (Macmiror tbl) 3 x 200 mg daily and a vaginal combined preparation containing nifuratel 500 mg + nystatin 200 kIU (Macmiror complex 500 glo vag) for the period of 7 days. In 50 women candida was demonstrated 24 times, presence of key cells 11 times, lactobacillus nine times with more than 50 in the field, six women were affected by aerobic vaginitis. In all these cases the pH was 4.8 or higher, leukocytes were significantly represented in all cases (> 15 in the field), as well as gram-negative bacteria and/or cocci (> 30 in the field), indicating a combined picture of mycosis, anaerobic vaginosis or lactobacillosis with aerobic vaginitis. The therapy was successful in all cases, the relapse of complaints during one month occurred in three cases. Aerobic vaginitis in a pure form or with anaerobic vaginosis, mycosis or lactobacillosis is frequently concealed under clinically uncertain pictures of vulvo-vaginal discomfort. The therapy by a combination of nifurated 3 x 200 mg orally together with the combined vaginal preparation nifuratel 500 mg + nystatin 200 kIU for the period of 7 days exerts high effect and a low number of relapses.

Physicians’ Perspectives on the Uncertainties and Implications of Chromosomal Microarray Testing of Children and Families

PubMed Central

Reiff, Marian; Ross, Kathryn; Mulchandani, Surabhi; Propert, Kathleen Joy; Pyeritz, Reed E.; Spinner, Nancy B.; Bernhardt, Barbara A.

2012-01-01

Chromosomal microarray analysis (CMA) has improved the diagnostic rate of genomic disorders in pediatric populations, but can produce uncertain and unexpected findings. This paper explores clinicians’ perspectives and identifies challenges in effectively interpreting results and communicating with families about CMA. Responses to an online survey were obtained from 40 clinicians who had ordered CMA. Content included practice characteristics and perceptions, and queries about a hypothetical case involving uncertain and incidental findings. Data were analyzed using non-parametric statistical tests. Clinicians’ comfort levels differed significantly for explaining uncertain, abnormal, and normal CMA results, with lowest levels for uncertain results. Despite clinical guidelines recommending informed consent, many clinicians did not consider it pertinent to discuss the potential for CMA to reveal information concerning biological parentage or predisposition to late-onset disease, in a hypothetical case. Many non-genetics professionals ordering CMA did not feel equipped to interpret the results for patients, and articulated needs for education and access to genetics professionals. This exploratory study highlights key challenges in the practice of genomic medicine, and identifies needs for education, disseminated practice guidelines, and access to genetics professionals, especially when dealing with uncertain or unexpected findings. PMID:22989118

Depression in dialysis patients.

PubMed

King-Wing Ma, Terry; Kam-Tao Li, Philip

2016-08-01

Depression is the most common psychiatric illness in patients with end-stage renal disease (ESRD). The reported prevalence of depression in dialysis population varied from 22.8% (interview-based diagnosis) to 39.3% (self- or clinician-administered rating scales). Such differences were attributed to the overlapping symptoms of uraemia and depression. Systemic review and meta-analysis of observational studies showed that depression was a significant predictor of mortality in dialysis population. The optimal screening tool for depression in dialysis patients remains uncertain. The Beck Depression Inventory (BDI), Patient Health Questionnaire (PHQ) and Center for Epidemiologic Studies Depression Scale (CESD) have been validated for screening purposes. Patients who scored ≥14 using BDI should be referred to a psychiatrist for early evaluation. Structured Clinical Interview for DSM disorders (SCID) remains the gold standard for diagnosis. Non-pharmacological treatment options include cognitive behavioural therapy and exercise training programs. Although frequent haemodialysis may have beneficial effects on patients' physical and mental well-being, it cannot and should not be viewed as a treatment of depression. Selective serotonin reuptake inhibitors (SSRIs) are generally effective and safe in ESRD patients, but most studies were small, non-randomized and uncontrolled. The European Renal Best Practice (ERBP) guideline suggests a trial of SSRI for 8 to 12 weeks in dialysis patients who have moderate-major depression. The treatment effect should be re-evaluated after 12 weeks to avoid prolonging ineffective medication. This review will discuss the current understanding in the diagnosis and management of depression in dialysis patients. © 2016 Asian Pacific Society of Nephrology.

Preliminary assessment of the diagnostic performances of a new rapid diagnostic test for the serodiagnosis of human cystic echinococcosis.

PubMed

Vola, Ambra; Tamarozzi, Francesca; Noordin, Rahmah; Yunus, Muhammad Hafiznur; Khanbabaie, Sam; De Silvestri, Annalisa; Brunetti, Enrico; Mariconti, Mara

2018-04-14

Rapid diagnostic tests for cystic echinococcosis (CE) are convenient to support ultrasound diagnosis in uncertain cases, especially in resource-limited settings. We found comparable diagnostic performances of the experimental Hyd Rapid Test and the commercial VIRapid HYDATIDOSIS Test, used in our diagnostic laboratory, using samples from well-characterized hepatic CE cases. Copyright © 2018 Elsevier Inc. All rights reserved.

[Renal angiomyolipomas without fat component: tomodensitometric and histologic characteristics, clinical course].

PubMed

Negre, T; Faure, A; Andre, M; Daniel, L; Coulange, C; Lechevallier, E

2011-11-01

Angiomyolipoma is the most frequent benign renal solid tumor. Because of the lack of fat component on the CT scan, diagnosis of this tumor is hard and can require percutaneous biopsy of unknown renal tumor. The follow-up of the poor fat CT scan component AML (PFCT AML) is uncertain. Five hundred percutaneous renal biopsy under tomodenstitometry have been realised between 1998 and 2008. There was 41 PFCT AML on the 500 biopsy. By definition, a PFCT AML is an AML where the diagnosis is done on a percutaneous biopsy but where there was no fat component on the first CT scan. We studied and compared clinical, tomodensitometric and histologic parameters of these 41 patients (mean age: 56, 9±11.04; sexe rate M/F: 6/35) where renal AML was diagnosed on percutaneous renal biopsy but without fat component on CT scan. Average size was 26.44±14.68mm. We phone-called 16 patients for the long-term follow-up. Average follow-up was 41±28.3 months. For four patients on 16, initial diagnosis was done in front of local symptoms, for one of the 16 diagnosis was done in front of general symptoms, for one of the diagnosis was done during Bourneville tuberous sclerosis evolution and 10 of the 16 was done fortuitously. After review of the initial CT scan, fat density was found on 24% of them. Ten percent was epithelioid angiomyolipoma. Four renal biopsy on 41 (10%) was epithelioid AML. No epithelioid AML had fat component after the second look of the CT scan. Among the 16 patients who were phone-called, three (19%) underwent a complication. Two had abdominal pain and was treated medically. Initial sizes were 26 and 30mm. Only one patient must be operated by radical nephrectomy for acute hemorrhage. Initial size was 45mm. No neoplasic degeneration was identified for those 16 patients. In our study, the PFCT AML rate was 8.2%. In 25% cases, CT scan read-through shown a fat component and could help for the diagnosis. PFCT AML evolution seems to be the same as a classic AML. Conservative treatment had a good covering because there was no death and no malignant evolution. However, we found 10% of epithelioid angiomyolipoma in which malignant risk is high. PFCT AML diagnosed on renal percutaneous biopsy of unknown renal tumor requires the same management than the classic AML. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

The Clinical Significance of Occult Gastrointestinal Primary Tumours in Metastatic Cancer: A Population Retrospective Cohort Study.

PubMed

Hannouf, Malek B; Winquist, Eric; Mahmud, Salaheddin M; Brackstone, Muriel; Sarma, Sisira; Rodrigues, George; Rogan, Peter K; Hoch, Jeffrey S; Zaric, Gregory S

2018-01-01

The purpose of this study was to estimate the incidence of occult gastrointestinal (GI) primary tumours in patients with metastatic cancer of uncertain primary origin and evaluate their influence on treatments and overall survival (OS). We used population heath data from Manitoba, Canada to identify all patients initially diagnosed with metastatic cancer between 2002 and 2011. We defined patients to have "occult" primary tumour if the primary was found at least 6 months after initial diagnosis. Otherwise, we considered primary tumours as "obvious." We used propensity-score methods to match each patient with occult GI tumour to four patients with obvious GI tumour on all known clinicopathologic features. We compared treatments and 2-year survival data between the two patient groups and assessed treatment effect on OS using Cox regression adjustment. Eighty-three patients had occult GI primary tumours, accounting for 17.6% of men and 14% of women with metastatic cancer of uncertain primary. A 1:4 matching created a matched group of 332 patients with obvious GI primary tumour. Occult cases compared to the matched group were less likely to receive surgical interventions and targeted biological therapy, and more likely to receive cytotoxic empiric chemotherapeutic agents. Having an occult GI tumour was associated with reduced OS and appeared to be a nonsignificant independent predictor of OS when adjusting for treatment differences. GI tumours are the most common occult primary tumours in men and the second most common in women. Patients with occult GI primary tumours are potentially being undertreated with available GI site-specific and targeted therapies.

Angiogenic factors and pregnant woman with new onset seizures.

PubMed

Quant, Hayley; Arden, Deborah; Takoudes, Tamara; Rana, Sarosh

2012-01-01

In patients with new onset seizures during pregnancy, it can be challenging to differentiate between eclampsia and other etiologies. Soluble fms-like tyrosine kinase (sFlt1) is an antiangiogenic protein that is elevated in preeclampsia and eclampsia. A multiparous woman presented at 22 weeks gestation with seizures. The initial presentation was highly suspicious for eclampsia, but blood pressure and laboratory data were equivocal. Further investigation suggested primary seizure disorder. Serum sFlt1 was normal for gestational age, supporting the exclusion of eclampsia. History, physical exam, and traditional laboratory data are the mainstays of eclampsia diagnosis; however, sFlt1 may help clinicians when the diagnosis is uncertain at preterm gestational ages.

[Focus: baker's asthma. Epidemiology, diagnosis and treatment of baker's asthma].

PubMed

Romano, Canzio

2014-01-01

Baker's asthma, though having been recognized and studied since long time, still stays one of the most common causes of occupational asthma. Moreover, our understanding of the causative agents, the pathophysiological mnechanisms, the usefulness of medical surveillance, the proper treatment and prevention of the disease is still scanty. This is due to either to its complex pathogenesis or to possible confoundings, besides the still inadequate quality and standardization of the tools available as far as the allergologic diagnosis is concerned. Proper medical surveillance, validated causal therapies, efficient primary prevention are still uncertain. Change of employment or relocation is often impossible, particularly among artisan workers. Various evidences have been critically revised and summarized.

Effective communication at the point of multiple sclerosis diagnosis.

PubMed

Solari, Alessandra

2014-04-01

As a consequence of the current shortened diagnostic workup, people with multiple sclerosis (PwMS) are rapidly confronted with a disease of uncertain prognosis that requires complex treatment decisions. This paper reviews studies that have assessed the experiences of PwMS in the peri-diagnostic period and have evaluated the efficacy of interventions providing information at this critical moment. The studies found that the emotional burden on PwMS at diagnosis was high, and emphasised the need for careful monitoring and management of mood symptoms (chiefly anxiety). Information provision did not affect anxiety symptoms but improved patients' knowledge of their condition, the achievement of 'informed choice', and satisfaction with the diagnosis communication. It is vital to develop and implement information and decision aids for PwMS, but this is resource intensive, and international collaboration may be a way forward. The use of patient self-assessed outcome measures that appraise the quality of diagnosis communication is also important to allow health services to understand and meet the needs and preferences of PwMS.

Sliding Mode Approaches for Robust Control, State Estimation, Secure Communication, and Fault Diagnosis in Nuclear Systems

NASA Astrophysics Data System (ADS)

Ablay, Gunyaz

Using traditional control methods for controller design, parameter estimation and fault diagnosis may lead to poor results with nuclear systems in practice because of approximations and uncertainties in the system models used, possibly resulting in unexpected plant unavailability. This experience has led to an interest in development of robust control, estimation and fault diagnosis methods. One particularly robust approach is the sliding mode control methodology. Sliding mode approaches have been of great interest and importance in industry and engineering in the recent decades due to their potential for producing economic, safe and reliable designs. In order to utilize these advantages, sliding mode approaches are implemented for robust control, state estimation, secure communication and fault diagnosis in nuclear plant systems. In addition, a sliding mode output observer is developed for fault diagnosis in dynamical systems. To validate the effectiveness of the methodologies, several nuclear plant system models are considered for applications, including point reactor kinetics, xenon concentration dynamics, an uncertain pressurizer model, a U-tube steam generator model and a coupled nonlinear nuclear reactor model.

Significance and Clinical Management of Persistent Low-Level Viremia and Very-Low-Level Viremia in HIV-1-Infected Patients

PubMed Central

Kelly, Sean; Li, Jonathan Z.; Harrigan, P. Richard; Taiwo, Babafemi

2014-01-01

A goal of HIV therapy is to sustain suppression of the plasma viral load below the detection limits of clinical assays. However, widely followed treatment guidelines diverge in their interpretation and recommended management of persistent viremia of low magnitude, reflecting the limited evidence base for this common clinical finding. Here, we review the incidence, risk factors, and potential consequences of low-level HIV viremia (LLV; defined in this review as a viremia level of 50 to 500 copies/ml) and very-low-level viremia (VLLV; defined as a viremia level of <50 copies/ml detected by clinical assays that have quantification cutoffs of <50 copies/ml). Using this framework, we discuss practical issues related to the diagnosis and management of patients experiencing persistent LLV and VLLV. Compared to viral suppression at <50 or 40 copies/ml, persistent LLV is associated with increased risk of antiretroviral drug resistance and overt virologic failure. Higher immune activation and HIV transmission may be additional undesirable consequences in this population. It is uncertain whether LLV of <200 copies/ml confers independent risks, as this level of viremia may reflect assay-dependent artifacts or biologically meaningful events during suppression. Resistance genotyping should be considered in patients with persistent LLV when feasible, and treatment should be modified if resistance is detected. There is a dearth of clinical evidence to guide management when genotyping is not feasible. Increased availability of genotypic assays for samples with viral loads of <400 copies/ml is needed. PMID:24733471

Predictive factors of thyroid cancer in patients with Graves' disease.

PubMed

Ren, Meng; Wu, Mu Chao; Shang, Chang Zhen; Wang, Xiao Yi; Zhang, Jing Lu; Cheng, Hua; Xu, Ming Tong; Yan, Li

2014-01-01

The best preoperative examination in Graves' disease with thyroid cancer still remains uncertain. The objectives of the present study were to investigate the prevalence of thyroid cancer in Graves' disease patients, and to identify the predictive factors and ultrasonographic features of thyroid cancer that may aid the preoperative diagnosis in Graves' disease. This retrospective study included 423 patients with Graves' disease who underwent surgical treatment from 2002 to 2012 at our institution. The clinical features and ultrasonographic findings of thyroid nodules were recorded. The diagnosis of thyroid cancer was determined according to the pathological results. Thyroid cancer was discovered in 58 of the 423 (13.7 %) surgically treated Graves' disease patients; 46 of those 58 patients had thyroid nodules, and the other 12 patients were diagnosed with incidentally discovered thyroid carcinomas without thyroid nodules. Among the 58 patients with thyroid cancer, papillary microcarcinomas were discovered in 50 patients, and multifocality and lymph node involvement were detected in the other 8 patients. Multivariate regression analysis showed younger age was the only significant factor predictive of metastatic thyroid cancer. Ultrasonographic findings of calcification and intranodular blood flow in thyroid nodules indicate that they are more likely to harbor thyroid cancers. Because the influencing factor of metastatic thyroid cancers in Graves' disease is young age, every suspicious nodule in Graves' disease patients should be evaluated and treated carefully, especially in younger patients because of the potential for metastasis.

Multiple spinal nerve enlargement and SOS1 mutation: Further evidence of overlap between neurofibromatosis type 1 and Noonan phenotype.

PubMed

Santoro, C; Giugliano, T; Melone, M A B; Cirillo, M; Schettino, C; Bernardo, P; Cirillo, G; Perrotta, S; Piluso, G

2018-01-01

Neurofibromatosis type 1 (NF1) has long been considered a well-defined, recognizable monogenic disorder, with neurofibromas constituting a pathognomonic sign. This dogma has been challenged by recent descriptions of patients with enlarged nerves or paraspinal tumors, suggesting that neurogenic tumors and hypertrophic neuropathy may be a complication of Noonan syndrome with multiple lentigines (NSML) or RASopathy phenotype. We describe a 15-year-old boy, whose mother previously received clinical diagnosis of NF1 due to presence of bilateral cervical and lumbar spinal lesions resembling plexiform neurofibromas and features suggestive of NS. NF1 molecular analysis was negative in the mother. The boy presented with Noonan features, multiple lentigines and pectus excavatum. Next-generation sequencing analysis of all RASopathy genes identified p.Ser548Arg missense mutation in SOS1 in the boy, confirmed in his mother. Brain and spinal magnetic resonance imaging scans were negative in the boy. No heart involvement or deafness was observed in proband or mother. This is the first report of a SOS1 mutation associated with hypertrophic neuropathy resembling plexiform neurofibromas, a rare complication in Noonan phenotypes with mutations in RASopathy genes. Our results highlight the overlap between RASopathies, suggesting that NF1 diagnostic criteria need rethinking. Genetic analysis of RASopathy genes should be considered when diagnosis is uncertain. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chronic intestinal pseudoobstruction syndrome: clinical analysis, outcome, and prognosis in 105 children. French-Speaking Group of Pediatric Gastroenterology.

PubMed

Faure, C; Goulet, O; Ategbo, S; Breton, A; Tounian, P; Ginies, J L; Roquelaure, B; Despres, C; Scaillon, M; Maurage, C; Paquot, I; Hermier, M; De Napoli, S; Dabadie, A; Huet, F; Baudon, J J; Larchet, M

1999-05-01

Our aim was to collect a large number of cases to characterize clinical presentation, outcome, and prognosis of chronic intestinal pseusoobstruction in children. We conducted a retrospective multicenter study that included children treated for chronic intestinal pseusoobstruction defined as recurrent episodes of intestinal obstruction with no mechanical obstruction, excluding Hirschsprung's disease. In all, 105 children, 57 boys and 48 girls, were studied, including five familial forms. Prenatal diagnosis was made in 18 patients. Eighty patients were less than 12 months old at onset; the disease began at birth for 37 patients. The most frequent signs were abdominal distension, vomiting, and constipation. Megacystis was noted in myopathies (7 cases), neuropathies (10 cases) and unclassified forms (13 cases). For all but three cases (two patients with CMV infection, one with Munchhausen-by-proxy syndrome), the associated diseases and disorders could not account for chronic intestinal pseusoobstruction as a secondary disorder. At least one full-thickness biopsy from the digestive tract was studied for 99 patients. The diagnosis recorded was visceral neuropathy in 58 cases, visceral myopathy in 17 cases, and uncertain or normal biopsy results in 24 cases. Seventy-eight children were fed intravenously, and only 18 were able to be fed orally throughout their illness. Seventy-one patients underwent surgery during their illness, and 217 surgical procedures, a mean of 3 per patient, were performed. Ostomy was the most performed procedure. Follow-up continued in 89 patients for 3 months to 16 years (mean 85 months). Forty-two patients were still fed by parenteral (39 patients) or enteral nutrition (3 patients) at the time of the study. Eleven patients died between the age of 1 month and 14 years 7 months.

The added value of using mutational profiling in addition to cytology in diagnosing aggressive pancreaticobiliary disease: review of clinical cases at a single center

PubMed Central

2014-01-01

Background This study aimed to better understand the supporting role that mutational profiling (MP) of DNA from microdissected cytology slides and supernatant specimens may play in the diagnosis of malignancy in fine-needle aspirates (FNA) and biliary brushing specimens from patients with pancreaticobiliary masses. Methods Cytology results were examined in a total of 30 patients with associated surgical (10) or clinical (20) outcomes. MP of DNA from microdissected cytology slides and from discarded supernatant fluid was analyzed in 26 patients with atypical, negative or indeterminate cytology. Results Cytology correctly diagnosed aggressive disease in 4 patients. Cytological diagnoses for the remaining 26 were as follows: 16 negative (9 false negative), 9 atypical, 1 indeterminate. MP correctly determined aggressive disease in 1 false negative cytology case and confirmed a negative cytology diagnosis in 7 of 7 cases of non-aggressive disease. Of the 9 atypical cytology cases, MP correctly diagnosed 7 as positive and 1 as negative for aggressive disease. One specimen that was indeterminate by cytology was correctly diagnosed as non-aggressive by MP. When first line malignant (positive) cytology results were combined with positive second line MP results, 12/21 cases of aggressive disease were identified, compared to 4/21 cases identified by positive cytology alone. Conclusions When first line cytology results were uncertain (atypical), questionable (negative), or not possible (non-diagnostic/indeterminate), MP provided additional information regarding the presence of aggressive disease. When used in conjunction with first line cytology, MP increased detection of aggressive disease without compromising specificity in patients that were difficult to diagnose by cytology alone. PMID:25084836

Which prognostic indicator should we use for clinical practice in the initial evaluation and follow-up of IIP: should we depend on PFT, HRCT or...what?

PubMed

Caminati, Antonella; Harari, Sergio

2005-12-01

Idiopathic interstitial pneumonias are a group of diffuse, inflammatory and fibrotic disorders of the lung parenchyma that cause restrictive physiology and impair gas exchange. Usual interstitial pneumonia and non-specific interstitial pneumonia comprise the majority of idiopathic interstitial pneumonia cases. Previous studies have identified the histopathologic pattern as the most important baseline factor in determining prognosis. The non-invasive diagnosis of these diseases is sometimes uncertain but histological evaluation is an imperfect gold-standard. In some cases, the biopsy specimen may not be representative of the entire lung. In other cases, there may be differences in interpretation of the histological findings. HRCT has also assumed a greater role in the diagnosis and management of patients with idiopathic interstitial pneumonia. Factors affecting prognosis are discussed controversially. Histological criteria, clinical features, or lung function parameters are not clear prognostic indicators. Increased interstitial abnormalities in the HRCT, parameters indicating restrictive lung function, desaturation at 6MWT and abnormal gas exchange are possible determinants of survival. The prognostic value of pulmonary function trends over time may prove more useful. Longitudinal behavior is a more accurate determinant of outcome than evaluation at a single point in time. It is important to remember that no predictor of survival can ever reliably predict an individual patient's prognosis. Physicians should realize this limitation, and use predictor tools as general prognostic guides, not crystal balls. However, due to the great variability in the natural history of the disease, close monitoring of the patients may be necessary to evaluate the individual course of each patient.

Molecular and Culture-Based Bronchoalveolar Lavage Fluid Testing for the Diagnosis of Cytomegalovirus Pneumonitis.

PubMed

Tan, Susanna K; Burgener, Elizabeth B; Waggoner, Jesse J; Gajurel, Kiran; Gonzalez, Sarah; Chen, Sharon F; Pinsky, Benjamin A

2016-01-01

Background.  Cytomegalovirus (CMV) is a major cause of morbidity and mortality in immunocompromised patients, with CMV pneumonitis among the most severe manifestations of infection. Although bronchoalveolar lavage (BAL) samples are frequently tested for CMV, the clinical utility of such testing remains uncertain. Methods.  Retrospective analysis of adult patients undergoing BAL testing via CMV polymerase chain reaction (PCR), shell vial culture, and conventional viral culture between August 2008 and May 2011 was performed. Cytomegalovirus diagnostic methods were compared with a comprehensive definition of CMV pneumonitis that takes into account signs and symptoms, underlying host immunodeficiency, radiographic findings, and laboratory results. Results.  Seven hundred five patients underwent 1077 bronchoscopy episodes with 1090 BAL specimens sent for CMV testing. Cytomegalovirus-positive patients were more likely to be hematopoietic cell transplant recipients (26% vs 8%, P < .0001) and less likely to have an underlying condition not typically associated with lung disease (3% vs 20%, P < .0001). Histopathology was performed in only 17.3% of CMV-positive bronchoscopy episodes. When CMV diagnostic methods were evaluated against the comprehensive definition, the sensitivity and specificity of PCR, shell vial culture, and conventional culture were 91.3% and 94.6%, 54.4% and 97.4%, and 28.3% and 96.5%, respectively. Compared with culture, PCR provided significantly higher sensitivity and negative predictive value (P ≤ .001), without significantly lower positive predictive value. Cytomegalovirus quantitation did not improve test performance, resulting in a receiver operating characteristic curve with an area under the curve of 0.53. Conclusions.  Cytomegalovirus PCR combined with a comprehensive clinical definition provides a pragmatic approach for the diagnosis of CMV pneumonitis.

Brain CT image similarity retrieval method based on uncertain location graph.

PubMed

Pan, Haiwei; Li, Pengyuan; Li, Qing; Han, Qilong; Feng, Xiaoning; Gao, Linlin

2014-03-01

A number of brain computed tomography (CT) images stored in hospitals that contain valuable information should be shared to support computer-aided diagnosis systems. Finding the similar brain CT images from the brain CT image database can effectively help doctors diagnose based on the earlier cases. However, the similarity retrieval for brain CT images requires much higher accuracy than the general images. In this paper, a new model of uncertain location graph (ULG) is presented for brain CT image modeling and similarity retrieval. According to the characteristics of brain CT image, we propose a novel method to model brain CT image to ULG based on brain CT image texture. Then, a scheme for ULG similarity retrieval is introduced. Furthermore, an effective index structure is applied to reduce the searching time. Experimental results reveal that our method functions well on brain CT images similarity retrieval with higher accuracy and efficiency.

A Dual Hesitant Fuzzy Multigranulation Rough Set over Two-Universe Model for Medical Diagnoses

PubMed Central

Zhang, Chao; Li, Deyu; Yan, Yan

2015-01-01

In medical science, disease diagnosis is one of the difficult tasks for medical experts who are confronted with challenges in dealing with a lot of uncertain medical information. And different medical experts might express their own thought about the medical knowledge base which slightly differs from other medical experts. Thus, to solve the problems of uncertain data analysis and group decision making in disease diagnoses, we propose a new rough set model called dual hesitant fuzzy multigranulation rough set over two universes by combining the dual hesitant fuzzy set and multigranulation rough set theories. In the framework of our study, both the definition and some basic properties of the proposed model are presented. Finally, we give a general approach which is applied to a decision making problem in disease diagnoses, and the effectiveness of the approach is demonstrated by a numerical example. PMID:26858772

Prognostic Implications of Single-Sample Confirmatory Testing for Undiagnosed Diabetes: A Prospective Cohort Study.

PubMed

Selvin, Elizabeth; Wang, Dan; Matsushita, Kunihiro; Grams, Morgan E; Coresh, Josef

2018-06-19

Current clinical definitions of diabetes require repeated blood work to confirm elevated levels of glucose or hemoglobin A1c (HbA1c) to reduce the possibility of a false-positive diagnosis. Whether 2 different tests from a single blood sample provide adequate confirmation is uncertain. To examine the prognostic performance of a single-sample confirmatory definition of undiagnosed diabetes. Prospective cohort study. The ARIC (Atherosclerosis Risk in Communities) study. 13 346 ARIC participants (12 268 without diagnosed diabetes) with 25 years of follow-up for incident diabetes, cardiovascular outcomes, kidney disease, and mortality. Confirmed undiagnosed diabetes was defined as elevated levels of fasting glucose (≥7.0 mmol/L [≥126 mg/dL]) and HbA1c (≥6.5%) from a single blood sample. Among 12 268 participants without diagnosed diabetes, 978 had elevated levels of fasting glucose or HbA1c at baseline (1990 to 1992). Among these, 39% had both (confirmed undiagnosed diabetes), whereas 61% had only 1 elevated measure (unconfirmed undiagnosed diabetes). The confirmatory definition had moderate sensitivity (54.9%) but high specificity (98.1%) for identification of diabetes cases diagnosed during the first 5 years of follow-up, with specificity increasing to 99.6% by 15 years. The 15-year positive predictive value was 88.7% compared with 71.1% for unconfirmed cases. Confirmed undiagnosed diabetes was significantly associated with cardiovascular and kidney disease and mortality, with stronger associations than unconfirmed diabetes. Lack of repeated measurements of fasting glucose and HbA1c. A single-sample confirmatory definition of diabetes had a high positive predictive value for subsequent diagnosis and was strongly associated with clinical end points. Our results support the clinical utility of using a combination of elevated fasting glucose and HbA1c levels from a single blood sample to identify undiagnosed diabetes in the population. National Institute of Diabetes and Digestive and Kidney Diseases and National Heart, Lung, and Blood Institute.

Cost-benefit value of microscopic examination of intervertebral discs.

PubMed

Grzybicki, D M; Callaghan, E J; Raab, S S

1998-09-01

Given the virtual absence of histologically detected, clinically unsuspected disease in intervertebral disc specimens, some authors have advocated that histological examination be discontinued. However, the examination of intervertebral disc specimens remains common practice in most pathology laboratories. No cost-benefit analysis of this practice has been made; therefore, the authors' goal in this study was perform such an analysis. Using the University of Iowa surgical pathology database, 1109 patients who had undergone a laminectomy were identified retrospectively. These cases were classified into four categories based on the patients' preoperative clinical diagnosis and final histopathological diagnosis: insignificant clinical diagnosis/insignificant pathological diagnosis (ICIP), significant clinical diagnosis/insignificant pathological diagnosis (SCIP), significant clinical diagnosis/significant pathological diagnosis (SCSP), and insignificant clinical diagnosis/significant pathological diagnosis (ICSP). A significant clinical diagnosis was defined as one other than a benign, noninfectious indication for laminectomy. A significant pathological diagnosis was a diagnosis other than degenerative changes. The cost-benefit value of performing a histological examination in cases with significant or insignificant clinical diagnoses was examined. The cases were classified as: 1068 ICIP, 17 SCIP, 21 SCSP, and three ICSP. On chart review, in all three cases of ICSP an epidural abscess was identified perioperatively and the subsequent histological diagnosis did not affect patient care. The costs per case of identifying a significant pathological diagnosis with a significant and an insignificant clinical diagnosis were $44.79 and $8811, respectively. Histological examination of intervertebral disc specimens is cost beneficial only if there is a significant preoperative clinical diagnosis.

Single-incision video-assisted anatomical segmentectomy with handsewn bronchial closure for endobronchial lipoma

PubMed Central

Sesma, Julio; Bolufer, Sergio; Lirio, Francisco; Navarro-Martinez, Jose; Galiana, Maria; Baschwitz, Benno; Rivera, Maria Jesus

2016-01-01

Endobronchial lipomas are rare benign tumors whose symptoms are usually confused with recurrent infections or even asthma diagnosis, and mostly caused by endobronquial obstructive component which also conditions severity. We report a case of a 60-year-old man with a right-lower lobe upper-segment endobronchial myxoid tumor with uncertain diagnosis. We performed a single incision video-assisted anatomical segmentectomy and wedge bronchoplasty with handsewn closure to achieve complete resection and definitive diagnosis. During the postoperative air leak was not observed and there was no complication, with low pain scores and complete recovery. Final pathological exam showed endobronchial lipoma. Single-incision (SI) anatomical segmentectomies are lung-sparing resections for benign or low-grade malignancies with diagnostic and therapeutic value, and the need for a wedge bronchoplasty is not a necessary indication for conversion to multiport or open thoracotomy. PMID:27570778

Single-incision video-assisted anatomical segmentectomy with handsewn bronchial closure for endobronchial lipoma.

PubMed

Galvez, Carlos; Sesma, Julio; Bolufer, Sergio; Lirio, Francisco; Navarro-Martinez, Jose; Galiana, Maria; Baschwitz, Benno; Rivera, Maria Jesus

2016-08-01

Endobronchial lipomas are rare benign tumors whose symptoms are usually confused with recurrent infections or even asthma diagnosis, and mostly caused by endobronquial obstructive component which also conditions severity. We report a case of a 60-year-old man with a right-lower lobe upper-segment endobronchial myxoid tumor with uncertain diagnosis. We performed a single incision video-assisted anatomical segmentectomy and wedge bronchoplasty with handsewn closure to achieve complete resection and definitive diagnosis. During the postoperative air leak was not observed and there was no complication, with low pain scores and complete recovery. Final pathological exam showed endobronchial lipoma. Single-incision (SI) anatomical segmentectomies are lung-sparing resections for benign or low-grade malignancies with diagnostic and therapeutic value, and the need for a wedge bronchoplasty is not a necessary indication for conversion to multiport or open thoracotomy.

Variants of uncertain significance in newborn screening disorders: implications for large-scale genomic sequencing.

PubMed

Narravula, Alekhya; Garber, Kathryn B; Askree, S Hussain; Hegde, Madhuri; Hall, Patricia L

2017-01-01

As exome and genome sequencing using high-throughput sequencing technologies move rapidly into the diagnostic process, laboratories and clinicians need to develop a strategy for dealing with uncertain findings. A commitment must be made to minimize these findings, and all parties may need to make adjustments to their processes. The information required to reclassify these variants is often available but not communicated to all relevant parties. To illustrate these issues, we focused on three well-characterized monogenic, metabolic disorders included in newborn screens: classic galactosemia, caused by GALT variants; phenylketonuria, caused by PAH variants; and medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, caused by ACADM variants. In 10 years of clinical molecular testing, we have observed 134 unique GALT variants, 46 of which were variants of uncertain significance (VUS). In PAH, we observed 132 variants, including 17 VUS, and for ACADM, we observed 64 unique variants, of which 33 were uncertain. After this review, 17 VUS (37%; 7 in ACADM, 9 in GALT, and 1 in PAH) were reclassified from uncertain (6 to benign or likely benign and 11 to pathogenic or likely pathogenic). We identified common types of missing information that would have helped make a definitive classification and categorized this information by ease and cost to obtain.Genet Med 19 1, 77-82.

International consensus criteria for the diagnosis of Raynaud's phenomenon.

PubMed

Maverakis, Emanual; Patel, Forum; Kronenberg, Daniel G; Chung, Lorinda; Fiorentino, David; Allanore, Yannick; Guiducci, Serena; Hesselstrand, Roger; Hummers, Laura K; Duong, Chris; Kahaleh, Bashar; Macgregor, Alexander; Matucci-Cerinic, Marco; Wollheim, Frank A; Mayes, Maureen D; Gershwin, M Eric

2014-01-01

Vasoconstriction accompanied by changes in skin color is a normal physiologic response to cold. The distinction between this normal physiology and Raynaud's phenomenon (RP) has yet to be well characterized. In anticipation of the 9th International Congress on Autoimmunity, a panel of 12 RP experts from 9 different institutes and four different countries were assembled for a Delphi exercise to establish new diagnostic criteria for RP. Relevant investigators with highly cited manuscripts in Raynaud's-related research were identified using the Web of Science and invited to participate. Surveys at each stage were administered to participants via the on-line SurveyMonkey software tool. The participants evaluated the level of appropriateness of statements using a scale of 1 (extremely inappropriate) through 9 (extremely appropriate). In the second stage, panel participants were asked to rank rewritten items from the first round that were scored as "uncertain" for the diagnosis of RP, items with significant disagreement (Disagreement Index > 1), and new items suggested by the panel. Results were analyzed using the Interpercentile Range Adjusted for Symmetry (IPRAS) method. A 3-Step Approach to diagnose RP was then developed using items the panelists "agreed" were "appropriate" diagnostic criteria. In the final stage, the panel was presented with the newly developed diagnostic criteria and asked to rate them against previous models. Following the first two iterations of the Delphi exercise, the panel of 12 experts agreed that 36 of the items were "appropriate", 12 items had "uncertain" appropriateness, and 13 items were "inappropriate" to use in the diagnostic criteria of RP. Using an expert committee, we developed a 3-Step Approach for the diagnosis of RP and 5 additional criteria for the diagnosis of primary RP. The committee came to an agreement that the proposed criteria were "appropriate and accurate" for use by physicians to diagnose patients with RP. Published by Elsevier Ltd.

c-KIT receptor expression is strictly associated with the biological behaviour of thyroid nodules

PubMed Central

2012-01-01

Background A large amount of information has been collected on the molecular tumorigenesis of thyroid cancer. A low expression of c-KIT gene has been reported during the transformation of normal thyroid epithelium to papillary carcinoma suggesting a possible role of the gene in the differentiation of thyroid tissue rather than in the proliferation. The initial presentation of thyroid carcinoma is through a nodule and the best way nowadays to evaluate it is by fine-needle aspiration (FNA). However many thyroid FNAs are not definitively benign or malignant, yielding an indeterminate or suspicious diagnosis which ranges from 10 to 25% of FNAs. BRAF mutational analysis is commonly used to assess the malignancy of thyroid nodules but unfortunately it still leaves indeterminate diagnoses. The development of molecular initial diagnostic tests for evaluating a thyroid nodule is needed in order to define optimal surgical approach for patients with uncertain diagnosis pre- and intra-operatively. Methods In this study we extracted RNA from 82 FNA smears, 46 malignant and 36 benign at the histology, in order to evaluate by quantitative Real Time PCR the expression levels of c-KIT gene. Results We have found a highly preferential decrease rather than increase in transcript of c-KIT in malignant thyroid lesions compared to the benign ones. To explore the diagnostic utility of c-KIT expression in thyroid nodules, its expression values were divided in four arbitrarily defined classes, with class I characterized by the complete silencing of the gene. Class I and IV represented the two most informative groups, with 100% of the samples found malignant or benign respectively. The molecular analysis was proven by ROC (receiver operating characteristic) analysis to be highly specific and sensitive improving the cytological diagnostic accuracy of 15%. Conclusion We propose the use of BRAF test (after uncertain cytological diagnosis) to assess the malignancy of thyroid nodules at first, then the use of the c-KIT expression to ultimately assess the diagnosis of the nodules that otherwise would remain suspicious. The c-KIT expression-based classification is highly accurate and may provide a tool to overcome the difficulties in today's preoperative diagnosis of thyroid suspicious malignancies. PMID:22233760

The complicated 'Yes': Decision-making processes and receptivity to lung cancer screening among head and neck cancer survivors.

PubMed

Seaman, Aaron T; Dukes, Kimberly; Hoffman, Richard M; Christensen, Alan J; Kendell, Nicholas; Sussman, Andrew L; Veléz-Bermúdez, Miriam; Volk, Robert J; Pagedar, Nitin A

2018-04-22

Shared decision making (SDM) is recommended when offering lung cancer screening (LCS)-which presents challenges with tobacco-related cancer survivors because they were excluded from clinical trials. Our objective was to characterize head and neck cancer (HNC) survivors' knowledge, attitudes, and beliefs toward LCS and SDM. Between November 2017 and June 2018, we conducted semi-structured qualitative interviews with 19 HNC survivors, focusing on patients' cancer and smoking history, receptivity to and perceptions of LCS, and decision-making preferences RESULTS: Participants were receptive to LCS, referencing their successful HNC outcomes. They perceived that LCS might reduce uncertainty and emphasized the potential benefits of early diagnosis. Some expressed concern over costs or overdiagnosis, but most minimized potential harms, including false positives and radiation exposure. Participants preferred in-person LCS discussions, often ideally with their cancer specialist. HNC survivors may have overly optimistic expectations for LCS, and clinicians need to account for this in SDM discussions. Supporting these patients in making informed decisions will be challenging because we lack clinical data on the potential benefits and harms of LCS for cancer survivors. While some patients prefer discussing LCS with their cancer specialists, the ability of specialists to support high-quality decision making is uncertain. Copyright © 2018 Elsevier B.V. All rights reserved.

STUMP un"stumped": anti-tumor response to anaplastic lymphoma kinase (ALK) inhibitor based targeted therapy in uterine inflammatory myofibroblastic tumor with myxoid features harboring DCTN1-ALK fusion.

PubMed

Subbiah, Vivek; McMahon, Caitlin; Patel, Shreyaskumar; Zinner, Ralph; Silva, Elvio G; Elvin, Julia A; Subbiah, Ishwaria M; Ohaji, Chimela; Ganeshan, Dhakshina Moorthy; Anand, Deepa; Levenback, Charles F; Berry, Jenny; Brennan, Tim; Chmielecki, Juliann; Chalmers, Zachary R; Mayfield, John; Miller, Vincent A; Stephens, Philip J; Ross, Jeffrey S; Ali, Siraj M

2015-06-11

Recurrent, metastatic mesenchymal myxoid tumors of the gynecologic tract present a management challenge as there is minimal evidence to guide systemic therapy. Such tumors also present a diagnostic dilemma, as myxoid features are observed in leiomyosarcomas, inflammatory myofibroblastic tumors (IMT), and mesenchymal myxoid tumors. Comprehensive genomic profiling was performed in the course of clinical care on a case of a recurrent, metastatic myxoid uterine malignancy (initially diagnosed as smooth muscle tumor of uncertain malignant potential (STUMP)), to guide identify targeted therapeutic options. To our knowledge, this case represents the first report of clinical response to targeted therapy in a tumor harboring a DCTN1-ALK fusion protein. Hybridization capture of 315 cancer-related genes plus introns from 28 genes often rearranged or altered in cancer was applied to >50 ng of DNA extracted from this sample and sequenced to high, uniform coverage. Therapy was given in the context of a phase I clinical trial ClinicalTrials.gov Identifier: ( NCT01548144 ). Immunostains showed diffuse positivity for ALK1 expression and comprehensive genomic profiling identified an in frame DCTN1-ALK gene fusion. The diagnosis of STUMP was revised to that of an IMT with myxoid features. The patient was enrolled in a clinical trial and treated with an anaplastic lymphoma kinase (ALK) inhibitor (crizotinib/Xalkori®) and a multikinase VEGF inhibitor (pazopanib/Votrient®). The patient experienced an ongoing partial response (6+ months) by response evaluation criteria in solid tumors (RECIST) 1.1 criteria. For myxoid tumors of the gynecologic tract, comprehensive genomic profiling can identify clinical relevant genomic alterations that both direct treatment targeted therapy and help discriminate between similar diagnostic entities.

Appropriateness of early management of newly diagnosed Crohn's disease in a European population-based cohort.

PubMed

Juillerat, Pascal; Pittet, Valérie; Mottet, Christian; Felley, Christian; Gonvers, Jean-Jacques; Vader, John-Paul; Burnand, Bernard; Froehlich, Florian; Wolters, Frank L; Stockbrügger, Reinhold W; Michetti, Pierre

2010-12-01

The European Panel on the Appropriateness of Crohn's disease Therapy (EPACT) has developed appropriateness criteria. We have applied these criteria retrospectively to the population-based inception cohort of Crohn's disease (CD) patients of the European Collaborative Study Group on Inflammatory Bowel Disease (EC-IBD). A total of 426 diagnosed CD patients from 13 European centers were enrolled at the time of diagnosis (first flare, naive patients). We used the EPACT definitions to identify 247 patients with active luminal CD. We then assessed the appropriateness of the initial drug prescription according to the EPACT criteria. Among the cohort patients 163 suffered from mild-to-moderate CD and 84 from severe CD. Among the mild-to-moderate disease group, 96 patients (59%) received an appropriate treatment, whereas for 66 patients (40%) the treatment was uncertain and in one case (1%) inappropriate. Among the severe disease group, 86% were treated medically and 14% required surgery. 59 (70%) were appropriately treated, whereas for one patient (1%) the procedure was considered uncertain and for 24 patients (29%) inappropriate. Initial treatment was appropriate in the majority of cases for non-complicated luminal CD. Inappropriate or uncertain treatment was given in a significant minority of patients, with an increased potential risk of adverse events.

Multiple myeloma: diagnosis and treatment.

PubMed

Nau, Konrad C; Lewis, William D

2008-10-01

Multiple myeloma, the most common bone malignancy, is occurring with increasing frequency in older persons. Typical symptoms are bone pain, malaise, anemia, renal insufficiency, and hypercalcemia. Incidental discovery on comprehensive laboratory panels is common. The disease is diagnosed with serum or urine protein electrophoresis or immunofixation and bone marrow aspirate analysis. Skeletal radiographs are important in staging multiple myeloma and revealing lytic lesions, vertebral compression fractures, and osteoporosis. Magnetic resonance imaging and positron emission tomography or computed tomography are emerging as useful tools in the evaluation of patients with myeloma; magnetic resonance imaging is preferred for evaluating acute spinal compression. Nuclear bone scans and dual energy x-ray absorptiometry have no role in the diagnosis and staging of myeloma. The differential diagnosis of monoclonal gammopathies includes monoclonal gammopathy of uncertain significance, smoldering (asymptomatic) and symptomatic multiple myeloma, amyloidosis, B-cell non-Hodgkin lymphoma, Waldenström macroglobulinemia, and rare plasma cell leukemia and heavy chain diseases. Patients with monoclonal gammopathy of uncertain significance or smoldering multiple myeloma should be followed closely, but not treated. Symptomatic multiple myeloma is treated with chemotherapy followed by autologous stem cell transplantation, if possible. Melphalan, prednisolone, dexamethasone, vincristine, doxorubicin, bortezomib, and thalidomide and its analogue lenalidomide have been used successfully. It is important that family physicians recognize and appropriately treat multiple myeloma complications. Bone pain is treated with opiates, bisphosphonates, radiotherapy, vertebroplasty, or kyphoplasty; nephrotoxic nonsteroidal anti-inflammatory drugs should be avoided. Hypercalcemia is treated with isotonic saline infusions, steroids, furosemide, or bisphosphonates. Because of susceptibility to infections, patients require broad-spectrum antibiotics for febrile illness and immunization against influenza, pneumococcus, and Haemophilus influenzae B. Five-year survival rates approach 33 percent, and the median survival rate is 33 months.

Serial hCG and progesterone levels to predict early pregnancy outcomes in pregnancies of uncertain viability: A prospective study.

PubMed

Puget, Claire; Joueidi, Yolaine; Bauville, Estelle; Laviolle, Bruno; Bendavid, Claude; Lavoué, Vincent; Le Lous, Maela

2018-01-01

To assess the value of serial hCG and progesterone serum level in the diagnosis of early pregnancy viability. It was a prospective cohort study. Women with a pregnancy of uncertain viability (PUV), defined as the presence of an intra-uterine embryo with a crown-rump length <7mm with no cardiac activity or an intra-uterine gestational sac size <25mm with no visible embryonic structure in a transvaginal ultrasound scan (TVS) were eligible. The diagnosis value of serial plasmatic hCG levels on the first day and 48h after as well as the initial progesterone level were evaluated to diagnose pregnancy viability. Pregnancy viability was assessed by TVS 7 to 14days after inclusion. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of an hCG H48/H0 ratio increase <11% to diagnose an early pregnancy loss were 70.6%, 100%, 100% and 85.3%, respectively. The sensitivity, specificity, PPV and NPV of a 6.2ng/ml progesterone level to diagnose an early pregnancy loss were 20%, 100%, 100% and 65.2%, respectively. The sensitivity, specificity, PPV and NPV of an hCG H48/H0 ratio increase >75% to diagnose a viable pregnancy were 100%, 31%, 45.9% and 100%, respectively. hCG H48/H0 ratio increase <11% was associated with early pregnancy loss in 100% of the cases. hCG H48/H0 ratio increase >75% was associated with 100% of viable pregnancies in 100% of the cases. Serial hCG levels alone permitted an early viability diagnosis within 48h for 41.1% of patients with PUV instead of 7 to 14days with TVS. Copyright © 2017 Elsevier B.V. All rights reserved.

An evaluation of consensus techniques for diagnostic interpretation

NASA Astrophysics Data System (ADS)

Sauter, Jake N.; LaBarre, Victoria M.; Furst, Jacob D.; Raicu, Daniela S.

2018-02-01

Learning diagnostic labels from image content has been the standard in computer-aided diagnosis. Most computer-aided diagnosis systems use low-level image features extracted directly from image content to train and test machine learning classifiers for diagnostic label prediction. When the ground truth for the diagnostic labels is not available, reference truth is generated from the experts diagnostic interpretations of the image/region of interest. More specifically, when the label is uncertain, e.g. when multiple experts label an image and their interpretations are different, techniques to handle the label variability are necessary. In this paper, we compare three consensus techniques that are typically used to encode the variability in the experts labeling of the medical data: mean, median and mode, and their effects on simple classifiers that can handle deterministic labels (decision trees) and probabilistic vectors of labels (belief decision trees). Given that the NIH/NCI Lung Image Database Consortium (LIDC) data provides interpretations for lung nodules by up to four radiologists, we leverage the LIDC data to evaluate and compare these consensus approaches when creating computer-aided diagnosis systems for lung nodules. First, low-level image features of nodules are extracted and paired with their radiologists semantic ratings (1= most likely benign, , 5 = most likely malignant); second, machine learning multi-class classifiers that handle deterministic labels (decision trees) and probabilistic vectors of labels (belief decision trees) are built to predict the lung nodules semantic ratings. We show that the mean-based consensus generates the most robust classi- fier overall when compared to the median- and mode-based consensus. Lastly, the results of this study show that, when building CAD systems with uncertain diagnostic interpretation, it is important to evaluate different strategies for encoding and predicting the diagnostic label.

[Pneumatosis cystoides intestinalis complicated with intestinal volvulus].

PubMed

Fuenmayor, Carmen Elena; Gainza, Carlos; García, Maryori; Zambrano, Richard; Torres, Gledys; Hernández, Yohanys; García, Anna

2017-01-01

Pneumatosis cystoides intestinalis is a rare condition in which multiple gas-filled cysts are found within the wall of the gastrointestinal tract either in the subserosa or submucosa. Its pathogenesis is uncertain and several pathogenic mechanisms have been proposed to explain its origin. The case of a male patient of 46 years with previous diagnosis of pneumatosis cystic intestinalis, who consulted for abdominal pain, vomiting and fever (39 °C) is presented. By the time of admission ther were signs of peritoneal irritation. The X-ray abdominal reported distension and intestinal hydro-air levels. Exploratory laparotomy was performed and revealed small bowel volvulus with strangulation of some intestinal segment. Histological diagnosis was pneumatosis cystic intestinalis complicated with Infarction trans-mural by intestinal volvulus. The patient evolved satisfactorily.

Intelligent Process Abnormal Patterns Recognition and Diagnosis Based on Fuzzy Logic.

PubMed

Hou, Shi-Wang; Feng, Shunxiao; Wang, Hui

2016-01-01

Locating the assignable causes by use of the abnormal patterns of control chart is a widely used technology for manufacturing quality control. If there are uncertainties about the occurrence degree of abnormal patterns, the diagnosis process is impossible to be carried out. Considering four common abnormal control chart patterns, this paper proposed a characteristic numbers based recognition method point by point to quantify the occurrence degree of abnormal patterns under uncertain conditions and a fuzzy inference system based on fuzzy logic to calculate the contribution degree of assignable causes with fuzzy abnormal patterns. Application case results show that the proposed approach can give a ranked causes list under fuzzy control chart abnormal patterns and support the abnormity eliminating.

Diagnosis and Treatment of Polycystic Ovary Syndrome: An Endocrine Society Clinical Practice Guideline

PubMed Central

Legro, Richard S.; Arslanian, Silva A.; Ehrmann, David A.; Hoeger, Kathleen M.; Murad, M. Hassan; Pasquali, Renato; Welt, Corrine K.

2013-01-01

Objective: The aim was to formulate practice guidelines for the diagnosis and treatment of polycystic ovary syndrome (PCOS). Participants: An Endocrine Society-appointed Task Force of experts, a methodologist, and a medical writer developed the guideline. Evidence: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. Consensus Process: One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of The Endocrine Society and the European Society of Endocrinology reviewed and commented on preliminary drafts of these guidelines. Two systematic reviews were conducted to summarize supporting evidence. Conclusions: We suggest using the Rotterdam criteria for diagnosing PCOS (presence of two of the following criteria: androgen excess, ovulatory dysfunction, or polycystic ovaries). Establishing a diagnosis of PCOS is problematic in adolescents and menopausal women. Hyperandrogenism is central to the presentation in adolescents, whereas there is no consistent phenotype in postmenopausal women. Evaluation of women with PCOS should exclude alternate androgen-excess disorders and risk factors for endometrial cancer, mood disorders, obstructive sleep apnea, diabetes, and cardiovascular disease. Hormonal contraceptives are the first-line management for menstrual abnormalities and hirsutism/acne in PCOS. Clomiphene is currently the first-line therapy for infertility; metformin is beneficial for metabolic/glycemic abnormalities and for improving menstrual irregularities, but it has limited or no benefit in treating hirsutism, acne, or infertility. Hormonal contraceptives and metformin are the treatment options in adolescents with PCOS. The role of weight loss in improving PCOS status per se is uncertain, but lifestyle intervention is beneficial in overweight/obese patients for other health benefits. Thiazolidinediones have an unfavorable risk-benefit ratio overall, and statins require further study. PMID:24151290

Radiotherapy for ductal carcinoma in situ and risk of second non-breast cancers.

PubMed

Withrow, Diana R; Morton, Lindsay M; Curtis, Rochelle E; Schonfeld, Sara J; Berrington de González, Amy

2017-11-01

Radiotherapy for ductal carcinoma (DCIS) is increasing, but the risks and benefits of the treatment remain uncertain. We aimed to investigate the relationship between radiotherapy for DCIS and risk of second non-breast cancers in a large US cohort. We conducted a retrospective cohort study of 52,556 women in 12 U.S. population-based cancer registries diagnosed with first primary DCIS during 1992-2008 at age 25-79 years. We estimated relative risks (RRs), attributable risks (AR), and excess absolute risks (EAR) of second non-breast cancers associated with radiotherapy using Poisson regression adjusted for age at year of diagnosis, grade, hormonal therapy (yes/no or unknown), and time since diagnosis. Approximately half of the women (46.3%) received radiotherapy. Radiotherapy was associated with an increased risk of all second non-breast cancers combined [RR 1.17, 95% confidence interval (CI) 1.08-1.28] and all in-field, radiation-related second cancers combined (RR 1.37, 95% CI 1.15-1.63), driven by second lung cancers (RR 1.33, 95% CI 1.10-1.60) and non-CLL leukemia (RR 1.71, 95% CI 1.02-2.86). The estimated cumulative excess risk of all second non-breast cancers was 0.8% by 15 years after DCIS diagnosis. Radiotherapy was associated with an increased risk of second non-breast cancers. The specific excess of cancers at sites likely in/near the radiotherapy field suggests the findings are unlikely due exclusively to confounding, but further research into factors related to receipt of radiotherapy is needed. Our risk estimates can be used to help assess the balance of the risks and benefits of radiotherapy for DCIS and to inform clinical practice.

The Appropriate Use of Neuroimaging in the Diagnostic Work-Up of Dementia

PubMed Central

2014-01-01

Background Diagnosis of dementia is challenging and requires both ruling out potentially treatable underlying causes and ruling in a diagnosis of dementia subtype to manage patients and suitably plan for the future. Objectives This analysis sought to determine the appropriate use of neuroimaging during the diagnostic work-up of dementia, including indications for neuroimaging and comparative accuracy of alternative technologies. Data Sources A literature search was performed using Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid Embase, the Wiley Cochrane Library, and the Centre for Reviews and Dissemination database, for studies published between 2000 and 2013. Review Methods Data on diagnostic accuracy and impact on clinical decision making were abstracted from included studies. Quality of evidence was assessed using GRADE. Results The search yielded 5,374 citations and 15 studies were included. Approximately 10% of dementia cases are potentially treatable, though less than 1% reverse partially or fully. Neither prediction rules nor clinical indications reliably select the subset of patients who will likely benefit from neuroimaging. Clinical utility is highest in ambiguous cases or where dementia may be mixed, and lowest for clinically diagnosed Alzheimer disease or clinically excluded vascular dementia. There is a lack of evidence that MRI is superior to CT in detecting a vascular component to dementia. Accuracy of structural imaging is moderate to high for discriminating different types of dementia. Limitations There was significant heterogeneity in estimates of diagnostic accuracy, which often prohibited a statistical summary of findings. The quality of data reported by studies prohibited calculation of likelihood ratios in the present analysis. No studies from primary care were found; thus, generalizability beyond tertiary care settings may be limited. Conclusions A diagnosis of reversible dementia is rare. Imaging has the most clinical utility in cases where there is potentially mixed dementia or ambiguity as to the type of dementia despite prolonged follow-up (e.g., 2 years or more). Both CT and MRI are useful for detecting a vascular component of dementia. Plain Language Summary Dementia is a devastating condition of memory loss and behaviour change that affects many Canadians, especially older adults. Diagnosis is complex because symptoms can be caused by different brain diseases, such as Alzheimer disease, and in some cases by other causes such a tumour or cerebrovascular disease. Although dementia rarely improves much, an accurate diagnosis is important because it determines the treatment a patient should receive and helps patients and families understand what the future holds. Brain imaging, using computed tomography (CT) or magnetic resonance imaging (MRI) scans, may help in the diagnosis by allowing doctors to see changes in brain structure or function that explain the dementia. Unfortunately, it is not well understood which patients will most likely benefit from a brain scan and which type of scan works best to diagnose dementia. This study reviewed the published evidence about these questions. The study found that relying on specific symptoms to decide who should have a brain scan, rather than imaging all dementia patients, is unreliable and can miss some potentially treatable conditions. The study also found that scans have most value when doctors are uncertain as to the type of dementia despite monitoring the patient for a while (e.g., 2 years) or when the patient may have a combination of dementia types. Brain scans are often less helpful in the diagnosis of Alzheimer disease, and doctors can often use clinical assessment to rule out vascular dementia (another common type of dementia, related to cerebrovascular disease). The evidence also shows that MRI is not better than CT in detecting vascular dementia as a contributing cause. For Alzheimer disease, Creutzfeldt-Jakob disease, and clinically ambiguous dementias, both CT and MRI are highly accurate in correctly ruling out these diagnoses, but both types of scans have only low to moderate ability to correctly identify patients with any of these conditions. Importantly, the quality of the evidence available for this study was limited by considerable differences in research and analysis methods. PMID:24592296

Corticosteroid treatment and timing of surgery in idiopathic granulomatous mastitis confusing with breast carcinoma.

PubMed

Erozgen, Fazilet; Ersoy, Yeliz E; Akaydin, Murat; Memmi, Naim; Celik, Aysun Simsek; Celebi, Fatih; Guzey, Deniz; Kaplan, Rafet

2010-09-01

Idiopathic granulomatous mastitis (IGM) is an uncommon chronic inflammatory lesion of the breast with an uncertain optimal treatment regimen, the physical examination, and radiologic features of which may be confused with breast carcinoma. In this study, we aimed to describe the clinicopathologic characteristics of 33 patients who admitted to our breast policlinic and took the diagnosis of granulomatous (idiopathic and non-idiopathic) mastitis, and report the place of corticosteroids and the timing of surgery in the treatment of patients with IGM. The clinical features of 33 patients who presented to our breast policlinic with the complaint of breast mass and reached the final diagnosis of GM between March 2005 and October 2009 were reported. The most common symptoms were mass (n: 27) and pain (n: 11). Ultrasonography (USG) and biopsy were performed in all of the patients. Mammography (MMG) was performed in 9, and magnetic resonance imaging (MRI) in 10 patients. The diagnosis of idiopathic lobular granulomatous mastitis (ILGM) was made in 25 patients and tuberculous mastitis (non-idiopathic GM) in the remaining 8 patients. Twenty-four patients received steroid treatment except one who was pregnant. After giving birth, she also received steroids. One of the patients who developed recurrence after 11 months repeated the steroid therapy. Eight patients with tuberculous mastitis were placed on a regimen of antituberculosis therapy for 6 months. In the diagnosis of IGM, physical examination, USG, MMG, and even MRI alone may sometimes not be enough. They should be discussed altogether and the treatment should begin after definitive histopathologic result. Fine needle aspiration biopsy for cytology will result in a high level of diagnostic accuracy, however, core biopsy will reinforce the exact result. Corticosteroid therapy has been shown to be efficacious for IGM, but in the existence of complications such as abscess formation, fistulae, and persistent wound infection, surgical treatment has been the first method of choice.

High-definition vs. standard-definition colonoscopy in the characterization of small colonic polyps: results from a randomized trial.

PubMed

Longcroft-Wheaton, G; Brown, J; Cowlishaw, D; Higgins, B; Bhandari, P

2012-10-01

The resolution of endoscopes has increased in recent years. Modern Fujinon colonoscopes have a charge-coupled device (CCD) pixel density of 650,000 pixels compared with the 410,000 pixel CCD in standard-definition scopes. Acquiring high-definition scopes represents a significant capital investment and their clinical value remains uncertain. The aim of the current study was to investigate the impact of high-definition endoscopes on the in vivo histology prediction of colonic polyps. Colonoscopy procedures were performed using Fujinon colonoscopes and EPX-4400 processor. Procedures were randomized to be performed using either a standard-definition EC-530 colonoscope or high-definition EC-530 and EC-590 colonoscopes. Polyps of <10 mm were assessed using both white light imaging (WLI) and flexible spectral imaging color enhancement (FICE), and the predicted diagnosis was recorded. Polyps were removed and sent for histological analysis by a pathologist who was blinded to the endoscopic diagnosis. The predicted diagnosis was compared with the histology to calculate the accuracy, sensitivity, and specificity of in vivo assessment using either standard or high-definition scopes. A total of 293 polyps of <10 mm were examined–150 polyps using the standard-definition colonoscope and 143 polyps using high-definition colonoscopes. There was no difference in sensitivity, specificity or accuracy between the two scopes when WLI was used (standard vs. high: accuracy 70% [95% CI 62–77] vs. 73% [95% CI 65–80]; P=0.61). When FICE was used, high-definition colonoscopes showed a sensitivity of 93% compared with 83% for standard-definition colonoscopes (P=0.048); specificity was 81% and 82%, respectively. There was no difference between high- and standard-definition colonoscopes when white light was used, but FICE significantly improved the in vivo diagnosis of small polyps when high-definition scopes were used compared with standard definition.

Heart failure: a weak link in CHA2 DS2 -VASc.

PubMed

Friberg, Leif; Lund, Lars H

2018-06-01

In atrial fibrillation, stroke risk is assessed by the CHA 2 DS 2 -VASc score. Heart failure is included in CHA 2 DS 2 -VASc, but the rationale is uncertain. Our objective was to test if heart failure is a risk factor for stroke, independent of other risk factors in CHA 2 DS 2 -VASc. We studied 300 839 patients with atrial fibrillation in the Swedish Patient Register 2005-11. Three definitions of heart failure were used in order to assess the robustness of the results. In the main analysis, heart failure was defined by a hospital discharge diagnosis of heart failure as first or second diagnosis and a filled prescription of a diuretic within 3 months before index + 30 days. The second definition counted first or second discharge diagnoses <1 year before index + 30 days and the third definition any heart failure diagnosis in open or hospital care before index + 30 days. Associations with outcomes were assessed with multivariable Cox analyses. Patients with heart failure were older (80.5 vs. 74.0 years, P < 0.001) and had higher CHA 2 DS 2 -VASc score (4.4 vs. 2.7, P < 0.001). The 1 year incidence of ischaemic stroke without warfarin was 4.4% with heart failure and 3.1% without. Adjustment for the cofactors in CHA 2 DS 2 -VASc eradicated the difference in stroke risk between patients with and without heart failure (hazard ratio 1.01 with 95% confidence interval 0.96-1.05). The area under the receiver operating characteristic curve for CHA 2 DS 2 -VASc was not improved by points for heart failure. A clinical diagnosis of heart failure was not an independent risk factor for stroke in patients with atrial fibrillation, which may have implications for anticoagulation management. © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

[Evaluation of T-SPOT.TB assay in the diagnosis of pulmonary tuberculosis within different age groups].

PubMed

Pan, Liping; Jia, Hongyan; Liu, Fei; Gao, Mengqiu; Sun, Huishan; Du, Boping; Sun, Qi; Xing, Aiying; Wei, Rongrong; Zhang, Zongde

2015-12-01

To evaluate the value of T-SPOT.TB assay in the diagnosis of pulmonary tuberculosis within different age groups. We analyzed 1 518 suspected pulmonary tuberculosis (PTB) patients who were admitted to the Beijing Chest Hospital from November 2012 to February 2014 and had valid T-SPOT.TB tests before anti-tuberculosis therapy. The 599 microbiologically and/or histopathologically-confirmed PTB patients (16-89 years old, 388 males and 211 females) and 235 non-TB patients (14-85 years old, 144 males and 91 females) were enrolled for the analysis of diagnostic performance of T-SPOT.TB, while patients with uncertain diagnosis or diagnosis based on clinical impression (n=684) were excluded from the analysis. The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio of the T-SPOT.TB were analyzed according to the final diagnosis. Furthermore, the diagnostic performance of T-SPOT.TB assay in the younger patients (14-59 years old) and elderly patients (60-89 years old) were also analyzed respectively. Categorical variables were compared by Pearson's Chi-square test, while continuous variables were compared by the Mann-Whitney U-test. The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio of the T-SPOT.TB in diagnosis of PTB were 90.1% (540/599), 65.5% (154/235), 86.9% (540/621), 72.3% (154/213), 2.61, and 0.15, respectively. The sensitivity and specificity of T-SPOT.TB assay were 92.6% (375/405) and 75.6% (99/131), respectively in the younger patients, and 85.0% (165/194), 52.9% (55/104) respectively in the elderly patients. The sensitivity and specificity of T-SPOT.TB assay in the younger patients were significantly higher than those in the elderly patients (P<0.01), and the spot forming cells in the younger PTB patients were significantly higher than in the elderly PTB patients [300 (126, 666)/10(6) PBMCs vs. 258 (79, 621)/10(6) PBMCs, P=0.037]. T-SPOT.TB is a promising test in the diagnosis of younger patients (14-59 years old) with suspected PTB, but the diagnostic performance in elderly patients (60-89 years old) is relatively reduced.

Flat Urothelial Lesions With Atypia: Interobserver Concordance and Added Value of Immunohistochemical Profiling.

PubMed

Lawless, Margaret E; Tretiakova, Maria S; True, Lawrence D; Vakar-Lopez, Funda

2018-03-01

Distinguishing urothelial carcinoma in situ (CIS) from other flat lesions of the urinary bladder with cytologic atypia is critically important for the management of patients with bladder neoplasia. However, there is high interpathologist variability in making these distinctions. The aim of this study is to assess interobserver agreement between general and specialized genitourinary pathologists, and to compare these diagnoses with those rendered after an immunohistochemical panel is performed. We hypothesized that addition of a set of immunohistochemical stains would reduce the number of cases classified within intermediate categories of atypia of uncertain significance and low-grade dysplasia. Two genitourinary pathologists independently assessed haematoxylin and eosin (H&E)-stained sections of 127 bladder biopsies from each of the 4 International Society of Urological Pathology/World Health Organization categories of flat lesions diagnosed by general pathologists. A subset of biopsies from 49 patients was reassessed after staining with a 3-antibody panel (CD44, CK20, and p53) and the results were correlated with patient follow-up. Based on these immunohistochemistry (IHC) stains, 26 cases (53.1%) were recategorized. Of most clinical importance, 5 of 27 cases (18.5%) originally diagnosed as either atypia of uncertain significance or low-grade dysplasia were recategorized as CIS, and recurrent disease was identified on subsequent biopsies. None of the 10 cases diagnosed as CIS based on H&E stains were recategorized. This triad of IHC stains can improve the precision of pathologic diagnosis of histologically atypical urothelial lesions of flat bladder mucosa. We recommend that pathologists apply this set of IHC stains to such lesions they find problematic based on H&E stains.

Clinical course of untreated cerebral cavernous malformations: a meta-analysis of individual patient data.

PubMed

Horne, Margaret A; Flemming, Kelly D; Su, I-Chang; Stapf, Christian; Jeon, Jin Pyeong; Li, Da; Maxwell, Susanne S; White, Philip; Christianson, Teresa J; Agid, Ronit; Cho, Won-Sang; Oh, Chang Wan; Wu, Zhen; Zhang, Jun-Ting; Kim, Jeong Eun; Ter Brugge, Karel; Willinsky, Robert; Brown, Robert D; Murray, Gordon D; Al-Shahi Salman, Rustam

2016-02-01

Cerebral cavernous malformations (CCMs) can cause symptomatic intracranial haemorrhage (ICH), but the estimated risks are imprecise and predictors remain uncertain. We aimed to obtain precise estimates and predictors of the risk of ICH during untreated follow-up in an individual patient data meta-analysis. We invited investigators of published cohorts of people aged at least 16 years, identified by a systematic review of Ovid MEDLINE and Embase from inception to April 30, 2015, to provide individual patient data on clinical course from CCM diagnosis until first CCM treatment or last available follow-up. We used survival analysis to estimate the 5-year risk of symptomatic ICH due to CCMs (primary outcome), multivariable Cox regression to identify baseline predictors of outcome, and random-effects models to pool estimates in a meta-analysis. Among 1620 people in seven cohorts from six studies, 204 experienced ICH during 5197 person-years of follow-up (Kaplan-Meier estimated 5-year risk 15·8%, 95% CI 13·7-17·9). The primary outcome of ICH within 5 years of CCM diagnosis was associated with clinical presentation with ICH or new focal neurological deficit (FND) without brain imaging evidence of recent haemorrhage versus other modes of presentation (hazard ratio 5·6, 95% CI 3·2-9·7) and with brainstem CCM location versus other locations (4·4, 2·3-8·6), but age, sex, and CCM multiplicity did not add independent prognostic information. The 5-year estimated risk of ICH during untreated follow-up was 3·8% (95% CI 2·1-5·5) for 718 people with non-brainstem CCM presenting without ICH or FND, 8·0% (0·1-15·9) for 80 people with brainstem CCM presenting without ICH or FND, 18·4% (13·3-23·5) for 327 people with non-brainstem CCM presenting with ICH or FND, and 30·8% (26·3-35·2) for 495 people with brainstem CCM presenting with ICH or FND. Mode of clinical presentation and CCM location are independently associated with ICH within 5 years of CCM diagnosis. These findings can inform decisions about CCM treatment. UK Medical Research Council, Chief Scientist Office of the Scottish Government, and UK Stroke Association. Copyright © 2016 Horne et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.

Empirical Support for DSM-IV Schizoaffective Disorder: Clinical and Cognitive Validators from a Large Patient Sample

PubMed Central

DeRosse, Pamela; Burdick, Katherine E.; Lencz, Todd; Siris, Samuel G.; Malhotra, Anil K.

2013-01-01

Objective The diagnosis of schizoaffective disorder has long maintained an uncertain status in psychiatric nosology. Studies comparing clinical and biological features of patients with schizoaffective disorder to patients with related disorders [e.g., schizophrenia and bipolar disorder] can provide an evidence base for judging the validity of the diagnostic category. However, because most prior studies of schizoaffective disorder have only evaluated differences between groups at a static timepoint, it is unclear how these disorders may be related when the entire illness course is taken into consideration. Methods We ascertained a large cohort [N = 993] of psychiatric patients with a range of psychotic diagnoses including schizophrenia with no history of major affective episodes [SZ−; N = 371], schizophrenia with a superimposed mood syndrome [SZ+; N = 224], schizoaffective disorder [SAD; N = 129] and bipolar I disorder with psychotic features [BPD+; N = 269]. Using cross-sectional data we designed key clinical and neurocognitive dependent measures that allowed us to test longitudinal hypotheses about the differences between these diagnostic entities. Results Large differences between diagnostic groups on several demographic and clinical variables were observed. Most notably, groups differed on a putative measure of cognitive decline. Specifically, the SAD group demonstrated significantly greater post-onset cognitive decline compared to the BP+ group, with the SZ− and SZ+ group both exhibiting levels of decline intermediate to BPD+ and SAD. Conclusions These results suggest that schizoaffective disorder may possess distinct features. Contrary to earlier formulations, schizoaffective disorder may be a more severe form of illness. PMID:23737946

Empirical support for DSM-IV schizoaffective disorder: clinical and cognitive validators from a large patient sample.

PubMed

DeRosse, Pamela; Burdick, Katherine E; Lencz, Todd; Siris, Samuel G; Malhotra, Anil K

2013-01-01

The diagnosis of schizoaffective disorder has long maintained an uncertain status in psychiatric nosology. Studies comparing clinical and biological features of patients with schizoaffective disorder to patients with related disorders [e.g., schizophrenia and bipolar disorder] can provide an evidence base for judging the validity of the diagnostic category. However, because most prior studies of schizoaffective disorder have only evaluated differences between groups at a static timepoint, it is unclear how these disorders may be related when the entire illness course is taken into consideration. We ascertained a large cohort [N = 993] of psychiatric patients with a range of psychotic diagnoses including schizophrenia with no history of major affective episodes [SZ-; N = 371], schizophrenia with a superimposed mood syndrome [SZ+; N = 224], schizoaffective disorder [SAD; N = 129] and bipolar I disorder with psychotic features [BPD+; N = 269]. Using cross-sectional data we designed key clinical and neurocognitive dependent measures that allowed us to test longitudinal hypotheses about the differences between these diagnostic entities. Large differences between diagnostic groups on several demographic and clinical variables were observed. Most notably, groups differed on a putative measure of cognitive decline. Specifically, the SAD group demonstrated significantly greater post-onset cognitive decline compared to the BP+ group, with the SZ- and SZ+ group both exhibiting levels of decline intermediate to BPD+ and SAD. These results suggest that schizoaffective disorder may possess distinct features. Contrary to earlier formulations, schizoaffective disorder may be a more severe form of illness.

Forward chaining method on diagnosis of diseases and pests corn crop

NASA Astrophysics Data System (ADS)

Nurlaeli, Subiyanto

2017-03-01

Integrated pest management should be done to control the explosion of plants pest and diseases due to climate change is uncertain. This paper is a present implementation of the forward chaining method in the diagnosis diseases and pests of corn crop to help farmers/agricultural facilitators in getting knowledge about disease and pest corn crop. Forward chaining method as inference engine is used to get a disease/pest that attacks the corn crop based on symptoms. The forward chaining method works based on the fact that there is to get a conclusion. Fact in this system derived from the symptoms of the selected user is matched with the premise on every rule in the knowledge base. A rule that matches the facts to be executed to be the conclusion in the form of diagnosis. This validation using 36 data test, 32 data showed the same diagnostic results between systems with an expert. So, the percentage accuracy of results of diagnosis using data test of 88%. Finally, it can be concluded that the diagnosis system of diseases and pests corn crop can be used to help farmers/agricultural facilitators to diagnose diseases and pests corn crop.

Evidence of a polyclonal nature of myositis ossificans.

PubMed

Leithner, Andreas; Weinhaeusel, Andreas; Zeitlhofer, Petra; Koch, Horst; Radl, Roman; Windhager, Reinhard; Beham, Alfred; Haas, Oskar A

2005-04-01

Myositis ossificans is a localized, self-limiting, reparative lesion that is composed of reactive hypercellular fibrous tissue and bone. Although it is clearly a benign lesion, its clinical, radiological, and histological appearance may sometimes mimic a malignant tumor. Whether myositis ossificans represents a monoclonal or polyclonal hyperplastic proliferation is not yet known. To address this question, we therefore extracted DNA from the respective paraffin-embedded tumor tissues of nine women with a median age of 50 years at diagnosis (range: 20-84 years) and studied the X inactivation pattern by means of methylation-sensitive polymerase chain reaction and primers that target the polymorphic CGG trinucleotide repeat of the FMR1 gene. The fact that we did not detect any skewing of the X inactivation pattern in the five successfully analyzed cases corroborates the notion that myositis ossificans results from a polyclonal proliferation and confirms that it is a reactive, reparative process. Analysis of the X inactivation pattern may, thus, supplement the differential diagnostic work-up of cases with an uncertain histology, at least in the informative proportion of female patients.

Pleomorphic Hyalinizing Angiectatic Tumour: A Rare Case Report and Discussion of Differential Diagnosis

PubMed Central

Arakeri, Surekha U; Javalgi, Anita P; Goyal, Shefali

2017-01-01

Pleomorphic Hyalinizing Angiectatic Tumour (PHAT) is one of the rare soft tissue tumour which is non-metastasizing. The origin of this tumour is yet uncertain. It occurs in adults as a slow growing subcutaneous mass mimicking clinically and histologically to various benign and malignant soft tissue tumours such as schwannoma, haemangioma and malignant fibrous histiocytoma. The microscopic features of this tumour include clusters of ectatic, fibrin containing, hyalinized blood vessels with pleomorphic and spindle shaped tumour cells showing intranuclear inclusions, stromal haemosiderin pigment and a variable inflammatory infiltrate. Despite marked pleomorphism, the lesion behaves as a low grade neoplasm, with frequent recurrences, but no metastases. The incidence of this tumour is very rare with less than 100 cases being published. Hence, awareness of this entity is must for proper management of the patient and to avoid misdiagnosis of the lesion. We report a case of pleomorphic hyalinizing angiectatic tumour in a 50-year-old man who presented with a slow growing mass in the left calf region since two years. PMID:28969147

Pre-hospitalization, hospitalization, and post-hospitalization costs of patients with neurocysticercosis treated at the Instituto Nacional de Neurologia y Neurocirugia (INNN) in Mexico City, Mexico.

PubMed

Bhattarai, Rachana; Carabin, Hélène; Flores-Rivera, Jose; Corona, Teresa; Proaño, Jefferson V; Flisser, Ana; Budke, Christine M

2018-01-01

The objective of this study was to estimate the direct costs associated with the diagnosis and treatment of neurocysticercosis (NCC) during pre-hospitalization, hospitalization, and post-hospitalization periods for 108 NCC patients treated at the Instituto Nacional de Neurologia y Neurocirugia (INNN) in Mexico City, Mexico. Information on clinical manifestations, diagnostic tests, hospitalizations, surgical procedures, prescription medication, and other treatments was collected via medical chart reviews. Uncertain values for costs and frequency of treatments were imputed using bootstrap techniques. The average per-patient pre-hospitalization and hospitalization costs were US$ 257 (95% CI: 185 - 329) and US$ 2,576 (95% CI: 2,244 - 2,908), respectively. Post-hospitalization costs tended to decrease over time, with estimates for the first five years post-hospitalization of US$ 475 (95% CI: 423 - 527), US$ 228 (95% CI: 167 - 288), US$ 157 (95% CI: 111 - 202), US$ 150 (95% CI: 106 - 204), and US$ 91 (95% CI: 27 - 154), respectively. NCC results in a significant economic burden for patients requiring hospitalization, with this burden continuing years post-hospitalization.

Mutant NDUFS3 subunit of mitochondrial complex I causes Leigh syndrome.

PubMed

Bénit, P; Slama, A; Cartault, F; Giurgea, I; Chretien, D; Lebon, S; Marsac, C; Munnich, A; Rötig, A; Rustin, P

2004-01-01

Respiratory chain complex I deficiency represents a genetically heterogeneous group of diseases resulting from mutations in mitochondrial or nuclear genes. Mutations have been reported in 13 of the 14 subunits encoding the core of complex I (seven mitochondrial and six nuclear genes) and these result in Leigh or Leigh-like syndromes or cardiomyopathy. In this study, a combination of denaturing high performance liquid chromatography and sequence analysis was used to study the NDUFS3 gene in a series of complex I deficient patients. Mutations found in this gene (NADH dehydrogenase iron-sulphur protein 3), coding for the seventh and last subunit of complex I core, were shown to cause late onset Leigh syndrome, optic atrophy, and complex I deficiency. A biochemical diagnosis of complex I deficiency on cultured amniocytes from a later pregnancy was confirmed through the identification of disease causing NDUFS3 mutations in these cells. While mutations in the NDUFS3 gene thus result in Leigh syndrome, a dissimilar clinical phenotype is observed in mutations in the NDUFV2 and NDUFS2 genes, resulting in encephalomyopathy and cardiomyopathy. The reasons for these differences are uncertain.

NegBio: a high-performance tool for negation and uncertainty detection in radiology reports.

PubMed

Peng, Yifan; Wang, Xiaosong; Lu, Le; Bagheri, Mohammadhadi; Summers, Ronald; Lu, Zhiyong

2018-01-01

Negative and uncertain medical findings are frequent in radiology reports, but discriminating them from positive findings remains challenging for information extraction. Here, we propose a new algorithm, NegBio, to detect negative and uncertain findings in radiology reports. Unlike previous rule-based methods, NegBio utilizes patterns on universal dependencies to identify the scope of triggers that are indicative of negation or uncertainty. We evaluated NegBio on four datasets, including two public benchmarking corpora of radiology reports, a new radiology corpus that we annotated for this work, and a public corpus of general clinical texts. Evaluation on these datasets demonstrates that NegBio is highly accurate for detecting negative and uncertain findings and compares favorably to a widely-used state-of-the-art system NegEx (an average of 9.5% improvement in precision and 5.1% in F1-score). https://github.com/ncbi-nlp/NegBio.

Validation of mobile eye-tracking as novel and efficient means for differentiating progressive supranuclear palsy from Parkinson's disease

PubMed Central

Marx, Svenja; Respondek, Gesine; Stamelou, Maria; Dowiasch, Stefan; Stoll, Josef; Bremmer, Frank; Oertel, Wolfgang H.; Höglinger, Günter U.; Einhäuser, Wolfgang

2012-01-01

Background: The decreased ability to carry out vertical saccades is a key symptom of Progressive Supranuclear Palsy (PSP). Objective measurement devices can help to reliably detect subtle eye movement disturbances to improve sensitivity and specificity of the clinical diagnosis. The present study aims at transferring findings from restricted stationary video-oculography (VOG) to a wearable head-mounted device, which can be readily applied in clinical practice. Methods: We investigated the eye movements in 10 possible or probable PSP patients, 11 Parkinson's disease (PD) patients, and 10 age-matched healthy controls (HCs) using a mobile, gaze-driven video camera setup (EyeSeeCam). Ocular movements were analyzed during a standardized fixation protocol and in an unrestricted real-life scenario while walking along a corridor. Results: The EyeSeeCam detected prominent impairment of both saccade velocity and amplitude in PSP patients, differentiating them from PD and HCs. Differences were particularly evident for saccades in the vertical plane, and stronger for saccades than for other eye movements. Differences were more pronounced during the standardized protocol than in the real-life scenario. Conclusions: Combined analysis of saccade velocity and saccade amplitude during the fixation protocol with the EyeSeeCam provides a simple, rapid (<20 s), and reliable tool to differentiate clinically established PSP patients from PD and HCs. As such, our findings prepare the ground for using wearable eye-tracking in patients with uncertain diagnoses. PMID:23248593

Carpal Tunnel Syndrome in Behçet's Disease.

PubMed

Lee, Jungsoo; Cho, Suhyun; Kim, Do Young; Zheng, Zhenlong; Park, Hoon; Bang, Dongsik

2015-07-01

Behçet's disease (BD) is a chronic inflammatory disease characterized by orogenital ulcers, skin and ocular lesions, in addition to articular, vascular, and neurologic symptoms. Carpal tunnel syndrome (CTS), can also occur in BD patients secondary to inflammation in the connective tissues, vessels, and tendons, as well as nerve involvement in BD itself. However, reports of patients who have CTS in BD are rare. The aim of this study was to evaluate the clinical characteristics of CTS in BD patients. Retrospective analysis of the medical records of 1750 BD patients, and 14 (0.8%) BD patients who were diagnosed with CTS was performed at the BD Specialty Clinic of Severance Hospital. Patient demographics, disease activity/severity for both diseases, and the clinical characteristics of CTS in BD were recorded and analyzed. All 14 BD patients with CTS were women. Twelve patients (85.7%) were diagnosed with active BD. The CTS was mild in 8 patients (57.2%), moderate in 3 patients (21.4%), and severe in 3 patients (21.4%). Ten patients (71.4%) had BD prior to the diagnosis of CTS, and these 10 patients all had active BD. CTS can occur as a result of the inflammation associated with BD and can also be the presenting symptom of nerve involvement in BD. CTS can also develop as the initial symptom of BD. Therefore, a higher degree of suspicion should be maintained for CTS in patients with BD and vice versa; however, the exact relationship is uncertain.

Pneumothorax caused by cystic and nodular lung metastases from a malignant uterine perivascular epithelioid cell tumor (PEComa).

PubMed

Okamoto, Shouichi; Komura, Moegi; Terao, Yasuhisa; Kurisaki-Arakawa, Aiko; Hayashi, Takuo; Saito, Tsuyoshi; Togo, Shinsaku; Shiokawa, Akira; Mitani, Keiko; Kobayashi, Etsuko; Kumasaka, Toshio; Takahashi, Kazuhisa; Seyama, Kuniaki

2017-01-01

Perivascular epithelioid cell tumors (PEComas) are mesenchymal neoplasms with immunoreactivity for both melanocytic and smooth muscle markers. PEComas occur at multiple sites, and malignant PEComas can undergo metastasis, recurrence and aggressive clinical courses. Although the lung is a common metastatic site of PEComas, they usually appear as multiple nodules but rarely become cystic or cavitary. Here, we describe a female patient whose lungs manifested multiple cystic, cavity-like and nodular metastases 3 years after the resection of uterine tumors tentatively diagnosed as epithelioid smooth muscle tumors with uncertain malignant potential. This patient's subsequent pneumothorax necessitated video-assisted thoracoscopic surgery, and examination of her resected lung specimens eventually led to correcting the diagnosis, i.e., to a PEComa harboring tuberous sclerosis complex 1 ( TSC1 ) loss-of-heterozygosity that originated in the uterus and then metastasized to the lungs. The administration of a gonadotropin-releasing hormone analogue later stabilized her clinical course. To the best of our knowledge, the present case is the first in the literature that associates PEComas with a TSC1 abnormality. Additionally, the pulmonary manifestations, including imaging appearance and pneumothorax, somewhat resembled those of lymphangioleiomyomatosis, a representative disease belonging to the PEComa family. Although PEComas are rare, clinicians, radiologists and pathologists should become aware of this disease entity, especially in the combined clinical setting of multiple cystic, cavity-like, nodular lesions on computed tomography of the chest and a past history of the tumor in the female reproductive system.

Auditory aura in nocturnal frontal lobe epilepsy: a red flag to suspect an extra-frontal epileptogenic zone.

PubMed

Ferri, Lorenzo; Bisulli, Francesca; Nobili, Lino; Tassi, Laura; Licchetta, Laura; Mostacci, Barbara; Stipa, Carlotta; Mainieri, Greta; Bernabè, Giorgia; Provini, Federica; Tinuper, Paolo

2014-11-01

To describe the anatomo-electro-clinical findings of patients with nocturnal hypermotor seizures (NHS) preceded by auditory symptoms, to evaluate the localizing value of auditory aura. Our database of 165 patients with nocturnal frontal lobe epilepsy (NFLE) diagnosis confirmed by videopolysomnography (VPSG) was reviewed, selecting those who reported an auditory aura as the initial ictal symptom in at least two NHS during their lifetime. Eleven patients were selected (seven males, four females). According to the anatomo-electro-clinical data, three groups were identified. Group 1 [defined epileptogenic zone (EZ)]: three subjects were studied with stereo-EEG. The EZ lay in the left superior temporal gyrus in two cases, whereas in the third case seizures arose from a dysplastic lesion located in the left temporal lobe. One of these three patients underwent left Heschl's gyrus resection, and is currently seizure-free. Group 2 (presumed EZ): three cases in which a presumed EZ was identified; in the left temporal lobe in two cases and in the left temporal lobe extending to the insula in one subject. Group 3 (uncertain EZ): five cases had anatomo-electro-clinical correlations discordant. This work suggests that auditory aura may be a helpful anamnestic feature suggesting an extra-frontal seizure origin. This finding could guide secondary investigations to improve diagnostic definition and selection of candidates for surgical treatment. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

[Microsurgical transplantation of bone tumors of uncertain prognosis in athymic nude mice].

PubMed

Duprez, A; Féry, A; Sommelet, J

1986-01-01

Eight cases of human bone or soft tissue tumours were transplanted to nude mice. After such transplants to nude mice which are immunologically deficient, the malignant tumors developed like benign tumours, but maintaining malignant cytological characteristics. The transplants of normal human tissues or of benign tumours decreased in size or remained stable. The technique allowed a change of an original diagnosis of osteosarcoma to a final diagnosis of chondrosarcoma. It made it possible to diagnose a benign osteoblastoma, the diagnosis of which was doubtful before the transplant between osteosarcoma and chondroblastoma. It was possible to diagnose the malignancy of a haemangiopericytoma of muscle. Two aggressive tumours--a non-ossifying fibroma and a giant-cell tumour--were rated as benign after transplantation. This technique also allowed a more precise diagnosis of the grade of one chondrosarcoma and one osteosarcoma. Finally, transplantation also made it possible to test the efficacy of chemotherapy. In a patient so treated, the extreme cell proliferation after transplantation to the nude mouse led to a change in the drugs administered.

Prenatal chromosomal microarray analysis in fetuses with congenital heart disease: a prospective cohort study.

PubMed

Wang, Yan; Cao, Li; Liang, Dong; Meng, Lulu; Wu, Yun; Qiao, Fengchang; Ji, Xiuqing; Luo, Chunyu; Zhang, Jingjing; Xu, Tianhui; Yu, Bin; Wang, Leilei; Wang, Ting; Pan, Qiong; Ma, Dingyuan; Hu, Ping; Xu, Zhengfeng

2018-02-01

Currently, chromosomal microarray analysis is considered the first-tier test in pediatric care and prenatal diagnosis. However, the diagnostic yield of chromosomal microarray analysis for prenatal diagnosis of congenital heart disease has not been evaluated based on a large cohort. Our aim was to evaluate the clinical utility of chromosomal microarray as the first-tier test for chromosomal abnormalities in fetuses with congenital heart disease. In this prospective study, 602 prenatal cases of congenital heart disease were investigated using single nucleotide polymorphism array over a 5-year period. Overall, pathogenic chromosomal abnormalities were identified in 125 (20.8%) of 602 prenatal cases of congenital heart disease, with 52.0% of them being numerical chromosomal abnormalities. The detection rates of likely pathogenic copy number variations and variants of uncertain significance were 1.3% and 6.0%, respectively. The detection rate of pathogenic chromosomal abnormalities in congenital heart disease plus additional structural anomalies (48.9% vs 14.3%, P < .0001) or intrauterine growth retardation group (50.0% vs 14.3%, P = .044) was significantly higher than that in isolated congenital heart disease group. Additionally, the detection rate in congenital heart disease with additional structural anomalies group was significantly higher than that in congenital heart disease with soft markers group (48.9% vs 19.8%, P < .0001). No significant difference was observed in the detection rates between congenital heart disease with additional structural anomalies and congenital heart disease with intrauterine growth retardation groups (48.9% vs 50.0%), congenital heart disease with soft markers and congenital heart disease with intrauterine growth retardation groups (19.8% vs 50.0%), or congenital heart disease with soft markers and isolated congenital heart disease groups (19.8% vs 14.3%). The detection rate in fetuses with congenital heart disease plus mild ventriculomegaly was significantly higher than in those with other types of soft markers (50.0% vs 15.6%, P < .05). Our study suggests chromosomal microarray analysis is a reliable and high-resolution technology and should be used as the first-tier test for prenatal diagnosis of congenital heart disease in clinical practice. Copyright © 2017 Elsevier Inc. All rights reserved.

Imaging in gynecological disease. 10: Clinical and ultrasound characteristics of decidualized endometriomas surgically removed during pregnancy.

PubMed

Mascilini, F; Moruzzi, C; Giansiracusa, C; Guastafierro, F; Savelli, L; De Meis, L; Epstein, E; Timor-Tritsch, I E; Mailath-Pokorny, M; Ercoli, A; Exacoustos, C; Benacerraf, B R; Valentin, L; Testa, A C

2014-09-01

To describe the clinical history and ultrasound findings in women with decidualized endometriomas surgically removed during pregnancy. In this retrospective study, women with a histological diagnosis of decidualized endometrioma during pregnancy who had undergone preoperative ultrasound examination were identified from the databases of seven ultrasound centers. The ultrasound appearance of the tumors was described on the basis of ultrasound images, ultrasound reports and research protocols (when applicable) by one author from each center using the terms and definitions of the International Ovarian Tumor Analysis (IOTA) group. In addition, two authors reviewed together available digital ultrasound images and used pattern recognition to describe the typical ultrasound appearance of decidualized endometriomas. Eighteen eligible women were identified. Median age was 34 (range, 20-43) years. Median gestational age at surgical removal of the decidualized endometrioma was 18 (range, 11-41) weeks. Seventeen women (94%) were asymptomatic and one presented with pelvic pain. In three of the 18 women an ultrasound diagnosis of endometrioma had been made before pregnancy. The original ultrasound examiner was uncertain whether the mass was benign or malignant in 10 (56%) women and suggested a diagnosis of benignity in nine (50%) women, borderline in eight women (44%), and invasive malignancy in one (6%) woman. Seventeen decidualized endometriomas contained a papillary projection, and in 16 of these at least one of the papillary projections was vascularized at power or color Doppler examination. The number of cyst locules varied between one (n = 11) and four. No woman had ascites. When using pattern recognition, most decidualized endometriomas (14/17, 82%) were described as manifesting vascularized rounded papillary projections with a smooth contour in an ovarian cyst with one or a few cyst locules and ground-glass or low-level echogenicity of the cyst fluid. Rounded vascularized papillary projections with smooth contours within an ovarian cyst with cyst contents of ground-glass or low-level echogenicity are typical of surgically removed decidualized endometriomas in pregnant women, most of whom are asymptomatic. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

The impact of eliminating age inequalities in stage at diagnosis on breast cancer survival for older women.

PubMed

Rutherford, M J; Abel, G A; Greenberg, D C; Lambert, P C; Lyratzopoulos, G

2015-03-31

Older women with breast cancer have poorer relative survival outcomes, but whether achieving earlier stage at diagnosis would translate to substantial reductions in mortality is uncertain. We analysed data on East of England women with breast cancer (2006-2010) aged 70+ years. We estimated survival for different stage-deprivation-age group strata using both the observed and a hypothetical stage distribution (assuming that all women aged 75+ years acquired the stage distribution of those aged 70-74 years). We subsequently estimated deaths that could be postponed beyond 5 years from diagnosis if women aged 75+ years had the hypothetical stage distribution. We projected findings to the English population using appropriate age and socioeconomic group weights. For a typically sized annual cohort in the East of England, 27 deaths in women with breast cancer aged 75+ years can be postponed within 5 years from diagnosis if their stage distribution matched that of the women aged 70-74 years (4.8% of all 566 deaths within 5 years post diagnosis in this population). Under assumptions, we estimate that the respective number for England would be 280 deaths (5.0% of all deaths within 5 years post diagnosis in this population). The findings support ongoing development of targeted campaigns aimed at encouraging prompt presentation in older women.

Differential associations of affective temperaments and diagnosis of major affective disorders with suicidal behavior.

PubMed

Baldessarini, Ross J; Innamorati, Marco; Erbuto, Denise; Serafini, Gianluca; Fiorillo, Andrea; Amore, Mario; Girardi, Paolo; Pompili, Maurizio

2017-03-01

Affective temperaments are associated with suicidal risk, but their predictive value relative to diagnosis of major affective disorder is uncertain. We compared diagnoses, affective-temperament ratings (TEMPS-A), and other potential risk factors in 956 psychiatric inpatients, using bivariate analyses and multivariable logistic regression modeling for associations with suicidal status. Lifetime suicide-attempt rates were high (43.9% overall), ranking by diagnosis: bipolar-II (58.4%), major depressive (50.0%), bipolar-I (44.6%), other (38.0%), and psychotic (33.9%) disorders. TEMPS-A scores for depressive (dep), cyclothymic (cyc), irritable (irr), and anxious (anx) temperaments and their sum were strongly associated with suicidal risk; hyperthymic (hyp) temperament scores were inversely associated; and a composite measure (dep+cyc+irr+anx - hyp), even more strongly associated. The composite score was highly, independently associated with suicidal behavior (p<0.0001), as was female sex (p=0.0002), but older age and diagnosis of major affective disorder, much less (both p=0.02). Measures of affective temperament-types were independently and more strongly associated with lifetime suicide attempt than was diagnosis of a major affective disorder. However, in this hospitalized cohort, suicide rates were high across diagnoses, possibly limiting the predictive value of diagnosis. Copyright © 2016 Elsevier B.V. All rights reserved.

The heterogeneous management of pediatric ankle traumas: A retrospective descriptive study.

PubMed

Voizard, Philippe; Moore, James; Leduc, Stéphane; Nault, Marie-Lyne

2018-06-01

Frequent misdiagnosis of pediatric ankle traumas leads to inappropriate management, which may result in residual pain, instability, slower return to physical activity, and long-term degenerative changes. The purpose of this study was to evaluate the consistency of diagnosis, management, and the treatment of acute lateral pediatric ankle trauma in a tertiary care pediatric hospital. The hypothesis was that the initial diagnosis is often incorrect, and the treatment varies considerably amongst orthopedic surgeons.We conducted a retrospective study of all cases of ankle sprains and Salter-Harris one (SH1) fractures referred to our orthopedic surgery service between May and August 2014. Exclusion criteria included ankle fractures other than SH1 types, and cases where treatment was initially undertaken elsewhere before referral to our service. Primary outcome was the difference between initial and final diagnosis.Among 3047 cases reviewed, 31 matched our inclusion criteria. Initial diagnosis was 20 SH1 fractures, 8 acute ankle sprains, and 3 uncertain, with a change in diagnosis for 48.5% at follow-up.Accurate diagnosis can be difficult in pediatric ankle trauma, with case management and specific treatments varying considerably. This study reinforces the need to evaluate the safety of a general treatment algorithm for all lateral ankle trauma with normal radiographs.Level of evidence III.

ACCF/ASNC/ACR/AHA/ASE/SCCT/SCMR/SNM 2009 appropriate use criteria for cardiac radionuclide imaging: a report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, the American Society of Nuclear Cardiology, the American College of Radiology, the American Heart Association, the American Society of Echocardiography, the Society of Cardiovascular Computed Tomography, the Society for Cardiovascular Magnetic Resonance, and the Society of Nuclear Medicine.

PubMed

Hendel, Robert C; Berman, Daniel S; Di Carli, Marcelo F; Heidenreich, Paul A; Henkin, Robert E; Pellikka, Patricia A; Pohost, Gerald M; Williams, Kim A

2009-06-09

The American College of Cardiology Foundation (ACCF), along with key specialty and subspecialty societies, conducted an appropriate use review of common clinical scenarios where cardiac radionuclide imaging (RNI) is frequently considered. This document is a revision of the original Single-Photon Emission Computed Tomography Myocardial Perfusion Imaging (SPECT MPI) Appropriateness Criteria, published 4 years earlier, written to reflect changes in test utilization and new clinical data, and to clarify RNI use where omissions or lack of clarity existed in the original criteria. This is in keeping with the commitment to revise and refine appropriate use criteria (AUC) on a frequent basis. The indications for this review were drawn from common applications or anticipated uses, as well as from current clinical practice guidelines. Sixty-seven clinical scenarios were developed by a writing group and scored by a separate technical panel on a scale of 1 to 9 to designate appropriate use, inappropriate use, or uncertain use. In general, use of cardiac RNI for diagnosis and risk assessment in intermediate- and high-risk patients with coronary artery disease (CAD) was viewed favorably, while testing in low-risk patients, routine repeat testing, and general screening in certain clinical scenarios were viewed less favorably. Additionally, use for perioperative testing was found to be inappropriate except for high selected groups of patients. It is anticipated that these results will have a significant impact on physician decision making, test performance, and reimbursement policy, and will help guide future research.

The overuse of serum ceruloplasmin measurement.

PubMed

Tapper, Elliot B; Rahni, David O; Arnaout, Ramy; Lai, Michelle

2013-10-01

Wilson disease is rare, found in 3 of 100,000 people (0.03%). Ceruloplasmin is often ordered to evaluate liver enzyme elevations. Because Wilson disease often presents before middle-age, the American Association for the Study of Liver Disease recommends screening patients between the ages of 3 and 55 years with liver abnormalities of uncertain cause. We evaluate guideline adherence and the clinical and economic impact of current clinical use of ceruloplasmin. We reviewed all ceruloplasmin measurements at a clinical laboratory that serves a large primary care network, specialty clinics, and a 600-bed tertiary referral center between January 1, 2003, and December 12, 2011. Ceruloplasmin was measured 5325 times in 5023 unique patients, resulting in 8 (0.16%) new Wilson disease diagnoses. Ceruloplasmin's positive predictive value was 8.4% (95% confidence interval, 7.7-9.3) and false-positive rate was 98.1% (95% confidence interval, 96.2-99.1). A total of 1109 ceruloplasmin levels (20.8%) were ordered in the 1066 patients aged more than 55 years (none with Wilson disease). A "shotgun" approach to liver disease diagnosis was found: Ceruloplasmin was ordered on the same day as hepatitis B (81.0%), hepatitis C (76.0%), autoimmune hepatitis (75.1%), and hemochromatosis (73.1%). Of 424 positive ceruloplasmin results, 91% were not pursued further. Guideline adherence restricts ceruloplasmin use to a population with a higher pre-test probability of Wilson disease: patients with chronic liver disease aged 3 to 55 years who have been tested for common causes of liver disease. The majority of the serum ceruloplasmin was measured in patients not indicated by the guidelines, resulting in poor test performance and wasted healthcare resources. Our data on ceruloplasmin use could serve as a touchstone for broader discussions on rational clinical decision making. Copyright © 2013 Elsevier Inc. All rights reserved.

Perceived Barriers and Facilitators to Positive Therapeutic Change for People with Intellectual Disabilities: Client, Carer and Clinical Psychologist Perspectives

ERIC Educational Resources Information Center

Ramsden, Sarah; Tickle, Anna; Dawson, David L.; Harris, Samantha

2016-01-01

Studies have highlighted successful outcomes of psychological therapies for people with intellectual disabilities. However, processes underlying these outcomes are uncertain. Thematic analysis was used to explore the perceptions of three clinical psychologists, six clients and six carers of barriers and facilitators to therapeutic change for…

Gender Differences in Structured Risk Assessment: Comparing the Accuracy of Five Instruments

ERIC Educational Resources Information Center

Coid, Jeremy; Yang, Min; Ullrich, Simone; Zhang, Tianqiang; Sizmur, Steve; Roberts, Colin; Farrington, David P.; Rogers, Robert D.

2009-01-01

Structured risk assessment should guide clinical risk management, but it is uncertain which instrument has the highest predictive accuracy among men and women. In the present study, the authors compared the Psychopathy Checklist-Revised (PCL-R; R. D. Hare, 1991, 2003); the Historical, Clinical, Risk Management-20 (HCR-20; C. D. Webster, K. S.…

[Mycoplasma pneumoniae meningoencephalitis].

PubMed

Cambonie, G; Sarran, N; Leboucq, N; Luc, F; Bongrand, A F; Slim, G; Lassus, P; Fournier-Favre, S; Montoya, F; Astruc, J; Rieu, D

1999-03-01

Severe central nervous system diseases, such as encephalitis, have been reported in association with Mycoplasma pneumoniae infections. After an ENT infection, a 9-year-old boy with Down's syndrome developed encephalitis revealed by an acute alteration in consciousness. Head computed tomography showed, after 2 weeks, an infiltration in the basal ganglia region. The diagnosis of Mycoplasma pneumoniae encephalitis was made; recovery was complete in a few weeks. Mycoplasma pneumoniae infection should be considered in all cases of acute encephalopathy; yet the pathogenesis of the disorder is unknown and the treatment uncertain.

Toward patient-centered cancer care: patient perceptions of problematic events, impact, and response.

PubMed

Mazor, Kathleen M; Roblin, Douglas W; Greene, Sarah M; Lemay, Celeste A; Firneno, Cassandra L; Calvi, Josephine; Prouty, Carolyn D; Horner, Kathryn; Gallagher, Thomas H

2012-05-20

Cancer treatments are complex, involving multiple clinicians, toxic therapies, and uncertain outcomes. Consequently, patients are vulnerable when breakdowns in care occur. This study explored cancer patients' perceptions of preventable, harmful events; the impact of these events; and interactions with clinicians after such events. In-depth telephone interviews were conducted with cancer patients from three clinical sites. Patients were eligible if they believed: something "went wrong" during their cancer care; the event could have been prevented; and the event caused, or could have caused, significant harm. Interviews focused on patients' perceptions of the event, its impact, and clinicians' responses to the event. Ninety-three of 416 patients queried believed something had gone wrong in their care that was preventable and caused or could have caused harm. Seventy-eight patients completed interviews. Of those interviewed, 28% described a problem with medical care, such as a delay in diagnosis or treatment; 47% described a communication problem, including problems with information exchange or manner; and 24% described problems with both medical care and communication. Perceived harms included physical and emotional harm, disruption of life, effect on family members, damaged physician-patient relationship, and financial expense. Few clinicians initiated discussion of the problematic events. Most patients did not formally report their concerns. Cancer patients who believe they experienced a preventable, harmful event during their cancer diagnosis or care often do not formally report their concerns. Systems are needed to encourage patients to report such events and to help physicians and health care systems respond effectively.

1st Evidence-based Italian consensus conference on cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal carcinosis from ovarian cancer.

PubMed

Cavaliere, Davide; Cirocchi, Roberto; Coccolini, Federico; Fagotti, Anna; Fambrini, Massimiliano; Federici, Orietta; Lorusso, Domenica; Vaira, Marco; Ceresoli, Marco; Delrio, Paolo; Garofalo, Alfredo; Pignata, Sandro; Scollo, Paolo; Trojano, Vito; Amadori, Andrea; Ansaloni, Luca; Cariti, Giuseppe; De Cian, Franco; De Iaco, Pierandrea; De Simone, Michele; Deraco, Marcello; Donini, Annibale; Fiorentini, Giammaria; Frigerio, Luigi; Greggi, Stefano; Macrì, Antonio; Pasqual, Enrico Maria; Roviello, Franco; Sammartino, Paolo; Sassaroli, Cinzia; Scambia, Giovanni; Staudacher, Carlo; Vici, Patrizia; Vizza, Enrico; Valle, Mario

2017-11-23

Ovarian cancer (OC) remains relatively rare, although it is among the top 4 causes of cancer death for women younger than 50. The aggressive nature of the disease and its often late diagnosis with peritoneal involvement have an impact on prognosis. The current scientific literature presents ambiguous or uncertain indications for management of peritoneal carcinosis (PC) from OC, both owing to the lack of sufficient scientific data and their heterogeneity or lack of consistency. Therefore, the Italian Society of Surgical Oncology (SICO), the Italian Society of Obstetrics and Gynaecology, the Italian Association of Hospital Obstetricians and Gynaecologists, and the Italian Association of Medical Oncology conducted a multidisciplinary consensus conference (CC) on management of advanced OC presenting with PC during the SICO annual meeting in Naples, Italy, on September 10-11, 2015. An expert committee developed questions on diagnosis and staging work-up, indications, and procedural aspects for peritonectomy, systemic chemotherapy, and hyperthermic intraperitoneal chemotherapy for PC from OC. These questions were provided to 6 invited speakers who answered with an evidence-based report. Each report was submitted to a jury panel, representative of Italian experts in the fields of surgical oncology, gynecology, and medical oncology. The jury panel revised the reports before and after the open discussion during the CC. This article is the final document containing the clinical evidence reports and statements, revised and approved by all the authors before submission.

The differential diagnosis of tiredness: a systematic review.

PubMed

Stadje, Rebekka; Dornieden, Katharina; Baum, Erika; Becker, Annette; Biroga, Tobias; Bösner, Stefan; Haasenritter, Jörg; Keunecke, Christian; Viniol, Annika; Donner-Banzhoff, Norbert

2016-10-20

Tiredness is one of the most frequent complaints in primary care. Although often self-limiting and frequently associated with psychosocial stress, patients but also their physicians are often uncertain regarding a serious cause and appropriate diagnostic work-up. We conducted a systematic review and meta-analysis of studies reporting on differential diagnosis of fatigue in primary care. MEDLINE, EMBASE and conference abstracts were searched for primary care based studies of patients presenting with tiredness. Twenty-six studies were included. We report on anaemia, malignancy, serious organic disease, depression and the chronic fatigue syndrome (CFS) as causes of tiredness as presenting complaint. We found considerable heterogeneity of estimates which was reduced by limiting our analysis to high quality studies. Prevalences were as follows-anaemia: 2.8 % (CI (confidence interval) 1.6-4.8 %); malignancy: 0.6 % (CI 0.3-1.3 %); serious somatic disease: 4.3 % (CI 2.7-6.7 %); depression 18.5 % (CI 16.2-21.0 %). Pooling was not appropriate for CFS. In studies with control groups of patients without the symptom of tiredness, prevalence of somatic disease was identical to those complaining of tiredness. Depression, however, was more frequent among those with tiredness. Serious somatic disease is rare in patients complaining of tiredness. Since prevalence is similar in patients without tiredness, the association may not be causal. Extensive investigations are only warranted in case of specific findings from the history or clinical examination. Instead, attention should focus on depression and psychosocial problems.

Dyspareunia in a Teenager Reveals a Rare Occurrence: Retroperitoneal Cervical Leiomyoma of the Left Pararectal Space.

PubMed

Giannella, Luca; Mfuta, Kabala; Tuzio, Antonella; Cerami, Lillo Bruno

2016-02-01

Retroperitoneal uterine leiomyoma is a very rare occurrence and to discover it as a cause of female sexual dysfunction in a teen is unusual. An 18-year-old black woman reported deep dyspareunia, resulting in severe distress. Gynecological and instrumental examinations showed a pelvic mass of 7 cm in diameter. The preoperative diagnosis was uterine fibroid, but the exact location of the leiomyoma was uncertain. Laparoscopic examination showed a pedunculated retroperitoneal cervical leiomyoma in the left pararectal space. After surgical excision of the mass, normal sexual activity was restored. When a teen experiences pain with intercourse, pelvic masses should be part of differential diagnosis of dyspareunia. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Prune Belly syndrome: A rare case report

PubMed Central

Samal, Sunil Kumar; Rathod, Setu

2015-01-01

Prune Belly syndrome (PBS) is a rare congenital anomaly of uncertain etiology almost exclusive to males. We report a case of term male baby born to a 39-year-old grand multipara with previous four normal vaginal births. There was no history of genetic or congenital anomaly in her family. Examination of the baby revealed hypotonia, deficient abdominal muscle, cryptorchidism, palpable kidney, and bladder. Ultrasound examination of the abdomen revealed bilateral gross hydronephrosis and megaureter. Provisional diagnosis of PBS was made and the baby was admitted in neonatal intensive care units for further management. Routine antenatal care with ultrasonography will help in detecting renal anomalies, which can be followed postnatally. Early diagnosis of this syndrome and determining its optimal treatment are very important in helping to avoid its fatal course. PMID:25810678

"It wasn't a disaster or anything": Parents' experiences of their child's uncertain chromosomal microarray result.

PubMed

Wilkins, Ella J; Archibald, Alison D; Sahhar, Margaret A; White, Susan M

2016-11-01

Chromosomal microarray is an increasingly utilized diagnostic test, particularly in the pediatric setting. However, the clinical significance of copy number variants detected by this technology is not always understood, creating uncertainties in interpreting and communicating results. The aim of this study was to explore parents' experiences of an uncertain microarray result for their child. This research utilized a qualitative approach with a phenomenological methodology. Semi-structured interviews were conducted with nine parents of eight children who received an uncertain microarray result for their child, either a 16p11.2 microdeletion or 15q13.3 microdeletion. Interviews were transcribed verbatim and thematic analysis was used to identify themes within the data. Participants were unprepared for the abnormal test result. They had a complex perception of the extent of their child's condition and a mixed understanding of the clinical relevance of the result, but were accepting of the limitations of medical knowledge, and appeared to have adapted to the result. The test result was empowering for parents in terms of access to medical and educational services; however, they articulated significant unmet support needs. Participants expressed hope for the future, in particular that more information would become available over time. This research has demonstrated that parents of children who have an uncertain microarray result appeared to adapt to uncertainty and limited availability of information and valued honesty and empathic ongoing support from health professionals. Genetic health professionals are well positioned to provide such support and aid patients' and families' adaptation to their situation as well as promote empowerment. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Toxic epidermal necrolysis: Part II. Prognosis, sequelae, diagnosis, differential diagnosis, prevention, and treatment.

PubMed

Schwartz, Robert A; McDonough, Patrick H; Lee, Brian W

2013-08-01

Toxic epidermal necrolysis (TEN) is a life-threatening, typically drug-induced, mucocutaneous disease. TEN has a high mortality rate, making early diagnosis and treatment of paramount importance. New but experimental diagnostic tools that measure serum granulysin and high-mobility group protein B1 (HMGB1) offer the potential to differentiate early TEN from other, less serious drug reactions, but these tests have not been validated and are not readily available. The mainstay of treatment for TEN involves discontinuation of the offending drug, specialized care in an intensive care unit or burn center, and supportive therapy. Pharmacogenetic studies have clearly established a link between human leukocyte antigen allotype and TEN. Human leukocyte antigen testing should be performed on patients of East Asian descent before the initiation of carbamezapine and on all patients before the initiation of abacavir. The effectiveness of systemic steroids, intravenous immunoglobulins, plasmapheresis, cyclosporine, biologics, and other agents is uncertain. Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Somatic GNAQ mutation in the forme fruste of Sturge-Weber syndrome

PubMed Central

Harvey, A. Simon; Malone, Stephen; Damiano, John A.; Do, Hongdo; Ye, Zimeng; McQuillan, Lara; Maixner, Wirginia; Kalnins, Renate; Nolan, Bernadette; Wood, Martin; Ozturk, Ezgi; Jones, Nigel C.; Gillies, Greta; Pope, Kate; Lockhart, Paul J.; Dobrovic, Alexander; Leventer, Richard J.; Scheffer, Ingrid E.

2018-01-01

Objective To determine whether the GNAQ R183Q mutation is present in the forme fruste cases of Sturge-Weber syndrome (SWS) to establish a definitive molecular diagnosis. Methods We used sensitive droplet digital PCR (ddPCR) to detect and quantify the GNAQ mutation in tissues from epilepsy surgery in 4 patients with leptomeningeal angiomatosis; none had ocular or cutaneous manifestations. Results Low levels of the GNAQ mutation were detected in the brain tissue of all 4 cases—ranging from 0.42% to 7.1% frequency—but not in blood-derived DNA. Molecular evaluation confirmed the diagnosis in 1 case in which the radiologic and pathologic data were equivocal. Conclusions We detected the mutation at low levels, consistent with mosaicism in the brain or skin (1.0%–18.1%) of classic cases. Our data confirm that the forme fruste is part of the spectrum of SWS, with the same molecular mechanism as the classic disease and that ddPCR is helpful where conventional diagnosis is uncertain. PMID:29725622

Late-Onset ADHD: Understanding the Evidence and Building Theoretical Frameworks.

PubMed

Caye, Arthur; Sibley, Margaret H; Swanson, James M; Rohde, Luis Augusto

2017-11-13

The traditional definition of Attention-Deficit/Hyperactivity Disorder (ADHD), assuming onset in childhood, has been challenged by evidence from four recent birth-cohort studies that reported most adults with ADHD lacked a childhood categorical ADHD diagnosis. Late onset of symptoms was evaluated in the long-term follow-up of the Multimodal Treatment study of ADHD (MTA). In most cases, other factors were present that discounted the late onset of ADHD symptoms and excluded the diagnosis of ADHD. We offer two theoretical frameworks for understanding the ADHD trajectory throughout the life cycle: (1) the complex phenotype model, and (2) the restricted phenotype model. We conclude that (a) late onset (after age 12) is a valid trajectory for ADHD symptoms, (b) the percentage of these cases with onset after adolescence is yet uncertain, and (c) the percentage meeting exclusion criteria for diagnosis of ADHD is influenced by the rigor of the methodology used to obtain evidence and whether or not DSM exclusionary criteria are applied.

Fine motor skills in children with prenatal alcohol exposure or fetal alcohol spectrum disorder.

PubMed

Doney, Robyn; Lucas, Barbara R; Jones, Taryn; Howat, Peter; Sauer, Kay; Elliott, Elizabeth J

2014-01-01

Prenatal alcohol exposure (PAE) can cause fetal alcohol spectrum disorders (FASD) and associated neurodevelopmental impairments. It is uncertain which types of fine motor skills are most likely to be affected after PAE or which assessment tools are most appropriate to use in FASD diagnostic assessments. This systematic review examined which types of fine motor skills are impaired in children with PAE or FASD; which fine motor assessments are appropriate for FASD diagnosis; and whether fine motor impairments are evident at both "low" and "high" PAE levels. A systematic review of relevant databases was undertaken using key terms. Relevant studies were extracted using a standardized form, and methodological quality was rated using a critical appraisal tool. Twenty-four studies met inclusion criteria. Complex fine motor skills, such as visual-motor integration, were more frequently impaired than basic fine motor skills, such as grip strength. Assessment tools that specifically assessed fine motor skills more consistently identified impairments than those which assessed fine motor skills as part of a generalized neurodevelopmental assessment. Fine motor impairments were associated with "moderate" to "high" PAE levels. Few studies reported fine motor skills of children with "low" PAE levels, so the effect of lower PAE levels on fine motor skills remains uncertain. Comprehensive assessment of a range of fine motor skills in children with PAE is important to ensure an accurate FASD diagnosis and develop appropriate therapeutic interventions for children with PAE-related fine motor impairments.

Obesity is Associated with Atypia in Breast Ductal Lavage of Women with Proliferative Breast Disease

PubMed Central

Djuric, Zora; Edwards, Ann; Madan, Shashi; Darga, Linda; Ren, Jianwei; Koletsky, Mathew; Heilbrun, Lance K.

2009-01-01

Background Benign proliferative breast disease without atypia slightly increases breast cancer risk but there are currently few clinical options for breast cancer prevention in this group of women. Methods We conducted a pilot study of women with a past diagnosis of proliferative breast disease with a goal to determine if the characteristics of cells obtained by breast ductal lavage were related to nutritional factors. Results There were 57 women who enrolled. A total of 39 women yielded nipple aspirate fluid (NAF) samples and 36 underwent breast ductal lavage. Five of the lavage samples were acellular and 28 had at least 200 cells. Surprisingly, atypia was present in 11 women. Presence of atypia was associated with slight changes in morphometric features of the epithelial cells such as measures of circularity) as obtained by image analysis, but the only variable significantly different in women with atypia (versus no atypia) was a higher mean body mass index. Body mass index also was significantly correlated with C-reactive protein (CRP) levels in the nipple aspirate fluid, indicating that obesity might have a pro-inflammatory effect on the breast that can contribute to increased rates of atypia. Conclusions Although the clinical significance of atypia in breast ductal lavage is uncertain, these results support further work on prevention of obesity as a strategy for reducing breast cancer risk. PMID:19683484

Obesity is associated with atypia in breast ductal lavage of women with proliferative breast disease.

PubMed

Djuric, Zora; Edwards, Ann; Madan, Shashi; Darga, Linda; Ren, Jianwei; Blake, Cassann; Koletsky, Mathew; Heilbrun, Lance K

2009-10-01

Benign proliferative breast disease without atypia slightly increases breast cancer risk but there are currently few clinical options for breast cancer prevention in this group of women. We conducted a pilot study of women with a past diagnosis of proliferative breast disease with a goal to determine if the characteristics of cells obtained by breast ductal lavage were related to nutritional factors. There were 57 women who enrolled. A total of 39 women yielded nipple aspirate fluid (NAF) samples and 36 underwent breast ductal lavage. Five of the lavage samples were acellular and 28 had at least 200 cells. Surprisingly, atypia was present in 11 women. Presence of atypia was associated with slight changes in morphometric features of the epithelial cells such as measures of circularity as obtained by image analysis, but the only variable significantly different in women with atypia (versus no atypia) was a higher mean body mass index. Body mass index was also significantly correlated with C-reactive protein (CRP) levels in the nipple aspirate fluid, indicating that obesity might have a pro-inflammatory effect on the breast that can contribute to increased rates of atypia. Although the clinical significance of atypia in breast ductal lavage is uncertain, these results support further work on prevention of obesity as a strategy for reducing breast cancer risk.

[Hypotonic syndrome in the newborn infant].

PubMed

Gaona, Víctor Alejandro

2013-09-06

Hypotonia is understood to refer to a pronounced decrease in muscle tone that affects normal motor development and that may affect the axial muscles as well as those of the limbs and, sometimes, the face. It is a very challenging clinical picture because it consists in a fairly wide range of conditions that affect different areas of the central and peripheral nervous system and may be the expression of pathologies that can be either benign or of an uncertain prognosis. These cover myopathies, metabolic disorders, diseases based on genetic causes, pathologies affecting the endocrine glands and progressive or chronic diseases, among other aetiologies. The important development of medicine today has made a number of tools available to the examiner with which to refine or pronounce a diagnosis. Such instruments include the developments achieved in genetic research, together with studies conducted in imaging and optical and electronic microscopy. However, in spite of having all this material available for use, it is still the clinical features that allow a rational use to be made of these advances to be able to point towards the possible causation, topographic location and developmental control. It is useful, for the diagnostic approach and the use of auxiliary methods, to know the topographic location of the disorder, whether it is situated in the brain, the cerebellum, the stem, the spinal cord, the peripheral nerves, the myoneural junction or the muscle.

Targeted therapy by combined inhibition of the RAF and mTOR kinases in malignant spindle cell neoplasm harboring the KIAA1549-BRAF fusion protein.

PubMed

Subbiah, Vivek; Westin, Shannon N; Wang, Kai; Araujo, Dejka; Wang, Wei-Lien; Miller, Vincent A; Ross, Jeffrey S; Stephens, Phillip J; Palmer, Gary A; Ali, Siraj M

2014-01-14

Oncologic patients who are extreme responders to molecularly targeted therapy provide an important opportunity to better understand the biologic basis of response and, in turn, inform clinical decision making. Malignant neoplasms with an uncertain histologic and immunohistochemical characterization present challenges both on initial diagnostic workups and then later in management, as current treatment algorithms are based on a morphologic diagnosis. Herein, we report a case of a difficult to characterize sarcoma-like lesion for which genomic profiling with clinical next generation sequencing (NGS) identified the molecular underpinnings of arrested progression(stable disease) under combination targeted therapy within a phase I clinical trial. Genomic profiling with clinical next generation sequencing was performed on the FoundationOne™ platform (Foundation Medicine, Cambridge MA). Histopathology and immunohistochemical studies were performed in the Department of Pathology, MD Anderson Cancer Center (Houston, TX). Treatment was administered in the context of a phase I clinical trial ClinicalTrials.gov Identifier: (NCT01187199). The histology of the tumor was that of a spindle cell neoplasm, grade 2 by FNCLCC standards. Immunohistochemical staining was positive for S100 and CD34. Genomic profiling identified the following alterations: a KIAA1549-BRAF gene fusion resulting from a tandem duplication event, a homozygous deletion of PTEN, and frameshift insertion/deletions in CDKN2A A68fs*51, SUFU E283fs*3, and MAP3K1 N325fs*3. The patient had a 25% reduction in tumor (RECIST v1.1) following combination therapy consisting of sorafenib, temsirolimus, and bevazicumab within a phase I clinical trial. The patient responded to combination targeted therapy that fortuitously targeted KIAA1549-BRAF and PTEN loss within a spindle cell neoplasm, as revealed by genomic profiling based on NGS. This is the first report of a tumor driven by a KIAA1549-BRAF fusion responding to sorafenib-based combination therapy.

Criteria for the validity of clinical trials of treatments of cohorts of cancer patients based on the Hardin Jones principle.

PubMed Central

Pauling, L; Herman, Z S

1989-01-01

With the assumption of the validity of the Hardin Jones principle that the death rate of members of a homogeneous cohort of cancer patients is constant, three criteria for the validity of clinical trials of cancer treatments are formulated. These criteria are satisfied by most published clinical trials, but one trial was found to violate all three, rendering the validity of its reported results uncertain. PMID:2780542

Clinical Practice Guideline: Evaluation of the Neck Mass in Adults.

PubMed

Pynnonen, Melissa A; Gillespie, M Boyd; Roman, Benjamin; Rosenfeld, Richard M; Tunkel, David E; Bontempo, Laura; Brook, Itzhak; Chick, Davoren Ann; Colandrea, Maria; Finestone, Sandra A; Fowler, Jason C; Griffith, Christopher C; Henson, Zeb; Levine, Corinna; Mehta, Vikas; Salama, Andrew; Scharpf, Joseph; Shatzkes, Deborah R; Stern, Wendy B; Youngerman, Jay S; Corrigan, Maureen D

2017-09-01

Objective Neck masses are common in adults, but often the underlying etiology is not easily identifiable. While infections cause most of the neck masses in children, most persistent neck masses in adults are neoplasms. Malignant neoplasms far exceed any other etiology of adult neck mass. Importantly, an asymptomatic neck mass may be the initial or only clinically apparent manifestation of head and neck cancer, such as squamous cell carcinoma (HNSCC), lymphoma, thyroid, or salivary gland cancer. Evidence suggests that a neck mass in the adult patient should be considered malignant until proven otherwise. Timely diagnosis of a neck mass due to metastatic HNSCC is paramount because delayed diagnosis directly affects tumor stage and worsens prognosis. Unfortunately, despite substantial advances in testing modalities over the last few decades, diagnostic delays are common. Currently, there is only 1 evidence-based clinical practice guideline to assist clinicians in evaluating an adult with a neck mass. Additionally, much of the available information is fragmented, disorganized, or focused on specific etiologies. In addition, although there is literature related to the diagnostic accuracy of individual tests, there is little guidance about rational sequencing of tests in the course of clinical care. This guideline strives to bring a coherent, evidence-based, multidisciplinary perspective to the evaluation of the neck mass with the intention to facilitate prompt diagnosis and enhance patient outcomes. Purpose The primary purpose of this guideline is to promote the efficient, effective, and accurate diagnostic workup of neck masses to ensure that adults with potentially malignant disease receive prompt diagnosis and intervention to optimize outcomes. Specific goals include reducing delays in diagnosis of HNSCC; promoting appropriate testing, including imaging, pathologic evaluation, and empiric medical therapies; reducing inappropriate testing; and promoting appropriate physical examination when cancer is suspected. The target patient for this guideline is anyone ≥18 years old with a neck mass. The target clinician for this guideline is anyone who may be the first clinician whom a patient with a neck mass encounters. This includes clinicians in primary care, dentistry, and emergency medicine, as well as pathologists and radiologists who have a role in diagnosing neck masses. This guideline does not apply to children. This guideline addresses the initial broad differential diagnosis of a neck mass in an adult. However, the intention is only to assist the clinician with a basic understanding of the broad array of possible entities. The intention is not to direct management of a neck mass known to originate from thyroid, salivary gland, mandibular, or dental pathology as management recommendations for these etiologies already exist. This guideline also does not address the subsequent management of specific pathologic entities, as treatment recommendations for benign and malignant neck masses can be found elsewhere. Instead, this guideline is restricted to addressing the appropriate work-up of an adult patient with a neck mass that may be malignant in order to expedite diagnosis and referral to a head and neck cancer specialist. The Guideline Development Group sought to craft a set of actionable statements relevant to diagnostic decisions made by a clinician in the workup of an adult patient with a neck mass. Furthermore, where possible, the Guideline Development Group incorporated evidence to promote high-quality and cost-effective care. Action Statements The development group made a strong recommendation that clinicians should order a neck computed tomography (or magnetic resonance imaging) with contrast for patients with a neck mass deemed at increased risk for malignancy. The development group made the following recommendations: (1) Clinicians should identify patients with a neck mass who are at increased risk for malignancy because the patient lacks a history of infectious etiology and the mass has been present for ≥2 weeks without significant fluctuation or the mass is of uncertain duration. (2) Clinicians should identify patients with a neck mass who are at increased risk for malignancy based on ≥1 of these physical examination characteristics: fixation to adjacent tissues, firm consistency, size >1.5 cm, or ulceration of overlying skin. (3) Clinicians should conduct an initial history and physical examination for patients with a neck mass to identify those with other suspicious findings that represent an increased risk for malignancy. (4) For patients with a neck mass who are not at increased risk for malignancy, clinicians or their designees should advise patients of criteria that would trigger the need for additional evaluation. Clinicians or their designees should also document a plan for follow-up to assess resolution or final diagnosis. (5) For patients with a neck mass who are deemed at increased risk for malignancy, clinicians or their designees should explain to the patient the significance of being at increased risk and explain any recommended diagnostic tests. (6) Clinicians should perform, or refer the patient to a clinician who can perform, a targeted physical examination (including visualizing the mucosa of the larynx, base of tongue, and pharynx) for patients with a neck mass deemed at increased risk for malignancy. (7) Clinicians should perform fine-needle aspiration (FNA) instead of open biopsy, or refer the patient to someone who can perform FNA, for patients with a neck mass deemed at increased risk for malignancy when the diagnosis of the neck mass remains uncertain. (8) For patients with a neck mass deemed at increased risk for malignancy, clinicians should continue evaluation of patients with a cystic neck mass, as determined by FNA or imaging studies, until a diagnosis is obtained and should not assume that the mass is benign. (9) Clinicians should obtain additional ancillary tests based on the patient's history and physical examination when a patient with a neck mass is deemed at increased risk for malignancy who does not have a diagnosis after FNA and imaging. (10) Clinicians should recommend evaluation of the upper aerodigestive tract under anesthesia, before open biopsy, for patients with a neck mass deemed at increased risk for malignancy and without a diagnosis or primary site identified with FNA, imaging, and/or ancillary tests. The development group recommended against clinicians routinely prescribing antibiotic therapy for patients with a neck mass unless there are signs and symptoms of bacterial infection.

Differences in clinical condition and genotype at time of diagnosis of cystic fibrosis by newborn screening or by symptoms.

PubMed

Vernooij-van Langen, A M M; Gerzon, F L G R; Loeber, J G; Dompeling, E; Dankert-Roelse, J E

2014-01-01

Early diagnosis through newborn screening (NBS) and early treatment of cystic fibrosis (CF) do lead to better prognosis. In the Netherlands, the median age for a clinical diagnosis is six months, and after newborn screening this is 30 days. It is unknown if being diagnosed at the age of six months or before two months leads to a clinically relevant difference of the clinical condition at the time of diagnosis. The aim of this study is to assess the differences in clinical parameters at diagnosis between children with CF identified by newborn screening (NBS) or by clinical diagnosis (CD) in the Netherlands. From July 1st, 2007 to January 1st, 2012 all newly diagnosed CF patients were reported to the Dutch Paediatric Surveillance Unit (DPSU). All paediatricians received a questionnaire to collect data on mutations and clinical condition at diagnosis. Non-classical CF was excluded from the analysis on clinical condition. 204 new CF diagnoses were reported to the DPSU, 33 were reported twice and three had no CF after further testing. 127 questionnaires were returned (76%); 85 children were diagnosed because of clinical symptoms, 40 after NBS and two because of a positive family history. The median age at diagnosis was 34 weeks for a clinical diagnosis and 3 weeks after NBS. Non-classical CF was more prevalent in the NBS group (6 clinical, 14 NBS), mostly F508del/R117H7T (12). Compared to the NBS group, significantly more patients in the CD group showed failure to thrive, respiratory symptoms, and hospitalizations. 62% of the CD group showed abnormal signs at physical examination compared to 4% of the NBS group. At the time of diagnosis infants detected after NBS are in a significantly better condition than after a clinical diagnosis. Growth retardation is already seen when after NBS the diagnosis is confirmed, but NBS leads to a diagnosis before respiratory symptoms have developed. Copyright © 2014 Elsevier Inc. All rights reserved.

An application of actuarial methods in psychiatric diagnosis.

PubMed

Overall, J E; Higgins, C W

1977-10-01

An actuarial program for psychiatric diagnosis is evaluated for agreement with final clinical diagnosis in a series of 288 patients. The acturial program provides a probability differential diagnosis based on an analysis of history and background data, symptom rating profiles, and MMPI clinical scale profiles. The observed agreement with final clinical diagnosis is approximately 50% higher than previously reported for psychological testing in this same setting. The results emphasize the importance for psychologists of clinical interview and observation skills.

Use of Management Pathways or Algorithms in Children With Chronic Cough: Systematic Reviews.

PubMed

Chang, Anne B; Oppenheimer, John J; Weinberger, Miles; Weir, Kelly; Rubin, Bruce K; Irwin, Richard S

2016-01-01

Use of appropriate cough pathways or algorithms may reduce the morbidity of chronic cough, lead to earlier diagnosis of chronic underlying illness, and reduce unnecessary costs and medications. We undertook three systematic reviews to examine three related key questions (KQ): In children aged ?14 years with chronic cough (> 4 weeks' duration), KQ1, do cough management protocols (or algorithms) improve clinical outcomes? KQ2, should the cough management or testing algorithm differ depending on the duration and/or severity? KQ3, should the cough management or testing algorithm differ depending on the associated characteristics of the cough and clinical history? We used the CHEST expert cough panel's protocol. Two authors screened searches and selected and extracted data. Only systematic reviews, randomized controlled trials (RCTs), and cohort studies published in English were included. Data were presented in Preferred Reporting Items for Systematic Reviews and Meta-analyses flowcharts and summary tabulated. Nine studies were included in KQ1 (RCT = 1; cohort studies = 7) and eight in KQ3 (RCT = 2; cohort = 6), but none in KQ2. There is high-quality evidence that in children aged ?14 years with chronic cough (> 4 weeks' duration), the use of cough management protocols (or algorithms) improves clinical outcomes and cough management or the testing algorithm should differ depending on the associated characteristics of the cough and clinical history. It remains uncertain whether the management or testing algorithm should depend on the duration or severity of chronic cough. Pending new data, chronic cough in children should be defined as > 4 weeks' duration and children should be systematically evaluated with treatment targeted to the underlying cause irrespective of the cough severity. Copyright © 2016 American College of Chest Physicians. All rights reserved.

Opiate-sensitivity: clinical characteristics and the role of skin prick testing.

PubMed

Nasser, S M; Ewan, P W

2001-07-01

The value of skin prick testing in opiate-sensitive individuals is uncertain as opiates cause non-specific weals by direct degranulation of mast cells. To define whether skin prick test (SPT) responses to opiates in opiate-sensitive individuals are different to those seen in the normal population and to describe the clinical characteristics of this group of subjects. The SPT responses of eight opiate-sensitive subjects to morphine 10 mg/mL, pethidine (meperidine) 50 mg/mL and papaveretum 15.4 mg/mL at four different concentrations (undiluted, 1/10, 1/50 and 1/100) were compared with the responses of 100 (32 atopic) non-opiate-sensitive control subjects. Four of the opiate-sensitive subjects had a clinical history of asthma, rhinitis or urticaria on occupational exposure to morphine. One subject developed urticaria with codeine, one developed urticaria and asthma with morphine and diamorphine and two subjects reacted to intravenous papaveretum with anaphylaxis or urticaria. Five out of the eight cases had opiate sensitivity confirmed by single-blind placebo-controlled oral challenge. Skin prick tests to all three opiates were not significantly different when the eight opiate-sensitive subjects were compared with either the entire normal control group or the subgroup of 47 definite opiate-tolerant controls that had previously received opiates for clinical indications. Furthermore, there were no significant differences in size of opiate SPT responses between atopic and non-atopic control subjects. In the control subjects, there was a positive correlation in SPT weal size between the three opiates. Skin prick testing is not useful in the diagnosis of opiate sensitivity and placebo-controlled challenge should be considered.

Effect of clinical information and previous exam execution on observer agreement and reliability in the analysis of hysteroscopic video-recordings.

PubMed

Martinho, Margarida Suzel Lopes; da Costa Santos, Cristina Maria Nogueira; Silva Carvalho, João Luís Mendonça; Bernardes, João Francisco Montenegro Andrade Lima

2018-02-01

Inter-observer agreement and reliability in hysteroscopic image assessment remain uncertain and the type of factors that may influence it has only been studied in relation to the experience of hysteroscopists. We aim to assess the effect of clinical information and previous exam execution on observer agreement and reliability in the analysis of hysteroscopic video-recordings. Ninety hysteroscopies were video-recorded and randomized into a group without (Group 1) and with clinical information (Group 2). The videos were independently analyzed by three hysteroscopists, regarding lesion location, dimension, and type, as well as decision to perform a biopsy. One of the hysteroscopists had executed all the exams before. Proportions of agreement (PA) and kappa statistics (κ) with 95% confidence intervals (95% CI) were used. In Group 2, there was a higher proportion of a normal diagnosis (p < 0.001) and a lower proportion of biopsies recommended (p = 0.027). Observer agreement and reliability were better in Group 2, with the PA and κ ranging, respectively, from 0.73 (95% CI 0.62, 0.83) and 0.44 (95% CI 0.26, 0.63), for image quality, to 0.94 (95% CI 0.88, 0.99) and 0.85 (95% CI 0.65, 0.95), for the decision to perform a biopsy. Execution of the exams before the analysis of the video-recordings did not significantly affect the results. With clinical information, agreement and reliability in the overall analysis of hysteroscopic video-recordings may reach almost perfect results and this was not significantly affected by the execution of the exams before the analysis. However, there is still uncertainty in the analysis of specific endometrial cavity abnormalities.

Phyllodes Tumor of Breast: A Review Article

PubMed Central

Mishra, Shashi Prakash; Tiwary, Satyendra Kumar; Mishra, Manjaree; Khanna, Ajay Kumar

2013-01-01

Introduction. Phyllodes tumours are rare fibroepithelial lesions. Accurate preoperative pathological diagnosis allows correct surgical planning and avoidance of reoperation. Treatment can be either wide local excision or mastectomy to achieve histologically clear margins. Discussion. The exact aetiology of phyllodes tumour and its relationship with fibroadenoma are unclear. Women aged between 35 and 55 years are commonly involved. The median tumour size is 4 cm but can grow even larger having dilated veins and a blue discoloration over skin. Palpable axillary lymphadenopathy can be identified in up to 10–15% of patients but <1% had pathological positive nodes. Mammography and ultrasonography are main imaging modalities. Cytologically the presence of both epithelial and stromal elements supports the diagnosis. The value of FNAC in diagnosis of phyllodes tumour remains controversial, but core needle biopsy has high sensitivity and negative predictive value. Surgical management is the mainstay and local recurrence in phyllodes tumours has been associated with inadequate local excision. The role of adjuvant radiotherapy and chemotherapy remains uncertain and use of hormonal therapy has not been fully investigated. Conclusion. The preoperative diagnosis and proper management are crucial in phyllodes tumours because of their tendency to recur and malignant potential in some of these tumours. PMID:23577269

Histopathologic diagnosis of eosinophilic conditions in the gastrointestinal tract.

PubMed

Hurrell, Jennifer M; Genta, Robert M; Melton, Shelby D

2011-09-01

Eosinophils, a constitutive component of the columnar-lined gastrointestinal tract, play an essential role in allergic responses and parasitic infections. The tissue density of these cells also increases in a variety of conditions of uncertain etiology. With the exception of the esophageal squamous epithelium, in which no eosinophils are normally present, the population of normal eosinophils in the remainder of the luminal gut is poorly defined. Therefore, histopathologists must rely on their subjective judgment to determine when a diagnosis of eosinophilic gastritis, enteritis, or colitis should be rendered. Eosinophilic esophagitis is currently the best defined and most studied eosinophilic condition of the digestive tract; therefore, the confidence in accurate diagnosis is increasing. In contrast, the characteristic clinicopathologic features of eosinophilic conditions affecting other parts of the digestive tract remain somewhat elusive. This review was designed to present pathologists with simple and practical information for the biopsy-based histopathologic diagnosis of eosinophilic esophagitis, gastritis, enteritis, and colitis. It was prepared by critically reviewing more than 200 articles on the topic, along with incorporating evidence accumulated through our own collective experience. We anticipate that by increasing pathologists' confidence in reporting these abnormal but often nameless eosinophilic infiltrates, we can help better define and characterize their significance.

Surgical management of benign and indeterminate hepatic lesions in the era of laparoscopic liver surgery.

PubMed

Abu Hilal, Mohammed; Di Fabio, Francesco; Teng, Mabel Joey; Godfrey, Dean Anthony; Primrose, John Neil; Pearce, Neil William

2011-01-01

The expansion of the laparoscopic approach for the management of benign liver lesions has raised concerns regarding the risk of widening surgical indications and compromising safety. Large single-centre series focusing on laparoscopic management of benign liver lesions are sporadic. We reviewed a prospectively collected database of patients undergoing pure laparoscopic liver resection (LLR) for benign liver lesions. All cases were individually discussed at a multidisciplinary team meeting. Forty-six patients underwent 50 LLRs for benign disease. Indications for surgery were: symptomatic lesions, preoperative diagnosis of adenoma or cystadenoma, and lesions with an indeterminate diagnosis. The preoperative diagnosis was uncertain in 11 cases. Of these, histological diagnosis was hepatocellular carcinoma in one (9%) and benign lesion in 10 patients (91%). Thirteen patients (28%) required major hepatectomy. Three patients (7%) developed postoperative complications. Mortality was nil. The median postoperative hospital stay following major and minor hepatectomy was 4 and 3 days, respectively. The laparoscopic approach represents a safe option for the management of benign and indeterminate liver lesions, even when major hepatectomy is required. LLR should be only performed in specialized centres to ensure safety and strict adherence to orthodox surgical indication. Copyright © 2011 S. Karger AG, Basel.

[Tardive dyskinesia--diagnosis and treatment].

PubMed

Kazamatsuri, H

1993-11-01

Tardive dyskinesia is defined as a syndrome consisting of abnormal, stereotypical involuntary movements usually of choreoathetoid type, principally affected the mouth, face, limbs and trunk, which occurs relatively late in the course of neuroleptic drug treatment and in the etiology of which the drug treatment is a necessary factor. Presently, the prevalence of tardive dyskinesia in the hospitalized patients in psychiatric hospitals in Japan is estimated to be 20-30%. Epidemiology, possible pathophysiology and symptomatology of tardive dyskinesia are briefly described. Differential diagnosis between this syndrome and other involuntary movements such as psychotic mannerism, senile orofacial dyskinesia, rabbit's syndrome, Pisa syndrome or Meige's syndrome is discussed. Several drugs to suppress involuntary movements of tardive dyskinesia are described. However, there appears to be no consistently reliable therapies for patients who develop the tardive dyskinesia. Treatment for this syndrome, other than neuroleptic withdrawal, are still uncertain.

The six most essential questions in psychiatric diagnosis: a pluralogue. Part 4: general conclusion

PubMed Central

2012-01-01

In the conclusion to this multi-part article I first review the discussions carried out around the six essential questions in psychiatric diagnosis – the position taken by Allen Frances on each question, the commentaries on the respective question along with Frances’ responses to the commentaries, and my own view of the multiple discussions. In this review I emphasize that the core question is the first – what is the nature of psychiatric illness – and that in some manner all further questions follow from the first. Following this review I attempt to move the discussion forward, addressing the first question from the perspectives of natural kind analysis and complexity analysis. This reflection leads toward a view of psychiatric disorders – and future nosologies – as far more complex and uncertain than we have imagined. PMID:23249629

Interactive videoconsultation is a feasible method for neurological in-patient assessment.

PubMed

Craig, J; Patterson, V; Russell, C; Wootton, R

2000-11-01

To evaluate the feasibility of interactive videoconsultation (IATV) as a means by which neurologists might assess patients admitted with neurological symptoms to hospitals distant from a neurological centre, we studied 25 unselected patients using interactive videoconsultation (IATV) and then validated the IATV diagnoses and management plans at a later face-to-face consultation. IATV consultation led to an eventual diagnosis in 23 out of 25 patients, with one diagnosis being changed and one remaining uncertain. The IATV management plans were felt to be appropriate for all patients in study. Twelve patients were able to be discharged from hospital on the same day as IATV on the advice of the neurologist. It is therefore practical to assess patients admitted with neurological symptoms to distant hospitals using IATV and this may result in more efficient use of in-patient resources.

Evaluation of Molecular and Immunohistochemical Adjunct Modalities in the Diagnosis of Soft Tissue Neoplasms.

PubMed

Mourtzoukou, Despoina; Fisher, Cyril; Thway, Khin

2015-12-01

The accurate diagnosis of soft tissue neoplasms has crucial therapeutic and prognostic importance. There is frequent morphologic overlap between entities, and ancillary modalities are used in the vast majority of diagnoses. Immunohistochemistry is rapid and inexpensive, and in addition to the older markers that mainly detected cytoplasmic proteins, antibodies can indirectly detect tumor-specific genetic and molecular abnormalities. The use of molecular diagnostic techniques is now widespread, with molecular services often integrated into routine histopathology laboratories; as their cost and turnaround times begin to parallel those for immunohistochemistry, we compared the usefulness of ancillary immunohistochemistry, molecular genetic, and molecular cytogenetic techniques in the diagnosis of soft tissue lesions. We evaluated the number and contribution of immunohistochemical tests and panels and of ancillary molecular techniques in the primary histopathologic diagnosis of 150 soft tissue lesions. Ninety of 150 cases required either only one immunohistochemical panel or minimal immunohistochemistry for diagnosis, while 39/150 required 2 to 4 panels. In 5/150, ancillary molecular tests alone (without immunohistochemistry) were diagnostically sufficient. The majority of cases required one immunohistochemical panel for diagnosis, with a smaller proportion requiring a second, and a minority requiring a third or fourth (which mainly comprised neoplasms for which the final diagnosis was uncertain). Certain neoplasms required both extensive immunohistochemistry and ancillary molecular testing, despite which the final diagnosis was inconclusive. Ancillary molecular techniques now make a significant contribution to soft tissue tumor diagnosis, being required in over one third (52/150) of cases, and were useful in confirming or excluding tumors that were not possible to conclusively diagnose with histology and immunohistochemistry. Only a small proportion of soft tissue neoplasms (16/150; all benign) did not require immunohistochemistry or ancillary molecular methods, with morphology alone being sufficient for diagnosis. © The Author(s) 2015.

BRCA1 and BRCA2 genetic testing—pitfalls and recommendations for managing variants of uncertain clinical significance

PubMed Central

Eccles, D. M.; Mitchell, G.; Monteiro, A. N. A.; Schmutzler, R.; Couch, F. J.; Spurdle, A. B.; Gómez-García, E. B.

2015-01-01

Background Increasing use of BRCA1/2 testing for tailoring cancer treatment and extension of testing to tumour tissue for somatic mutation is moving BRCA1/2 mutation screening from a primarily prevention arena delivered by specialist genetic services into mainstream oncology practice. A considerable number of gene tests will identify rare variants where clinical significance cannot be inferred from sequence information alone. The proportion of variants of uncertain clinical significance (VUS) is likely to grow with lower thresholds for testing and laboratory providers with less experience of BRCA. Most VUS will not be associated with a high risk of cancer but a misinterpreted VUS has the potential to lead to mismanagement of both the patient and their relatives. Design Members of the Clinical Working Group of ENIGMA (Evidence-based Network for the Interpretation of Germline Mutant Alleles) global consortium (www.enigmaconsortium.org) observed wide variation in practices in reporting, disclosure and clinical management of patients with a VUS. Examples from current clinical practice are presented and discussed to illustrate potential pitfalls, explore factors contributing to misinterpretation, and propose approaches to improving clarity. Results and conclusion Clinicians, patients and their relatives would all benefit from an improved level of genetic literacy. Genetic laboratories working with clinical geneticists need to agree on a clinically clear and uniform format for reporting BRCA test results to non-geneticists. An international consortium of experts, collecting and integrating all available lines of evidence and classifying variants according to an internationally recognized system, will facilitate reclassification of variants for clinical use. PMID:26153499

A systematic review of decision aids that facilitate elements of shared decision-making in chronic illnesses: a review protocol.

PubMed

Wieringa, Thomas H; Kunneman, Marleen; Rodriguez-Gutierrez, Rene; Montori, Victor M; de Wit, Maartje; Smets, Ellen M A; Schoonmade, Linda J; Spencer-Bonilla, Gabriela; Snoek, Frank J

2017-08-07

Shared decision-making (SDM) is a patient-centred approach in which clinicians and patients work side-by-side to decide together on the best course of action for each patient's particular situation. Six key elements of SDM can be distinguished: situation diagnosis, choice awareness, option clarification, discussion of harms and benefits, deliberation of patient preferences and making the decision. Decision aids (DAs) are tools that facilitate SDM. The impact of DAs for chronic illnesses on SDM, clinical and patient reported outcomes remains uncertain. We will perform a systematic review aiming to describe (a) which SDM elements are incorporated in DAs for adult patients with chronic conditions and (b) the effects of DA use on SDM, clinical and patient reported outcomes. This manuscript reports on the protocol for this systematic review. The following databases will be searched for relevant articles: PubMed, Embase, Web of Science, CINAHL and PsycINFO, from their inception to October 2016. We will ascertain ongoing research by querying experts and searching trial registries. To enhance feasibility, we will limit the review to randomized controlled trials (RCTs) including patients with chronic cardiovascular and/or respiratory diseases and/or diabetes. SDM elements incorporated in DAs, DA effects and DA itself will be described. This study will characterize DAs for chronic illness and will provide an overview of their effects on SDM, clinical and patient reported outcomes. We anticipate this review will bring to light knowledge gaps and inform further research into the design and use of DAs for patients with chronic conditions. PROSPERO registration number: CRD42016050320 .

Review: Occult hepatitis C virus infection: still remains a controversy.

PubMed

Vidimliski, Pavlina Dzekova; Nikolov, Igor; Geshkovska, Nadica Matevska; Dimovski, Aleksandar; Rostaing, Lionel; Sikole, Aleksandar

2014-09-01

Occult hepatitis C virus (HCV) infection is characterized by the presence of HCV RNA in the liver cells or peripheral blood mononuclear cells of the patients whose serum samples test negative for HCV RNA, with or without presence of HCV antibodies. The present study reviews the existing literature on the persistence of occult hepatitis C virus infection, with description of the clinical characteristics and methods for identification of occult hepatitis C. Occult hepatitis C virus infection was detected in patients with abnormal results of liver function tests of unknown origin, with HCV antibodies and HCV RNA negativity in serum, and also in patients with spontaneous or treatment-induced recovery from hepatitis C. The viral replication in the liver cells and/or peripheral blood mononuclear cells was present in all clinical presentations of occult hepatitis C. The peripheral blood mononuclear cells represent an extra-hepatic site of HCV replication. The reason why HCV RNA was not detectable in the serum of patients with occult hepatitis C, could be the low number of circulating viral particles not detectable by the diagnostic tests with low sensitivity. It is uncertain whether occult hepatitis C is a different clinical entity or just a form of chronic hepatitis C virus infection. Data accumulated over the last decade demonstrated that an effective approach to the diagnosis of HCV infection would be the implementation of more sensitive HCV RNA diagnostic assays, and also, examination of the presence of viral particles in the cells of the immune system. © 2014 Wiley Periodicals, Inc.

[Symptomatic extramedullary haematopoiesis in β-thalassemia: A retrospective single centre study].

PubMed

Maazoun, F; Gellen Dautremer, J; Boutekadjirt, A; Pissard, S; Habibi, A; Bachir, D; Rahmouni, A; Bartolucci, P; Debbache, K; Lagrange, J-L; Michel, M; Galacteros, F

2016-01-01

Symptomatic extramedullary hematopoiesis (EH) is a rare but potentially severe phenomenon which occurs in β-thalassemia. There are no treatment guidelines. Retrospective single centre study including the cases of symptomatic EH encountered between 1997 and 2014 in a unit specialised in red blood cell genetic disorders. Description of clinical, biological and radiological characteristics of the patients, treatments received, and outcomes. Among 182 β-thalassemia patients followed during the study period, 7 cases of symptomatic EH were diagnosed. They were 5 men and 2 women, and their mean age was 37 years. Four patients were splenectomised, two patients were regularly transfused, and four patients had already received erythropoietin. EH was localised in intravertebral areas and responsible for dorsal spinal cord compression in 5 patients, in paravertebral dorsal area in 1 patient, and in presacral area in 1 patient. The mean hemoglobin level at diagnosis was 7.9 g/dL. Treatment administered included: red cell transfusion in 6 cases, associated with hydroxyurea in 5 cases and/or radiotherapy in 3 patients. One patient was treated with surgery and HU. After a median follow-up of 41 months, clinical recovery was complete in 2 patients and partial in 5 patients. EH must be suspected in β-thalassemia in patients presenting clinical signs of organ compression, and a typical radiological aspect. The functional prognosis depends on the rapidity of treatment, which includes red blood cell transfusion, hydroxyurea, radiotherapy, and rarely surgery. Long-term outcome is uncertain. Copyright © 2015. Published by Elsevier SAS.

How accurate are medical oncologists' impressions of management of metastatic colorectal cancer in Australia?

PubMed

Au, Lewis; Turner, Natalie; Wong, Hui-Li; Field, Kathryn; Lee, Belinda; Boadle, David; Cooray, Prasad; Karikios, Deme; Kosmider, Suzanne; Lipton, Lara; Nott, Louise; Parente, Phillip; Tie, Jeanne; Tran, Ben; Wong, Rachel; Yip, Desmond; Shapiro, Jeremy; Gibbs, Peter

2018-04-01

Current efforts to understand patient management in clinical practice are largely based on clinician surveys with uncertain reliability. The TRACC (Treatment of Recurrent and Advanced Colorectal Cancer) database is a multisite registry collecting comprehensive treatment and outcome data on consecutive metastatic colorectal cancer (mCRC) patients at multiple sites across Australia. This study aims to determine the accuracy of oncologists' impressions of real-word practice by comparing clinicians' estimates to data captured by TRACC. Nineteen medical oncologists from nine hospitals contributing data to TRACC completed a 34-question survey regarding their impression of the management and outcomes of mCRC at their own practice and other hospitals contributing to the database. Responses were then compared with TRACC data to determine how closely their impressions reflected actual practice. Data on 1300 patients with mCRC were available. Median clinician estimated frequency of KRAS testing within 6 months of diagnosis was 80% (range: 20-100%); the TRACC documented rate was 43%. Clinicians generally overestimated the rates of first-line treatment, particularly in patients over 75 years. Estimate for bevacizumab in first line was 60% (35-80%) versus 49% in TRACC. Estimated rate for liver resection varied substantially (5-35%), and the estimated median (27%) was inconsistent with the TRACC rate (12%). Oncologists generally felt their practice was similar to other hospitals. Oncologists' estimates of current clinical practice varied and were discordant with the TRACC database, often with a tendency to overestimate interventions. Clinician surveys alone do not reliably capture contemporary clinical practices in mCRC. © 2017 John Wiley & Sons Australia, Ltd.

Projected Clinical, Resource Use, and Fiscal Impacts of Implementing Low-Dose Computed Tomography Lung Cancer Screening in Medicare.

PubMed

Roth, Joshua A; Sullivan, Sean D; Goulart, Bernardo H L; Ravelo, Arliene; Sanderson, Joanna C; Ramsey, Scott D

2015-07-01

The Centers for Medicare and Medicaid Services (CMS) recently issued a national coverage determination that provides reimbursement for low-dose computed tomography (CT) lung cancer screening for enrollees age 55 to 77 years with ≥ 30-pack-year smoking history who currently smoke or quit in the last 15 years. The clinical, resource use, and fiscal impacts of this change in screening coverage policy remain uncertain. We developed a simulation model to forecast the 5-year health outcome impacts of the CMS low-dose CT screening policy in Medicare compared with no screening. The model used data from the National Lung Screening Trial, CMS enrollment statistics and reimbursement schedules, and peer-reviewed literature. Outcomes included counts of screening examinations, patient cases of lung cancer detected, stage distribution, and total and per-enrollee per-month fiscal impact. Over 5 years, we project that low-dose CT screening will result in 10.7 million more low-dose CT scans, 52,000 more lung cancers detected, and increased overall expenditure of $6.8 billion ($2.22 per Medicare enrollee per month). The most fiscally impactful factors were the average cost-per-screening episode, proportion of enrollees eligible for screening, and cost of treating stage I lung cancer. Low-dose CT screening is expected to increase lung cancer diagnoses, shift stage at diagnosis toward earlier stages, and substantially increase Medicare expenditures over a 5-year time horizon. These projections can inform planning efforts by Medicare administrators, contracted health care providers, and other stakeholders. Copyright © 2015 by American Society of Clinical Oncology.

Clinicopathologic Correlation of White, Non scrapable Oral Mucosal Surface Lesions: A Study of 100 Cases.

PubMed

Abidullah, Mohammed; Raghunath, Vandana; Karpe, Tanveer; Akifuddin, Syed; Imran, Shahid; Dhurjati, Venkata Naga Nalini; Aleem, Mohammed Ahtesham; Khatoon, Farheen

2016-02-01

White, non scrapable lesions are commonly seen in the oral cavity. Based on their history and clinical appearance, most of these lesions can be easily diagnosed, but sometimes diagnosis may go wrong. In order to arrive to a confirmative diagnosis, histopathological assessment is needed in many cases, if not all. 1) To find out the prevalence of clinically diagnosed oral white, non scrapable lesions. 2) To find out the prevalence of histopathologically diagnosed oral white, non scrapable lesions. 3) To correlate the clinical and histopathological diagnosis in the above lesions. A total of 100 cases of oral white, non scrapable lesions were included in the study. Based on their history and clinical presentation, clinical provisional diagnosis was made. Then biopsy was done and confirmatory histopathological diagnosis was given and both were correlated. In order to correlate clinical and histopathological diagnosis Discrepancy Index (DI) was calculated for all the cases. Based on clinical diagnosis, there were 59 cases (59%) of leukoplakia, 29 cases (29%) of lichen planus and six cases (6%) of lichenoid reaction; whereas, based on histopathological diagnosis, there were 66 cases (66%) of leukoplakia epithelial hyperplasia and hyperkeratosis (leukoplakia) and 30 cases (30%) of lichen planus. Seventy eight clinically diagnosed cases (78%) correlated with the histopathological diagnosis and 22 cases (22%) did not correlate. The total discrepancy index was 22%. A clinician needs to be aware of oral white, non scrapable lesions. Due to the overlapping of many clinical features in some of these lesions and also due to their malignant potential, a histopathological confirmative diagnosis is recommended.

[Clinical value of genome-wide high resolution chromosomal microarray analysis in etiological study of fetuses with congenital heart defects].

PubMed

Wu, Xiaoli; Fu, Fang; Li, Ru; Pan, Min; Han, Jin; Zhen, Li; Yang, Xin; Zhang, Yongling; Li, Fatao; Liao, Can

2014-12-01

To explore the clinical value of genome-wide high resolution chromosomal microarray analysis (CMA) in etiological study of fetuses with congenital heart disease (CHD) diagnosed by fetal echocardiography. A total of 176 fetuses diagnosed CHD by fetal echocardiography were analyzed, and invasive prenatal diagnosis was performed at Guangzhou Women and Children's Medical Center from January 2012 to January 2014. Among them, 158 fetuses were proved to have normal karyotype, and 88 fetuses (50.0%, 88/176) underwent CMA testing. The parental blood specimens were also collected for assisting the diagnosis of variants of uncertain clinical significance (VOUS). The 88 fetuses were divided into two groups: isolated CHD (n = 68) and CHD with extra-cardiac structural abnormalities (n = 20). The phenotypes of the two groups were subclassified. Copy number variations (CNV) were classified as benign CNV, pathogenic CNV (pCNV) or VOUS. (1) 58 fetuses (66%, 58/88) were with simple CHD and 30 fetuses were with complicated CHD (34%, 30/88). In the 45 fetuses with isolated and simple CHD, the pCNV detection rate was 11% (5/45). In the 23 fetuses with isolated and complicated CHD, the pCNV detection rate was 17% (4/23). In the 13 fetuses with simple CHD and extra-cardiac structural abnormalities, the pCNV detection rate was 5/13. In the 7 fetuses with complicated CHD and extra-cardiac structural abnormalities, the pCNV detection rate was 0. (2) The total detection rate for pCNV detection was 16% (14/88) in the 88 fetuses. The pCNV detection rates for isolated CHD and CHD with extra-cardiac structural abnormalities were 13% (9/68) and 25% (5/20), respectively (P > 0.05). The pCNV detection rates for simple and complicated CHD were 17% (10/58) and 13% (4/30), respectively (P > 0.05). (3) Eighteen fetuses (10.2%, 18/176) had abnormal karyotype results. (4) CMA test was performed in 88 fetuses. CNV detected in 8 fetuses were classified as VOUS initially. After parental microarray analysis, CNV in 5 fetuses were inherited and interpreted as benign. CNV in the other 3 fetuses (3%, 3/88) were remained unknown significance. CNV in 14 fetuses (16% ) were interpreted as pCNV. In fetuses with CHD and normal karyotype, the application of CMA could increase the detection rate of pCNV. Genome-wide CMA could be used as a regular tool in the prenatal diagnosis of fetuses with CHD and normal karyotype. This technology may benefit evaluation of fetal prognosis in prenatal genetic counselling.

Prognostic impact of blood and urinary angiogenic factor levels at diagnosis and during treatment in patients with osteosarcoma: a prospective study.

PubMed

Tabone, Marie-Dominique; Brugières, Laurence; Piperno-Neumann, Sophie; Selva, Marie-Ange; Marec-Bérard, Perrine; Pacquement, Hélène; Lervat, Cyril; Corradini, Nadège; Gentet, Jean-Claude; Couderc, Rémy; Chevance, Aurélie; Mahier-Ait Oukhatar, Céline; Entz-Werle, Natacha; Blay, Jean-Yves; Le Deley, Marie-Cecile

2017-06-15

Angiogenesis is essential for the progression and metastatic spread of solid tumours. Expression of vascular endothelial growth factor (VEGF) has been linked to poor survival among osteosarcoma patients but the clinical relevance of monitoring blood and urine angiogenic factors is uncertain. The aim of this study was to determine the prognostic significance of blood VEGF and blood and urinary basic fibroblast growth factor (bFGF) levels in osteosarcoma patients, both at diagnosis and during treatment. Patients with localised or metastatic osteosarcoma enrolled in OS2005 and OS2006 studies between 2005 and 2011 were prospectively included in this study. VEGF and bFGF levels in serum and plasma and bFGF levels in urine were measured by ELISA at diagnosis, before surgery, and at the end of treatment. Endpoints considered for the prognostic analysis were histological response, progression-free and overall survival. Kruskal-Wallis tests were used to compare the distribution of baseline biomarker values across the different subgroups, and paired sample Wilcoxon rank tests were used to analyze changes over time. Association between biomarker levels and outcomes were assessed in multivariable models (logistic regression for histologic response, and Cox models for survival). Samples were available at diagnosis for 269 patients (54% males; age ≤ 18 years: 73%; localised disease in 68%, doubtful lung lesions in 17%, and metastases in 15%). High serum VEGF and bFGF levels were observed in respectively 61% and 51% of patients. Serum and plasma VEGF values were not strongly correlated with one another (r = 0.53). High serum and plasma VEGF levels were significantly more frequent in patients with large tumours (≥10 cm; p = 0.003 and p = 0.02, respectively). VEGF levels fell significantly during pre-operative chemotherapy (p < 0.0001). No significant correlation was found between this variation and either the histological response, progression-free survival or overall survival (p = 0.26, p = 0.67, and p = 0.87, respectively). No significant association was found between blood or urinary bFGF levels and clinical characteristics, histological response, or survival. Levels of VEGF and bFGF angiogenic factors are high in most osteosarcoma patients, but have no significant impact on response to chemotherapy or outcome in this large prospective series. OS 2006 TRIAL REGISTRATION NUMBER: clinicaltrials.gov NCT00470223; date of registration: May 3th 2007.

Clinical practice guideline: Allergic rhinitis.

PubMed

Seidman, Michael D; Gurgel, Richard K; Lin, Sandra Y; Schwartz, Seth R; Baroody, Fuad M; Bonner, James R; Dawson, Douglas E; Dykewicz, Mark S; Hackell, Jesse M; Han, Joseph K; Ishman, Stacey L; Krouse, Helene J; Malekzadeh, Sonya; Mims, James Whit W; Omole, Folashade S; Reddy, William D; Wallace, Dana V; Walsh, Sandra A; Warren, Barbara E; Wilson, Meghan N; Nnacheta, Lorraine C

2015-02-01

Allergic rhinitis (AR) is one of the most common diseases affecting adults. It is the most common chronic disease in children in the United States today and the fifth most common chronic disease in the United States overall. AR is estimated to affect nearly 1 in every 6 Americans and generates $2 to $5 billion in direct health expenditures annually. It can impair quality of life and, through loss of work and school attendance, is responsible for as much as $2 to $4 billion in lost productivity annually. Not surprisingly, myriad diagnostic tests and treatments are used in managing this disorder, yet there is considerable variation in their use. This clinical practice guideline was undertaken to optimize the care of patients with AR by addressing quality improvement opportunities through an evaluation of the available evidence and an assessment of the harm-benefit balance of various diagnostic and management options. The primary purpose of this guideline is to address quality improvement opportunities for all clinicians, in any setting, who are likely to manage patients with AR as well as to optimize patient care, promote effective diagnosis and therapy, and reduce harmful or unnecessary variations in care. The guideline is intended to be applicable for both pediatric and adult patients with AR. Children under the age of 2 years were excluded from the clinical practice guideline because rhinitis in this population may be different than in older patients and is not informed by the same evidence base. The guideline is intended to focus on a limited number of quality improvement opportunities deemed most important by the working group and is not intended to be a comprehensive reference for diagnosing and managing AR. The recommendations outlined in the guideline are not intended to represent the standard of care for patient management, nor are the recommendations intended to limit treatment or care provided to individual patients. The development group made a strong recommendation that clinicians recommend intranasal steroids for patients with a clinical diagnosis of AR whose symptoms affect their quality of life. The development group also made a strong recommendation that clinicians recommend oral second-generation/less sedating antihistamines for patients with AR and primary complaints of sneezing and itching. The panel made the following recommendations: (1) Clinicians should make the clinical diagnosis of AR when patients present with a history and physical examination consistent with an allergic cause and 1 or more of the following symptoms: nasal congestion, runny nose, itchy nose, or sneezing. Findings of AR consistent with an allergic cause include, but are not limited to, clear rhinorrhea, nasal congestion, pale discoloration of the nasal mucosa, and red and watery eyes. (2) Clinicians should perform and interpret, or refer to a clinician who can perform and interpret, specific IgE (skin or blood) allergy testing for patients with a clinical diagnosis of AR who do not respond to empiric treatment, or when the diagnosis is uncertain, or when knowledge of the specific causative allergen is needed to target therapy. (3) Clinicians should assess patients with a clinical diagnosis of AR for, and document in the medical record, the presence of associated conditions such as asthma, atopic dermatitis, sleep-disordered breathing, conjunctivitis, rhinosinusitis, and otitis media. (4) Clinicians should offer, or refer to a clinician who can offer, immunotherapy (sublingual or subcutaneous) for patients with AR who have inadequate response to symptoms with pharmacologic therapy with or without environmental controls. The panel recommended against (1) clinicians routinely performing sinonasal imaging in patients presenting with symptoms consistent with a diagnosis of AR and (2) clinicians offering oral leukotriene receptor antagonists as primary therapy for patients with AR. The panel group made the following options: (1) Clinicians may advise avoidance of known allergens or may advise environmental controls (ie, removal of pets; the use of air filtration systems, bed covers, and acaricides [chemical agents formulated to kill dust mites]) in patients with AR who have identified allergens that correlate with clinical symptoms. (2) Clinicians may offer intranasal antihistamines for patients with seasonal, perennial, or episodic AR. (3) Clinicians may offer combination pharmacologic therapy in patients with AR who have inadequate response to pharmacologic monotherapy. (4) Clinicians may offer, or refer to a surgeon who can offer, inferior turbinate reduction in patients with AR with nasal airway obstruction and enlarged inferior turbinates who have failed medical management. (5) Clinicians may offer acupuncture, or refer to a clinician who can offer acupuncture, for patients with AR who are interested in nonpharmacologic therapy. The development group provided no recommendation regarding the use of herbal therapy for patients with AR. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.

ALS syndrome in patients with HIV-1 infection.

PubMed

Verma, Ashok; Berger, Joseph R

2006-01-15

A viral etiology of amyotrophic lateral sclerosis (ALS) has been proposed because of the selective vulnerability of motor neurons to certain viruses. During the last 20 years, at least 19 cases of ALS or ALS-like disease have been reported in HIV-1 (HIV) seropositive individuals. To describe two cases of clinically definite ALS in patients with HIV infection and to review the previously reported cases of HIV-associated ALS syndrome. A multidisciplinary ALS center and Neuro-AIDS clinic at a tertiary care university hospital. We investigated and prospectively monitored two patients who had developed clinically definite ALS by El Escorial criteria several years after acquiring the HIV infection. The previously reported cases of ALS or ALS-like disease in patients with HIV infection were reviewed for comparison and contrast with the characteristics of sporadic ALS. The clinical course of ALS in our two HIV seropositive individuals mirrored that of classical sporadic ALS. A review of previously described 19 patients with ALS syndrome revealed clinically definite ALS in 4 cases and clinically probable or possible ALS in 15. ALS commenced at different stages of the HIV disease; in 7 patients, HIV infection was discovered contemporaneously with diagnosis of ALS. CD4+ T cell count ranged from 2 to 560 cells/mm3. Three (1 definite ALS) of the fatal cases were studied at autopsy and all exhibited pathology outside the motor neuron pool. Unlike our patients, 7 of 8 patients with HIV-associated ALS syndrome receiving HAART demonstrated at least partial recovery of their motor deficit. ALS-like syndrome can occur in association with HIV infection; however, the causal relationship remains uncertain. Patients with ALS syndrome related to HIV infection are generally younger in age and often demonstrate pathology outside the motor neuron system. Patients with HIV-associated ALS syndrome may improve following antiretroviral therapy. An aggressive HAART regimen to reduce viral load should be pursued in all such cases.

Clinical variability of neuroacanthocytosis syndromes-a series of six patients with long follow-up.

PubMed

Dulski, J; Sołtan, W; Schinwelski, M; Rudzińska, M; Wójcik-Pędziwiatr, M; Wictor, L; Schön, F; Puschmann, A; Klempíř, J; Tilley, L; Roth, J; Tacik, P; Fujioka, S; Drozdowski, W; Sitek, E J; Wszolek, Z; Sławek, J

2016-08-01

To provide clinical clues to differential diagnosis in patients with chorea and other movement disorders with blood acanthocytes. We present a long-term video accompanied follow-up of six Caucasian patients with neuroacanthocytosis from several centers, three diagnosed with chorea-acanthocytosis (ChAc): 34-y.o.(no.1), 36-y.o.(no.2), 43-y.o.(no.3), two diagnosed with McLeod Syndrome (MLS): 52-y.o.(no.4), 61-y.o.(no.5) and one 63-y.o.(no.6), a brother of no.5, with clinical suspicion of MLS. Additionally we report pathological findings of the mother of two brothers with MLS reported in our series with acanthocytes on peripheral blood smear The patients had an unremarkable family history and were asymptomatic until adulthood. Patients no. 1,2,4,5,6 developed generalized chorea and patient no. 3 had predominant bradykinesia. Patients no. 1,2,3 had phonic and motor tics, additionally patients no. 1 and 2 exhibited peculiar oromandibular dystonia with tongue thrusting. In patients no. 2 and 3 dystonic supination of feet was observed, patient no. 3 subsequently developed bilateral foot drop. Patients no. 2 and 4 had signs of muscle atrophy. Tendon reflexes were decreased or absent and electroneurography demonstrated sensorimotor neuropathy in patients no. 1,2,3,4,5, except no. 6. Generalized seizures were seen in patients no. 2,3,5,6 and myoclonic jerks in patient no. 1. Cognitive deterioration was reported in patients no. 1,2,3,5,6. Serum creatine kinase levels were elevated in all six patients. We highlight the variability of clinical presentation of neuroacanthocytosis syndromes and the long time from the onset to diagnosis with the need to screen the blood smears in uncertain cases, however, as in one of our cases acanthocytes may even be not found. Based on our observations and data from the literature we propose several red flags that should raise the suspicion of an NA syndrome in a patient with a movement disorder: severe orofacial dyskinesia with tongue and lip-biting (typical of ChAc), feeding dystonia, psychiatric and cognitive disturbances, seizures, peripheral neuropathy, elevation of creatine kinase, elevation of transaminases, hepatosplenomegaly, cardiomyopathy and arrhythmias, and an X-linked pattern of inheritance (McLeod Syndrome, MLS). Copyright © 2016 Elsevier B.V. All rights reserved.

Development and Evaluation of Reference Standards for Image-based Telemedicine Diagnosis and Clinical Research Studies in Ophthalmology

PubMed Central

Ryan, Michael C.; Ostmo, Susan; Jonas, Karyn; Berrocal, Audina; Drenser, Kimberly; Horowitz, Jason; Lee, Thomas C.; Simmons, Charles; Martinez-Castellanos, Maria-Ana; Chan, R.V. Paul; Chiang, Michael F.

2014-01-01

Information systems managing image-based data for telemedicine or clinical research applications require a reference standard representing the correct diagnosis. Accurate reference standards are difficult to establish because of imperfect agreement among physicians, and discrepancies between clinical vs. image-based diagnosis. This study is designed to describe the development and evaluation of reference standards for image-based diagnosis, which combine diagnostic impressions of multiple image readers with the actual clinical diagnoses. We show that agreement between image reading and clinical examinations was imperfect (689 [32%] discrepancies in 2148 image readings), as was inter-reader agreement (kappa 0.490-0.652). This was improved by establishing an image-based reference standard defined as the majority diagnosis given by three readers (13% discrepancies with image readers). It was further improved by establishing an overall reference standard that incorporated the clinical diagnosis (10% discrepancies with image readers). These principles of establishing reference standards may be applied to improve robustness of real-world systems supporting image-based diagnosis. PMID:25954463

Uncertain translation, uncertain benefit and uncertain risk: ethical challenges facing first-in-human trials of induced pluripotent stem (ips) cells.

PubMed

Fung, Ronald K F; Kerridge, Ian H

2013-02-01

The discovery of induced pluripotent stem (iPS) cells in 2006 was heralded as a major breakthrough in stem cell research. Since then, progress in iPS cell technology has paved the way towards clinical application, particularly cell replacement therapy, which has refueled debate on the ethics of stem cell research. However, much of the discourse has focused on questions of moral status and potentiality, overlooking the ethical issues which are introduced by the clinical testing of iPS cell replacement therapy. First-in-human trials, in particular, raise a number of ethical concerns including informed consent, subject recruitment and harm minimisation as well as the inherent uncertainty and risks which are involved in testing medical procedures on humans for the first time. These issues, while a feature of any human research, become more complex in the case of iPS cell therapy, given the seriousness of the potential risks, the unreliability of available animal models, the vulnerability of the target patient group, and the high stakes of such an intensely public area of science. Our paper will present a detailed case study of iPS cell replacement therapy for Parkinson's disease to highlight these broader ethical and epistemological concerns. If we accept that iPS cell technology is fraught with challenges which go far beyond merely refuting the potentiality of the stem cell line, we conclude that iPS cell research should not replace, but proceed alongside embryonic and adult somatic stem cell research to promote cross-fertilisation of knowledge and better clinical outcomes. © 2011 Blackwell Publishing Ltd.

The clinical effectiveness of preimplantation genetic diagnosis for aneuploidy in all 24 chromosomes (PGD-A): systematic review.

PubMed

Lee, Evelyn; Illingworth, Peter; Wilton, Leeanda; Chambers, Georgina Mary

2015-02-01

Is preimplantation genetic diagnosis for aneuploidy (PGD-A) with analysis of all chromosomes during assisted reproductive technology (ART) clinically and cost effective? The majority of published studies comparing a strategy of PGD-A with morphologically assessed embryos have reported a higher implantation rate per embryo using PGD-A, but insufficient data has been presented to evaluate the clinical and cost-effectiveness of PGD-A in the clinical setting. Aneuploidy is a leading cause of implantation failure, miscarriage and congenital abnormalities in humans, and a significant cause of ART failure. Preclinical evidence of PGD-A indicates that the selection and transfer of euploid embryos during ART should improve clinical outcomes. A systematic review of the literature was performed for full text English language articles using MEDLINE, EMBASE, SCOPUS, Cochrane Library databases, NHS Economic Evaluation Database and EconLit. The Downs and Black scoring checklist was used to assess the quality of studies. Clinical effectiveness was measured in terms of pregnancy, live birth and miscarriage rates. Nineteen articles meeting the inclusion criteria, comprising three RCTs in young and good prognosis patients and 16 observation studies were identified. Five of the observational studies included a control group of patients where embryos were selected based on morphological criteria (matched cohort studies). Of the five studies that included a control group and reported implantation rates, four studies (including two RCTs) demonstrated improved implantation rates in the PGD-A group. Of the eight studies that included a control group, six studies (including two RCTs) reported significantly higher pregnancy rates in the PGD-A group, and in the remaining two studies, equivalent pregnancies rates were reported despite fewer embryos being transferred in the PGD-A group. The three RCTs demonstrated benefit in young and good prognosis patients in terms of clinical pregnancy rates and the use of single embryo transfer. However, studies relating to patients of advanced maternal age, recurrent miscarriage and implantation failure were restricted to matched cohort studies, limiting the ability to draw meaningful conclusions. Relevant studies may have been missed and findings from RCTs currently being undertaken could not be included. Given the uncertain role of PGD-A techniques, high-quality experimental studies using intention-to-treat analysis and cumulative live birth rates including the comparative outcomes from remaining cryopreserved embryos are needed to evaluate the overall role of PGD-A in the clinical setting. It is only in this way that the true contribution of PGD-A to ART can be understood. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

ACCF/SCAI/AATS/AHA/ASE/ASNC/HFSA/HRS/SCCM/SCCT/SCMR/STS 2012 appropriate use criteria for diagnostic catheterization: a report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, Society for Cardiovascular Angiography and Interventions, American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society of Critical Care Medicine, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Thoracic Surgeons.

PubMed

Patel, Manesh R; Bailey, Steven R; Bonow, Robert O; Chambers, Charles E; Chan, Paul S; Dehmer, Gregory J; Kirtane, Ajay J; Wann, L Samuel; Ward, R Parker

2012-05-29

The American College of Cardiology Foundation, in collaboration with the Society for Cardiovascular Angiography and Interventions and key specialty and subspecialty societies, conducted a review of common clinical scenarios where diagnostic catheterization is frequently considered. The indications (clinical scenarios) were derived from common applications or anticipated uses, as well as from current clinical practice guidelines and results of studies examining the implementation of noninvasive imaging appropriate use criteria. The 166 indications in this document were developed by a diverse writing group and scored by a separate independent technical panel on a scale of 1 to 9, to designate appropriate use (median 7 to 9), uncertain use (median 4 to 6), and inappropriate use (median 1 to 3). Diagnostic catheterization may include several different procedure components. The indications developed focused primarily on 2 aspects of diagnostic catheterization. Many indications focused on the performance of coronary angiography for the detection of coronary artery disease with other procedure components (e.g., hemodynamic measurements, ventriculography) at the discretion of the operator. The majority of the remaining indications focused on hemodynamic measurements to evaluate valvular heart disease, pulmonary hypertension, cardiomyopathy, and other conditions, with the use of coronary angiography at the discretion of the operator. Seventy-five indications were rated as appropriate, 49 were rated as uncertain, and 42 were rated as inappropriate. The appropriate use criteria for diagnostic catheterization have the potential to impact physician decision making, healthcare delivery, and reimbursement policy. Furthermore, recognition of uncertain clinical scenarios facilitates identification of areas that would benefit from future research.

Communicating microarray results of uncertain clinical significance in consultation summary letters and implications for practice.

PubMed

Paul, Jean Lillian; Pope-Couston, Rachel; Wake, Samantha; Burgess, Trent; Tan, Tiong Yang

2016-01-01

Letter-writing is an integral practice for genetic health professionals. In Victoria, Australia, patients with a chromosomal variant of uncertain clinical significance (VUS) referred to a clinical geneticist (CG) for evaluation receive consultation summary letters. While communication of uncertainty has been explored in research to some extent, little has focused on how uncertainty is communicated within consultation letters. We aimed to develop a multi-layered understanding of the ways in which CGs communicate diagnostic uncertainty in consultation summary letters. We used theme-oriented discourse analysis of 49 consultation summary letters and thematic analysis of a focus group involving eight CGs. Results showed that CGs have become more confident in their description of VUS as 'contributing factors' to patients' clinical features, but remain hesitant to assign definitive causality. CGs displayed strong epistemic stance when discussing future technological improvements to provide hope and minimise potentially disappointing outcomes for patients and families. CGs reported feeling overwhelmed by their workload associated with increasing numbers of patients with VUS, and this has led to a reduction in the number of review appointments offered over time. This study provides a rich description of the content and process of summary letters discussing VUS. Our findings have implications for letter-writing and workforce management. Furthermore, these findings may be of relevance to VUS identified by genomic sequencing in clinical practice.

The Weiss score and beyond--histopathology for adrenocortical carcinoma.

PubMed

Papotti, Mauro; Libè, Rossella; Duregon, Eleonora; Volante, Marco; Bertherat, Jerome; Tissier, Frederique

2011-12-01

The pathological diagnosis of adrenocortical carcinoma (ACC) is still challenging for its rarity and the presence of special variants (pediatric, oncocytic, myxoid, and sarcomatoid). It is based on the recognition at light microscopy of at least three among nine morphological parameters, according to the Weiss scoring system, which has been introduced 27 years ago and nowadays is the most widely employed. Nevertheless, the diagnostic performance of this system is very high but does not reach a sensitivity and specificity of 100%, its diagnostic applicability is potentially low among non-expert pathologists, and a group of borderline cases with only one or two criteria exist of uncertain behavior. Moreover, it is scarcely reproducible in the ACC morphological variants. In fact, specifically for the pure oncocytic neoplasms that seem to have a better prognosis in comparison to the conventional ACCs, a modified system (the Lin-Weiss-Bisceglia) has been proposed. With the aim to simplify the ACC diagnosis, 2 years ago, the "reticulin" diagnostic algorithm has been proposed, based on the observation that the tumoral reticulin framework (highlighted by reticulin silver-based histochemical staining) is consistently disrupted in malignant cases but only in a small subset of benign cases. Following this algorithm, in the presence of reticulin alterations, malignancy is further defined through the identification of at least one of the following parameters: necrosis, high mitotic rate, and venous invasion. As a complement to the morphological approach, some immunohistochemical markers (such as steroidogenic factor 1) have been proposed as diagnostic and prognostic adjuncts but still lack wide clinical validation.

Prevalence of food allergy in infants and pre-schoolers in Brazil.

PubMed

Gonçalves, L C P; Guimarães, T C P; Silva, R M; Cheik, M F A; de Ramos Nápolis, A C; Barbosa E Silva, G; Segundo, G R S

Food allergy is an increasing problem in public health, especially in childhood. Its incidence has increased in the last decade. Despite this, estimates of the actual incidence and prevalence are uncertain. The aim of this study was to estimate the prevalence of food allergy in infants and pre-schoolers. The parents of 3897 children completed questionnaires on the occurrence of any reaction to food. Children with parentally reported reactions were selected for further examination including a clinical interview, physical examination, allergic tests, and if necessary, oral food challenge to conclude the diagnosis of FA. The estimated prevalence of allergy in children aged 4-59 months was 0.61%, being, 1.9% in infants and 0.4% in pre-schoolers. Among the 604 patients physicians evaluated with parent-reported FA, 24 (4%) had a confirmed diagnosis of food allergy, and 580 (96%) were excluded in the remaining. Of these, approximately half (51/52.6%) of 97 infants and (128/48%) of 487 pre-schoolers already performed the diet exclusion suspected food for a period of time. This study shows that high overall prevalence of parental belief of current food allergy however the same was not observed in the in physician-diagnosed food allergy. The prevalence of food allergy was lower than that observed in the literature. This study alerts health professionals to the risk entailed by overestimation of cases of food allergy and unnecessary dietary exclusion, which may result in impairment in growth and development of children, especially in their first years of life. Copyright © 2016. Published by Elsevier España, S.L.U.

Potential protein biomarkers for burning mouth syndrome discovered by quantitative proteomics.

PubMed

Ji, Eoon Hye; Diep, Cynthia; Liu, Tong; Li, Hong; Merrill, Robert; Messadi, Diana; Hu, Shen

2017-01-01

Burning mouth syndrome (BMS) is a chronic pain disorder characterized by severe burning sensation in normal looking oral mucosa. Diagnosis of BMS remains to be a challenge to oral healthcare professionals because the method for definite diagnosis is still uncertain. In this study, a quantitative saliva proteomic analysis was performed in order to identify target proteins in BMS patients' saliva that may be used as biomarkers for simple, non-invasive detection of the disease. By using isobaric tags for relative and absolute quantitation labeling and liquid chromatography-tandem mass spectrometry to quantify 1130 saliva proteins between BMS patients and healthy control subjects, we found that 50 proteins were significantly changed in the BMS patients when compared to the healthy control subjects ( p ≤ 0.05, 39 up-regulated and 11 down-regulated). Four candidates, alpha-enolase, interleukin-18 (IL-18), kallikrein-13 (KLK13), and cathepsin G, were selected for further validation. Based on enzyme-linked immunosorbent assay measurements, three potential biomarkers, alpha-enolase, IL-18, and KLK13, were successfully validated. The fold changes for alpha-enolase, IL-18, and KLK13 were determined as 3.6, 2.9, and 2.2 (burning mouth syndrome vs. control), and corresponding receiver operating characteristic values were determined as 0.78, 0.83, and 0.68, respectively. Our findings indicate that testing of the identified protein biomarkers in saliva might be a valuable clinical tool for BMS detection. Further validation studies of the identified biomarkers or additional candidate biomarkers are needed to achieve a multi-marker prediction model for improved detection of BMS with high sensitivity and specificity.

Fibulin-3 as a diagnostic biomarker in patients with malignant mesothelioma.

PubMed

Kaya, Halide; Demir, Melike; Taylan, Mahsuk; Sezgi, Cengizhan; Tanrikulu, Abdullah Cetin; Yilmaz, Sureyya; Bayram, Mehmet; Kaplan, Ibrahim; Senyigit, Abdurrahman

2015-01-01

New tumour biomarkers are being intensely investigated for malignant mesothelioma (MM). Fibulin-3 is produced in MM but its role remains uncertain. The aim of this study was to evaluate the validity of measuring serum fibulin-3 in the diagnosis and prognosis of MM. This prospective study was performed on 43 patients and 40 healthy controls who were admitted to our hospital between January 2012 and January 2014. Data from MM patients, including demographic and clinical features, routine laboratory data, levels of serum fibulin-3, and treatment outcomes were defined as potential prognostic factors. The receiver operating characteristic (ROC) curve for fibulin-3 was used to detect the cut-off value with highest sensitivity and specificity. Univariate survival analysis was performed using the Kaplan-Meier method in patients with MM. Afterwards, the possible factors identified with univariate analyses were entered into the cox regression analysis. Our results revealed that patients with MM had significantly higher serum levels of fibulin-3 than controls. The results showed that the best cut-off point was 36.6 ng/ml with an AUC (area under the curve)=0.976, sensitivity=93.0% and specificity=90.0. In our study, the initial significant poor prognostic factors were advanced stage, high white blood cell count, high platelet count, high C-reactive protein (p<0.05 for each variable). Later, according to multivariate analysis the results showed only advanced stage as significant parameter (p=0.040). We determined that real use for serum fibulin-3 was not for prognosis but for diagnosis in MM. Also advanced stage was associated with poor MM prognosis.

Clinicopathologic Correlation of White, Non scrapable Oral Mucosal Surface Lesions: A Study of 100 Cases

PubMed Central

Raghunath, Vandana; Karpe, Tanveer; Akifuddin, Syed; Imran, Shahid; Dhurjati, Venkata Naga Nalini; Aleem, Mohammed Ahtesham; Khatoon, Farheen

2016-01-01

Introduction White, non scrapable lesions are commonly seen in the oral cavity. Based on their history and clinical appearance, most of these lesions can be easily diagnosed, but sometimes diagnosis may go wrong. In order to arrive to a confirmative diagnosis, histopathological assessment is needed in many cases, if not all. Aims 1) To find out the prevalence of clinically diagnosed oral white, non scrapable lesions. 2) To find out the prevalence of histopathologically diagnosed oral white, non scrapable lesions. 3) To correlate the clinical and histopathological diagnosis in the above lesions. Materials and Methods A total of 100 cases of oral white, non scrapable lesions were included in the study. Based on their history and clinical presentation, clinical provisional diagnosis was made. Then biopsy was done and confirmatory histopathological diagnosis was given and both were correlated. In order to correlate clinical and histopathological diagnosis Discrepancy Index (DI) was calculated for all the cases. Results Based on clinical diagnosis, there were 59 cases (59%) of leukoplakia, 29 cases (29%) of lichen planus and six cases (6%) of lichenoid reaction; whereas, based on histopathological diagnosis, there were 66 cases (66%) of leukoplakia epithelial hyperplasia and hyperkeratosis (leukoplakia) and 30 cases (30%) of lichen planus. Seventy eight clinically diagnosed cases (78%) correlated with the histopathological diagnosis and 22 cases (22%) did not correlate. The total discrepancy index was 22%. Conclusion A clinician needs to be aware of oral white, non scrapable lesions. Due to the overlapping of many clinical features in some of these lesions and also due to their malignant potential, a histopathological confirmative diagnosis is recommended. PMID:27042583

Pleural neoplastic pathology.

PubMed

Karpathiou, Georgia; Stefanou, Dimitrios; Froudarakis, Marios E

2015-08-01

Malignant pleural effusion is a frequent situation in pulmonary medicine. However, it is sometimes difficult to recognize the underlying etiology. The aim of this review is to provide the key characteristics of primary and metastatic pleural neoplasms. A review of the recent literature regarding pleural neoplasia is provided. Malignant pleural mesothelioma (MPM) is the commonest primary pleural epithelial tumor showing remarkable histological heterogeneity often with prognostic significance. Various genetic alterations like changes in INK4 locus, NF2, BAP1 but also epigenetic changes are present in MPM. It should be distinguished from atypical mesothelial hyperplasia, mainly through morphological and clinical criteria, and from other rare primary and metastatic tumors, for which immunohistochemistry is rather important. Solitary fibrous tumor, the commonest primary pleural mesenchymal tumor is characterized by STAT6 overexpression. Other primary tumors, like adenomatoid tumor, well-differentiated papillary mesothelioma, synovial sarcoma, vascular tumors, various other sarcomas, thymic tumors and tumors of uncertain histogenesis are rarely encountered in the pleura. In contrast, metastatic disease is the commonest neoplasia of the pleura, and especially lung, breast and lymphoid malignancies. The basic pathological, immunohistochemical and molecular characteristics of these entities are provided in the current review, along with their differential diagnosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Autopsy diagnosis of fat embolism syndrome.

PubMed

Miller, Peter; Prahlow, Joseph A

2011-09-01

The fat embolism syndrome (FES) is considered a clinical diagnosis. It typically occurs within several days following major traumatic injury, usually involving fractures of the pelvis and/or lower extremities. Fat embolism syndrome is characterized by the onset of respiratory, neurological, cutaneous, and hematologic manifestations and is thought to be related to intravascular embolization of fat, presumably arising from within the fractured bone marrow space. In its most severe form, FES can be lethal. The presence of fat emboli within the microvasculature of the lungs, brain, and sometimes other organs verifies the clinical impression of FES. Despite its relatively well-known clinical characterization, debate exists within the clinical literature regarding the most appropriate diagnostic criteria for FES. Given this fact, along with the fact that FES is a clinical diagnosis, it is not surprising that forensic pathologists may be somewhat reluctant to make a postmortem diagnosis of FES, especially in cases where insufficient clinical information is available. A case of fatal FES is presented in which rapid clinical deterioration occurred, followed by death, such that a clinical diagnosis of FES was never rendered. We propose that, given the correct circumstances, clinical scenario, and autopsy findings, it is appropriate and acceptable to make a postmortem diagnosis of FES. A multitiered approach to the postmortem diagnosis of FES is presented.

Research with Pregnant Women: New Insights on Legal Decision-Making

PubMed Central

Mastroianni, Anna C.; Henry, Leslie Meltzer; Robinson, David; Bailey, Theodore; Faden, Ruth R.; Little, Margaret O.; Lyerly, Anne Drapkin

2017-01-01

Although pregnant women rely on medical interventions to treat and prevent a wide variety of health conditions, they are frequently excluded or underrepresented in clinical research. The resulting dearth of pregnancy-specific evidence to guide clinical decisionmaking routinely exposes pregnant women, and their future offspring, to risk of uncertain harms for uncertain benefits. The two legal factors regularly cited as obstacles to such research are the federal regulatory scheme and fear of liability. This article reveals a far more nuanced and complex view of the legal context. First, legal professionals may—at any time from product conception to marketing—influence decisions about research with pregnant women. Second, factors not previously articulated in the literature may prompt legal professionals to slow or halt such research. They include: financial interests, regulatory ambiguity, obstacles to risk management, and site-specific laws unrelated to research. Any efforts to promote the ethical inclusion of pregnant women in research must acknowledge the role of legal decisionmakers and address their professional concerns. PMID:28543423

[Definition of the Diagnosis Osteomyelitis-Osteomyelitis Diagnosis Score (ODS)].

PubMed

Schmidt, H G K; Tiemann, A H; Braunschweig, R; Diefenbeck, M; Bühler, M; Abitzsch, D; Haustedt, N; Walter, G; Schoop, R; Heppert, V; Hofmann, G O; Glombitza, M; Grimme, C; Gerlach, U-J; Flesch, I

2011-08-01

The disease "osteomyelitis" is characterised by different symptoms and parameters. Decisive roles in the development of the disease are played by the causative bacteria, the route of infection and the individual defense mechanisms of the host. The diagnosis is based on different symptoms and findings from the clinical history, clinical symptoms, laboratory results, diagnostic imaging, microbiological and histopathological analyses. While different osteomyelitis classifications have been published, there is to the best of our knowledge no score that gives information how sure the diagnosis "osteomyelitis" is in general. For any scientific study of a disease a valid definition is essential. We have developed a special osteomyelitis diagnosis score for the reliable classification of clinical, laboratory and technical findings. The score is based on five diagnostic procedures: 1) clinical history and risk factors, 2) clinical examination and laboratory results, 3) diagnostic imaging (ultrasound, radiology, CT, MRI, nuclear medicine and hybrid methods), 4) microbiology, and 5) histopathology. Each diagnostic procedure is related to many individual findings, which are weighted by a score system, in order to achieve a relevant value for each assessment. If the sum of the five diagnostic criteria is 18 or more points, the diagnosis of osteomyelitis can be viewed as "safe" (diagnosis class A). Between 8-17 points the diagnosis is "probable" (diagnosis class B). Less than 8 points means that the diagnosis is "possible, but unlikely" (class C diagnosis). Since each parameter can score six points at a maximum, a reliable diagnosis can only be achieved if at least 3 parameters are scored with 6 points. The osteomyelitis diagnosis score should help to avoid the false description of a clinical presentation as "osteomyelitis". A safe diagnosis is essential for the aetiology, treatment and outcome studies of osteomyelitis. © Georg Thieme Verlag KG Stuttgart · New York.

Cost implications of PSA screening differ by age.

PubMed

Rao, Karthik; Liang, Stella; Cardamone, Michael; Joshu, Corinne E; Marmen, Kyle; Bhavsar, Nrupen; Nelson, William G; Ballentine Carter, H; Albert, Michael C; Platz, Elizabeth A; Pollack, Craig E

2018-05-09

Multiple guidelines seek to alter rates of prostate-specific antigen (PSA)-based prostate cancer screening. The costs borne by payers associated with PSA-based screening for men of different age groups-including the costs of screening and subsequent diagnosis, treatment, and adverse events-remain uncertain. We sought to develop a model of PSA costs that could be used by payers and health care systems to inform cost considerations under a range of different scenarios. We determined the prevalence of PSA screening among men aged 50 and higher using 2013-2014 data from a large, multispecialty group, obtained reimbursed costs associated with screening, diagnosis, and treatment from a commercial health plan, and identified transition probabilities for biopsy, diagnosis, treatment, and complications from the literature to generate a cost model. We estimated annual total costs for groups of men ages 50-54, 55-69, and 70+ years, and varied annual prostate cancer screening prevalence in each group from 5 to 50% and tested hypothetical examples of different test characteristics (e.g., true/false positive rate). Under the baseline screening patterns, costs of the PSA screening represented 10.1% of the total costs; costs of biopsies and associated complications were 23.3% of total costs; and, although only 0.3% of all screen eligible patients were treated, they accounted for 66.7% of total costs. For each 5-percentage point decrease in PSA screening among men aged 70 and older for a single calendar year, total costs associated with prostate cancer screening decreased by 13.8%. For each 5-percentage point decrease in PSA screening among men 50-54 and 55-69 years old, costs were 2.3% and 7.3% lower respectively. With constrained financial resources and with national pressure to decrease use of clinically unnecessary PSA-based prostate cancer screening, there is an opportunity for cost savings, especially by focusing on the downstream costs disproportionately associated with screening men 70 and older.

Rett syndrome: revised diagnostic criteria and nomenclature.

PubMed

Neul, Jeffrey L; Kaufmann, Walter E; Glaze, Daniel G; Christodoulou, John; Clarke, Angus J; Bahi-Buisson, Nadia; Leonard, Helen; Bailey, Mark E S; Schanen, N Carolyn; Zappella, Michele; Renieri, Alessandra; Huppke, Peter; Percy, Alan K

2010-12-01

Rett syndrome (RTT) is a severe neurodevelopmental disease that affects approximately 1 in 10,000 live female births and is often caused by mutations in Methyl-CpG-binding protein 2 (MECP2). Despite distinct clinical features, the accumulation of clinical and molecular information in recent years has generated considerable confusion regarding the diagnosis of RTT. The purpose of this work was to revise and clarify 2002 consensus criteria for the diagnosis of RTT in anticipation of treatment trials. RettSearch members, representing the majority of the international clinical RTT specialists, participated in an iterative process to come to a consensus on a revised and simplified clinical diagnostic criteria for RTT. The clinical criteria required for the diagnosis of classic and atypical RTT were clarified and simplified. Guidelines for the diagnosis and molecular evaluation of specific variant forms of RTT were developed. These revised criteria provide clarity regarding the key features required for the diagnosis of RTT and reinforce the concept that RTT is a clinical diagnosis based on distinct clinical criteria, independent of molecular findings. We recommend that these criteria and guidelines be utilized in any proposed clinical research.

How many sleep stages do we need for an efficient automatic insomnia diagnosis?

PubMed

Hamida, Sana Tmar-Ben; Glos, Martin; Penzel, Thomas; Ahmed, Beena

2016-08-01

Tools used by clinicians to diagnose and treat insomnia typically include sleep diaries and questionnaires. Overnight polysomnography (PSG) recordings are used when the initial diagnosis is uncertain due to the presence of other sleep disorders or when the treatment, either behavioral or pharmacologic, is unsuccessful. However, the analysis and the scoring of PSG data are time-consuming. To simplify the diagnosis process, in this paper we have proposed an efficient insomnia detection algorithm based on a central single electroencephalographic (EEG) channel (C3) using only deep sleep. We also analyzed several spectral and statistical EEG features of good sleeper controls and subjects suffering from insomnia in different sleep stages to identify the features that offered the best discrimination between the two groups. Our proposed algorithm was evaluated using EEG recordings from 19 patients diagnosed with primary insomnia (11 females, 8 males) and 16 matched control subjects (11 females, 5 males). The sensitivity of our algorithm is 92%, the specificity is 89.9%, the Cohen's kappa is 0.81 and the agreement is 91%, indicating the effectiveness of our proposed method.

Should diagnosis codes from emergency department data be used for case selection for emergency department key performance indicators?

PubMed

Howell, Stuart C; Wills, Rachael A; Johnston, Trisha C

2014-02-01

The aim of the present study was to assess the suitability of emergency department (ED) discharge diagnosis for identifying patient cohorts included in the definitions of key performance indicators (KPIs) that are used to evaluate ED performance. Hospital inpatient episodes of care with a principal diagnosis that corresponded to an ED-defined KPI were extracted from the Queensland Hospital Admitted Patient Data Collection (QHAPDC) for the year 2010-2011. The data were then linked to the corresponding ED patient record and the diagnoses applied in the two settings were compared. The asthma and injury cohorts produced favourable results with respect to matching the QHAPDC principal diagnosis with the ED discharge diagnosis. The results were generally modest when the QHAPDC principal diagnosis was upper respiratory tract infection, poisoning and toxic effects or a mental health diagnosis, and were quite poor for influenza. There is substantial variation in the capture of patient cohorts using discharge diagnosis as recorded on Queensland Hospital Emergency Department data. WHAT IS KNOWN ABOUT THE TOPIC? There are several existing KPIs that are defined according to the diagnosis recorded on ED data collections. However, there have been concerns over the quality of ED diagnosis in Queensland and other jurisdictions, and the value of these data in identifying patient cohorts for the purpose of assessing ED performance remains uncertain. WHAT DOES THIS PAPER ADD? This paper identifies diagnosis codes that are suitable for use in capturing the patient cohorts that are used to evaluate ED performance, as well as those codes that may be of limited value. WHAT ARE THE IMPLICATIONS FOR PRACTITIONERS? The limitations of diagnosis codes within ED data should be understood by those seeking to use these data items for healthcare planning and management or for research into healthcare quality and outcomes.

Antiseptics and Antibiotics for Surgical Wounds Healing by Secondary Intention: Summary of a Cochrane Review.

PubMed

Norman, Gill; Dumville, Jo C; Crosbie, Emma J

2016-11-01

Do antiseptics and antibiotics benefit surgical wounds healing by secondary intention (SWHSI)? No high-quality randomized clinical trials have addressed this question. Current evidence is limited and insufficient; it is uncertain whether treating SWHSI with antiseptics or antibiotics is beneficial.

The importance of functional tests to assess the effect of a new CFTR variant when genotype-phenotype correlation is not possible.

PubMed

Hinzpeter, Alexandre; Reboul, Marie-Pierre; Callebaut, Isabelle; Zordan, Cécile; Costes, Bruno; Guichoux, Julie; Iron, Albert; Lacombe, Didier; Martin, Natacha; Arveiler, Benoit; Fanen, Pascale; Fergelot, Patricia; Girodon, Emmanuelle

2017-05-01

In vitro functional tests aimed to investigate CFTR dysfunction appear critical to help elucidate the functional impact of new variants of uncertain clinical significance and solve inconclusive cases, especially in early deceased newborns.

Core Pedagogy: Individual Uncertainty, Shared Practice, Formative Ethos

ERIC Educational Resources Information Center

Dotger, Benjamin H.

2015-01-01

Attention to the core practices of teaching necessitates core pedagogies in teacher preparation. This article outlines the diffusion of one such pedagogy from medical to teacher education. The concept of clinical simulations is outlined through the lens of "signature pedagogies" and their uncertain, engaging, formative qualities.…

BRCA1 and BRCA2 genetic testing-pitfalls and recommendations for managing variants of uncertain clinical significance.

PubMed

Eccles, D M; Mitchell, G; Monteiro, A N A; Schmutzler, R; Couch, F J; Spurdle, A B; Gómez-García, E B

2015-10-01

Increasing use of BRCA1/2 testing for tailoring cancer treatment and extension of testing to tumour tissue for somatic mutation is moving BRCA1/2 mutation screening from a primarily prevention arena delivered by specialist genetic services into mainstream oncology practice. A considerable number of gene tests will identify rare variants where clinical significance cannot be inferred from sequence information alone. The proportion of variants of uncertain clinical significance (VUS) is likely to grow with lower thresholds for testing and laboratory providers with less experience of BRCA. Most VUS will not be associated with a high risk of cancer but a misinterpreted VUS has the potential to lead to mismanagement of both the patient and their relatives. Members of the Clinical Working Group of ENIGMA (Evidence-based Network for the Interpretation of Germline Mutant Alleles) global consortium (www.enigmaconsortium.org) observed wide variation in practices in reporting, disclosure and clinical management of patients with a VUS. Examples from current clinical practice are presented and discussed to illustrate potential pitfalls, explore factors contributing to misinterpretation, and propose approaches to improving clarity. Clinicians, patients and their relatives would all benefit from an improved level of genetic literacy. Genetic laboratories working with clinical geneticists need to agree on a clinically clear and uniform format for reporting BRCA test results to non-geneticists. An international consortium of experts, collecting and integrating all available lines of evidence and classifying variants according to an internationally recognized system, will facilitate reclassification of variants for clinical use. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Comparison of locus-specific databases for BRCA1 and BRCA2 variants reveals disparity in variant classification within and among databases.

PubMed

Vail, Paris J; Morris, Brian; van Kan, Aric; Burdett, Brianna C; Moyes, Kelsey; Theisen, Aaron; Kerr, Iain D; Wenstrup, Richard J; Eggington, Julie M

2015-10-01

Genetic variants of uncertain clinical significance (VUSs) are a common outcome of clinical genetic testing. Locus-specific variant databases (LSDBs) have been established for numerous disease-associated genes as a research tool for the interpretation of genetic sequence variants to facilitate variant interpretation via aggregated data. If LSDBs are to be used for clinical practice, consistent and transparent criteria regarding the deposition and interpretation of variants are vital, as variant classifications are often used to make important and irreversible clinical decisions. In this study, we performed a retrospective analysis of 2017 consecutive BRCA1 and BRCA2 genetic variants identified from 24,650 consecutive patient samples referred to our laboratory to establish an unbiased dataset representative of the types of variants seen in the US patient population, submitted by clinicians and researchers for BRCA1 and BRCA2 testing. We compared the clinical classifications of these variants among five publicly accessible BRCA1 and BRCA2 variant databases: BIC, ClinVar, HGMD (paid version), LOVD, and the UMD databases. Our results show substantial disparity of variant classifications among publicly accessible databases. Furthermore, it appears that discrepant classifications are not the result of a single outlier but widespread disagreement among databases. This study also shows that databases sometimes favor a clinical classification when current best practice guidelines (ACMG/AMP/CAP) would suggest an uncertain classification. Although LSDBs have been well established for research applications, our results suggest several challenges preclude their wider use in clinical practice.

An Audit on the Appropriateness of Coronary Computed Tomography Angiography Referrals in a Tertiary Cardiac Center.

PubMed

Alderazi, Ahmed Ali; Lynch, Mary

2017-01-01

In response to growing concerns regarding the overuse of coronary computed tomography angiography (CCTA) in the clinical setting, multiple societies, including the American College of Cardiology Foundation, have jointly published revised criteria regarding the appropriate use of this imaging modality. However, previous research indicates significant discrepancies in the rate of adherence to these guidelines. To assess the appropriateness of CCTA referrals in a tertiary cardiac center in Bahrain. This retrospective clinical audit examined the records of patients referred to CCTA between the April 1, 2015 and December 31, 2015 in Mohammed bin Khalifa Cardiac Center. Using information from medical records, each case was meticulously audited against guidelines to categorize it as appropriate, inappropriate, or uncertain. Of the 234 records examined, 176 (75.2%) were appropriate, 47 (20.1%) were uncertain, and 11 (4.7%) were inappropriate. About 74.4% of all referrals were to investigate coronary artery disease (CAD). The most common indication that was deemed appropriate was the detection of CAD in the setting of suspected ischemic equivalent in patients with an intermediate pretest probability of CAD (65.9%). Most referrals deemed inappropriate were requested to detect CAD in asymptomatic patients at low or intermediate risk of CAD (63.6%). This audit demonstrates a relatively low rate of inappropriate CCTA referrals, indicating the appropriate and efficient use of this resource in the Mohammed bin Khalifa Cardiac Center. Agreement on and reclassification of "uncertain" cases by guideline authorities would facilitate a deeper understanding of referral appropriateness.

Has Lean improved organizational decision making?

PubMed

Simons, Pascale; Benders, Jos; Bergs, Jochen; Marneffe, Wim; Vandijck, Dominique

2016-06-13

Purpose - Sustainable improvement is likely to be hampered by ambiguous objectives and uncertain cause-effect relations in care processes (the organization's decision-making context). Lean management can improve implementation results because it decreases ambiguity and uncertainties. But does it succeed? Many quality improvement (QI) initiatives are appropriate improvement strategies in organizational contexts characterized by low ambiguity and uncertainty. However, most care settings do not fit this context. The purpose of this paper is to investigate whether a Lean-inspired change program changed the organization's decision-making context, making it more amenable for QI initiatives. Design/methodology/approach - In 2014, 12 professionals from a Dutch radiotherapy institute were interviewed regarding their perceptions of a Lean program in their organization and the perceived ambiguous objectives and uncertain cause-effect relations in their clinical processes. A survey (25 questions), addressing the same concepts, was conducted among the interviewees in 2011 and 2014. The structured interviews were analyzed using a deductive approach. Quantitative data were analyzed using appropriate statistics. Findings - Interviewees experienced improved shared visions and the number of uncertain cause-effect relations decreased. Overall, more positive (99) than negative Lean effects (18) were expressed. The surveys revealed enhanced process predictability and standardization, and improved shared visions. Practical implications - Lean implementation has shown to lead to greater transparency and increased shared visions. Originality/value - Lean management decreased ambiguous objectives and reduced uncertainties in clinical process cause-effect relations. Therefore, decision making benefitted from Lean increasing QI's sustainability.

Presumptive specific clinical diagnosis of genital ulcer disease (GUD) in a primary health care setting in Nairobi.

PubMed

Ndinya-Achola, J O; Kihara, A N; Fisher, L D; Krone, M R; Plummer, F A; Ronald, A; Holmes, K K

1996-01-01

Of 22,274 patients 12 years of age or older attending a primary health care clinic in Nairobi, 1076 (4.8%) complained of symptoms suggesting a sexually transmitted disease (STD). Of these, 518 females and 462 males underwent complete clinical evaluation, and 78% had objective microbiologic or clinical evidence of STD, including 168 (17.1%) with genital ulcer disease (GUD). Presumptive specific clinical diagnoses on initial physical examination in cases of GUD were chancroid (131 patients), syphilis (25), genital herpes (15) and lymphogranuloma venereum (LGV) (1). Clinical diagnoses correlated only weakly with microbiological and serological diagnoses. Haemophilus ducreyi was isolated from 51 (41%) of the 125 with a clinical diagnosis of chancroid, and 4 (22%) of 18 with a diagnosis of syphilis, herpes, or LGV (P = 0.13). The rapid plasma reagin (RPR) test was reactive in 6 (24%) of 25 with a clinical diagnosis of syphilis, 18 (12.3%) of 146 with a diagnosis of chancroid or herpes, and 37 (4.7%) of 786 without a genital ulcer (P < 0.001, GUD vs no GUD). Sensitivity, specificity, and positive predictive value for presumptive clinical diagnosis of chancroid, relative to H. ducreyi isolation, were 93%, 16%, and 41%; and for diagnosis of syphilis, relative to reactive RPR, were 25%, 88% and 25%. Specific treatment based on presumptive specific clinical diagnosis frequently was inadequate for syphilis among patients with GUD and reactive RPR test. Syndromic treatment of GUD with antimicrobial combinations active against both chancroid and syphilis would be preferable to treatment with single drugs based on presumptive specific clinical diagnoses for this population.

Diagnosis of vulvovaginitis: comparison of clinical and microbiological diagnosis.

PubMed

Esim Buyukbayrak, Esra; Kars, Bulent; Karsidag, Ayse Yasemin Karageyim; Karadeniz, Bernan Ilkay; Kaymaz, Ozge; Gencer, Serap; Pirimoglu, Zehra Meltem; Unal, Orhan; Turan, Mehmet Cem

2010-11-01

The purpose of the present study was to compare the current diagnostic clinical and laboratory approaches to women with vulvovaginal discharge complaint. The secondary outcomes were to determine the prevalence of infections in our setting and to look for the relation between vulvovaginal infections and predisposing factors if present. Premenopausal women applying to our gynecology outpatient clinic with vaginal discharge complaint were enrolled prospectively into the study. Each patient evaluated clinically with direct observation of vaginal secretions, wet mount examination, whiff test, vaginal pH testing and chlamydia rapid antigen test. Each patient also evaluated microbiologically with vaginal discharge culture and gram staining. Clinical diagnosis was compared with the microbiological diagnosis (the gold standard). Diagnostic accuracy was measured with sensitivity, specificity, positive (ppv) and negative predictive values (npv). 460 patients were included in the study. 89.8% of patients received a clinical diagnosis whereas only 36% of them had microbiological diagnosis. The sensitivity, specificity, ppv, npv of clinical diagnosis over microbiological culture results were 95, 13, 38, 82%, respectively. The most commonly encountered microorganisms by culture were Candida species (17.4%) and Gardnerella vaginalis (10.2%). Clinically, the most commonly made diagnoses were mixed infection (34.1%), bacterial vaginosis (32.4%) and fungal infection (14.1%). Symptoms did not predict laboratory results. Predisposing factors (DM, vaginal douching practice, presence of IUD and usage of oral contraceptive pills) were not found to be statistically important influencing factors for vaginal infections. Clinical diagnosis based on combining symptoms with office-based testing improves diagnostic accuracy but is insufficient. The most effective approach also incorporates laboratory testing as an adjunct when a diagnosis is in question or treatment is failing.

Use of locally delivered dequalinium chloride in the treatment of vaginal infections: a review.

PubMed

Mendling, Werner; Weissenbacher, Ernst Rainer; Gerber, Stefan; Prasauskas, Valdas; Grob, Philipp

2016-03-01

Vaginal infections are responsible for a large proportion of gynaecological outpatient visits. Those are bacterial vaginosis (BV), vulvovaginal candidosis (VVC), aerobic vaginitis (AV) associated with aerobic bacteria, and mixed infections. Usual treatments show similar acceptable short-term efficacy, but frequent recurrences and increasing microbial resistance are unsolved issues. Furthermore, vaginal infections are associated with a variety of serious adverse outcomes in pregnancy and generally have a major impact on quality of life. Identifying the correct therapy can be challenging for the clinician, particularly in mixed infections. Dequalinium chloride (DQC) is an anti-microbial antiseptic agent with a broad bactericidal and fungicidal activity. Systemic absorption after vaginal application of DQC is very low and systemic effects negligible. Vaginal DQC (Fluomizin vaginal tablets) has been shown to have equal clinical efficacy as clindamycin in the treatment of BV. Its broad antimicrobial activity makes it appropriate for the treatment of mixed vaginal infections and in case of uncertain diagnosis. Moreover, resistance of pathogens is unlikely due to its multiple mode of action, and vaginal DQC provides also a reduced risk for post-treatment vaginal infections. Vaginal DQC (10 mg) as 6-day therapy offers a safe and effective option for empiric therapy of different vaginal infections in daily practice. This review summarizes the available and relevant pharmacological and clinical data for the therapy of vaginal infections with vaginal DQC and provides the rationale for its use in daily gynaecologic practice.

Lynch Syndrome Patients' Views of and Preferences for Return of Results Following Whole Exome Sequencing

PubMed Central

Joseph, Galen; Guiltinan, Jenna; Kianmahd, Jessica; Youngblom, Janey; Blanco, Amie

2015-01-01

Whole exome sequencing (WES) uses next generation sequencing technology to provide information on nearly all functional, protein-coding regions in an individual's genome. Due to the vast amount of information and incidental findings that can be generated from this technology, patient preferences must be investigated to help clinicians consent and return results to patients. Patients (n=19) who were previously clinically diagnosed with Lynch syndrome, but received uninformative negative Lynch syndrome genetic results through traditional molecular testing methods participated in semi-structured interviews after WES testing but before return of results to explore their views of WES and preferences for return of results. Analyses of interview results found that nearly all participants believed that the benefits of receiving all possible results generated from WES outweighed the undesirable effects. The majority of participants conveyed that relative to coping with a cancer diagnosis, information generated from WES would be manageable. Importantly, participants' experience with Lynch syndrome influenced their notions of genetic determinism, tolerance for uncertain results, and family communication plans. Participants would prefer to receive WES results in person from a genetic counselor or medical geneticist so that an expert could help explain the meaning and implications of the potentially large quantity and range of complicated results. These results underscore the need to study various populations with regard to the clinical use of WES in order to effectively and empathetically communicate the possible implications of this new technology and return results. PMID:24449059

[Gliomatosis cerebri].

PubMed

Bruna, J; Velasco, R

2010-04-01

gliomatosis cerebri (GC) is a rare, diffusely growing glial tumour characterized by extensive brain infiltration. The diversity of histological subtype and grade on presentation among different subjects, in addition to the usually poor response to treatment make GC an uncertain entity where many questions still remain unanswered. One article in this issue of NEUROLOGIA describes a series of 22 patients with GC, where clinical, therapeutic and outcome results are detailed. clinical presentation of GC is non-specific and, although the neuroimage is characteristic, the spectrum of differential diagnosis is wide. Despite the fact that known prognostic factors in glioma also seem to be involved in GC, the heterogeneity of pathology and molecular findings on biopsy samples makes it difficult to characterise GC correctly. Therefore, variability of outcome and response to therapy is the rule. Evidence on therapeutic strategies is based on case-series. According to this, the optimal treatment is not well established. Part of current research is focused on identifying molecular predictor factors of response to chemotherapy. the addition of chemotherapy in the classic treatment schedule based on radiotherapy seems to produce better responses in GC patients. However, the outcome of these patients remains poor with low survival rates. Phase III multi-centre trials to evaluate different therapeutic strategies in GC are essential. Further knowledge on the histological profile and molecular prognostic factors is also required. Patients should be stratified according to the prognostic factors identified. Published by Elservier España, S.L. All rights reserved.

Association of craniopharyngioma and pituitary adenoma.

PubMed

Guaraldi, Federica; Prencipe, Nunzia; di Giacomo, Valentina; Scanarini, Massimo; Gasco, Valentina; Gardiman, Marina Paola; Berton, Alessandro M; Ghigo, Ezio; Grottoli, Silvia

2013-08-01

Intracranial tumors of different histologic types infrequently affect patients with pituitary adenomas and no history of head irradiation. The association with craniopharyngioma is extremely rare. Aims of this paper are: (1) to provide a critical literature review of typical features of pituitary adenoma presenting in association with craniopharyngioma; (2) to describe the first documented (clinically, biochemically, histologically, and radiologically) case of aggressive, suprasellar papillary craniopharyngioma presenting with amenorrhea, progressive reduction of visual field, and severe headache in a 38-year-old woman, a decade after surgical cure for microprolactinoma associated with empty sella, during which she had carried two pregnancies; and (3) to discuss common etiopathogenetic mechanisms, in relation to the management of these lesions. Systematic literature search for English literature focusing on the association of craniopharyngioma and pituitary adenoma was performed using PubMed database. Additional relevant articles from references lists were also included. Clinical, laboratory, and radiological examinations performed in our patient for the two brain lesions at diagnosis and follow up were collected. Literature search retrieved nine articles. Typically, craniopharyngioma were of adamantinomatous type, occurred simultaneously to pituitary adenoma, presented with headache and visual loss, and affected men. No case of clearly documented metachronous lesion affecting a woman after pregnancy had been described before. Although very rare and with uncertain etiopathogenesis, second tumors (i.e., craniopharyngioma) should be considered in patients with a history of pituitary adenoma, presenting with suggestive signs and symptoms, even after a long disease-free period, in order to provide proper and prompt treatment.

Models and mechanisms of anxiety: evidence from startle studies

PubMed Central

Grillon, Christian

2009-01-01

Rationale Preclinical data indicates that threat stimuli elicit two classes of defensive behaviors, those that are associated with imminent danger and are characterized by avoidance or fight (fear), and those that are associated with temporally uncertain danger and are characterized by sustained apprehension and hypervigilance (anxiety). Objective To 1) review evidence for a distinction between fear and anxiety in animal and human experimental models using the startle reflex as an operational measure of aversive states, 2) describe experimental models of anxiety, as opposed to fear, in humans, 3) examine the relevance of these models to clinical anxiety. Results The distinction between phasic fear to imminent threat and sustained anxiety to temporally uncertain danger is suggested by psychopharmacological and behavioral evidence from ethological studies and can be traced back to distinct neuroanatomical systems, the amygdala and the bed nucleus of the stria terminalis. Experimental models of anxiety, not fear, are relevant to non-phobic anxiety disorders. Conclusions Progress in our understanding of normal and abnormal anxiety is critically dependent on our ability to model sustained aversive states to temporally uncertain threat. PMID:18058089

ACCF/SCCT/ACR/AHA/ASE/ASNC/NASCI/SCAI/SCMR 2010 appropriate use criteria for cardiac computed tomography. A report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, the Society of Cardiovascular Computed Tomography, the American College of Radiology, the American Heart Association, the American Society of Echocardiography, the American Society of Nuclear Cardiology, the North American Society for Cardiovascular Imaging, the Society for Cardiovascular Angiography and Interventions, and the Society for Cardiovascular Magnetic Resonance.

PubMed

Taylor, Allen J; Cerqueira, Manuel; Hodgson, John McB; Mark, Daniel; Min, James; O'Gara, Patrick; Rubin, Geoffrey D; Kramer, Christopher M; Berman, Daniel; Brown, Alan; Chaudhry, Farooq A; Cury, Ricardo C; Desai, Milind Y; Einstein, Andrew J; Gomes, Antoinette S; Harrington, Robert; Hoffmann, Udo; Khare, Rahul; Lesser, John; McGann, Christopher; Rosenberg, Alan; Schwartz, Robert; Shelton, Marc; Smetana, Gerald W; Smith, Sidney C

2010-11-23

The American College of Cardiology Foundation (ACCF), along with key specialty and subspecialty societies, conducted an appropriate use review of common clinical scenarios where cardiac computed tomography (CCT) is frequently considered. The present document is an update to the original CCT/cardiac magnetic resonance (CMR) appropriateness criteria published in 2006, written to reflect changes in test utilization, to incorporate new clinical data, and to clarify CCT use where omissions or lack of clarity existed in the original criteria (1). The indications for this review were drawn from common applications or anticipated uses, as well as from current clinical practice guidelines. Ninety-three clinical scenarios were developed by a writing group and scored by a separate technical panel on a scale of 1 to 9 to designate appropriate use, inappropriate use, or uncertain use. In general, use of CCT angiography for diagnosis and risk assessment in patients with low or intermediate risk or pretest probability for coronary artery disease (CAD) was viewed favorably, whereas testing in high-risk patients, routine repeat testing, and general screening in certain clinical scenarios were viewed less favorably. Use of noncontrast computed tomography (CT) for calcium scoring was rated as appropriate within intermediate- and selected low-risk patients. Appropriate applications of CCT are also within the category of cardiac structural and functional evaluation. It is anticipated that these results will have an impact on physician decision making, performance, and reimbursement policy, and that they will help guide future research.

ACCF/ACR/SCCT/SCMR/ASNC/NASCI/SCAI/SIR 2006 appropriateness criteria for cardiac computed tomography and cardiac magnetic resonance imaging. A report of the American College of Cardiology Foundation Quality Strategic Directions Committee Appropriateness Criteria Working Group.

PubMed

2006-10-01

Under the auspices of the American College of Cardiology Foundation (ACCF) together with key specialty and subspecialty societies, appropriateness reviews were conducted for 2 relatively new clinical cardiac imaging modalities, cardiac computed tomography (CCT) and cardiac magnetic resonance (CMR) imaging. The reviews assessed the risks and benefits of the imaging tests for several indications or clinical scenarios and scored them based on a scale of 1 to 9, where the upper range (7 to 9) implies that the test is generally acceptable and is a reasonable approach, and the lower range (1 to 3) implies that the test is generally not acceptable and is not a reasonable approach. The mid-range (4 to 6) indicates an uncertain clinical scenario. The indications for these reviews were drawn from common applications or anticipated uses, as few clinical practice guidelines currently exist for these techniques. These indications were reviewed by an independent group of clinicians and modified by the Working Group, and then panelists rated the indications based on the ACCF Methodology for Evaluating the Appropriateness of Cardiovascular Imaging, which blends scientific evidence and practice experience. A modified Delphi technique was used to obtain first and second round ratings of clinical indications after the panelists were provided with a set of literature reviews, evidence tables, and seminal references. The final ratings were evenly distributed among the 3 categories of appropriateness for both CCT and CMR. Use of tests for structure and function and for diagnosis in symptomatic, intermediate coronary artery disease (CAD) risk patients was deemed appropriate, while repeat testing and general screening uses were viewed less favorably. It is anticipated that these results will have a significant impact on physician decision making and performance, reimbursement policy, and future research directions.

Germline mutations of BRCA1 gene exon 11 are not associated with platinum response neither with survival advantage in patients with primary ovarian cancer: understanding the clinical importance of one of the biggest human exons. A study of the Tumor Bank Ovarian Cancer (TOC) Consortium.

PubMed

Dimitrova, Desislava; Ruscito, Ilary; Olek, Sven; Richter, Rolf; Hellwag, Alexander; Türbachova, Ivana; Woopen, Hannah; Baron, Udo; Braicu, Elena Ioana; Sehouli, Jalid

2016-09-01

Germline mutations in BRCA1 gene have been reported in up to 20 % of epithelial ovarian cancer (EOC) patients. Distinct clinical characteristics have been attributed to this special EOC population. We hypothesized that mutations in different BRCA1 gene exons may differently affect the clinical course of the disease. The aim of this study was to analyze, in a large cohort of primary EOCs, the clinical impact of mutations in BRCA1 gene exon 11, the largest exon of the gene sequence encoding the 60 % of BRCA1 protein. Two hundred sixty-three primary EOC patients, treated between 2000 and 2008 at Charité University Hospital of Berlin, were included. Patients' blood samples were obtained from the Tumor Ovarian Cancer (TOC) Network ( www.toc-network.de ). Direct sequencing of BRCA1 gene exon 11 was performed for each patient to detect mutations. Based on their BRCA1 exon 11 mutational status, patients were compared regarding clinico-pathological variables and survival. Mutations in BRCA1 exon 11 were found in 18 out of 263 patients (6.8 %). Further 10/263 (3.8 %) cases showed variants of uncertain significance (VUS). All exon 11 BRCA1-positive tumors (100 %) were Type 2 ovarian carcinomas (p = 0.05). Age at diagnosis was significantly younger in Type 2 exon 11 mutated patients (p = 0.01). On multivariate analysis, BRCA1 exon 11 mutational status was not found to be an independent predictive factor for optimal cytoreduction, platinum response, or survival. Mutations in BRCA1 gene exon 11 seem to predispose women to exclusively develop a Type 2 ovarian cancer at younger age. Exon 11 BRCA1-mutated EOC patients showed distinct clinico-pathological features but similar clinical outcome with respect to sporadic EOC patients.

ACCF/SCCT/ACR/AHA/ASE/ASNC/NASCI/SCAI/SCMR 2010 Appropriate Use Criteria for Cardiac Computed Tomography. A Report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, the Society of Cardiovascular Computed Tomography, the American College of Radiology, the American Heart Association, the American Society of Echocardiography, the American Society of Nuclear Cardiology, the North American Society for Cardiovascular Imaging, the Society for Cardiovascular Angiography and Interventions, and the Society for Cardiovascular Magnetic Resonance.

PubMed

Taylor, Allen J; Cerqueira, Manuel; Hodgson, John McB; Mark, Daniel; Min, James; O'Gara, Patrick; Rubin, Geoffrey D

2010-01-01

The American College of Cardiology Foundation (ACCF), along with key specialty and subspecialty societies, conducted an appropriate use review of common clinical scenarios where cardiac computed tomography (CCT) is frequently considered. The present document is an update to the original CCT/cardiac magnetic resonance (CMR) appropriateness criteria published in 2006, written to reflect changes in test utilization, to incorporate new clinical data, and to clarify CCT use where omissions or lack of clarity existed in the original criteria (1). The indications for this review were drawn from common applications or anticipated uses, as well as from current clinical practice guidelines. Ninety-three clinical scenarios were developed by a writing group and scored by a separate technical panel on a scale of 1 to 9 to designate appropriate use, inappropriate use, or uncertain use. In general, use of CCT angiography for diagnosis and risk assessment in patients with low or intermediate risk or pretest probability for coronary artery disease (CAD) was viewed favorably, whereas testing in high-risk patients, routine repeat testing, and general screening in certain clinical scenarios were viewed less favorably. Use of noncontrast computed tomography (CT) for calcium scoring was rated as appropriate within intermediate- and selected low-risk patients. Appropriate applications of CCT are also within the category of cardiac structural and functional evaluation. It is anticipated that these results will have an impact on physician decision making, performance, and reimbursement policy, and that they will help guide future research. © 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

ACCF/SCCT/ACR/AHA/ASE/ASNC/NASCI/SCAI/SCMR 2010 Appropriate Use Criteria for Cardiac Computed Tomography. A Report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, the Society of Cardiovascular Computed Tomography, the American College of Radiology, the American Heart Association, the American Society of Echocardiography, the American Society of Nuclear Cardiology, the North American Society for Cardiovascular Imaging, the Society for Cardiovascular Angiography and Interventions, and the Society for Cardiovascular Magnetic Resonance.

PubMed

Taylor, Allen J; Cerqueira, Manuel; Hodgson, John McB; Mark, Daniel; Min, James; O'Gara, Patrick; Rubin, Geoffrey D

2010-11-23

The American College of Cardiology Foundation, along with key specialty and subspecialty societies, conducted an appropriate use review of common clinical scenarios where cardiac computed tomography (CCT) is frequently considered. The present document is an update to the original CCT/cardiac magnetic resonance appropriateness criteria published in 2006, written to reflect changes in test utilization, to incorporate new clinical data, and to clarify CCT use where omissions or lack of clarity existed in the original criteria. The indications for this review were drawn from common applications or anticipated uses, as well as from current clinical practice guidelines. Ninety-three clinical scenarios were developed by a writing group and scored by a separate technical panel on a scale of 1 to 9 to designate appropriate use, inappropriate use, or uncertain use. In general, use of CCT angiography for diagnosis and risk assessment in patients with low or intermediate risk or pretest probability for coronary artery disease was viewed favorably, whereas testing in high-risk patients, routine repeat testing, and general screening in certain clinical scenarios were viewed less favorably. Use of noncontrast computed tomography for calcium scoring was rated as appropriate within intermediate- and selected low-risk patients. Appropriate applications of CCT are also within the category of cardiac structural and functional evaluation. It is anticipated that these results will have an impact on physician decision making, performance, and reimbursement policy, and that they will help guide future research.

The cost and cost-effectiveness of rapid testing strategies for yaws diagnosis and surveillance.

PubMed

Fitzpatrick, Christopher; Asiedu, Kingsley; Sands, Anita; Gonzalez Pena, Tita; Marks, Michael; Mitja, Oriol; Meheus, Filip; Van der Stuyft, Patrick

2017-10-01

Yaws is a non-venereal treponemal infection caused by Treponema pallidum subspecies pertenue. The disease is targeted by WHO for eradication by 2020. Rapid diagnostic tests (RDTs) are envisaged for confirmation of clinical cases during treatment campaigns and for certification of the interruption of transmission. Yaws testing requires both treponemal (trep) and non-treponemal (non-trep) assays for diagnosis of current infection. We evaluate a sequential testing strategy (using a treponemal RDT before a trep/non-trep RDT) in terms of cost and cost-effectiveness, relative to a single-assay combined testing strategy (using the trep/non-trep RDT alone), for two use cases: individual diagnosis and community surveillance. We use cohort decision analysis to examine the diagnostic and cost outcomes. We estimate cost and cost-effectiveness of the alternative testing strategies at different levels of prevalence of past/current infection and current infection under each use case. We take the perspective of the global yaws eradication programme. We calculate the total number of correct diagnoses for each strategy over a range of plausible prevalences. We employ probabilistic sensitivity analysis (PSA) to account for uncertainty and report 95% intervals. At current prices of the treponemal and trep/non-trep RDTs, the sequential strategy is cost-saving for individual diagnosis at prevalence of past/current infection less than 85% (81-90); it is cost-saving for surveillance at less than 100%. The threshold price of the trep/non-trep RDT (below which the sequential strategy would no longer be cost-saving) is US$ 1.08 (1.02-1.14) for individual diagnosis at high prevalence of past/current infection (51%) and US$ 0.54 (0.52-0.56) for community surveillance at low prevalence (15%). We find that the sequential strategy is cost-saving for both diagnosis and surveillance in most relevant settings. In the absence of evidence assessing relative performance (sensitivity and specificity), cost-effectiveness is uncertain. However, the conditions under which the combined test only strategy might be more cost-effective than the sequential strategy are limited. A cheaper trep/non-trep RDT is needed, costing no more than US$ 0.50-1.00, depending on the use case. Our results will help enhance the cost-effectiveness of yaws programmes in the 13 countries known to be currently endemic. It will also inform efforts in the much larger group of 71 countries with a history of yaws, many of which will have to undertake surveillance to confirm the interruption of transmission.

Idiopathic anaphylaxis.

PubMed

Fenny, Nana; Grammer, Leslie C

2015-05-01

Idiopathic anaphylaxis is a diagnosis of exclusion after other causes have been thoroughly evaluated and excluded. The pathogenesis of idiopathic anaphylaxis remains uncertain, although increased numbers of activated lymphocytes and circulating histamine-releasing factors have been implicated. Signs and symptoms of patients diagnosed with idiopathic anaphylaxis are indistinguishable from the manifestations of other forms of anaphylaxis. Treatment regimens are implemented based on the frequency and severity of patient symptoms and generally include the use of epinephrine autoinjectors, antihistamines, and steroids. The prognosis of idiopathic anaphylaxis is generally favorable with well-established treatment regimens and effective patient education. Copyright © 2015 Elsevier Inc. All rights reserved.

Giant floating thrombus localized in the ascending aorta.

PubMed

Akyildiz, Mahmut; Zorman, Yilmaz; Aksoy, Tamer; Yilmazer, Mustafa S; Erturk, Esra; Onar, Cagatay L; Midi, Ahmet

2010-06-01

We report the case of a 32-year-old male patient with symptoms of cerebrovascular accident manifesting with dysarthria. A transesophageal echocardiogram showed a floating mass localized in the ascending aorta, and a multislice computed tomography evaluation confirmed the diagnosis. With a comprehensive assessment of the mass, we decided on surgical intervention. A pedunculated and fragile mass was seen just near the right coronary ostium. The measured dimensions were 7.7 x 1.0 x 1.5 cm. The removed mass has been analyzed histopathologically and found to be the cause of the neurologic findings with an uncertain underlying etiology.

Leadership Training Program for Medical Staff in Belgium

ERIC Educational Resources Information Center

Claes, Neree; Brabanders, Valérie

2016-01-01

Today healthcare is facing many challenges in a volatile, uncertain, complex and ambiguous environment. There is a need to develop strong leaders who can cope with these challenges. This article describes the process of a leadership training program for healthcare professionals in Belgium (named "Clinical Leadership Program" or…

Study of MGUS, Smoldering Myeloma, Early MDS and CLL to Assess Molecular Events of Progression and Clinical Outcome

ClinicalTrials.gov

2017-08-25

Monoclonal Gammopathy of Undetermined Significance (MGUS); Chronic Lymphocytic Leukemia (CLL); Myelodysplastic-Myeloproliferative Diseases; Hematological Malignancies; B-cell Malignancy, Low-grade; Myelodysplastic Syndrome With Low-grade Lesions; IgG Monoclonal Gammopathy of Uncertain Significance; Smoldering Multiple Myeloma; Waldenstrom Macroglobulinemia

Amylase in drain fluid for the diagnosis of pancreatic leak in post-pancreatic resection.

PubMed

Davidson, Tsetsegdemberel Bat-Ulzii; Yaghoobi, Mohammad; Davidson, Brian R; Gurusamy, Kurinchi Selvan

2017-04-07

The treatment of people with clinically significant postoperative pancreatic leaks is different from those without clinically significant pancreatic leaks. It is important to know the diagnostic accuracy of drain fluid amylase as a triage test for the detection of clinically significant pancreatic leaks, so that an informed decision can be made as to whether the patient with a suspected pancreatic leak needs further investigations and treatment. There is currently no systematic review of the diagnostic test accuracy of drain fluid amylase for the diagnosis of clinically relevant pancreatic leak. To determine the diagnostic accuracy of amylase in drain fluid at 48 hours or more for the diagnosis of pancreatic leak in people who had undergone pancreatic resection. We searched MEDLINE, Embase, the Science Citation Index Expanded, and the National Institute for Health Research Health Technology Assessment (NIHR HTA) websites up to 20 February 2017. We searched the references of the included studies to identify additional studies. We did not restrict studies based on language or publication status, or whether data were collected prospectively or retrospectively. We also performed a 'related search' and 'citing reference' search in MEDLINE and Embase. We included all studies that evaluated the diagnostic test accuracy of amylase in the drain fluid at 48 hours or more for the diagnosis of pancreatic leak in people who had undergone pancreatic resection excluding total pancreatectomy. We planned to exclude case-control studies because these studies are prone to bias, but did not find any. At least two authors independently searched and screened the references produced by the search to identify relevant studies. Two review authors independently extracted data from the included studies. The included studies reported drain fluid amylase on different postoperative days and measured at different cut-off levels, so it was not possible to perform a meta-analysis using the bivariate model as planned. We have reported the sensitivity, specificity, post-test probability of a positive and negative drain fluid amylase along with 95% confidence interval (CI) on each of the different postoperative days and measured at different cut-off levels. A total of five studies including 868 participants met the inclusion criteria for this review. The five studies included in this review reported the value of drain fluid amylase at different thresholds and different postoperative days. The sensitivities and specificities were variable; the sensitivities ranged between 0.72 and 1.00 while the specificities ranged between 0.73 and 0.99 for different thresholds on different postoperative days. At the median prevalence (pre-test probability) of 15.9%, the post-test probabilities for pancreatic leak ranged between 35.9% and 95.4% for a positive drain fluid amylase test and ranged between 0% and 5.5% for a negative drain fluid amylase test.None of the studies used the reference standard of confirmation by surgery or by a combination of surgery and clinical follow-up, but used the International Study Group on Pancreatic Fistula (ISGPF) grade B and C as the reference standard. The overall methodological quality was unclear or high in all the studies. Because of the paucity of data and methodological deficiencies in the studies, we are uncertain whether drain fluid amylase should be used as a method for testing for pancreatic leak in an unselected population after pancreatic resection; and we judge that the optimal cut-off of drain fluid amylase for making the diagnosis of pancreatic leak is also not clear. Further well-designed diagnostic test accuracy studies with pre-specified index test threshold of drain fluid amylase (at three times more on postoperative day 5 or another suitable pre-specified threshold), appropriate follow-up (for at least six to eight weeks to ensure that there are no pancreatic leaks), and clearly defined reference standards (of surgical, clinical, and radiological confirmation of pancreatic leak) are important to reliably determine the diagnostic accuracy of drain fluid amylase in the diagnosis of pancreatic leak.

Cost-Effectiveness of Automated Digital Microscopy for Diagnosis of Active Tuberculosis.

PubMed

Jha, Swati; Ismail, Nazir; Clark, David; Lewis, James J; Omar, Shaheed; Dreyer, Andries; Chihota, Violet; Churchyard, Gavin; Dowdy, David W

2016-01-01

Automated digital microscopy has the potential to improve the diagnosis of tuberculosis (TB), particularly in settings where molecular testing is too expensive to perform routinely. The cost-effectiveness of TB diagnostic algorithms using automated digital microscopy remains uncertain. Using data from a demonstration study of an automated digital microscopy system (TBDx, Applied Visual Systems, Inc.), we performed an economic evaluation of TB diagnosis in South Africa from the health system perspective. The primary outcome was the incremental cost per new TB diagnosis made. We considered costs and effectiveness of different algorithms for automated digital microscopy, including as a stand-alone test and with confirmation of positive results with Xpert MTB/RIF ('Xpert', Cepheid, Inc.). Results were compared against both manual microscopy and universal Xpert testing. In settings willing to pay $2000 per incremental TB diagnosis, universal Xpert was the preferred strategy. However, where resources were not sufficient to support universal Xpert, and a testing volume of at least 30 specimens per day could be ensured, automated digital microscopy with Xpert confirmation of low-positive results could facilitate the diagnosis of 79-84% of all Xpert-positive TB cases, at 50-60% of the total cost. The cost-effectiveness of this strategy was $1280 per incremental TB diagnosis (95% uncertainty range, UR: $340-$3440) in the base case, but improved under conditions likely reflective of many settings in sub-Saharan Africa: $677 per diagnosis (95% UR: $450-$935) when sensitivity of manual smear microscopy was lowered to 0.5, and $956 per diagnosis (95% UR: $40-$2910) when the prevalence of multidrug-resistant TB was lowered to 1%. Although universal Xpert testing is the preferred algorithm for TB diagnosis when resources are sufficient, automated digital microscopy can identify the majority of cases and halve the cost of diagnosis and treatment when resources are more scarce and multidrug-resistant TB is not common.

Rett Syndrome: Revised Diagnostic Criteria and Nomenclature

PubMed Central

Neul, Jeffrey L.; Kaufmann, Walter E.; Glaze, Daniel G.; Christodoulou, John; Clarke, Angus J.; Bahi-Buisson, Nadia; Leonard, Helen; Bailey, Mark E. S.; Schanen, N. Carolyn; Zappella, Michele; Renieri, Alessandra; Huppke, Peter; Percy, Alan K.

2010-01-01

Objective Rett syndrome (RTT) is a severe neurodevelopmental disease that affects approximately 1 in 10,000 live female births and is often caused by mutations in Methyl-CpG-binding protein 2 (MECP2). Despite distinct clinical features, the accumulation of clinical and molecular information in recent years has generated considerable confusion regarding the diagnosis of RTT. The purpose of this work was revise and clarify 2002 consensus criteria for the diagnosis of RTT in anticipation of treatment trials. Method RettSearch members, representing the majority of the international clinical RTT specialists, participated in an iterative process to come to a consensus on a revised and simplified clinical diagnostic criteria for RTT. Results The clinical criteria required for the diagnosis of classic and atypical RTT were clarified and simplified. Guidelines for the diagnosis and molecular evaluation of specific variant forms of RTT were developed. Interpretation These revised criteria provide clarity regarding the key features required for the diagnosis of RTT and reinforce the concept that RTT is a clinical diagnosis based on distinct clinical criteria, independent of molecular findings. We recommend that these criteria and guidelines be utilized in any proposed clinical research. PMID:21154482

Prototypicality ratings of DSM-III criteria for personality disorders.

PubMed

Livesley, W J; Reiffer, L I; Sheldon, A E; West, M

1987-07-01

Although DSM-III personality disorder criteria have demonstrated acceptable reliability, the question of validity has not been adequately addressed. A first step in establishing the validity of diagnoses is to establish the validity of the criteria used to assess each diagnosis. The content validity of diagnostic criteria was investigated in relation to the larger set of potential criteria culled from the psychiatric literature. For each DSM-III axis II diagnosis, a panel of clinicians rated how prototypical each potential criterion was of the diagnosis in question. The results reveal problems with the organization and content of the criteria for most diagnoses. Many DSM-III criteria are composed of several statements linked by conjunctions or disjunctions. These component statements often received markedly different ratings, suggesting that criteria should be single statements. For most diagnoses, traits not included in DSM-III received higher ratings than did some DSM-III criteria. Suggestions are made to improve the distinctiveness and content validity of paranoid, schizoid, antisocial, borderline, avoidant, dependent, and compulsive personality disorders. The results for schizotypal personality disorder suggest that many clinicians are uncertain about this diagnosis. These findings provide a systematic way to modify definitions that contrasts with the more arbitrary ways in which diagnoses have previously been defined and redefined.

An Improved Evidential-IOWA Sensor Data Fusion Approach in Fault Diagnosis

PubMed Central

Zhou, Deyun; Zhuang, Miaoyan; Fang, Xueyi; Xie, Chunhe

2017-01-01

As an important tool of information fusion, Dempster–Shafer evidence theory is widely applied in handling the uncertain information in fault diagnosis. However, an incorrect result may be obtained if the combined evidence is highly conflicting, which may leads to failure in locating the fault. To deal with the problem, an improved evidential-Induced Ordered Weighted Averaging (IOWA) sensor data fusion approach is proposed in the frame of Dempster–Shafer evidence theory. In the new method, the IOWA operator is used to determine the weight of different sensor data source, while determining the parameter of the IOWA, both the distance of evidence and the belief entropy are taken into consideration. First, based on the global distance of evidence and the global belief entropy, the α value of IOWA is obtained. Simultaneously, a weight vector is given based on the maximum entropy method model. Then, according to IOWA operator, the evidence are modified before applying the Dempster’s combination rule. The proposed method has a better performance in conflict management and fault diagnosis due to the fact that the information volume of each evidence is taken into consideration. A numerical example and a case study in fault diagnosis are presented to show the rationality and efficiency of the proposed method. PMID:28927017

The CanPain SCI Clinical Practice Guidelines for Rehabilitation Management of Neuropathic Pain after Spinal Cord: screening and diagnosis recommendations.

PubMed

Mehta, S; Guy, S D; Bryce, T N; Craven, B C; Finnerup, N B; Hitzig, S L; Orenczuk, S; Siddall, P J; Widerström-Noga, E; Casalino, A; Côté, I; Harvey, D; Kras-Dupuis, A; Lau, B; Middleton, J W; Moulin, D E; O'Connell, C; Parrent, A G; Potter, P; Short, C; Teasell, R; Townson, A; Truchon, C; Wolfe, D; Bradbury, C L; Loh, E

2016-08-01

Clinical practice guidelines. To develop the first Canadian clinical practice guidelines for screening and diagnosis of neuropathic pain in people with spinal cord injury (SCI). The guidelines are relevant for inpatient and outpatient SCI rehabilitation settings in Canada. The CanPainSCI Working Group reviewed evidence to address clinical questions regarding screening and diagnosis of neuropathic pain after SCI. A consensus process was followed to achieve agreement on recommendations and clinical considerations. Twelve recommendations, based on expert consensus, were developed for the screening and diagnosis of neuropathic pain after SCI. The recommendations address methods for assessment, documentation tools, team member accountability, frequency of screening and considerations for diagnostic investigation. Important clinical considerations accompany each recommendation. The expert Working Group developed recommendations for the screening and diagnosis of neuropathic pain after SCI that should be used to inform practice.

Arthroscopy in the diagnosis of chondromalacia patellae.

PubMed Central

Leslie, I J; Bentley, G

1978-01-01

Chondromalacia patellae is difficult to diagnosis clinically with accuracy. In order to clarify the relevant symptoms and signs, 78 patients presenting with a clinical diagnosis of chondromalacia were examined by arthroscopy. In 49% of the knees no abnormalities were found. Presenting symptoms were similar in the normal and abnormal groups. Physical signs were more helpful in diagnosis and it is considered that the presence of an effusion, quadriceps wasting, and patello-femoral crepitus are the most important clinical findings in the diagnosis of chondromalacia patellae. The arthroscope is valuable instrument in establishing the diagnosis of chondromalacia patellae especially in the teenage female. Images PMID:749700

Scrotal calculi in clinical practice and their role in scrotal pain: A prospective study.

PubMed

Aslan, Ahmet; Tan, Sinan; Yıldırım, Halil; Dönmez, Uğur; Çam, Ali; Gezer, Mehmet Can; Teber, Mehmet Akif; Arslan, Halil

2015-09-01

Scrotal calculi are rare, and their clinical significance is uncertain. Scrotal pain is a frequent, hard-to-manage problem in urology clinics. Our purpose in this study was to determine the relationship between the presence of scrotal calculi and scrotal pain in a prospective manner. Sonography and color Doppler ultrasound of the scrotum were performed in 758 consecutive patients referred with scrotal pain. The pain was rated by using an 11-point numeric rating scale; scores were compared among patients with scrotal calculi with and without additional scrotal pathology. Scrotal calculi were detected in 73 of the 758 patients (9.6%). Scrotal pain (n = 50 [61%]) and a palpable mass in the scrotum (n = 25 [30.5%]) were the most common complaints in patients with scrotal calculi. Hydrocele (n = 17 [29.8%]) and varicocele (n = 15 [26.3%]) were the most commonly associated abnormalities; there was a statistically significant association between the presence of scrotal calculi and hydrocele (p < 0.01). Scrotal pain was present in 61 (83.5%) patients with scrotal calculi, and this association was significant (p < 0.001). The presence of scrotal pain and the correlation between location of calculi and pain in patients without additional scrotal abnormalities were also significant (p = 0.04 and p < 0.004, respectively). The prevalence of scrotal calculi was 9.6%, and hydrocele was found to be associated with scrotal calculi. We also found a significant relationship between the presence of calculi and scrotal pain. Because the etiology of scrotal pain is essential for appropriate treatment, scrotal calculi should be kept in mind when making a differential diagnosis of scrotal pain. © 2014 Wiley Periodicals, Inc. J Clin Ultrasound 43:406-411, 2015. © 2014 Wiley Periodicals, Inc.

A comparative immunohistochemical and immunophenotypical study on lymphocytes expression in patients affected by oral lichen planus.

PubMed

Lorenzini, Guido; Viviano, Massimo; Chisci, Elettra; Chisci, Glauco; Picciotti, Maria

2013-09-01

Oral lichen planus (OLP) is an immune-mediated mucocutaneous disease of uncertain aetiology. OLP has many manifestations: reticular, erosive, atrophic, plaque like, papular, bullous, with unique etiopathogenetic working. The purpose of this study is to find a link between different clinical types of lichen and the alterations of lymphocytes on peripheral blood and oral mucosa. A total of 21 patients were enrolled in this study. The mean age of patients was 53.82 years, between 31 and 78 years. OLP Diagnosis was afterwards confirmed by histopathology. Selected patients underwent to clinical evaluation, lesion characterization, incisional biopsy, samples histological analysis, peripheral blood collection. Blood specimens were submitted to cell count determination with differential, characterization of populations and circulating lymphocyte subpopulations using monoclonal antibodies in flow cytometry. Referring to the clinical presentation of lesions, patients were divided in two groups: red lesions (RL) and white lesions (WL) and compared with an age-matched control group. The results of the immunophenotypic study showed correlation between WL and the expression of CD19 lymphocytes (r = 0.693, P = 0.0005). The results of immunohistochemical study performed on histological specimens showed a significant correlation between RL group and expression of all lymphocyte tested (CD3 r = 0.722 P = 0.0002, CD4 r = 0.579 P = 0.0060, CD56 r = 0.513 P = 0.0173, CD8 r = 0.548 P = 0.0102). We assume there is the responsibility of the expression of lymphocytes, not only type but also as quantity, in determining RL or WL manifestation of OLP. Circulating lymphocytes may have a role, too. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Thyroid-Like Follicular Carcinoma of the Kidney in a Patient with Skull and Meningeal Metastasis: A Unique Case Report and Review of the Literature.

PubMed

Dong, Liang; Huang, Jiayu; Huang, Luke; Shi, Oumin; Liu, Qiang; Chen, Haige; Xue, Wei; Huang, Yiran

2016-04-01

Thyroid-like follicular carcinoma of the kidney (TLFCK) is an extremely rare subtype of renal cell carcinoma with close resemblance to the well-differentiated thyroid follicular neoplasms. TLFCK has not been included in the 2004 World Health Organization (WHO) classification due to the limited data available. Only 27 cases have been reported in the literature to date. Herein, we report a unique case of TLFCK that presented as a striking skull and meningeal metastasis 5 years after the initial diagnosis; this is the first case of TLFCK with such a novel metastasis pattern. A 68-year-old woman was found to have a right renal lesion using computed tomography (CT) during her regular clinical follow-up visit for bladder cancer, but she exhibited no obvious clinical symptoms. The CT scan showed a 4.4-cm diameter, slightly lobulated soft tissue mass in the right lower kidney, the pathological findings of which showed a TLFCK. Five years later, the patient had progressed to skull and meningeal metastasis. Both the renal tumor and the metastasis lesion were composed almost entirely of follicles with a dense, colloid-like material that resembled thyroid follicular carcinoma. However, no lesion was found in the thyroid gland. The neoplastic epithelial cells were strongly immunoreactive for cytokeratin 7 (and vimentin but negative for thyroid transcription factor-1 and thyroglobulin. This is the first reported case of TLFCK to consist of widespread metastases to the skull and meninges and provides evidence that this rare variant of renal cell carcinoma has uncertain malignant potential and can be more clinically aggressive than previously believed.

[Cancer screening in clinical practice: the value of shared decision-making].

PubMed

Cornuz, Jacques; Junod, Noëlle; Pasche, Olivier; Guessous, Idris

2010-07-14

Shared decision-making approach to uncertain clinical situations such as cancer screening seems more appropriate than ever. Shared decision making can be defined as an interactive process where physician and patient share all the stages of the decision making process. For patients who wish to be implicated in the management of their health conditions, physicians might express difficulty to do so. Use of patient decision aids appears to improve such process of shared decision making.

An evidence-based approach to assessing surgical versus clinical diagnosis of symptomatic endometriosis.

PubMed

Taylor, Hugh S; Adamson, G David; Diamond, Michael P; Goldstein, Steven R; Horne, Andrew W; Missmer, Stacey A; Snabes, Michael C; Surrey, Eric; Taylor, Robert N

2018-05-05

Challenges intrinsic to the accurate diagnosis of endometriosis contribute to an extended delay between the onset of symptoms and clinical confirmation. Intraoperative visualization, preferably with histologic verification, is considered by many professional organizations to be the gold standard by which endometriosis is diagnosed. Clinical diagnosis of symptomatic endometriosis via patient history, physical examination, and noninvasive tests, though more easily executed, is generally viewed as less accurate than surgical diagnosis. Technological advances and increased understanding of the pathophysiology of endometriosis warrant continuing reevaluation of the standard method for diagnosing symptomatic disease. A review of the published literature was therefore performed with the goal of comparing the accuracy of clinical diagnostic measures with that of surgical diagnosis. The current body of evidence suggests that clinical diagnosis of symptomatic endometriosis is more reliable than previously recognized and that surgical diagnosis has limitations that could be underappreciated. Regardless of the methodology used, women with suspected symptomatic endometriosis would be well served by a diagnostic paradigm that is reliable, conveys minimal risk of under- or over-diagnosis, lessens the time from symptom development to diagnosis, and guides the appropriate use of medical and surgical management strategies. © 2018 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.

Urologist characteristics predict use of androgen deprivation therapy for prostate cancer

PubMed Central

Shahinian, Vahakn B.; Kuo, Yong-fang; Freeman, Jean L.; Orihuela, Eduardo; Goodwin, James S.

2007-01-01

Purpose We have previously reported wide variations among urologists in use of androgen deprivation for prostate cancer. Using Surveillance, Epidemiology and End-Results (SEER)-Medicare linked data we examined how individual urologist characteristics influenced use of androgen deprivation therapy. Methods Participants included 82,375 men with prostate cancer diagnosed from January 1, 1992, through December 31, 2002, and 2,080 urologists providing care to them. Multi-level analyses were used to estimate likelihood of androgen deprivation use within six months of diagnosis in the overall cohort, a subgroup where use would be of uncertain benefit (primary therapy for localized prostate cancer), and a subgroup where use would be evidence-based (adjuvant therapy with radiation for locally advanced disease). Results In the overall cohort of patients, a multi-level model adjusted for patient, tumor and urologist characteristics (board certification, academic affiliation, patient panel size, years since medical school graduation) showed that the likelihood of androgen deprivation use was significantly higher for patients who saw urologists without an academic affiliation. This pattern was also noted when the analysis was limited to settings where androgen deprivation would have been of uncertain benefit. Odds ratios for use in that context were 1.66 (95%CI: 1.27-2.16) for no academic affiliation and 1.45 (95%CI:1.13-1.85) for minor versus major academic affiliation. Conclusion Use of androgen deprivation for prostate cancer varies by the characteristics of the urologist. Patients of non-academically affiliated urologists were significantly more likely to receive primary androgen deprivation therapy for localized prostate cancer, a setting where the benefits are uncertain. PMID:18048816

Stability and change in the clinical course of schizoaffective disorder.

PubMed

Durla, Anca; Lenciu, M; Bredicean, C; Papava, I; Cristanovici, M

2013-01-01

Schizoaffective disorder currently raises several questions, one of them being related to the stability of the clinical diagnosis over time. The aim of this study is to identify the clinical and evolutional particularities in the longitudinal course of schizoaffective disorder. 44 subjects with a current diagnosis of schizoaffective disorder have been assessed prospectively. Following parameters were analyzed: socio-demographic (age at onset, gender, educational, professional and marital status at onset) and clinical (total duration of evolution, diagnosis at onset, duration of the evolution until the switch to the schizoaffective disorder diagnosis). Socio-demographic parameters are similar to those in literature and the clinical assessment revealed that schizoaffective disorder is present as a diagnosis along with the longitudinal course of other types of psychosis. Schizoaffective disorder appears as a heterogeneous pathology in terms of the longitudinal course.

Certainty, leaps of faith, and tradition: rethinking clinical interventions.

PubMed

Dzurec, L C

1998-12-01

Clinical decision making requires that clinicians think quickly and in ways that will foster optimal, safe client care. Tradition influences clinical decision making, enhancing efficiency of resulting nursing action; however, since many decisions must be based on data that are either uncertain, incomplete, or indirect, clinicians are readily ensnared in processes involving potentially faulty logic associated with tradition. The author addresses the tenacity of tradition and then focuses on three processes--consensus formation, the grounding of certainty in inductive reasoning, and affirming the consequent--that have affected clinical decision making. For some recipients of care, tradition has had a substantial and invalid influence on their ability to access care.

Research on the Method of Big Data Collecting, Storing and Analyzing of Tongue Diagnosis System

NASA Astrophysics Data System (ADS)

Chen, Xiaowei; Wu, Qingfeng

2018-03-01

This paper analyzes the contents of the clinical data of tongue diagnosis of TCM (Traditional Chinese Medicine), and puts forward a method to collect, store and analyze the clinical data of tongue diagnosis. Under the guidance of TCM theory of syndrome differentiation and treatment, this method combines with Hadoop, which is a distributed computing system with strong expansibility, and integrates the functions of analysis and conversion of big data of clinic tongue diagnosis. At the same time, the consistency, scalability and security of big data in tongue diagnosis are realized.

Impact of live interactive teledermatology on diagnosis, disease management, and clinical outcomes.

PubMed

Lamel, Sonia; Chambers, Cindy J; Ratnarathorn, Mondhipa; Armstrong, April W

2012-01-01

To assess the impact of live interactive teledermatology consultations on changes in diagnosis, disease management, and clinical outcomes. We conducted a retrospective analysis of 1500 patients evaluated via live interactive teledermatology between 2003 and 2005 at the University of California, Davis. We compared diagnoses and treatment plans between the referring physicians and the teledermatologists. Patients with 2 or more teledermatology visits within a 1-year period were assessed for changes in clinical outcomes. Academic medical center with an established teledermatology program since 1996. Medical records were evaluated for 1500 patients who underwent live interactive teledermatology consultation. Patients seen for more than 1 teledermatology visit were included in the clinical outcome assessment. Live interactive teledermatology consultation. Changes in diagnosis, disease management, and clinical outcome. Compared with diagnoses and treatment plans from referring physicians, the 1500 live interactive teledermatology consultations resulted in changes in diagnosis in 69.9% of patients and changes in disease management in 97.7% of patients. Among 313 patients with at least 2 teledermatology visits within 1 year, clinical improvement was observed in 68.7% of patients. Multivariate analysis showed that changes in diagnosis (P = .01), changes in disease management (P < .001), and the number of teledermatology visits (P < .001) were significantly associated with improved clinical outcomes. Live interactive teledermatology consultations result in changes in diagnosis and disease management in most consultations. The numbers of live interactive teledermatology visits and changes in diagnosis and disease management are significantly associated with improved clinical outcomes.

Effects of an Uncertain Literature on All Facets of Clinical Decision Making

ERIC Educational Resources Information Center

Sammons, Morgan T.; Newman, Russ

2010-01-01

Greenberg (2010) is correct in his assertion that the investigational heuristic used to measure the efficacy of antidepressants is flawed. Robust placebo effects are endemic in the psychiatric literature, particularly in studies of antidepressants, and estimates of placebo responding have increased over time (Rief et al., 2009). In the case of…

Parents' Perceptions of the Usefulness of Chromosomal Microarray Analysis for Children with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Reiff, Marian; Giarelli, Ellen; Bernhardt, Barbara A.; Easley, Ebony; Spinner, Nancy B.; Sankar, Pamela L.; Mulchandani, Surabhi

2015-01-01

Clinical guidelines recommend chromosomal microarray analysis (CMA) for all children with autism spectrum disorders (ASDs). We explored the test's perceived usefulness among parents of children with ASD who had undergone CMA, and received a result categorized as pathogenic, variant of uncertain significance, or negative. Fifty-seven parents…

A historical note on the association between the legal status of expedited partner therapy and physician practice.

PubMed

Cramer, Ryan; Hogben, Matthew; Handsfield, H Hunter

2013-05-01

Potential legal liability for practicing expedited partner therapy is a common concern among providers, although it has been uncertain how these concerns translate into clinical practice. This study suggests that providers are more likely to practice expedited partner therapy in more favorable legal environments.

[Clinical characteristics, complications and mortality in 506 patients with infective endocarditis and determinants of survival rate at 10 years].

PubMed

Oyonarte, Miguel; Montagna, Rodrigo; Braun, Sandra; Rojo, Pamela; Jara, José L; Cereceda, Mauricio; Morales, Marcelo; Nazzal, Carolina; Nazal, Carolina; Alonso, Faustino

2012-12-01

Rates of morbidity and mortality in Infective Endocarditis (IE) remain high and prognosis in this disease is still difficult and uncertain. To study IE in Chile in its active phase during inpatient hospital stay and long term survival rates. Observational prospective national cohort study of 506 consecutive patients included between June 1,1998 and July 31, 2008, from 37 Chilean hospitals (secondary and tertiary centers) nationwide. The main findings were the presence of Rheumatic valve disease in 22.1 % of patients, a history of intravenous drug abuse (IVDA) only in 0.7%, the presence of Staphylococcus aureus in 29.2% of blood cultures, negative blood cultures in 33.2%, heart failure in 51.7% and native valve involvement in 86% of patients. Echocardiographic diagnosis was achieved in 94% of patients. Hospital mortality was 26.1% and its prognostics factors were persisting infection (Odds ratio (OR) 6.43, Confidence Interval (CI) 1.45-28.33%), failure of medical treatment and no surgical intervention (OR 48.8; CI 6.67-349.9). Five and 10 years survival rates were 75.6 and 48.6%, respectively. The significant prognostic factors for long term mortality, determined by multivariate analysis were the presence of diabetes, Staphylococcus aureus infection, sepsis, heart failure, renal failure and lack of surgical treatment during the IE episode. The microbiologic diagnosis of IE must be urgently improved in Chile. Mortality rates are still high (26.1%) partly because of a high incidence of negative blood cultures and the need for more surgical valve interventions during in-hospital period. Long term prognostic factors for mortality should be identified early to improve outcome.

Predictive value of the present-on-admission indicator for hospital-acquired venous thromboembolism.

PubMed

Khanna, Raman R; Kim, Sharon B; Jenkins, Ian; El-Kareh, Robert; Afsarmanesh, Nasim; Amin, Alpesh; Sand, Heather; Auerbach, Andrew; Chia, Catherine Y; Maynard, Gregory; Romano, Patrick S; White, Richard H

2015-04-01

Hospital-acquired venous thromboembolic (HA-VTE) events are an important, preventable cause of morbidity and death, but accurately identifying HA-VTE events requires labor-intensive chart review. Administrative diagnosis codes and their associated "present-on-admission" (POA) indicator might allow automated identification of HA-VTE events, but only if VTE codes are accurately flagged "not present-on-admission" (POA=N). New codes were introduced in 2009 to improve accuracy. We identified all medical patients with at least 1 VTE "other" discharge diagnosis code from 5 academic medical centers over a 24-month period. We then sampled, within each center, patients with VTE codes flagged POA=N or POA=U (insufficient documentation) and POA=Y or POA=W (timing clinically uncertain) and abstracted each chart to clarify VTE timing. All events that were not clearly POA were classified as HA-VTE. We then calculated predictive values of the POA=N/U flags for HA-VTE and the POA=Y/W flags for non-HA-VTE. Among 2070 cases with at least 1 "other" VTE code, we found 339 codes flagged POA=N/U and 1941 flagged POA=Y/W. Among 275 POA=N/U abstracted codes, 75.6% (95% CI, 70.1%-80.6%) were HA-VTE; among 291 POA=Y/W abstracted events, 73.5% (95% CI, 68.0%-78.5%) were non-HA-VTE. Extrapolating from this sample, we estimated that 59% of actual HA-VTE codes were incorrectly flagged POA=Y/W. POA indicator predictive values did not improve after new codes were introduced in 2009. The predictive value of VTE events flagged POA=N/U for HA-VTE was 75%. However, sole reliance on this flag may substantially underestimate the incidence of HA-VTE.

[Etiology of initially unexplained confusion of excitability in deadly nightshade poisoning with suicidal intent. Symptoms, differential diagnosis, toxicology and physostigmine therapy of anticholinergic syndrome].

PubMed

Heindl, S; Binder, C; Desel, H; Matthies, U; Lojewski, I; Bandelow, B; Kahl, G F; Chemnitius, J M

2000-11-10

After a walk in a wood a 55-year-old teacher was admitted to the emergency unit of a university hospital because of somnolence and excitability. Her rectal temperature was 37.8 degrees C, she had sinus tachycardia (rate of 130/min) but no other significant findings. With the exception of C-reactive protein (10 mg/dl), MCV (101 fl), MCH (34 pg) and arterial blood gases (pH 7.483, pCO2 35.5 mmHg, base excess 5.1 mmp/l) laboratory tests were within normal limits. Qualitative screening of serum for benzodiazepines, barbiturates and antidepressives was negative. Neurological examination, including lumbar puncture and cranial computed tomography were noncontributory. 10 hours after admission the patient developed signs of an anticholinergic syndrome with mydriasis, dry mouth, tachycardia, hot skin and an atonic bladder. Physostigmine 2 mg completely reversed the neurological and mental symptoms. After gas chromatography, mass-spectrometry of a urine sample showed an atropine molecular fragment with a molecular weight of 271. At intervals of 3 to 5 hours the recurrence of confusion and excitability required 4 further i.v. injection of physostigmine. The patient subsequently became accessible to psychiatric examination and reported that during the walk she had swallowed 8-10 berries of deadly nightshade with suicidal intent. In case of excitability and confusion as well as somnolence or coma of uncertain aetiology an anticholinergic syndrome caused by ingestion of atropine-containing plants or psychoactive drugs (phenothiazines, butyrophenones, tri- or tetracyclic antidepressants) should be included in the differential diagnosis. If there are suggestive clinical findings (tachycardia, somnolence, coma or threatened respiratory arrest, physostigmine should be given if there are no contraindications.

A case of idiopathic hypertrophic pachymeningitis presenting with chronic headache and multiple cranial nerve palsies: A case report.

PubMed

Huang, Yuanyuan; Chen, Jun; Gui, Li

2017-07-01

Idiopathic hypertrophic pachymeningitis (IHP) is a rare condition, characterized by a chronic fibrosing inflammatory process usually involving either the intracranial or spinal dura mater, but rarely both. Here, we report a rare case of IHP affecting both the intracranial and spinal dura mater. We also discussed the diagnosis, management, and outcome of IHP. We reviewed the case of a 60-year-old woman presenting with chronic headache, multiple cranial nerve palsies and gait disturbance. Magnetic resonance imaging (MRI) of her head revealed thickened and contrast-enhanced dura in the craniocervical region as well as obstructive hydrocephalus and cerebellar tonsillar herniation. The patient had a suboccipital craniectomy and posterior decompression through C1 plus a total laminectomy. The dura was partially resected to the extent of the bony decompression, and a duroplasty was performed. Microscopic examination of the surgically resected sample showed chronic inflammatory changes, lymphoplasmacytic cell infiltration, fibrous tissue hyperplasia, and hyaline degeneration. Blood tests to evaluate the secondary causes of hypertrophic pachymeningitis (HP) were unremarkable. Steroid was used to treat suspected IHP. Postoperatively, the patient showed gradual improvement in her headache, glossolalia, and bucking. Prior to discharge, a follow-up MRI showed improvement of the dura mater thickening. IHP is a chronic inflammatory disorder of the dura mater that usually causes neurological deficits. Clinical manifestations of IHP, MRI findings, and laboratory abnormalities are the essential components for making an accurate diagnosis. When the radiological or laboratory evaluation is uncertain, but neurological deficits are present, a prompt surgical approach should be considered. Postoperative steroid therapy and close observation for recurrence are necessary to ensure a good long-term outcome.

Cancer-specific mortality, cure fraction, and noncancer causes of death among diffuse large B-cell lymphoma patients in the immunochemotherapy era.

PubMed

Howlader, Nadia; Mariotto, Angela B; Besson, Caroline; Suneja, Gita; Robien, Kim; Younes, Naji; Engels, Eric A

2017-09-01

Survival after the diagnosis of diffuse large B-cell lymphoma (DLBCL) has been increasing since 2002 because of improved therapies; however, long-term outcomes for these patients in the modern treatment era are still unknown. Using Surveillance, Epidemiology, and End Results data, this study first assessed factors associated with DLBCL-specific mortality during 2002-2012. An epidemiologic risk profile, based on clinical and demographic characteristics, was used to stratify DLBCL cases into low-, medium-, and high-risk groups. The proportions of DLBCL cases that might be considered cured in these 3 risk groups was estimated. Risks of death due to various noncancer causes among DLBCL cases versus the general population were also calculated with standardized mortality ratios (SMRs). Overall, 8274 deaths were recorded among 18,047 DLBCL cases; 76% of the total deaths were attributed to DLBCL, and 24% were attributed to noncancer causes. The 10-year survival rates for the low-, medium-, and high-risk groups were 80%, 60%, and 36%, respectively. The estimated cure proportions for the low-, medium-, and high-risk groups were 73%, 49%, and 27%, respectively; however, these cure estimates were uncertain because of the need to extrapolate the survival curves beyond the follow-up time. Mortality risks calculated with SMRs were elevated for conditions including vascular diseases (SMR, 1.3), infections (SMR, 3.1), gastrointestinal diseases (SMR, 2.5), and blood diseases (SMR, 4.6). These mortality risks were especially high within the initial 5 years after the diagnosis and declined after 5 years. Some DLBCL patients may be cured of their cancer, but they continue to experience excess mortality from lymphoma and other noncancer causes. Cancer 2017;123:3326-34. © 2017 American Cancer Society. © 2017 American Cancer Society.

Potential protein biomarkers for burning mouth syndrome discovered by quantitative proteomics

PubMed Central

Ji, Eoon Hye; Diep, Cynthia; Liu, Tong; Li, Hong; Merrill, Robert; Messadi, Diana

2017-01-01

Burning mouth syndrome (BMS) is a chronic pain disorder characterized by severe burning sensation in normal looking oral mucosa. Diagnosis of BMS remains to be a challenge to oral healthcare professionals because the method for definite diagnosis is still uncertain. In this study, a quantitative saliva proteomic analysis was performed in order to identify target proteins in BMS patients’ saliva that may be used as biomarkers for simple, non-invasive detection of the disease. By using isobaric tags for relative and absolute quantitation labeling and liquid chromatography-tandem mass spectrometry to quantify 1130 saliva proteins between BMS patients and healthy control subjects, we found that 50 proteins were significantly changed in the BMS patients when compared to the healthy control subjects (p ≤ 0.05, 39 up-regulated and 11 down-regulated). Four candidates, alpha-enolase, interleukin-18 (IL-18), kallikrein-13 (KLK13), and cathepsin G, were selected for further validation. Based on enzyme-linked immunosorbent assay measurements, three potential biomarkers, alpha-enolase, IL-18, and KLK13, were successfully validated. The fold changes for alpha-enolase, IL-18, and KLK13 were determined as 3.6, 2.9, and 2.2 (burning mouth syndrome vs. control), and corresponding receiver operating characteristic values were determined as 0.78, 0.83, and 0.68, respectively. Our findings indicate that testing of the identified protein biomarkers in saliva might be a valuable clinical tool for BMS detection. Further validation studies of the identified biomarkers or additional candidate biomarkers are needed to achieve a multi-marker prediction model for improved detection of BMS with high sensitivity and specificity. PMID:28326926

Prevalence of hypothyroidism in patients with frozen shoulder.

PubMed

Schiefer, Marcio; Teixeira, Patricia F Santos; Fontenelle, Cesar; Carminatti, Tiago; Santos, Daniel A; Righi, Lucas D; Conceição, Flavia Lucia

2017-01-01

Hypothyroidism and frozen shoulder (FS) have been associated, although this relationship remains uncertain. The main objective of this study was to determine the prevalence of hypothyroidism in patients with FS. A case-control study was performed to compare FS patients (cases) with patients who visited an orthopedic service for other clinical conditions (controls). FS was diagnosed according to specific criteria based on anamnesis, physical examination, and shoulder radiographs. A specific questionnaire was applied, and measurements of serum thyroid-stimulating hormone (TSH) and free tetraiodothyronine were performed in all subjects. We evaluated 401 shoulders from 93 FS patients and 151 controls. The prevalence of hypothyroidism diagnosis was significantly higher in the FS group (27.2% vs. 10.7%; P = .001). There was also a tendency for higher prevalence of bilateral FS among patients with elevated TSH levels (P = .09). Mean serum TSH levels were higher in patients with bilateral FS compared with those with unilateral compromise (3.39 vs. 2.28; P = .05) and were higher in patients with severe FS compared with those with mild and moderate FS together (3.15 vs. 2.21; P = .03). Multivariate analysis showed that FS was independently related to a diagnosis of hypothyroidism (odds ratio, 3.1 [1.5-6.4]; P = .002). There was a trend toward independent association between high serum TSH levels and both severe (odds ratio, 3.5 [0.8-14.9]; P = .09) and bilateral (odds ratio, 11.7 [0.9-144.8]; P = .05) compromise. The prevalence of hypothyroidism was significantly higher in FS patients than in controls. The results suggest that higher serum TSH levels are associated with bilateral and severe cases of FS. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Accuracy of clinical diagnosis of Parkinson disease: A systematic review and meta-analysis.

PubMed

Rizzo, Giovanni; Copetti, Massimiliano; Arcuti, Simona; Martino, Davide; Fontana, Andrea; Logroscino, Giancarlo

2016-02-09

To evaluate the diagnostic accuracy of clinical diagnosis of Parkinson disease (PD) reported in the last 25 years by a systematic review and meta-analysis. We searched for articles published between 1988 and August 2014. Studies were included if reporting diagnostic parameters regarding clinical diagnosis of PD or crude data. The selected studies were subclassified based on different study setting, type of test diagnosis, and gold standard. Bayesian meta-analyses of available data were performed. We selected 20 studies, including 11 using pathologic examination as gold standard. Considering only these 11 studies, the pooled diagnostic accuracy was 80.6% (95% credible interval [CrI] 75.2%-85.3%). Accuracy was 73.8% (95% CrI 67.8%-79.6%) for clinical diagnosis performed mainly by nonexperts. Accuracy of clinical diagnosis performed by movement disorders experts rose from 79.6% (95% CrI 46%-95.1%) of initial assessment to 83.9% (95% CrI 69.7%-92.6%) of refined diagnosis after follow-up. Using UK Parkinson's Disease Society Brain Bank Research Center criteria, the pooled diagnostic accuracy was 82.7% (95% CrI 62.6%-93%). The overall validity of clinical diagnosis of PD is not satisfying. The accuracy did not significantly improve in the last 25 years, particularly in the early stages of disease, where response to dopaminergic treatment is less defined and hallmarks of alternative diagnoses such as atypical parkinsonism may not have emerged. Misclassification rate should be considered to calculate the sample size both in observational studies and randomized controlled trials. Imaging and biomarkers are urgently needed to improve the accuracy of clinical diagnosis in vivo. © 2016 American Academy of Neurology.

A novel research design can aid disinvestment from existing health technologies with uncertain effectiveness, cost-effectiveness, and/or safety.

PubMed

Haines, Terry; O'Brien, Lisa; McDermott, Fiona; Markham, Donna; Mitchell, Deb; Watterson, Dina; Skinner, Elizabeth

2014-02-01

Disinvestment is critical for ensuring the long-term sustainability of health-care services. Key barriers to disinvestment are heterogeneity between research and clinical settings, absence of evidence of effectiveness of some health technologies, and exposure of patients and organizations to risks and poor outcomes. We aimed to develop a feasible research design that can evaluate disinvestment in health technologies of uncertain effectiveness or cost-effectiveness. This article (1) establishes the need for disinvestment methodologies, (2) identifies the ethical concerns and feasibility constraints of conventional research designs for this issue, (3) describes the planning, implementation, and analytical framework for a novel disinvestment-specific study design, and (4) describes potential limitations in application of this design. The stepped-wedge, roll-in cluster randomized controlled trial can facilitate the disinvestment process, whereas generating evidence to determine whether the decision to disinvest was sound in the clinical environment. A noninferiority research paradigm may be applied to this methodology to demonstrate that the removal of a health technology does not adversely affect outcomes. This research design can be applied across multiple fields and will assist determination of whether specific health technologies are clinically effective, cost-effective, and safe. Copyright © 2014 Elsevier Inc. All rights reserved.

Celiac Disease: Diagnosis.

PubMed

Byrne, Greg; Feighery, Conleth F

2015-01-01

Historically the diagnosis of celiac disease has relied upon clinical, serological, and histological evidence. In recent years the use of sensitive serological methods has meant an increase in the diagnosis of celiac disease. The heterogeneous nature of the disorder presents a challenge in the study and diagnosis of the disease with patients varying from subclinical or latent disease to patients with overt symptoms. Furthermore the related gluten-sensitive disease dermatitis herpetiformis, while distinct in some respects, shares clinical and serological features with celiac disease. Here we summarize current best practice for the diagnosis of celiac disease and briefly discuss newer approaches. The advent of next-generation assays for diagnosis and newer clinical protocols may result in more sensitive screening and ultimately the possible replacement of the intestinal biopsy as the gold standard for celiac disease diagnosis.

The schizoaffective disorder diagnosis: a conundrum in the clinical setting.

PubMed

Wilson, Jo Ellen; Nian, Hui; Heckers, Stephan

2014-02-01

The term schizoaffective was introduced to describe the co-occurrence of both psychotic and affective symptoms. Overtime, as the diagnosis schizoaffective disorder was added to diagnostic manuals, significant concerns were raised as to the reliability and clinical utility of the diagnosis. We recruited 134 psychiatrically hospitalized subjects who had received a diagnosis of schizophrenia, schizoaffective disorder or bipolar disorder with psychotic features by their treating clinician. The subjects were also diagnosed by trained research personnel with the Structured Clinical Interview of the DSM-IV-TR, employing an explicit time threshold for criterion C of the schizoaffective disorder diagnosis. We found significant differences between the clinical and research diagnoses. Clinicians diagnosed 48 patients (36%) with schizophrenia, 50 patients (37%) with schizoaffective disorder and 36 patients (27%) with psychotic bipolar disorder. In contrast, researchers diagnosed 64 patients (48%) with schizophrenia, 38 patients (28%) with schizoaffective disorder and 32 patients (24%) with psychotic bipolar disorder. This was a statistically significant disagreement between the research and clinical diagnoses (p = 0.003) and indicates that clinicians choose the less severe diagnosis for psychotic patients. We conclude that a more stringent criterion C for the schizoaffective disorder diagnosis will address an implicit bias in clinical practice and will affect the prevalence of the psychotic disorder diagnoses.

The schizoaffective disorder diagnosis: A conundrum in the clinical setting

PubMed Central

Wilson, Jo Ellen; Nian, Hui; Heckers, Stephan

2014-01-01

The term schizoaffective was introduced to describe the co-occurrence of both psychotic and affective symptoms. Over time, as the diagnosis schizoaffective disorder was added to diagnostic manuals, significant concerns were raised as to the reliability and clinical utility of the diagnosis. We recruited 134 psychiatrically hospitalized subjects who had received a diagnosis of schizophrenia, schizoaffective disorder or bipolar disorder with psychotic features by their treating clinician. The subjects were also diagnosed by trained research personnel with the Structured Clinical Interview of the DSM-IV-TR, employing an explicit time threshold for criterion C of the schizoaffective disorder diagnosis. We found significant differences between the clinical and research diagnoses. Clinicians diagnosed 48 patients (36%) with schizophrenia, 50 patients (37%) with schizoaffective disorder and 36 patients (27%) with psychotic bipolar disorder. In contrast, researchers diagnosed 64 patients (48%) with schizophrenia, 38 patients (28%) with schizoaffective disorder and 32 patients (24%) with psychotic bipolar disorder. This was a statistically significant disagreement between the research and clinical diagnoses (p = 0.003) and indicates that clinicians choose the less severe diagnosis for psychotic patients. We conclude that a more stringent criterion C for the schizoaffective disorder diagnosis will address an implicit bias in clinical practice and will affect the prevalence of the psychotic disorder diagnoses. PMID:23625467

Comprehensive molecular diagnosis of 179 Leber congenital amaurosis and juvenile retinitis pigmentosa patients by targeted next generation sequencing

PubMed Central

Wang, Xia; Wang, Hui; Sun, Vincent; Tuan, Han-Fang; Keser, Vafa; Wang, Keqing; Ren, Huanan; Lopez, Irma; Zaneveld, Jacques E; Siddiqui, Sorath; Bowles, Stephanie; Khan, Ayesha; Salvo, Jason; Jacobson, Samuel G; Iannaccone, Alessandro; Wang, Feng; Birch, David; Heckenlively, John R; Fishman, Gerald A; Traboulsi, Elias I; Li, Yumei; Wheaton, Dianna; Koenekoop, Robert K; Chen, Rui

2014-01-01

Background Leber congenital amaurosis (LCA) and juvenile retinitis pigmentosa (RP) are inherited retinal diseases that cause early onset severe visual impairment. An accurate molecular diagnosis can refine the clinical diagnosis and allow gene specific treatments. Methods We developed a capture panel that enriches the exonic DNA of 163 known retinal disease genes. Using this panel, we performed targeted next generation sequencing (NGS) for a large cohort of 179 unrelated and prescreened patients with the clinical diagnosis of LCA or juvenile RP. Systematic NGS data analysis, Sanger sequencing validation, and segregation analysis were utilised to identify the pathogenic mutations. Patients were revisited to examine the potential phenotypic ambiguity at the time of initial diagnosis. Results Pathogenic mutations for 72 patients (40%) were identified, including 45 novel mutations. Of these 72 patients, 58 carried mutations in known LCA or juvenile RP genes and exhibited corresponding phenotypes, while 14 carried mutations in retinal disease genes that were not consistent with their initial clinical diagnosis. We revisited patients in the latter case and found that homozygous mutations in PRPH2 can cause LCA/juvenile RP. Guided by the molecular diagnosis, we reclassified the clinical diagnosis in two patients. Conclusions We have identified a novel gene and a large number of novel mutations that are associated with LCA/juvenile RP. Our results highlight the importance of molecular diagnosis as an integral part of clinical diagnosis. PMID:23847139

Psychomedical care in gender identity dysphoria during adolescence.

PubMed

Sánchez Lorenzo, Isabel; Mora Mesa, Juan José; Oviedo de Lúcas, Olga

In the clinical literature, the term gender dysphoria is used to define the perception of rejection that a person has to the fact of being male or female. In children and adolescents, gender identity dysphoria is a complex clinical entity. The result of entity is variable and uncertain, but in the end only a few will be transsexuals in adulthood. METHODOLOGY: RESULTS AND CONCLUSIONS. Copyright © 2015 SEP y SEPB. Publicado por Elsevier España, S.L.U. All rights reserved.

[Interventional radiology: current problems and new directions].

PubMed

Santos Martín, E; Crespo Vallejo, E

2014-01-01

In recent years, vascular and interventional radiology has become one of the fastest growing diagnostic and therapeutic specialties. This growth has been based on a fundamental concept: performing minimally invasive procedures under imaging guidance. This attractive combination has led to the interest of professionals from other clinical specialties outside radiology in performing this type of intervention. The future of vascular and interventional radiology, although uncertain, must be linked to clinical practice and multidisciplinary teamwork. Copyright © 2011 SERAM. Published by Elsevier Espana. All rights reserved.

[Thinking about the present primary open angle glaucoma early diagnosis concepts and methods].

PubMed

Ren, Zeqin

2014-05-01

Early diagnosis of primary open-angle glaucoma has not been clear and consistent in concepts and methods. At present, according to the pathophysiology process of optic nerve damage and its detection technology, early diagnosis on the concept still belongs to the early clinical diagnosis instead of preclinical diagnosis, and on the method depends on the fundus as morphological index combined with the visual field as functional index. The direction of early clinical diagnosis mainly lies in exploring more effective diagnosis index, rather than blindly adopt new diagnostic technology.

ACCF/SCAI/AATS/AHA/ASE/ASNC/HFSA/HRS/SCCM/SCCT/SCMR/STS 2012 appropriate use criteria for diagnostic catheterization: American College of Cardiology Foundation Appropriate Use Criteria Task Force Society for Cardiovascular Angiography and Interventions American Association for Thoracic Surgery American Heart Association, American Society of Echocardiography American Society of Nuclear Cardiology Heart Failure Society of America Heart Rhythm Society, Society of Critical Care Medicine Society of Cardiovascular Computed Tomography Society for Cardiovascular Magnetic Resonance Society of Thoracic Surgeons.

PubMed

Patel, Manesh R; Bailey, Steven R; Bonow, Robert O; Chambers, Charles E; Chan, Paul S; Dehmer, Gregory J; Kirtane, Ajay J; Wann, L Samuel; Ward, R Parker; Douglas, Pamela S; Patel, Manesh R; Bailey, Steven R; Altus, Philip; Barnard, Denise D; Blankenship, James C; Casey, Donald E; Dean, Larry S; Fazel, Reza; Gilchrist, Ian C; Kavinsky, Clifford J; Lakoski, Susan G; Le, D Elizabeth; Lesser, John R; Levine, Glenn N; Mehran, Roxana; Russo, Andrea M; Sorrentino, Matthew J; Williams, Mathew R; Wong, John B; Wolk, Michael J; Bailey, Steven R; Douglas, Pamela S; Hendel, Robert C; Kramer, Christopher M; Min, James K; Patel, Manesh R; Shaw, Leslee; Stainback, Raymond F; Allen, Joseph M

2012-09-01

The American College of Cardiology Foundation, in collaboration with the Society for Cardiovascular Angiography and Interventions and key specialty and subspecialty societies, conducted a review of common clinical scenarios where diagnostic catheterization is frequently considered. The indications (clinical scenarios) were derived from common applications or anticipated uses, as well as from current clinical practice guidelines and results of studies examining the implementation of noninvasive imaging appropriate use criteria. The 166 indications in this document were developed by a diverse writing group and scored by a separate independent technical panel on a scale of 1 to 9, to designate appropriate use (median 7 to 9), uncertain use (median 4 to 6), and inappropriate use (median 1 to 3). Diagnostic catheterization may include several different procedure components. The indications developed focused primarily on 2 aspects of diagnostic catheterization. Many indications focused on the performance of coronary angiography for the detection of coronary artery disease with other procedure components (e.g., hemodynamic measurements, ventriculography) at the discretion of the operator. The majority of the remaining indications focused on hemodynamic measurements to evaluate valvular heart disease, pulmonary hypertension, cardiomyopathy, and other conditions, with the use of coronary angiography at the discretion of the operator. Seventy-five indications were rated as appropriate, 49 were rated as uncertain, and 42 were rated as inappropriate. The appropriate use criteria for diagnostic catheterization have the potential to impact physician decision making, healthcare delivery, and reimbursement policy. Furthermore, recognition of uncertain clinical scenarios facilitates identification of areas that would benefit from future research. © 2012 Wiley Periodicals, Inc. Copyright © 2012 Wiley Periodicals, Inc.

Added Diagnostic Value of Cerebrospinal Fluid Biomarkers for Differential Dementia Diagnosis in an Autopsy-Confirmed Cohort.

PubMed

Niemantsverdriet, Ellis; Feyen, Bart F E; Le Bastard, Nathalie; Martin, Jean-Jacques; Goeman, Johan; De Deyn, Peter Paul; Bjerke, Maria; Engelborghs, Sebastiaan

2018-01-01

Differential dementia diagnosis remains a challenge due to overlap of clinical profiles, which often results in diagnostic doubt. Determine the added diagnostic value of cerebrospinal fluid (CSF) biomarkers for differential dementia diagnosis as compared to autopsy-confirmed diagnosis. Seventy-one dementia patients with autopsy-confirmed diagnoses were included in this study. All neuropathological diagnoses were established according to standard neuropathological criteria and consisted of Alzheimer's disease (AD) or other dementias (NONAD). CSF levels of Aβ1 - 42, T-tau, and P-tau181 were determined and interpreted based on the IWG-2 and NIA-AA criteria, separately. A panel of three neurologists experienced with dementia made clinical consensus dementia diagnoses. Clinical and CSF biomarker diagnoses were compared to the autopsy-confirmed diagnoses. Forty-two patients (59%) had autopsy-confirmed AD, whereas 29 patients (41%) had autopsy-confirmed NONAD. Of the 24 patients with an ambiguous clinical dementia diagnosis, a correct diagnosis would have been established in 67% of the cases applying CSF biomarkers in the context of the IWG-2 or the NIA-AA criteria respectively. AD CSF biomarkers have an added diagnostic value in differential dementia diagnosis and can help establishing a correct dementia diagnosis in case of ambiguous clinical dementia diagnoses.

Comparison of clinical diagnosis and microbiological test results in vaginal infections.

PubMed

Karaca, M; Bayram, A; Kocoglu, M E; Gocmen, A; Eksi, F

2005-01-01

Lower genital tract infections continue to be a problem due to the fact that the clinical diagnosis is usually inadequate, and subsequent care is suboptimal. This study aimed at evaluating the accuracy of clinical diagnosis by comparing it with microbiologic test results, and to determine the causative agents of vaginal infections. Sixty-seven nonpregnant women (18-45 years of age) with the clinical diagnosis of lower genital tract infection were enrolled in the study. Patients were not included if they had a history of vaginal infection during the previous three-month period or intrauterine device. The clinical diagnosis was based on the combinations of symptoms, direct observation of wet mount, homogeneous discharge, vaginal pH > 4.5, and detection of the amine odor after exposure of vaginal secretions to 10% KOH. Vaginal samples were taken with two cotton swabs, one was used for pH determination, and the second was utilized for microbiological tests. Gram staining and cultures with Sabouraud agar and chocolate agar were performed for microbiological diagnosis, and the results were compared. The clinical diagnoses included 26 (38.8%) candidiasis, 18 (26.8%) bacterial vaginosis, three (4.5%) trichomoniasis, and 20 (29.9%) mixed vaginal infections. Of the 26 patients with clinical diagnoses of candidiasis, 12 (46.1%) revealed Candiada albicans, nine (34.6) patients revealed microorganisms other than candida species, and five (19.2%) patients had no growth. Five (27.8%) bacterial vaginosis patients revealed Gardnarella vaginalis and 12 patients (66.6%) did not grow any microorganism. The overall rate of accurate clinical diagnoses confirmed by microbiological test results was 43.2%. Seventeen (43.6) of the 39 microbiological test results correlated with clinical diagnosis, and no growth was observed in 28 (41.8%) cultures. We conclude that the clinical diagnosis of vaginal infection is inadequate and should be confirmed with microbiological testing if the resources are avaliable.

Self-expanding stent for spontaneous coronary artery dissection: a rational choice.

PubMed

Mele, Marco; Langialonga, Tommaso; Maggi, Alessandro; Villella, Massimo; Villella, Alessandro

2016-12-01

: Spontaneous coronary artery dissection (SCAD) is a rare and poorly understood cause of acute coronary syndrome in relatively young patients. Nowadays, the optimal treatment of SCAD is uncertain. A conservative approach seems to be preferable, but in particular conditions, an invasive strategy is necessary. The poor rate of procedural success, the high risk of procedural complications and the uncertain long and mid-term results make the interventional treatment of SCAD a challenge. We report a case of a young male patient presenting with SCAD successfully treated with a sirolimus-eluting self-expanding coronary stent. To our knowledge, the use of self-expanding coronary stent for SCAD has never been described yet and we discuss about the rationale of a possible larger use in clinical practice.

Travel itinerary uncertainty and the pre-travel consultation--a pilot study.

PubMed

Flaherty, Gerard; Md Nor, Muhammad Najmi

2016-01-01

Risk assessment relies on the accuracy of the information provided by the traveller. A questionnaire was administered to 83 consecutive travellers attending a travel medicine clinic. The majority of travellers was uncertain about destinations within countries, transportation or type of accommodation. Most travellers were uncertain if they would be visiting malaria regions. The degree of uncertainty about itinerary potentially impacts on the ability of the travel medicine specialist to perform an adequate risk assessment, select appropriate vaccinations and prescribe malaria prophylaxis. This study reveals high levels of traveller uncertainty about their itinerary which may potentially reduce the effectiveness of their pre-travel consultation. © The Author 2016. Published by Oxford University Press on behalf of International society of travel medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Magnetic resonance imaging is often misleading when used as an adjunct to ultrasound in the management of placenta accreta spectrum disorders.

PubMed

Einerson, Brett D; Rodriguez, Christina E; Kennedy, Anne M; Woodward, Paula J; Donnelly, Meghan A; Silver, Robert M

2018-06-01

Magnetic resonance imaging is reported to have good sensitivity and specificity in the diagnosis of placenta accreta spectrum disorders, and is often used as an adjunct to ultrasound. But the additional utility of obtaining magnetic resonance imaging to assist in the clinical management of patients with placenta accreta spectrum disorders, above and beyond the information provided by ultrasound, is unknown. We aimed to determine whether magnetic resonance imaging provides data that may inform clinical management by changing the sonographic diagnosis of placenta accreta spectrum disorders. In all, 78 patients with sonographic evidence or clinical suspicion of placenta accreta spectrum underwent magnetic resonance imaging of the abdomen and pelvis in orthogonal planes through the uterus utilizing T1- and T2-weighted imaging sequences at the University of Utah and the University of Colorado from 1997 through 2017. The magnetic resonance imaging was interpreted by radiologists with expertise in diagnosis of placenta accreta spectrum who had knowledge of the sonographic interpretation and clinical risk factors for placenta accreta spectrum disorders. The primary outcome was a change in diagnosis from sonographic interpretation that could alter clinical management, which was defined a priori. Diagnostic accuracy was verified by surgical and histopathologic diagnosis at the time of delivery. A change in diagnosis that could potentially alter clinical management occurred in 28 (36%) cases. Magnetic resonance imaging correctly changed the diagnosis in 15 (19%), and correctly confirmed the diagnosis in 34 (44%), but resulted in an incorrect change in diagnosis in 13 (17%), and an incorrect confirmation of ultrasound diagnosis in 15 (21%). Magnetic resonance imaging was not more likely to change a diagnosis in the 24 cases of posterior and lateral placental location compared to anterior location (33% vs 37%, P = .84). Magnetic resonance imaging resulted in overdiagnosis in 23% and in underdiagnosis in 14% of all cases. When ultrasound suspected severe disease (percreta) in 14 cases, magnetic resonance imaging changed the diagnosis in only 2 cases. Lastly, the proportion of accurate diagnosis with magnetic resonance imaging did not improve over time (61-65%, P = .96 for trend) despite increasing volume and increasing numbers of changed diagnoses. Magnetic resonance imaging resulted in a change in diagnosis that could alter clinical management of placenta accreta spectrum disorders in more than one third of cases, but when changed, the diagnosis was often incorrect. Given its high cost and limited clinical value, magnetic resonance imaging should not be used routinely as an adjunct to ultrasound in the diagnosis of placenta accreta spectrum until evidence for utility is clearly demonstrated by more definitive prospective studies. Copyright © 2018 Elsevier Inc. All rights reserved.

Psychosocial Response to Uncertain Newborn Screening Results for Cystic Fibrosis.

PubMed

Hayeems, Robin Z; Miller, Fiona A; Barg, Carolyn J; Bombard, Yvonne; Carroll, June C; Tam, Karen; Kerr, Elizabeth; Chakraborty, Pranesh; Potter, Beth K; Patton, Sarah; Bytautas, Jessica P; Taylor, Louise; Davies, Christine; Milburn, Jennifer; Price, April; Gonska, Tanja; Keenan, Katherine; Ratjen, Felix; Guttmann, Astrid

2017-05-01

To explore the psychosocial implications of diagnostic uncertainty that result from inconclusive results generated by newborn bloodspot screening (NBS) for cystic fibrosis (CF). Using a mixed methods prospective cohort study of children who received NBS for CF, we compared psychosocial outcomes of parents whose children who received persistently inconclusive results with those whose children received true positive or screen-negative results. Mothers of infants who received inconclusive results (n = 17), diagnoses of CF (n = 15), and screen-negative results (n = 411) were surveyed; 23 parent interviews were completed. Compared with mothers of infants with true positive/screen-negative results, mothers of infants with inconclusive results reported greater perceived uncertainty (P < .006) but no differences in anxiety or vulnerability (P > .05). Qualitatively, parents valued being connected to experts but struggled with the meaning of an uncertain diagnosis, worried about their infant's health-related vulnerability, and had mixed views about surveillance. Inconclusive CF NBS results were not associated with anxiety or vulnerability but led to health-related uncertainty and qualitative concerns. Findings should be considered alongside efforts to optimize protocols for CF screening and surveillance. Educational and psychosocial supports are warranted for these families. Copyright © 2017 Elsevier Inc. All rights reserved.

What's in a Label? Is Diagnosis the Start or the End of Clinical Reasoning?

PubMed

Ilgen, Jonathan S; Eva, Kevin W; Regehr, Glenn

2016-04-01

Diagnostic reasoning has received substantial attention in the literature, yet what we mean by "diagnosis" may vary. Diagnosis can align with assignment of a "label," where a constellation of signs, symptoms, and test results is unified into a solution at a single point in time. This "diagnostic labeling" conceptualization is embodied in our case-based learning curricula, published case reports, and research studies, all of which treat diagnostic accuracy as the primary outcome. However, this conceptualization may oversimplify the richly iterative and evolutionary nature of clinical reasoning in many settings. Diagnosis can also represent a process of guiding one's thoughts by "making meaning" from data that are intrinsically dynamic, experienced idiosyncratically, negotiated among team members, and rich with opportunities for exploration. Thus, there are two complementary constructions of diagnosis: 1) the correct solution resulting from a diagnostic reasoning process, and 2) a dynamic aid to an ongoing clinical reasoning process. This article discusses the importance of recognizing these two conceptualizations of "diagnosis," outlines the unintended consequences of emphasizing diagnostic labeling as the primary goal of clinical reasoning, and suggests how framing diagnosis as an ongoing process of meaning-making might change how we think about teaching and assessing clinical reasoning.

Towards Real-time, On-board, Hardware-Supported Sensor and Software Health Management for Unmanned Aerial Systems

NASA Technical Reports Server (NTRS)

Schumann, Johann; Rozier, Kristin Y.; Reinbacher, Thomas; Mengshoel, Ole J.; Mbaya, Timmy; Ippolito, Corey

2013-01-01

Unmanned aerial systems (UASs) can only be deployed if they can effectively complete their missions and respond to failures and uncertain environmental conditions while maintaining safety with respect to other aircraft as well as humans and property on the ground. In this paper, we design a real-time, on-board system health management (SHM) capability to continuously monitor sensors, software, and hardware components for detection and diagnosis of failures and violations of safety or performance rules during the flight of a UAS. Our approach to SHM is three-pronged, providing: (1) real-time monitoring of sensor and/or software signals; (2) signal analysis, preprocessing, and advanced on the- fly temporal and Bayesian probabilistic fault diagnosis; (3) an unobtrusive, lightweight, read-only, low-power realization using Field Programmable Gate Arrays (FPGAs) that avoids overburdening limited computing resources or costly re-certification of flight software due to instrumentation. Our implementation provides a novel approach of combining modular building blocks, integrating responsive runtime monitoring of temporal logic system safety requirements with model-based diagnosis and Bayesian network-based probabilistic analysis. We demonstrate this approach using actual data from the NASA Swift UAS, an experimental all-electric aircraft.

[Comparison of clinical and histological diagnosis in kidney post-transplantation period].

PubMed

de Castro, M C; Chocair, P R; Saldanha, L B; Nahas, W; Arap, S; Sabbaga, E; Ianhez, L E

1998-01-01

To assess the agreement between clinical and histopathological diagnosis in a renal transplantation center, 40 episodes of acute renal failure were studied. Kidney biopsies were performed at the moment that a clinical diagnosis was made by the staff. Nineteen episodes of acute tubular necrosis (ATN), eighteen episodes of acute cellular rejection (ACR), 2 humoral rejections and 1 acute cyclosporin nephrotoxicity episodes were diagnosed. ATN episodes were confirmed by renal biopsy in 84.21%, ACR episodes in 83.33%, humoral rejections in 100%. Renal biopsy showed ATN in the occurrence of clinical cyclosporin nephrotoxicity. Total agreement was 82.5%. There is a good relationship between clinical and histopathological diagnosis in the post-transplantation period. Diagnostic mistakes occurred mainly when oliguria was present.

Difficulties in clinical diagnosis of measles: proposal for modified clinical case definition.

PubMed

Ferson, M J; Young, L C; Robertson, P W; Whybin, L R

1995-10-02

To examine the accuracy of clinical diagnosis of measles and to develop an improved measles clinical case definition. Case survey. Eastern Sydney, December 1990 to August 1993. All cases of measles notified to the Eastern Sydney Public Health Unit without or before serological confirmation. Demographic and clinical details, measles- and rubella-specific IgM and measles complement fixation titres in acute and convalescent (when available) sera and epidemiological links with confirmed measles cases. Of 49 subjects reported and with complete follow-up, 24 were confirmed with measles, four with rubella and 21 had no definite diagnosis. Clinical diagnosis of measles had a false positive rate of 51%. Subjects with confirmed measles were significantly more likely to have a cough (23/24) than those with no definite diagnosis (15/21; P = 0.03) and to be febrile on the day of rash onset (23/24 versus 10/21; P = 0.001). The Centers for Disease Control definition had a sensitivity of 92% but specificity of only 24%. A modified case definition of rash, cough and fever present at onset of rash had equal sensitivity but greater specificity (57%). As measles is no longer common in Australia, clinical diagnosis is unreliable. When a public health response is needed, cases should be confirmed by serological tests or, if not available, we propose use of our modified clinical case definition.

The impact of personalized probabilistic wall thickness models on peak wall stress in abdominal aortic aneurysms.

PubMed

Biehler, J; Wall, W A

2018-02-01

If computational models are ever to be used in high-stakes decision making in clinical practice, the use of personalized models and predictive simulation techniques is a must. This entails rigorous quantification of uncertainties as well as harnessing available patient-specific data to the greatest extent possible. Although researchers are beginning to realize that taking uncertainty in model input parameters into account is a necessity, the predominantly used probabilistic description for these uncertain parameters is based on elementary random variable models. In this work, we set out for a comparison of different probabilistic models for uncertain input parameters using the example of an uncertain wall thickness in finite element models of abdominal aortic aneurysms. We provide the first comparison between a random variable and a random field model for the aortic wall and investigate the impact on the probability distribution of the computed peak wall stress. Moreover, we show that the uncertainty about the prevailing peak wall stress can be reduced if noninvasively available, patient-specific data are harnessed for the construction of the probabilistic wall thickness model. Copyright © 2017 John Wiley & Sons, Ltd.

Oral melanoacanthoma and oral melanotic macule: a report of 8 cases, review of the literature, and immunohistochemical analysis.

PubMed

Carlos-Bregni, Román; Contreras, Elisa; Netto, Ana Carolina; Mosqueda-Taylor, Adalberto; Vargas, Pablo Agustin; Jorge, Jacks; León, Jorge Esquiche; de Almeida, Oslei Paes

2007-09-01

Oral melanoacanthoma (MA) is a rare, benign pigmented lesion, similar to cutaneous MA, characterized by hyperplasia of spinous keratinocytes and dendritic melanocytes. The pathogenesis of oral MA remains uncertain, although its clinical behavior is suggestive of a reactive origin. The most common intraoral sites are the buccal mucosa, lip, palate and gingiva. The average age of presentation is 28 years, mainly in blacks, with a strong female predilection. The oral melanotic macule (MM) is a small, well-circumscribed brown-to-black macule that occurs on the lips and mucous membranes. The etiology is not clear and it may represent a physiologic or reactive process. The average age of presentation is 43 years, with a female predilection. A biopsy is recommended to distinguish these lesions from each other and from other oral melanocytic lesions. We depict four cases each of oral MA and MM, affecting Caucasian and Latin American mestizo patients. The clinicopathological features of these cases reflect its ample spectrum, and to the best of our knowledge, it is the first example of oral MA affecting a Caucasian boy reported in the English literature. Therefore oral MA and MM should be considered in the differential diagnosis of pigmented lesions in the oral mucosa in these populations.

Skin diseases associated with Agent Orange and other organochlorine exposures.

PubMed

Patterson, Andrew T; Kaffenberger, Benjamin H; Keller, Richard A; Elston, Dirk M

2016-01-01

Organochlorine exposure is an important cause of cutaneous and systemic toxicity. Exposure has been associated with industrial accidents, intentional poisoning, and the use of defoliants, such as Agent Orange in the Vietnam War. Although long-term health effects are systematically reviewed by the Institute of Medicine, skin diseases are not comprehensively assessed. This represents an important practice gap as patients can present with cutaneous findings. This article provides a systematic review of the cutaneous manifestations of known mass organochlorine exposures in military and industrial settings with the goal of providing clinically useful recommendations for dermatologists seeing patients inquiring about organochlorine effects. Patients with a new diagnosis of chloracne, porphyria cutanea tarda, cutaneous lymphomas (non-Hodgkin lymphoma), and soft-tissue sarcomas including dermatofibrosarcoma protuberans and leiomyosarcomas should be screened for a history of Vietnam service or industrial exposure. Inconclusive evidence exists for an increased risk of other skin diseases in Vietnam veterans exposed to Agent Orange including benign fatty tumors, melanomas, nonmelanoma skin cancers, milia, eczema, dyschromias, disturbance of skin sensation, and rashes not otherwise specified. Affected veterans should be informed of the uncertain data in those cases. Referral to Department of Veterans Affairs for disability assessment is indicated for conditions with established associations. Copyright © 2015 American Academy of Dermatology, Inc. All rights reserved.

Results of a randomized trial comparing high-dose chemotherapy plus Auto-SCT and R-FC in CLL at diagnosis.

PubMed

Magni, M; Di Nicola, M; Patti, C; Scimè, R; Mulè, A; Rambaldi, A; Intermesoli, T; Viero, P; Tarella, C; Gueli, A; Bergui, L; Trentin, L; Barzan, A; Benedetti, F; Ambrosetti, A; Di Raimondo, F; Chiarenza, A; Parvis, G; Billio, A; Attolico, I; Olivieri, A; Montanari, M; Carlo-Stella, C; Matteucci, P; Devizzi, L; Guidetti, A; Viviani, S; Valagussa, P; Gianni, A M

2014-04-01

The importance of early therapy intensification in B-cell CLL (B-CLL) patients remains to be defined. Even though several studies have been published, no randomized trials comparing directly autologous stem cell transplant (ASCT) and the accepted conventional therapy (that is, rituximab, fludarabine and CY; R-FC) have been reported so far. To assess the benefit of a first-line aggressive therapy, we designed a multicenter, randomized, phase 3 trial comparing R-FC and high-dose chemotherapy supported by ASCT in patients under 65 years of age, with stage B(II) or C B-CLL. Primary end point was CR: 96 patients were enrolled (48 in each arm). On an intent-to-treat basis, the CR rates in the ASCT and R-FC arms were 62.5% and 58%, respectively. After 5 years of follow-up, PFS was 60.4% in the ASCT arm and 65.1% in the R-FC arm, time to progression 65.8 and 70.5%, and overall survival 88% vs 88.1%, respectively. Our trial demonstrates, for the first time in a randomized manner, that frontline ASCT does not translate into a survival advantage when compared with benchmark chemoimmunotherapy in B-CLL patients; the possibility of its clinical benefit in certain subgroups remains uncertain.

Polycystic ovary syndrome: a common reproductive syndrome with long-term metabolic consequences.

PubMed

Yau, T Tl; Ng, N Yh; Cheung, L P; Ma, R Cw

2017-12-01

Polycystic ovary syndrome is the most common endocrine disorder among women of reproductive age. Although traditionally viewed as a reproductive disorder, there is increasing appreciation that it is associated with significantly increased risk of cardiometabolic disorders. Women with polycystic ovary syndrome may present to clinicians via a variety of different routes and symptoms. Although the impact on reproduction predominates during the reproductive years, the increased cardiometabolic problems are likely to become more important at later stages of the life course. Women with polycystic ovary syndrome have an approximately 2- to 5-fold increased risk of dysglycaemia or type 2 diabetes, and hence regular screening with oral glucose tolerance test is warranted. Although the diagnostic criteria for polycystic ovary syndrome are still evolving and are undergoing revision, the diagnosis is increasingly focused on the presence of hyperandrogenism, with the significance of polycystic ovarian morphology in the absence of associated hyperandrogenism or anovulation remaining uncertain. The management of women with polycystic ovary syndrome should focus on the specific needs of the individual, and may change according to different stages of the life course. In view of the clinical manifestations of the condition, there is recent debate about whether the current name is misleading, and whether the condition should be renamed as metabolic reproductive syndrome.

Herpes simplex encephalitis : from virus to therapy.

PubMed

Rozenberg, Flore; Deback, Claire; Agut, Henri

2011-06-01

Herpes simplex virus (HSV) is the cause of herpes simplex encephalitis (HSE), a devastating human disease which occurs in 2-4 cases per million/year. HSE results either from a primary infection or virus reactivation, in accordance with the common pattern of HSV infection which is a chronic lifelong process. However its pathophysiology remains largely unknown and its poor prognosis is in contrast with the usually good tolerance of most clinical herpetic manifestations. HSE is due to HSV type 1 (HSV-1) in most cases but HSV type 2 (HSV-2) may be also implicated, especially in infants in the context of neonatal herpes. Polymerase chain reaction detection of HSV DNA in cerebrospinal fluid is the diagnosis of choice for HSE. Acyclovir, a nucleoside analogue which inhibits viral DNA polymerase activity, is the reference treatment of HSE while foscarnet constitutes an alternative therapy and the efficacy of cidofovir is currently uncertain in that context. The emergence of HSV resistance to acyclovir, a phenomenon which is mainly observed among immunocompromised patients, is a current concern although no case of HSE due to an acyclovir-resistant HSV strain has been reported to date. Nevertheless the identification and development of novel therapeutic strategies against HSV appears to be a non dispensable objective for future research in virology.

A Qualitative Study to Explore the Views and Attitudes towards Prenatal Testing in Adults Who Have Muenke Syndrome and their Partners.

PubMed

Phipps, Julie; Skirton, Heather

2017-10-01

Muenke syndrome constitutes the most common syndromic form of craniosynostosis, occurring in 1 in 30,000 live births. The phenotype is variable, ranging from no clinical findings to complex presentation. Facilitating reproductive decision making for couples at genetic risk of having a child with Muenke syndrome is an important aspect of genetic counselling. Prenatal genetic testing for Muenke syndrome is accurate; however the value of testing is uncertain with a variable phenotype. The purpose of this study was to explore attitudes towards prenatal testing in couples where one partner had tested positive for the Muenke mutation. We used a qualitative approach based on thematic analysis and collected data using individual semi-structured interviews with eight parents. Five key themes were: The Muenke journey; Impact and knowledge of diagnosis; Knowledge and attitude to prenatal testing; Stigma and sharing of information; and Information retention. Knowledge of Muenke syndrome and prenatal testing was poor. Genetic information was provided when treatment of their affected child was their paramount concern. Couples reported not sharing genetic information with family due to fear of stigmatisation. Couples cannot make reproductive decisions if lacking appropriate understanding of the choices: timely genetic counselling regarding prenatal testing is needed when relevant to them.

Assessment and classification of patients with myocardial injury and infarction in clinical practice

PubMed Central

Chapman, Andrew R; Adamson, Philip D

2017-01-01

Myocardial injury is common in patients without acute coronary syndrome, and international guidelines recommend patients with myocardial infarction are classified by aetiology. The universal definition differentiates patients with myocardial infarction due to plaque rupture (type 1) from those due to myocardial oxygen supply-demand imbalance (type 2) secondary to other acute illnesses. Patients with myocardial necrosis, but no symptoms or signs of myocardial ischaemia, are classified as acute or chronic myocardial injury. This classification has not been widely adopted in practice, because the diagnostic criteria for type 2 myocardial infarction encompass a wide range of presentations, and the implications of the diagnosis are uncertain. However, both myocardial injury and type 2 myocardial infarction are common, occurring in more than one-third of all hospitalised patients. These patients have poor short-term and long-term outcomes with two-thirds dead in 5 years. The classification of patients with myocardial infarction continues to evolve, and future guidelines are likely to recognise the importance of identifying coronary artery disease in type 2 myocardial infarction. Clinicians should consider whether coronary artery disease has contributed to myocardial injury, as selected patients are likely to benefit from further investigation and in these patients targeted secondary prevention has the potential to improve outcomes. PMID:27806987

Electroconvulsive therapy--efficacy and side-effects.

PubMed

Moksnes, Kjell Martin; Ilner, Stein Opjordsmoen

2010-12-16

Efficacy of electroconvulsive therapy (ECT) and duration of associated side effects is uncertain. We wanted to study indications, efficacy, time to response and side effects. ECT-protocols and medical records (from the period 1960-95) in three psychiatric wards of Dikemark Mental Hospital, Norway were systematically assessed. 141 persons underwent 241 ECT series comprising 1960 treatment sessions. Major depressive disorder was the main diagnosis in most patients 124 [88 %]. Before ECT, 129 (91 %) patients had been treated with at least one antidepressant, 107 (76 %) with at least two and 67 (48 %) with two different classes of antidepressants without sufficient clinical recovery from the incident. 31 (22 %) had received lithium before ECT. Within four weeks after the first ECT, 120 (85 %) patients had recovered. 61 of these achieved remission and were discharged within four weeks. After the first ECT series, 92 patients showed signs of improvement. 71 (77 %) had signs of improvement within 6 days. Side effects were noted after 123 of totally 241 series (51 %). Five patients experienced serious complications. Interpretation. The immediate effect of ECT was good and signs of recovery were observed in most patients during the first week. Depressed psychotic patients and the elderly seemed to respond best. Considering these patients' serious and long-lasting disorders ECT was fairly safe and well tolerated.

Functional analysis of rare variants in mismatch repair proteins augments results from computation-based predictive methods

PubMed Central

Arora, Sanjeevani; Huwe, Peter J.; Sikder, Rahmat; Shah, Manali; Browne, Amanda J.; Lesh, Randy; Nicolas, Emmanuelle; Deshpande, Sanat; Hall, Michael J.; Dunbrack, Roland L.; Golemis, Erica A.

2017-01-01

ABSTRACT The cancer-predisposing Lynch Syndrome (LS) arises from germline mutations in DNA mismatch repair (MMR) genes, predominantly MLH1, MSH2, MSH6, and PMS2. A major challenge for clinical diagnosis of LS is the frequent identification of variants of uncertain significance (VUS) in these genes, as it is often difficult to determine variant pathogenicity, particularly for missense variants. Generic programs such as SIFT and PolyPhen-2, and MMR gene-specific programs such as PON-MMR and MAPP-MMR, are often used to predict deleterious or neutral effects of VUS in MMR genes. We evaluated the performance of multiple predictive programs in the context of functional biologic data for 15 VUS in MLH1, MSH2, and PMS2. Using cell line models, we characterized VUS predicted to range from neutral to pathogenic on mRNA and protein expression, basal cellular viability, viability following treatment with a panel of DNA-damaging agents, and functionality in DNA damage response (DDR) signaling, benchmarking to wild-type MMR proteins. Our results suggest that the MMR gene-specific classifiers do not always align with the experimental phenotypes related to DDR. Our study highlights the importance of complementary experimental and computational assessment to develop future predictors for the assessment of VUS. PMID:28494185

Evaluating Malaria Prevalence Using Clinical Diagnosis Compared with Microscopy and Rapid Diagnostic Tests in a Tertiary Healthcare Facility in Rivers State, Nigeria.

PubMed

Wogu, M N; Nduka, F O

2018-01-01

The World Health Organization's policy on laboratory test of all suspected malaria cases before treatment has not yielded significant effects in several rural areas of Sub-Saharan Africa due to inadequate diagnostic infrastructure, leading to high morbidity and mortality rates. A cross-sectional randomized study was conducted to evaluate the validity of clinical malaria diagnosis through comparison with microscopy and rapid diagnostic test kits (RDTs) using 1000 consenting outpatients of a tertiary hospital in Nigeria. Physicians conducted clinical diagnosis, and blood samples were collected through venous procedure and analyzed for malaria parasites using Giemsa microscopy and RDT kits. Microscopy was considered the diagnostic "gold standard" and all data obtained were statistically analyzed using Chi-square test with a P value <0.05 considered significant. Malaria prevalence values of 20.1%, 43.1%, and 29.7% were obtained for clinical diagnosis, microscopy, and RDTs, respectively ( P < 0.05). Values of 47.2%, 95.9%, and 77.8% were obtained for sensitivity, specificity, and diagnostic accuracy, respectively, in clinical diagnosis, while RDTs had sensitivity, specificity, and diagnostic accuracy values of 73.7%, 97.3%, and 88.3%, respectively, when compared to microscopy ( P < 0.05). Clinical diagnosed malaria cases should be confirmed with a parasite-based laboratory diagnosis and more qualitative research is needed to explore why clinicians still use clinical diagnosis despite reported cases of its ineffectiveness.

Comparisons of Prognosis between Surgically and Clinically Diagnosed Idiopathic Pulmonary Fibrosis Using Gap Model

PubMed Central

Lee, Sang Hoon; Kim, Song Yee; Kim, Dong Soon; Kim, Young Whan; Chung, Man Pyo; Uh, Soo Taek; Park, Choon Sik; Jeong, Sung Hwan; Park, Yong Bum; Lee, Hong Lyeol; Shin, Jong Wook; Lee, Eun Joo; Lee, Jin Hwa; Jegal, Yangin; Lee, Hyun Kyung; Kim, Yong Hyun; Song, Jin Woo; Park, Moo Suk

2016-01-01

Abstract Although a multidisciplinary approach has become an important criterion for an idiopathic pulmonary fibrosis (IPF) diagnosis, lung biopsies remain crucial. However, the prognosis of patients with surgically diagnosed IPF (sIPF) is uncertain. We aimed to investigate the prognosis of patients with clinically diagnosed IPF (cIPF) and sIPF. In this retrospective observational study, the Korean Interstitial Lung Disease Study Group conducted a national survey to evaluate the clinical, physiological, radiological, and survival characteristics of patients with IPF from January 1, 2003 to December 31, 2007. Patients were recruited from 54 universities and teaching hospitals across the Republic of Korea. IPF diagnoses were established according to the 2002 American Thoracic Society (ATS)/European Respiratory Society criteria (ERS) guideline. A total of 1685 patients with IPF (1027 cIPF and 658 sIPF) were enrolled. Patients with sIPF were significantly younger, predominantly female, and nonsmokers (all P < 0.001). sIPF group had significantly better initial pulmonary function. The proportion of computed tomography-based honeycomb findings of patients with cIPF was higher than in those with sIPF (P < 0.001). A Kaplan-Meier analysis showed that the sIPF group had a better prognosis (P = 0.001). A survival analysis showed that age, pulmonary function parameters, pulmonary oxygen tension, honeycombing change, and combined lung cancer had a significant influence on patient prognosis. However, there was no significant difference in prognosis between the cIPF and sIPF groups after adjusting for GAP (gender, age, physiology) stage. The patients with sIPF had better clinical features than those with cIPF. However, after adjusting for GAP stage, the sIPF group showed similar prognoses as the cIPF group. This study showed that after adjusting for GAP stage, the prognosis of patients with IPF is the same regardless of the diagnostic method used. PMID:26986154

Absence of epithelial atypia in B3-lesions of the breast is associated with decreased risk for malignancy.

PubMed

Mayer, Sebastian; Kayser, Gian; Rücker, Gerta; Bögner, Diana; Hirschfeld, Marc; Hug, Christiane; Stickeler, Elmar; Gitsch, Gerald; Erbes, Thalia

2017-02-01

Lesions of uncertain malignant potential (B3) represent a heterogeneous group with an overall risk for malignancy of 9.85-35.1% after total resection. Positive predictive values (PPV) for malignancy vary depending on B3 subtype. The aim of this study was to evaluate the PPV for malignancy in B3 lesions and to determine the clinical significance of atypia-dependent sub-classification (a = without epithelial atypia; b = with epithelial atypia) of B3 into B3a and B3b and papillary lesions (PL) in PLa and PLb. 219 patients with histopathologically proven B3 lesions on core needle/vacuum-assisted biopsy who subsequently underwent diagnostic excision biopsy were included in this study. PPVs for malignancy were reported for B3 in general and all B3 sub-categories. Logistic regression analysis identified associations between B3-subgroups and outcome after excision biopsy as well as the impact of clinical and diagnostic findings on excision diagnosis. The overall PPV rate was 10.0% (22/219). Excision histology exhibited a higher malignancy rate in PLb (2/7; PPV: 28.6%) than in PLa (6/127; PPV: 4.7%) (p = 0.057) and in B3b (12/50; PPV: 24.0%) compared to B3a category (8/165; PPV: 4.8%) (p < 0.001). These findings support the necessity of B3 lesion sub-classification into B3a and B3b and of PL into PLa and PLb when considering epithelial atypia. The determination of atypia status represents a relevant factor in risk-stratification for clinical management of B3 lesions. Should future studies using the sub-classification of PL confirm these results, observation may be a safe option for the clinical management of patients with asymptomatic PLa lesions. Copyright © 2016 Elsevier Ltd. All rights reserved.

improbable molecular results and the need to reevaluate a priori genetic risks: A report of 2 neuromuscular disorders

DOE Office of Scientific and Technical Information (OSTI.GOV)

Giardine, R.M.; Rose, N.C.; Fischbeck, K.H.

Case 1: A 27-year-old woman whose brother and deceased father were diagnosed with myotonic dystrophy presented for preconceptional counseling. Three other first and second degree relatives were judged clinically affected on the basis of myotonia by positive electromyelograms (EMGs). The proband appeared to be clinically affected with mild percussion myotonia and a positive EMG. Initial studies by linkage analysis required postulation that the at-risk chromosome 19 inherited by the patient and her brother had undergone recombination in the brother between 2 very closely linked RFLP markers. Conclusion: Molecular testing did not support a unifying diagnosis for myotonia in this family.more » In addition to one classic example of myotonic dystrophy, it is possible a milder form of myotonia is also segregating in this pedigree. Case 2: The maternal aunt of a young man with Becker`s muscular dystrophy (BMD) presented for reproductive counseling. Serum CK values were elevated in her mother, who shared an X chromosome haplotype with the affected grandson and was judged an obligate carrier. The aunt was judged a likely carrier because of elevated serum CK values. Three maternal uncles, including ones with the same X chromosome haplotype as the affected nephew, were clinically normal. Finally, dosage analysis for dystrophin exons deleted in the grandson showed the grandmother and aunt to be non-carriers, but the mother of the affected boy to be a somatic carrier. The grandmother and aunt are not BMD carriers. Since the elevated CK levels do not segregate with the affected X chromosome, they may reflect autosomal inheritance or nongenetic influences; in either case their clinical significance is uncertain. These cases reinforce the importance of periodic reevaluation of initial genetic assignments, particularly when rare events must be invoked to explain molecular studies.« less

Over-the-Counter Supplement Interventions to Prevent Cognitive Decline, Mild Cognitive Impairment, and Clinical Alzheimer-Type Dementia: A Systematic Review.

PubMed

Butler, Mary; Nelson, Victoria A; Davila, Heather; Ratner, Edward; Fink, Howard A; Hemmy, Laura S; McCarten, J Riley; Barclay, Terry R; Brasure, Michelle; Kane, Robert L

2018-01-02

Optimal interventions to prevent or delay cognitive decline, mild cognitive impairment (MCI), or dementia are uncertain. To summarize the evidence on efficacy and harms of over-the-counter (OTC) supplements to prevent or delay cognitive decline, MCI, or clinical Alzheimer-type dementia in adults with normal cognition or MCI but no dementia diagnosis. Multiple electronic databases from 2009 to July 2017 and bibliographies of systematic reviews. English-language trials of at least 6 months' duration that enrolled adults without dementia and compared cognitive outcomes with an OTC supplement versus placebo or active controls. Extraction performed by a single reviewer and confirmed by a second reviewer; dual-reviewer assessment of risk of bias; consensus determination of strength of evidence. Thirty-eight trials with low to medium risk of bias compared ω-3 fatty acids, soy, ginkgo biloba, B vitamins, vitamin D plus calcium, vitamin C or β-carotene, multi-ingredient supplements, or other OTC interventions with placebo or other supplements. Few studies examined effects on clinical Alzheimer-type dementia or MCI, and those that did suggested no benefit. Daily folic acid plus vitamin B12 was associated with improvements in performance on some objectively measured memory tests that were statistically significant but of questionable clinical significance. Moderate-strength evidence showed that vitamin E had no benefit on cognition. Evidence about effects of ω-3 fatty acids, soy, ginkgo biloba, folic acid alone or with other B vitamins, β-carotene, vitamin C, vitamin D plus calcium, and multivitamins or multi-ingredient supplements was either insufficient or low-strength, suggesting that these supplements did not reduce risk for cognitive decline. Adverse events were rarely reported. Studies had high attrition and short follow-up and used a highly variable set of cognitive outcome measures. Evidence is insufficient to recommend any OTC supplement for cognitive protection in adults with normal cognition or MCI. Agency for Healthcare Research and Quality.

Comparisons of Prognosis between Surgically and Clinically Diagnosed Idiopathic Pulmonary Fibrosis Using Gap Model: A Korean National Cohort Study.

PubMed

Lee, Sang Hoon; Kim, Song Yee; Kim, Dong Soon; Kim, Young Whan; Chung, Man Pyo; Uh, Soo Taek; Park, Choon Sik; Jeong, Sung Hwan; Park, Yong Bum; Lee, Hong Lyeol; Shin, Jong Wook; Lee, Eun Joo; Lee, Jin Hwa; Jegal, Yangin; Lee, Hyun Kyung; Kim, Yong Hyun; Song, Jin Woo; Park, Moo Suk

2016-03-01

Although a multidisciplinary approach has become an important criterion for an idiopathic pulmonary fibrosis (IPF) diagnosis, lung biopsies remain crucial. However, the prognosis of patients with surgically diagnosed IPF (sIPF) is uncertain. We aimed to investigate the prognosis of patients with clinically diagnosed IPF (cIPF) and sIPF. In this retrospective observational study, the Korean Interstitial Lung Disease Study Group conducted a national survey to evaluate the clinical, physiological, radiological, and survival characteristics of patients with IPF from January 1, 2003 to December 31, 2007. Patients were recruited from 54 universities and teaching hospitals across the Republic of Korea. IPF diagnoses were established according to the 2002 American Thoracic Society (ATS)/European Respiratory Society criteria (ERS) guideline. A total of 1685 patients with IPF (1027 cIPF and 658 sIPF) were enrolled. Patients with sIPF were significantly younger, predominantly female, and nonsmokers (all P < 0.001). sIPF group had significantly better initial pulmonary function. The proportion of computed tomography-based honeycomb findings of patients with cIPF was higher than in those with sIPF (P < 0.001). A Kaplan-Meier analysis showed that the sIPF group had a better prognosis (P = 0.001). A survival analysis showed that age, pulmonary function parameters, pulmonary oxygen tension, honeycombing change, and combined lung cancer had a significant influence on patient prognosis. However, there was no significant difference in prognosis between the cIPF and sIPF groups after adjusting for GAP (gender, age, physiology) stage. The patients with sIPF had better clinical features than those with cIPF. However, after adjusting for GAP stage, the sIPF group showed similar prognoses as the cIPF group. This study showed that after adjusting for GAP stage, the prognosis of patients with IPF is the same regardless of the diagnostic method used.

Oral candidiasis: pathogenesis, clinical presentation, diagnosis and treatment strategies.

PubMed

Lalla, Rajesh V; Patton, Lauren L; Dongari-Bagtzoglou, Anna

2013-04-01

Oral candidiasis is a clinical fungal infection that is the most common opportunistic infection affecting the human oral cavity. This article reviews the pathogenesis, clinical presentations, diagnosis and treatmentstrategies for oral candidiasis.

Appropriate Use Criteria for Hyaluronic Acid in the Treatment of Knee Osteoarthritis in the United States

PubMed Central

Bhadra, Arup K.; Altman, Roy; Dasa, Vinod; Myrick, Karen; Rosen, Jeffrey; Vad, Vijay; Vitanzo, Peter; Bruno, Michelle; Kleiner, Hillary; Just, Caryn

2016-01-01

Objective: A workgroup of clinical experts has developed an Appropriate Use Criteria (AUC) for the use of hyaluronic acid (HA) in the treatment of osteoarthritis (OA) of the knee. The increasingly broad and varied use of HA injections, lack of published clinical guidance, and limited coverage for their use has created the imperative to establish appropriateness criteria. Methods: The experts of this workgroup represent rheumatology, orthopedic surgery, physiatry, sports medicine, and nursing clinicians with substantive knowledge of intra-articular HA therapy. This workgroup utilized the results of a systematic review of evidence, expert clinical opinion, and current evidence-based clinical practice guidelines to develop appropriateness criteria for the use of intra-articular HA for knee OA in 17 real-world clinical scenarios. Results: The workgroup scored the appropriateness of treatment of each patient scenario using a 9-point scale to designate a treatment as appropriate (7-9), uncertain (4-6), or inappropriate (1-3). Six scenarios were scored as appropriate, 10 scenarios were scored as uncertain, and 1 scenario was scored as inappropriate. Conclusion: This article can assist clinicians in shared decision-making by providing best practices in considering HA injections for knee OA treatment. Moreover, this AUC article can aid payers and policy makers in determining reimbursement and preauthorization policies and more appropriately managing health care resources. It is clear that further research is still necessary—particularly in patient populations differentiated by OA severity—that may benefit the greatest from the use of HA injections for the treatment of knee OA. PMID:28618868

Asphyxia in the Newborn: Evaluating the Accuracy of ICD Coding, Clinical Diagnosis and Reimbursement: Observational Study at a Swiss Tertiary Care Center on Routinely Collected Health Data from 2012-2015

PubMed Central

Rimle, Carole; Zwahlen, Marcel; Triep, Karen; Raio, Luigi; Nelle, Mathias

2017-01-01

Background The ICD-10 categories of the diagnosis “perinatal asphyxia” are defined by clinical signs and a 1-minute Apgar score value. However, the modern conception is more complex and considers metabolic values related to the clinical state. A lack of consistency between the former clinical and the latter encoded diagnosis poses questions over the validity of the data. Our aim was to establish a refined classification which is able to distinctly separate cases according to clinical criteria and financial resource consumption. The hypothesis of the study is that outdated ICD-10 definitions result in differences between the encoded diagnosis asphyxia and the medical diagnosis referring to the clinical context. Methods Routinely collected health data (encoding and financial data) of the University Hospital of Bern were used. The study population was chosen by selected ICD codes, the encoded and the clinical diagnosis were analyzed and each case was reevaluated. The new method categorizes the diagnoses of perinatal asphyxia into the following groups: mild, moderate and severe asphyxia, metabolic acidosis and normal clinical findings. The differences of total costs per case were determined by using one-way analysis of variance. Results The study population included 622 cases (P20 “intrauterine hypoxia” 399, P21 “birth asphyxia” 233). By applying the new method, the diagnosis asphyxia could be ruled out with a high probability in 47% of cases and the variance of case related costs (one-way ANOVA: F (5, 616) = 55.84, p < 0.001, multiple R-squared = 0.312, p < 0.001) could be best explained. The classification of the severity of asphyxia could clearly be linked to the complexity of cases. Conclusion The refined coding method provides clearly defined diagnoses groups and has the strongest effect on the distribution of costs. It improves the diagnosis accuracy of perinatal asphyxia concerning clinical practice, research and reimbursement. PMID:28118380

Evaluation of idiopathic transverse myelitis revealing specific myelopathy diagnoses.

PubMed

Zalewski, Nicholas L; Flanagan, Eoin P; Keegan, B Mark

2018-01-09

To evaluate specific myelopathy diagnoses made in patients with suspected idiopathic transverse myelitis (ITM). A total of 226 patients 18 years and older were referred to Mayo Clinic Neurology for suspected ITM from December 1, 2010, to December 31, 2015. Electronic medical records were reviewed for detailed clinical presentation and course, laboratory and electrophysiologic investigations, and neuroimaging to determine the etiology. Current diagnostic criteria for ITM and alternative myelopathy diagnoses were applied. All cases where any discrepancy was suspected from the final reported clinical diagnosis were reviewed by each author and a consensus final diagnosis was made. The diagnostic criteria for ITM were met in 41 of 226 patients (18.1%). In 158 patients (69.9%), an alternative specific myelopathy diagnosis was made: multiple sclerosis or clinically isolated syndrome, 75; vascular myelopathy, 41; neurosarcoidosis, 12; neuromyelitis optica spectrum disorder, 12; myelin oligodendrocyte glycoprotein myelopathy, 5; neoplastic, 4; compressive, 3; nutritional, 3; infectious, 2; and other, 2. A myelopathy was not confirmed in 27 patients. Time from symptom onset to final clinical diagnosis in patients without ITM was a median of 9 months (range 0-288). Fifty-five patients (24%) required treatment changes according to their final clinical diagnosis. The majority of patients with suspected ITM have an alternative specific myelopathy diagnosis. A presumptive diagnosis of ITM can lead to premature diagnostic conclusions affecting patient treatment. Copyright © 2017 American Academy of Neurology.

[Investigation of human brucellosis diagnosis and report quality in medical institutions in key areas of Shanxi province].

PubMed

Zeng, L J; Yang, W W; Tie, P; Liu, X R; Gao, X R; Li, Z Y; Hou, P; Zhi, Y; Bai, Y F; Geng, M J; Chen, Q L; Cui, B Y; Li, Z J; Wang, L P

2017-11-10

Objective: To evaluate the accuracy of human brucellosis diagnosis and reporting in medical institutions in Shanxi province, and understand the performance of clinical doctors to diagnose human brucellosis according to diagnostic criteria. Methods: Field investigation was conducted in 6 medical institutions in the key areas of human brucellosis in Shanxi province. The diagnosis data of the reported brucellosis cases in 2015 were collected and reviewed retrospectively for the evaluation of the diagnosis accuracy with systematic sampling method. The database was established with Excel 2010 and the descriptive analysis and statistical test were conducted with software R 3.3.2. Results: The diagnosis consistent rate of the 377 brucellosis cases reviewed was 70.8% (267/377), the diagnosis consistent rates in medical institutions at city-level and country-level were 77.0% (127/165) and 66.0% (140/212) respectively, the differences had significance ( χ (2)=5.4, P =0.02). Among the reviewed cases, the diagnosis consistent rate of laboratory diagnosis and clinical diagnosis were 87.1% (256/294) and 13.3% (11/83) respectively, and the differences had significance ( χ (2)=170.7, P <0.001). Among the 21 investigated clinical doctors, the numbers of the doctors who correctly diagnosed the suspected cases, probable cases and lab-confirmed cases were only 3, 0 and 8 respectively. All of the clinical doctors knew that it is necessary to report the brucellosis cases within 24 hours after diagnosis. Conclusion: The accuracy of human brucellosis diagnosis in key areas of human brucellosis in Shanxi was low, and the performance of the clinical doctors to diagnose human brucellosis according to diagnostic and case classification criteria was unsatisfied.

Systematic evaluation of a targeted gene capture sequencing panel for molecular diagnosis of retinitis pigmentosa.

PubMed

Huang, Hui; Chen, Yanhua; Chen, Huishuang; Ma, Yuanyuan; Chiang, Pei-Wen; Zhong, Jing; Liu, Xuyang; Asan; Wu, Jing; Su, Yan; Li, Xin; Deng, Jianlian; Huang, Yingping; Zhang, Xinxin; Li, Yang; Fan, Ning; Wang, Ying; Tang, Lihui; Shen, Jinting; Chen, Meiyan; Zhang, Xiuqing; Te, Deng; Banerjee, Santasree; Liu, Hui; Qi, Ming; Yi, Xin

2018-01-01

Inherited eye diseases are major causes of vision loss in both children and adults. Inherited eye diseases are characterized by clinical variability and pronounced genetic heterogeneity. Genetic testing may provide an accurate diagnosis for ophthalmic genetic disorders and allow gene therapy for specific diseases. A targeted gene capture panel was designed to capture exons of 283 inherited eye disease genes including 58 known causative retinitis pigmentosa (RP) genes. 180 samples were tested with this panel, 68 were previously tested by Sanger sequencing. Systematic evaluation of our method and comprehensive molecular diagnosis were carried on 99 RP patients. 96.85% targeted regions were covered by at least 20 folds, the accuracy of variants detection was 99.994%. In 4 of the 68 samples previously tested by Sanger sequencing, mutations of other diseases not consisting with the clinical diagnosis were detected by next-generation sequencing (NGS) not Sanger. Among the 99 RP patients, 64 (64.6%) were detected with pathogenic mutations, while in 3 patients, it was inconsistent between molecular diagnosis and their initial clinical diagnosis. After revisiting, one patient's clinical diagnosis was reclassified. In addition, 3 patients were found carrying large deletions. We have systematically evaluated our method and compared it with Sanger sequencing, and have identified a large number of novel mutations in a cohort of 99 RP patients. The results showed a sufficient accuracy of our method and suggested the importance of molecular diagnosis in clinical diagnosis.

Systematic evaluation of a targeted gene capture sequencing panel for molecular diagnosis of retinitis pigmentosa

PubMed Central

Ma, Yuanyuan; Chiang, Pei-Wen; Zhong, Jing; Liu, Xuyang; Asan; Wu, Jing; Su, Yan; Li, Xin; Deng, Jianlian; Huang, Yingping; Zhang, Xinxin; Li, Yang; Fan, Ning; Wang, Ying; Tang, Lihui; Shen, Jinting; Chen, Meiyan; Zhang, Xiuqing; Te, Deng; Banerjee, Santasree; Liu, Hui; Qi, Ming; Yi, Xin

2018-01-01

Background Inherited eye diseases are major causes of vision loss in both children and adults. Inherited eye diseases are characterized by clinical variability and pronounced genetic heterogeneity. Genetic testing may provide an accurate diagnosis for ophthalmic genetic disorders and allow gene therapy for specific diseases. Methods A targeted gene capture panel was designed to capture exons of 283 inherited eye disease genes including 58 known causative retinitis pigmentosa (RP) genes. 180 samples were tested with this panel, 68 were previously tested by Sanger sequencing. Systematic evaluation of our method and comprehensive molecular diagnosis were carried on 99 RP patients. Results 96.85% targeted regions were covered by at least 20 folds, the accuracy of variants detection was 99.994%. In 4 of the 68 samples previously tested by Sanger sequencing, mutations of other diseases not consisting with the clinical diagnosis were detected by next-generation sequencing (NGS) not Sanger. Among the 99 RP patients, 64 (64.6%) were detected with pathogenic mutations, while in 3 patients, it was inconsistent between molecular diagnosis and their initial clinical diagnosis. After revisiting, one patient’s clinical diagnosis was reclassified. In addition, 3 patients were found carrying large deletions. Conclusions We have systematically evaluated our method and compared it with Sanger sequencing, and have identified a large number of novel mutations in a cohort of 99 RP patients. The results showed a sufficient accuracy of our method and suggested the importance of molecular diagnosis in clinical diagnosis. PMID:29641573

Clinically Practical Magnetic Resonance Protocol for Improved Specificity in Breast Cancer Diagnosis

DTIC Science & Technology

2007-06-01

Protocol for Improved Specificity in Breast Cancer Diagnosis PRINCIPAL INVESTIGATOR: Luminita Alina Tudorica, Ph.D. CONTRACTING...TITLE AND SUBTITLE 5a. CONTRACT NUMBER Clinically Practical Magnetic Resonance Protocol for Improved Specificity in Breast Cancer Diagnosis 5b... breast cancer study in a clinical setting. This study aims to improve specificity of breast cancer detection by using a combined MRI/MRS protocol. In

Limited endoscopic transsphenoidal approach for cavernous sinus biopsy: illustration of 3 cases and discussion.

PubMed

Graillon, T; Fuentes, S; Metellus, P; Adetchessi, T; Gras, R; Dufour, H

2014-01-01

Advances in transsphenoidal surgery and endoscopic techniques have opened new perspectives for cavernous sinus (CS) approaches. The aim of this study was to assess the advantages and disadvantages of limited endoscopic transsphenoidal approach, as performed in pituitary adenoma surgery, for CS tumor biopsy illustrated with three clinical cases. The first case was a 46-year-old woman with a prior medical history of parotid adenocarcinoma successfully treated 10 years previously. The cavernous sinus tumor was revealed by right third and sixth nerve palsy and increased over the past three years. A tumor biopsy using a limited endoscopic transsphenoidal approach revealed an adenocarcinoma metastasis. Complementary radiosurgery was performed. The second case was a 36-year-old woman who consulted for diplopia with right sixth nerve palsy and amenorrhea with hyperprolactinemia. Dopamine agonist treatment was used to restore the patient's menstrual cycle. Cerebral magnetic resonance imaging (MRI) revealed a right sided CS tumor. CS biopsy, via a limited endoscopic transsphenoidal approach, confirmed a meningothelial grade 1 meningioma. Complementary radiosurgery was performed. The third case was a 63-year-old woman with progressive installation of left third nerve palsy and visual acuity loss, revealing a left cavernous sinus tumor invading the optic canal. Surgical biopsy was performed using an enlarged endoscopic transsphenoidal approach to the decompress optic nerve. Biopsy results revealed a meningothelial grade 1 meningioma. Complementary radiotherapy was performed. In these three cases, no complications were observed. Mean hospitalization duration was 4 days. Reported anatomical studies and clinical series have shown the feasibility of reaching the cavernous sinus using an endoscopic endonasal approach. Trans-foramen ovale CS percutaneous biopsy is an interesting procedure but only provides cell analysis results, and not tissue analysis. However, radiotherapy and radiosurgery have proven effective for SC meningiomas. When histological diagnosis is required, limited endoscopic transsphenoidal approach appears as a safe, fast, and useful alternative to the classical endocranial approach. Also, a tailored enlargement of the approach could be performed if optic nerve decompression is required. The feasibility of CS endoscopic transsphenoidal biopsy has prompted us to consider CS biopsy when the diagnosis of CS meningioma is uncertain. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Do Young and Older Adults Rely on Different Processes in Source Memory Tasks? A Neuropsychological Study

ERIC Educational Resources Information Center

Glisky, Elizabeth L.; Kong, Lauren L.

2008-01-01

Source memory has consistently been associated with prefrontal function in both normal and clinical populations. Nevertheless, the exact contribution of this brain region to source memory remains uncertain, and evidence suggests that processes used by young and older adults may differ. The authors explored the extent to which scores on composite…

The Effects of the Previous Outcome on Probabilistic Choice in Rats

PubMed Central

Marshall, Andrew T.; Kirkpatrick, Kimberly

2014-01-01

This study examined the effects of previous outcomes on subsequent choices in a probabilistic-choice task. Twenty-four rats were trained to choose between a certain outcome (1 or 3 pellets) versus an uncertain outcome (3 or 9 pellets), delivered with a probability of .1, .33, .67, and .9 in different phases. Uncertain outcome choices increased with the probability of uncertain food. Additionally, uncertain choices increased with the probability of uncertain food following both certain-choice outcomes and unrewarded uncertain choices. However, following uncertain-choice food outcomes, there was a tendency to choose the uncertain outcome in all cases, indicating that the rats continued to “gamble” after successful uncertain choices, regardless of the overall probability or magnitude of food. A subsequent manipulation, in which the probability of uncertain food varied within each session as a function of the previous uncertain outcome, examined how the previous outcome and probability of uncertain food affected choice in a dynamic environment. Uncertain-choice behavior increased with the probability of uncertain food. The rats exhibited increased sensitivity to probability changes and a greater degree of win–stay/lose–shift behavior than in the static phase. Simulations of two sequential choice models were performed to explore the possible mechanisms of reward value computations. The simulation results supported an exponentially decaying value function that updated as a function of trial (rather than time). These results emphasize the importance of analyzing global and local factors in choice behavior and suggest avenues for the future development of sequential-choice models. PMID:23205915

Ancestral assumptions and the clinical uncertainty of evolutionary medicine.

PubMed

Cournoyea, Michael

2013-01-01

Evolutionary medicine is an emerging field of medical studies that uses evolutionary theory to explain the ultimate causes of health and disease. Educational tools, online courses, and medical school modules are being developed to help clinicians and students reconceptualize health and illness in light of our evolutionary past. Yet clinical guidelines based on our ancient life histories are epistemically weak, relying on the controversial assumptions of adaptationism and advocating a strictly biophysical account of health. To fulfill the interventionist goals of clinical practice, it seems that proximate explanations are all we need to develop successful diagnostic and therapeutic guidelines. Considering these epistemic concerns, this article argues that the clinical relevance of evolutionary medicine remains uncertain at best.

Mucinous cystic neoplasms of the mesentery: a case report and review of the literature

PubMed Central

Metaxas, Georgios; Tangalos, Athanasios; Pappa, Polyxeni; Papageorgiou, Irene

2009-01-01

Background Mucinous cystic neoplasms arise in the ovary and various extra-ovarian sites. While their pathogenesis remains conjectural, their similarities suggest a common pathway of development. There have been rare reports involving the mesentery as a primary tumour site. Case presentation A cystic mass of uncertain origin was demonstrated radiologically in a 22 year old female with chronic abdominal pain. At laparotomy, the mass was fixed within the colonic mesentery. Histology demonstrated a benign mucinous cystadenoma. Methods and results We review the literature on mucinous cystic neoplasms of the mesentery and report on the pathogenesis, biologic behavior, diagnosis and treatment of similar extra-ovarian tumors. We propose an updated classification of mesenteric cysts and cystic tumors. Conclusion Mucinous cystic neoplasms of the mesentery present almost exclusively in women and must be considered in the differential diagnosis of mesenteric tumors. Only full histological examination of a mucinous cystic neoplasm can exclude a borderline or malignant component. An updated classification of mesenteric cysts and cystic tumors is proposed. PMID:19454018

Acinic Cell Carcinoma of the Parotid Gland with Four Morphological Features

PubMed Central

Rosero, David S; Alvarez, Ramiro; Gambó, Paula; Alastuey, María; Valero, Alberto; Torrecilla, Nerea; Roche, A. Belén; Simón, Sara

2016-01-01

Acinic cell carcinoma arising in salivary glands is a rare tumor, accounting for 2% to 5% of the primary neoplasms of the parotid gland. When these tumors are well-differentiated, the neoplasia has innocuous aspect, due to the similarity to normal parotid tissue. This makes the diagnosis difficult. Initially the malignancy of this tumor was uncertain; however, recent studies have declared it as malignant. The female / male ratio is 3:2. The nodule usually presents as solitary and well defined shape. Several authors have used different terms to describe histomorphological patterns of these tumors. Four descriptive categories (solid, microcystic, papillary-cystic and follicular) are useful for pathologists. Here we report a case of a 49 yr old man with a left parotid nodule of 5 cm. Parotidectomy was performed at the Hospital Universitario Miguel Servet, in Zaragoza (Spain). The microscopy showed a tumor with acinic semblance, having the four morphologic patterns previously described. The morphological and immunohistochemical study was consistent with the diagnosis of acinic cell carcinoma. PMID:27499783

Acinic Cell Carcinoma of the Parotid Gland with Four Morphological Features.

PubMed

Rosero, David S; Alvarez, Ramiro; Gambó, Paula; Alastuey, María; Valero, Alberto; Torrecilla, Nerea; Roche, A Belén; Simón, Sara

2016-01-01

Acinic cell carcinoma arising in salivary glands is a rare tumor, accounting for 2% to 5% of the primary neoplasms of the parotid gland. When these tumors are well-differentiated, the neoplasia has innocuous aspect, due to the similarity to normal parotid tissue. This makes the diagnosis difficult. Initially the malignancy of this tumor was uncertain; however, recent studies have declared it as malignant. The female / male ratio is 3:2. The nodule usually presents as solitary and well defined shape. Several authors have used different terms to describe histomorphological patterns of these tumors. Four descriptive categories (solid, microcystic, papillary-cystic and follicular) are useful for pathologists. Here we report a case of a 49 yr old man with a left parotid nodule of 5 cm. Parotidectomy was performed at the Hospital Universitario Miguel Servet, in Zaragoza (Spain). The microscopy showed a tumor with acinic semblance, having the four morphologic patterns previously described. The morphological and immunohistochemical study was consistent with the diagnosis of acinic cell carcinoma.

[Portopulmonary hypertension: Updated review].

PubMed

Rodríguez-Almendros, Nielzer; Toapanta-Yanchapaxi, Liz N; Aguirre Valadez, Jonathan; Espinola Zavaleta, Nilda; Muñoz-Martínez, Sergio G; García-Juárez, Ignacio

Portopulmonary hypertension (PPH) is a rare condition worldwide, although epidemiological data are unknown in Mexico. However, chronic liver diseases are very prevalent in Mexico. PPH is the 4th subtype in frequency in the group of pulmonary arterial hypertension. Its diagnosis is made within 2 scenarios: patients with suspected pulmonary hypertension and candidates for orthotopic liver transplantation (OLT). Both echocardiogram and a right cardiac catheterisation are crucial for diagnosis in both cases. PPH is a challenge for OLT, since it can significantly increase perioperative mortality. The use of specific therapy is the cornerstone of this disease, as a measure to improve the outcome of those who become candidates for OLT with moderate to severe PPH. It is important to recognise that PPH can be a contraindication to OLT. The role of lung-liver transplantation or heart-lung-liver transplantation as a measure to heal pulmonary vascular disease in patients with PPH is still uncertain. Copyright © 2016 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

Clinical Characteristics of Seven Patients with Lanthanum Phosphate Deposition in the Stomach.

PubMed

Murakami, Naoko; Yoshioka, Masao; Iwamuro, Masaya; Nasu, Junichirou; Nose, Soichiro; Shiode, Junji; Okada, Hiroyuki; Yamamoto, Kazuhide

2017-08-15

Objective To analyze the clinical characteristics and endoscopic features of patients with lanthanum deposition in the stomach. Patients We retrospectively reviewed seven patients with lanthanum deposition in the stomach who were diagnosed at Okayama Saiseikai General Hospital. We investigated the patient sex, age at diagnosis, medical and medication histories, gastrointestinal symptoms, complications, presence or absence of gastric atrophy, and outcome. We also investigated any changes in the endoscopic features if previous endoscopic images were available. Results Seven patients (six males and one female) had lanthanum deposition. The median age was 65 years (range, 50-79 years). All patients had been undergoing dialysis (continuous ambulatory peritoneal dialysis in one patient, hemodialysis in six patients). The dialysis period ranged from 16 to 73 months (median, 52 months). The patients had all been taking lanthanum carbonate for a period ranging from 5 to 45 months (median, 27 months). Gastric atrophy was noted in 6 patients (85.7%). One patient had difficulty swallowing, and 1 other patient had appetite loss. The other 5 patients were asymptomatic. Endoscopic features included annular whitish mucosa (n = 4), diffuse whitish mucosa (n = 3), and whitish spots (n = 2). Five patients underwent multiple esophagogastroduodenoscopy. The endoscopic features were unchanged in 2 patients, whereas the whitish mucosa became apparent and spread during the course in 3 patients. Conclusion We identified 7 patients with lanthanum deposition in the stomach. All patients showed whitish lesions macroscopically. Although the pathogenicity of gastric lanthanum deposition is uncertain, lanthanum-related lesions in the stomach progressed during continuous lanthanum phosphate intake in several patients.

Cerebral amyloid angiopathy - The modified Boston criteria in clinical practice.

PubMed

Caetano, André; Ladeira, Filipa; Barbosa, Raquel; Calado, Sofia; Viana-Baptista, Miguel

2018-01-15

Early identification of patients with cerebral amyloid angiopathy (CAA) is relevant considering the increased risk for cerebral hemorrhage. A new set of diagnostic criteria for CAA was recently proposed, which include the presence of superficial siderosis. We aimed to assess the impact of applying these criteria regarding use of antithrombotic therapy. Review of consecutive patients admitted to a Neurology Department from 2014 to 2016, with acute parenchymal or subarachnoid hemorrhage and/or atypical transient focal neurological episodes. Patients with a possible or probable CAA according to the original and modified Boston criteria were included. Information was collected regarding presentation, imaging findings and concomitant therapy. Among a total of 1436 admitted patients, 52 with acute hemorrhagic lesions or atypical TFNE were screened: 22 met criteria for CAA; 4 were deemed too young; 21 had other causes for hemorrhagic parenchymal lesions; and 5 had uncertain diagnosis. Using the modified Boston criteria, 8 patients fulfilled criteria for probable CAA and 14 for possible CAA. When we applied the original Boston criteria to the same patients, only 7 fulfilled criteria for probable CAA and 8 for possible CAA. Among the additional patients identified with the modified Boston criteria, 4 were using antithrombotic therapy. The use of the modified Boston criteria allowed for the identification of 7 additional patients, more than half of which were taking antithrombotic therapy. Systematic use of these criteria could have an important impact in clinical practice. Raising awareness on the different presentations of CAA among clinicians is of the utmost importance. Copyright © 2017 Elsevier B.V. All rights reserved.

Peanut allergy: is maternal transmission of antigens during pregnancy and breastfeeding a risk factor?

PubMed

DesRoches, A; Infante-Rivard, C; Paradis, L; Paradis, J; Haddad, E

2010-01-01

Peanut allergy is an important public health problem in western countries. However, the risk factors associated with this allergy remain uncertain. To determine whether the consumption of peanuts during pregnancy and breastfeeding is a risk factor for peanut allergy in infants. We enrolled 403 infants in a case-control study. The cases were infants aged 18 months or less with a diagnosis of peanut allergy based on a history of clinical reaction after exposure to peanuts and the presence of peanut-specific immunoglobulin E. Controls were age-matched infants with no known clinical history or signs of atopic disease. The mothers of the children filled out a detailed questionnaire about maternal diet during pregnancy and breastfeeding, the infant's diet, the presence of peanut products in the infant's environment, and family history of atopy. The mean (SD) age of cases was 1.23 (0.03) years. The groups were comparable in terms of the rate and duration of breastfeeding. However, the reported consumption of peanuts during pregnancy and breastfeeding was higher in the case group and associated with an increased risk of peanut allergy in offspring (odds ratio [OR], 4.22 [95% confidence interval [CI], 1.57-11.30 and OR, 2.28 [95% CI, 1.31-3.97] for pregnancy and breastfeeding, respectively). Overall, the infants with peanut allergy did not seem to be more exposed to peanut products in their environment than the controls. Early exposure to peanut allergens, whether in utero or through human breast milk, seems to increase the risk of developing peanut allergy.

Defining malnutrition: A plea to rethink.

PubMed

Soeters, P; Bozzetti, F; Cynober, L; Forbes, A; Shenkin, A; Sobotka, L

2017-06-01

In a recent consensus report in Clinical Nutrition the undernourished category of malnutrition was proposed to be defined and diagnosed on the basis of a low BMI or unintentional weight loss combined with low BMI or FFMI with certain cut off points. The definition was endorsed by ESPEN despite recent endorsement of a very different definition. The approach aims to assess whether nutritional intake is sufficient but is imprecise because a low BMI does not always indicate malnutrition and individuals with increasing BMI's may have decreasing FFM's. The pathophysiology of individuals, considered to be malnourished in rich countries and in areas with endemic malnutrition, results predominantly from deficient nutrition combined with infection/inflammation. Both elements jointly determine body composition and function and consequently outcome of disease, trauma or treatment. When following the consensus statement only an imprecise estimate is acquired of nutritional intake without knowing the impact of inflammation. Most importantly, functional abilities are not assessed. Consequently it will remain uncertain how well the individual can overcome stressful events, what the causes are of dysfunction, how to set priorities for treatment and how to predict the effect of nutritional support. We therefore advise to consider the pathophysiology of malnourished individuals leading to inclusion of the following elements in the definition of malnutrition: a disordered nutritional state resulting from a combination of inflammation and a negative nutrient balance, leading to changes in body composition, function and outcome. A precise diagnosis of malnutrition should be based on assessment of these elements. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Strategies for preventing type 2 diabetes: an update for clinicians

PubMed Central

Amer, Halima; Ibrahim, Bashar; Brownrigg, Jack

2013-01-01

Diabetes is a major and growing public health challenge which threatens to overwhelm medical services in the future. Type 2 diabetes confers significant morbidity and mortality, most notably with target organ damage to the eyes, kidneys, nerves and heart. The magnitude of cardiovascular risk associated with diabetes is best illustrated by its position as a coronary heart disease risk equivalent. Complications related to neuropathy are also vast, often working in concert with vascular abnormalities and resulting in serious clinical consequences such as foot ulceration. Increased understanding of the natural history of this disorder has generated the potential to intervene and halt pathological progression before overt disease ensues, after which point management becomes increasingly challenging. The concept of prediabetes as a formal diagnosis has begun to be translated from the research setting to clinical practice, but with continually updated guidelines, varied nomenclature, emerging pharmacotherapies and an ever-changing evidence base, clinicians may be left uncertain of best practice in identifying and managing patients at the prediabetic stage. This review aims to summarize the epidemiological data, new concepts in disease pathogenesis and guideline recommendations in addition to lifestyle, pharmacological and surgical therapies targeted at stopping progression of prediabetes to diabetes. While antidiabetic medications, with newer anti-obesity medications and interventional bariatric procedures have shown some promising benefits, diet and therapeutic lifestyle change remains the mainstay of management to improve the metabolic profile of individuals with glucose dysregulation. New risk stratification tools to identify at-risk individuals, coupled with unselected population level intervention hold promise in future practice. PMID:23997928

Updates in the genetic evaluation of the child with global developmental delay or intellectual disability.

PubMed

Flore, Leigh Anne; Milunsky, Jeff M

2012-12-01

Global developmental delay (GDD) and intellectual disability (ID) occur in up to 3% of the general population and are even more commonly encountered in the setting of the pediatric neurology clinic. New advances in technology and in the understanding of genetic disorders have led to changes in the diagnostic approach to a child with unexplained GDD or ID. Chromosomal microarray has become a first-line test for evaluation of patients in this population and has both significantly increased diagnostic yield and introduced new challenges in the interpretation of copy number variants of uncertain significance. The G-banded karyotype is now frequently utilized as an adjunct to the microarray rather than as a first-line test in individuals with GDD or ID. Fragile X DNA testing continues to be recommended in the initial evaluation of the child with GDD or ID. The presence or absence of certain cardinal features (such as microcephaly or macrocephaly, seizures, autism, abnormal neurologic examination, and facial dysmorphism) can be utilized to direct single-gene molecular testing. The availability of next-generation and massively parallel sequencing technologies has enabled the use of genetic testing panels, in which dozens of genes associated with GDD or ID may be rapidly analyzed. Most recently, the clinical availability of whole-genome and whole-exome sequencing has opened new possibilities for the evaluation of individuals with GDD or ID who have previously eluded a genetic diagnosis. Consultation with a medical geneticist is recommended when progressing beyond first-tier analyses to most efficiently prioritize testing. Copyright © 2012 Elsevier Inc. All rights reserved.

Comparison of the epidemiologic features and patterns of initial care for prostate cancer between public and private institutions: a survey by the Brazilian Society of Urology.

PubMed

Nardi, Aguinaldo Cesar; Reis, Rodolfo Borges dos; Zequi, Stenio de Cassio; Nardozza, Archimedes

2012-01-01

To describe the epidemiological features and patterns of initial care for prostate cancer at public and private institutions in the State of Sao Paulo, Brazil. A total of 1,082 physicians affiliated to the Sao Paulo Section of the Brazilian Society of Urology were invited to participate in this cross-sectional, web-based survey. Between September 2004 and September 2005, participating urologists entered data on demographic, clinical and pathological characteristics of patients diagnosed with prostate cancer in their practice. Data on patients attended at public institutions were analyzed and compared with those patients attended at private practice. One hundred and ten society members contributed with data from 1915 patients, 1026 (53.6%) of whom from public institutions. When compared with patients attended at private institutions, those attended at public institutions were older and more likely to be black, had higher serum prostate specific antigen (PSA) levels, had a higher probability of being diagnosed with metastatic disease, but were less likely to undergo prostatectomy (all P < 0.001). In multivariate analysis, age, biopsy Gleason score, and being attended at a public institution were independently associated with metastatic disease upon diagnosis. The significant predictors of nonsurgical treatment were age, black race, and higher serum levels of PSA. A statewide registry provides valuable information regarding patient demographics, clinical features, and patterns of care. The results of this study suggest that significant disparities exist for patients with prostate cancer attended at different health-care systems. The relative contribution of biological versus socioeconomic features remains uncertain.

Intestinal permeability defects: Is it time to treat?

PubMed Central

Odenwald, Matthew A.; Turner, Jerrold R.

2013-01-01

An essential role of the intestinal epithelium is to separate luminal contents from the interstitium, a function primarily determined by the integrity of the epithelium and the tight junction that seals the paracellular space. Intestinal tight junctions are selectively-permeable, and intestinal permeability can be increased physiologically in response to luminal nutrients or pathologically by mucosal immune cells and cytokines, the enteric nervous system, and pathogens. Compromised intestinal barrier function is associated with an array of clinical conditions, both intestinal and systemic. While most available data are correlative, some studies support a model where cycles of increased intestinal permeability, intestinal immune activation, and subsequent immune-mediated barrier loss contribute to disease progression. This model is applicable to intestinal and systemic diseases. However, it has not been proven and both mechanistic and therapeutic studies are ongoing. Nevertheless, the correlation between increased intestinal permeability and disease has caught the attention of the public, leading to a rise in popularity of the diagnosis of “leaky gut syndrome,” which encompasses a range of systemic disorders. Proponents claim that barrier restoration will cure underlying disease, but this has not been demonstrated in clinical trials. Moreover, human and mouse studies show that intestinal barrier loss alone is insufficient to initiate disease. It is therefore uncertain if increased permeability in these patients is a cause or effect of the underlying disorder. Although drug targets that may mediate barrier restoration have been proposed, none have been proven effective. As such, current treatments for barrier dysfunction should target the underlying disease. PMID:23851019

Utility of gastric aspirates for diagnosing tuberculosis in children in a low prevalence area: predictors of positive cultures and significance of non-tuberculous mycobacteria.

PubMed

Kordy, Faisal; Richardson, Susan E; Stephens, Derek; Lam, Ray; Jamieson, Frances; Kitai, Ian

2015-01-01

In countries with low rates of tuberculosis (TB), yields of gastric aspirates (GAs) for Mycobacterium tuberculosis (MTB) culture are low. The significance of non-tuberculous mycobacteria (NTM) isolated from GA is uncertain. We reviewed clinical, microbiologic and radiologic data for children who underwent GA between 1999 and 2011 at Sick Kids, Toronto. Radiologic features of cases were compared with those of age matched controls. 785 GAs were obtained from 285 patients of whom 20 (7%) had positive MTB cultures: in 15 patients the GA was the only positive culture for MTB. Of 15 culture-positive patients who underwent exactly 3 GAs, MTB was isolated from the first lavage in 10 (67%), only from the second in 3 (20%) and only from the third in 2 (13%). On univariate analysis, miliary disease and intrathoracic lymphadenopathy were associated with a positive GA MTB culture. On multiple conditional logistic regression analysis, adenopathy remained significant (OR 10.2 [95% CI 2.0-51.4] p =0.005). Twelve patients had NTM isolated, most commonly M. avium complex: none had evidence of invasive NTM disease during a median duration of 12 months of follow-up. Causal pathogens different from the GA NTM culture were isolated from biopsies or bronchoalveolar lavage in 3. GAs continue to be important for TB diagnosis in children. Three GAs have a yield better than 1. Those with miliary or disseminated TB and intrathoracic lymphadenopathy have highest yields. NTM isolates from GA are likely unimportant and can be clinically misleading.

Differential diagnosis of suspected multiple sclerosis: a consensus approach

PubMed Central

Miller, DH; Weinshenker, BG; Filippi, M; Banwell, BL; Cohen, JA; Freedman, MS; Galetta, SL; Hutchinson, M; Johnson, RT; Kappos, L; Kira, J; Lublin, FD; McFarland, HF; Montalban, X; Panitch, H; Richert, JR; Reingold, SC; Polman, CH

2008-01-01

Background and objectives Diagnosis of multiple sclerosis (MS) requires exclusion of diseases that could better explain the clinical and paraclinical findings. A systematic process for exclusion of alternative diagnoses has not been defined. An International Panel of MS experts developed consensus perspectives on MS differential diagnosis. Methods Using available literature and consensus, we developed guidelines for MS differential diagnosis, focusing on exclusion of potential MS mimics, diagnosis of common initial isolated clinical syndromes, and differentiating between MS and non-MS idiopathic inflammatory demyelinating diseases. Results We present recommendations for 1) clinical and paraclinical red flags suggesting alternative diagnoses to MS; 2) more precise definition of “clinically isolated syndromes” (CIS), often the first presentations of MS or its alternatives; 3) algorithms for diagnosis of three common CISs related to MS in the optic nerves, brainstem, and spinal cord; and 4) a classification scheme and diagnosis criteria for idiopathic inflammatory demyelinating disorders of the central nervous system. Conclusions Differential diagnosis leading to MS or alternatives is complex and a strong evidence base is lacking. Consensus-determined guidelines provide a practical path for diagnosis and will be useful for the non-MS specialist neurologist. Recommendations are made for future research to validate and support these guidelines. Guidance on the differential diagnosis process when MS is under consideration will enhance diagnostic accuracy and precision. PMID:18805839

Reliability of clinical diagnosis and laboratory testing techniques currently used for identification of canine parvovirus enteritis in clinical settings

PubMed Central

FAZ, Mirna; MARTÍNEZ, José Simón; QUIJANO-HERNÁNDEZ, Israel; FAJARDO, Raúl

2016-01-01

Canine parvovirus type 2 (CPV-2) is the main etiological agent of viral enteritis in dogs. Actually in literature, CPV-2 has been reported with clinical signs that vary from the classical disease, and immunochromatography test and PCR technique have been introduced to veterinary hospitals to confirm CPV-2 diagnosis and other infections. However, the reliability of these techniques has been poorly analyzed. In this study, we evaluated the sensitivity and specificity of veterinary clinical diagnosis, immunochromatography test and PCR technique. Our data indicate that variations in the clinical signs of CPV-2 complicate the gathering of an appropriate diagnosis; and immunochromatography test and PCR technique do not have adequate sensitivity to diagnose positive cases. PMID:27818461

New insights into family relationships within the avian superfamily Sylvioidea (Passeriformes) based on seven molecular markers

PubMed Central

2012-01-01

Background The circumscription of the avian superfamily Sylvioidea is a matter of long ongoing debate. While the overall inclusiveness has now been mostly agreed on and 20 families recognised, the phylogenetic relationships among the families are largely unknown. We here present a phylogenetic hypothesis for Sylvioidea based on one mitochondrial and six nuclear markers, in total ~6.3 kbp, for 79 ingroup species representing all currently recognised families and some species with uncertain affinities, making this the most comprehensive analysis of this taxon. Results The resolution, especially of the deeper nodes, is much improved compared to previous studies. However, many relationships among families remain uncertain and are in need of verification. Most families themselves are very well supported based on the total data set and also by indels. Our data do not support the inclusion of Hylia in Cettiidae, but do not strongly reject a close relationship with Cettiidae either. The genera Scotocerca and Erythrocercus are closely related to Cettiidae, but separated by relatively long internodes. The families Paridae, Remizidae and Stenostiridae clustered among the outgroup taxa and not within Sylvioidea. Conclusions Although the phylogenetic position of Hylia is uncertain, we tentatively support the recognition of the family Hyliidae Bannerman, 1923 for this genus and Pholidornis. We propose new family names for the genera Scotocerca and Erythrocercus, Scotocercidae and Erythrocercidae, respectively, rather than including these in Cettiidae, and we formally propose the name Macrosphenidae, which has been in informal use for some time. We recommend that Paridae, Remizidae and Stenostiridae are not included in Sylvioidea. We also briefly discuss the problems of providing a morphological diagnosis when proposing a new family-group name (or genus-group name) based on a clade. PMID:22920688

Teaching Differential Diagnosis by Computer: A Pathophysiological Approach

ERIC Educational Resources Information Center

Goroll, Allan H.; And Others

1977-01-01

An interactive, computer-based teaching exercise in diagnosis that emphasizes pathophysiology in the analysis of clinical data is described. Called the Jaundice Program, its objective is to simplify the pattern recognition problem by relating clinical findings to diagnosis via reference to disease mechanisms. (LBH)

Infantile botulism: a case report.

PubMed

Lavoie, Danielle; Pawar, Gauri; Khan, Atiya

2006-01-01

Although rare, botulism should be a consideration in the differential diagnosis of hypotonia in children. The pattern of clinical presentation and physical examination should raise the suspicion to make the appropriate diagnosis. Prompt clinical diagnosis and immediate appropriate treatment reduce morbidity and/or mortality in this disease.

[Differential chronic hepatitis diagnosis].

PubMed

Hinterberger, W

2000-01-01

Chronic hepatitis comprises a group of disorders of the liver exhibiting a chronic necroinflammatory process that differs in etiology, clinical course and treatment strategies. A diagnosis of chronic hepatitis is usually made when inflammation and liver cell necrosis persist for longer than 6 months. Clinical manifestations range from asymptomatic patients to those with advanced hepatic failure. Both sexes and all age groups are affected. Chronic hepatitis may emerge as a sequelae of hepatitis C and less often after hepatitis B. Both diseases are treatable and require rapid and exact diagnosis. The differential diagnosis must exclude autoimmune hepatitis, chronic steatohepatitis, congenital metabolic hepatopathies and drug-induced hepatopathies. Laboratory tests, histologic investigations and clinical differential diagnosis must exclude other causes of chronic liver disease.

Regulating trust in pediatric clinical trials.

PubMed

Pinxten, Wim; Nys, Herman; Dierickx, Kris

2008-12-01

The participation of minors in clinical trials is essential to provide safe and effective medical care to children. Because few drugs have been tested in children, pediatricians are forced to prescribe medications off-label with uncertain efficacy and safety. In this article, we analyze how the enrollment of minors in clinical trials is negotiated within relationships of mutual trust between clinicians, minors, and their parents. After a brief description of the problems associated with involving minors in clinical research, we consider how existing "relationships of trust" can be used as a place where the concerns of research subjects can be more fully discussed and addressed. Building on the tacit recognition of trust found in The European Clinical Trials Directive we make policy recommendations that allow for clearer, more ethically informed guidelines for enrolling minors in clinical research.

Clinico-pathological study to evaluate oral lichen planus for the establishment of clinical and histopathological diagnostic criteria.

PubMed

Hiremath, Santhosh; Kale, Alka D; Hallikerimath, Seema

2015-01-01

Lichen planus and lichenoid lesions affecting the oral cavity show similar clinico-pathological features creating a diagnostic dilemma. Hence, the aim of the present study was to establish a clinical and histopathological correlation in the diagnosis of oral lichen planus, based on the modified WHO diagnostic criteria of oral lichen planus and oral lichenoid lesions proposed by Van der Meij and Van der Waal in 2003. In the present study, 100 cases of oral lichen planus were clinically and histopathologically analyzed. Out of the 100 cases, 50 were prospective and 50 were retrospective cases. Prospective cases were collected based on the clinical diagnosis of oral lichen planus and oral lichenoid lesion. Retrospective cases were collected based on the histopathological diagnosis of oral lichen planus. Both the clinical and histopathological analyses were performed based on a proposal for a set of modified diagnostic criteria of oral lichen planus and oral lichenoid lesion. A final diagnosis of oral lichen planus was made only after the correlation of the clinical diagnosis with the histopathological diagnosis. The interobserver agreement among three observers for both prospective and retrospective cases in the final diagnosis of oral lichen planus was found to be "good" to "very good" indicating high reproducibility. However, the final diagnoses of true oral lichen planus after clinico-pathological correlation in prospective and retrospective study groups appeared to be 38.0% and 54.0% respectively. The results of the present study revealed mild to moderate clinico-pathological correlation in the final diagnosis of oral lichen planus for the prospective and retrospective study groups respectively.

Chronic Glaucoma in Dogs: Relationships Between Histologic Lesions and the Gonioscopic Diagnosis of Pectinate Ligament Dysplasia.

PubMed

Bauer, B S; Sandmeyer, L S; Philibert, H; Feng, C X; Grahn, B H

2016-11-01

Pectinate ligament dysplasia (PLD) is a common cause of canine glaucoma and the definitive clinical diagnosis is based on gonioscopy. Although the histologic lesions of PLD have been described, it has not been determined whether these changes are specific for PLD or if similar histologic changes can develop as a consequence of secondary glaucoma. The filtration angles of 61 enucleated canine globes with chronic glaucoma were evaluated with light microscopy by 3 examiners who were masked to the clinical history, signalment, and gonioscopic results. A histologic diagnosis of PLD versus non-PLD was determined by each examiner based on previously reported morphologic criteria and compared with the clinical gonioscopic diagnosis. Of the 61 enucleated glaucomatous eyes, 40 were clinically diagnosed with PLD. For all 3 examiners, a histologic diagnosis of PLD corresponded poorly with the clinical diagnosis of PLD (range of kappa score: 0.149-0.269; range of AUC: 0.592-0.621). There was no difference between examiners in their ability to correctly diagnose PLD histologically (P = .978). A fair degree of agreement was noted among examiners in obtaining their suspected histologic diagnosis of PLD (kappa score 0.256). No individual or sets of histologic ICA features were consistent with clinical PLD. The results indicate the histologic ICA changes proposed to be characteristic of PLD are also noted in canine globes affected with chronic secondary glaucoma. Therefore, using routine histologic evaluation, a histologic diagnosis of PLD is not possible in the face of chronic canine glaucoma. © The Author(s) 2016.

[The relative analysis of clinical endocrine features and pathological types of pituitary microadenomas].

PubMed

Yan, Qing; Zhang, Hua-qiu; Wang, He-ping; Guo, Dong-sheng; Lei, Ting; Li, Ling

2010-06-15

To study the relationship between the clinical presentation, endocrinal findings and pathological types in patients with pituitary microadenomas, so as to improve the accuracy of clinical diagnosis and choose the best therapy strategy before the operation. From January 2007 to June 2009, the clinical data of 94 patients who were surgically removed pituitary microadenomas were obtained, including the clinical presentation, endocrinal findings and pathological diagnosis. The analysis was accomplished with Chi-square test. Hormonal symptoms were found in 86 patients (91.5%), it occurred more frequently in immunopositive patients (85/92, 92.4%) than in immunonegative patients (1/2, 50.0%) (P < 0.05). The coincidence of hormonal symptoms and immunohistochemistry diagnosis was 71.7%; 88.9% patients had the symptoms of amenorrhea, galactorrhea and sexual function diseases in prolactin (PRL) positive group and 28.1% patients had the symptoms of gigantism or acromegaly in growth hormone (GH) positive group. The coincidence of endocrinal findings and immunohistochemistry diagnosis was 69.0%; 87.7% patients had high level of blood PRL in PRL positive group and 21.9% patients had high level of blood GH in GH positive group. There is an obvious relationship between the clinical presentation, endocrinal findings and pathological diagnosis in patients with pituitary microadenomas, which may contribute to the clinical diagnosis and treatment of pituitary secreting microadenomas.

Accuracy of dentists in the clinical diagnosis of oral lesions.

PubMed

Kondori, Ida; Mottin, Roberta W; Laskin, Daniel M

2011-01-01

Dentists play an important role in the early diagnosis and treatment of oral lesions. However, treatment based solely on a clinical impression of the diagnosis, without histologic confirmation, can result in serious consequences, particularly when the lesion is precancerous or cancerous. The purpose of this study was to determine the overall accuracy of clinical diagnoses made by dentists as well as to compare the diagnostic ability of general practitioners with members of various dental specialties. The biopsy reports of 976 specimens submitted to the Department of Oral and Maxillofacial Pathology, Virginia Commonwealth University School of Dentistry, between January 2009 and January 2010 were reviewed. The presumptive clinical diagnosis made by the practitioner and the final histologic diagnosis on each specimen were recorded in addition to whether the submitting dentist was a general practitioner or a specialist. Of the clinical diagnoses made by the submitting dentists, 43% were incorrect. General dentists misdiagnosed 45.9%, oral and maxillofacial surgeons 42.8%, endodontists 42.2%, and periodontists 41.2% of the time. The most commonly missed clinical diagnoses were hyperkeratosis (16%), focal inflammatory fibrous hyperplasia (10%), fibroma (8%), periapical granuloma (7%), and radicular cyst (6%). Cancerous lesions were misdiagnosed 5.6% of the time. The high rates of clinical misdiagnosis by dental practitioners indicate that all excised lesions should to be submitted for histologic diagnosis.

Neuropathological Assessment as an Endpoint in Clinical Trial Design.

PubMed

Gentleman, Steve; Liu, Alan King Lun

2018-01-01

Different neurodegenerative conditions can have complex, overlapping clinical presentations that make accurate diagnosis during life very challenging. For this reason, confirmation of the clinical diagnosis still requires postmortem verification. This is particularly relevant for clinical trials of novel therapeutics where it is important to ascertain what disease and/or pathology modifying effects the therapeutics have had. Furthermore, it is important to confirm that patients in the trial actually had the correct clinical diagnosis as this will have a major bearing on the interpretation of trial results. Here we present a simple protocol for pathological assessment of neurodegenerative changes.

Clinical validation of the nursing diagnosis of dysfunctional family processes related to alcoholism.

PubMed

Mangueira, Suzana de Oliveira; Lopes, Marcos Venícios de Oliveira

2016-10-01

To evaluate the clinical validity indicators for the nursing diagnosis of dysfunctional family processes related to alcohol abuse. Alcoholism is a chronic disease that negatively affects family relationships. Studies on the nursing diagnosis of dysfunctional family processes are scarce in the literature. This diagnosis is currently composed of 115 defining characteristics, hindering their use in practice and highlighting the need for clinical validation. This was a diagnostic accuracy study. A sample of 110 alcoholics admitted to a reference centre for alcohol treatment was assessed during the second half of 2013 for the presence or absence of the defining characteristics of the diagnosis. Operational definitions were created for each defining characteristic based on concept analysis and experts evaluated the content of these definitions. Diagnostic accuracy measures were calculated from latent class models with random effects. All 89 clinical indicators were found in the sample and a set of 24 clinical indicators was identified as clinically valid for a diagnostic screening for family dysfunction from the report of alcoholics. Main clinical indicators with high specificity included sexual abuse, disturbance in academic performance in children and manipulation. The main indicators that showed high sensitivity values were distress, loss, anxiety, low self-esteem, confusion, embarrassment, insecurity, anger, loneliness, deterioration in family relationships and disturbance in family dynamics. Eighteen clinical indicators showed a high capacity for diagnostic screening for alcoholics (high sensitivity) and six indicators can be used for confirmatory diagnosis (high specificity). © 2016 John Wiley & Sons Ltd.

Neuropathologic features associated with Alzheimer disease diagnosis

PubMed Central

Grinberg, L.T.; Miller, B.; Kawas, C.; Yaffe, K.

2011-01-01

Objective: To examine whether the association between clinical Alzheimer disease (AD) diagnosis and neuropathology and the precision by which neuropathology differentiates people with clinical AD from those with normal cognition varies by age. Methods: We conducted a cross-sectional analysis of 2,014 older adults (≥70 years at death) from the National Alzheimer's Coordinating Center database with clinical diagnosis of normal cognition (made ≤1 year before death, n = 419) or AD (at ≥65 years, n = 1,595) and a postmortem neuropathologic examination evaluating AD pathology (neurofibrillary tangles, neuritic plaques) and non-AD pathology (diffuse plaques, amyloid angiopathy, Lewy bodies, macrovascular disease, microvascular disease). We used adjusted logistic regression to analyze the relationship between clinical AD diagnosis and neuropathologic features, area under the receiver operating characteristic curve (c statistic) to evaluate how precisely neuropathology differentiates between cognitive diagnoses, and an interaction to identify effect modification by age group. Results: In a model controlling for coexisting neuropathologic features, the relationship between clinical AD diagnosis and neurofibrillary tangles was significantly weaker with increasing age (p < 0.001 for interaction). The aggregate of all neuropathologic features more strongly differentiated people with clinical AD from those without in younger age groups (70–74 years: c statistic, 95% confidence interval: 0.93, 0.89–0.96; 75–84 years: 0.95, 0.87–0.95; ≥85 years: 0.83, 0.80–0.87). Non-AD pathology significantly improved precision of differentiation across all age groups (p < 0.004). Conclusion: Clinical AD diagnosis was more weakly associated with neurofibrillary tangles among the oldest old compared to younger age groups, possibly due to less accurate clinical diagnosis, better neurocompensation, or unaccounted pathology among the oldest old. PMID:22031532

Low clinical diagnostic accuracy of early vs advanced Parkinson disease: clinicopathologic study.

PubMed

Adler, Charles H; Beach, Thomas G; Hentz, Joseph G; Shill, Holly A; Caviness, John N; Driver-Dunckley, Erika; Sabbagh, Marwan N; Sue, Lucia I; Jacobson, Sandra A; Belden, Christine M; Dugger, Brittany N

2014-07-29

Determine diagnostic accuracy of a clinical diagnosis of Parkinson disease (PD) using neuropathologic diagnosis as the gold standard. Data from the Arizona Study of Aging and Neurodegenerative Disorders were used to determine the predictive value of a clinical PD diagnosis, using 2 clinical diagnostic confidence levels, PossPD (never treated or not clearly responsive) and ProbPD (responsive to medications). Neuropathologic diagnosis was the gold standard. Based on first visit, 9 of 34 (26%) PossPD cases had neuropathologically confirmed PD while 80 of 97 (82%) ProbPD cases had confirmed PD. PD was confirmed in 8 of 15 (53%) ProbPD cases with <5 years of disease duration and 72 of 82 (88%) with ≥5 years of disease duration. Using final diagnosis at time of death, 91 of 107 (85%) ProbPD cases had confirmed PD. Clinical variables that improved diagnostic accuracy were medication response, motor fluctuations, dyskinesias, and hyposmia. Using neuropathologic findings of PD as the gold standard, this study establishes the novel findings of only 26% accuracy for a clinical diagnosis of PD in untreated or not clearly responsive subjects, 53% accuracy in early PD responsive to medication (<5 years' duration), and >85% diagnostic accuracy of longer duration, medication-responsive PD. Caution is needed when interpreting clinical studies of PD, especially studies of early disease that do not have autopsy confirmation. The need for a tissue or other diagnostic biomarker is reinforced. This study provides Class II evidence that a clinical diagnosis of PD identifies patients who will have pathologically confirmed PD with a sensitivity of 88% and specificity of 68%. © 2014 American Academy of Neurology.

Interpretation bias for uncertain threat: A replication and extension.

PubMed

Oglesby, Mary E; Raines, Amanda M; Short, Nicole A; Capron, Daniel W; Schmidt, Norman B

2016-06-01

Intolerance of uncertainty (IU) has been proposed as an important transdiagnostic variable within various anxiety-related disorders. Research has suggested that individuals high in IU may interpret ambiguous information in a more threatening manner, suggesting a negative interpretation bias for uncertain information. However, interpretation biases within IU have not been adequately tested in the literature. The current study evaluated negative interpretation biases for uncertain information by directly measuring an individual's interpretations of ambiguous information across two samples. Participants consisted of 76 (Study 1; 72.4% female) and 31 (Study 2; 81% female) undergraduate students. Results indicated that individuals high in IU interpret ambiguous scenarios as more threatening compared to negative and/or positive scenarios (β = .45, p = .02). In addition, individuals high in IU showed a negative interpretation bias for ambiguous information, but not benign information (Study 1: β = -.40, p < .001; Study 2: β = -.57, p = .002). Future research should attempt to replicate these findings within clinical populations. In addition, future work would benefit from the inclusion of behavioral assessments of IU. These findings are the first to detect the presence of a negative interpretation bias for uncertain information among individuals high in IU utilizing a task designed to directly measure an individual's interpretation of information. Given the efficacy and low economic burden associated with interpretation bias modification protocols, and the transdiagnostic nature of IU, targeting IU within these protocols could have a tremendous public health impact. Copyright © 2015 Elsevier Ltd. All rights reserved.

Severe hypertriglyceridemia in Japan: Differences in causes and therapeutic responses.

PubMed

Murase, Toshio; Okubo, Minoru; Ebara, Tetsu; Mori, Yasumichi

Severe hypertriglyceridemia (>1000 mg/dL) has a variety of causes and frequently leads to life-threating acute pancreatitis. However, the origins of this disorder are unclear for many patients. We aimed to characterize the causes of and responses to therapy in rare cases of severe hypertriglyceridemia in a group of Japanese patients. We enrolled 121 patients from a series of case studies that spanned 30 years. Subjects were divided into 3 groups: (1) primary (genetic causes); (2) secondary (acquired); and (3) disorders of uncertain causes. In the last group, we focused on 3 possible risks factors for hypertriglyceridemia: obesity, diabetes mellitus, and heavy alcohol intake. Group A (n = 20) included 13 patients with familial lipoprotein lipase deficiency, 3 patients with apolipoprotein CII deficiency, and other genetic disorders in the rest of the group. Group B patients (n = 15) had various metabolic and endocrine diseases. In Group C (uncertain causes; n = 86), there was conspicuous gender imbalance (79 males, 3 females) and most male subjects were heavy alcohol drinkers. In addition, 18 of 105 adult patients (17%) had histories of acute pancreatitis. The cause of severe hypertriglyceridemia is uncertain in many patients. In primary genetic forms of severe hypertriglyceridemia, genetic diversity between populations is unknown. In the acquired forms, we found fewer cases of estrogen-induced hypertriglyceridemia than in Western countries. In our clinical experience, the cause of most hypertriglyceridemia is uncertain. Our work suggests that genetic factors for plasma triglyceride sensitivity to alcohol should be explored. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Early diagnosis of amyotrophic lateral sclerosis mimic syndromes: pros and cons of current clinical diagnostic criteria.

PubMed

Cortés-Vicente, Elena; Pradas, Jesús; Marín-Lahoz, Juan; De Luna, Noemi; Clarimón, Jordi; Turon-Sans, Janina; Gelpí, Ellen; Díaz-Manera, Jordi; Illa, Isabel; Rojas-Garcia, Ricard

2017-08-01

To describe the frequency and clinical characteristics of patients referred to a tertiary neuromuscular clinic as having amyotrophic lateral sclerosis (ALS) but who were re-diagnosed as having an ALS mimic syndrome, and to identify the reasons that led to the revision of the diagnosis. We reviewed the final diagnosis of all patients prospectively registered in the Sant Pau-MND register from 1 January 2004 to 31 December 2015. A detailed clinical evaluation and a clinically-guided electrophysiological study were performed at first evaluation. Twenty of 314 (6.4%) patients included were re-diagnosed as having a condition other than ALS, in 18 cases already at first evaluation. An alternative specific diagnosis was identified in 17 of those 20, consisting of a wide range of conditions. The main finding leading to an alternative diagnosis was the result of the electrophysiological study. Fifty per cent did not fulfil the El Escorial revised criteria (EECr) for ALS. The most common clinical phenotype at onset in patients with ALS mimic syndromes was progressive muscular atrophy (PMA). Misdiagnosing ALS is still a common problem. Early identification of ALS mimic syndromes is possible based on atypical clinical features and a clinically-guided electrophysiological study. Patients should be attended in specialised centres. The application of EECr helps to identify ALS misdiagnoses.

Systematic review with meta-analysis: diagnostic performance of the combination of pepsinogen, gastrin-17 and anti-Helicobacter pylori antibodies serum assays for the diagnosis of atrophic gastritis.

PubMed

Zagari, R M; Rabitti, S; Greenwood, D C; Eusebi, L H; Vestito, A; Bazzoli, F

2017-10-01

The combination of pepsinogen, gastrin-17 and anti-H. pylori antibodies serological assays (panel test) is a non-invasive tool for the diagnosis of atrophic gastritis. However, the diagnostic reliability of this test is still uncertain. To assess the diagnostic performance of the serum panel test for the diagnosis of atrophic gastritis. Medline via PubMed, Embase, Scopus, Cochrane Library databases and abstracts of international conferences proceedings were searched from January 1995 to December 2016 using the primary keywords "pepsinogens," "gastrin," "atrophic gastritis," "gastric precancerous lesions." Studies were included if they assessed the accuracy of the serum panel test for the diagnosis of atrophic gastritis using histology according to the updated Sydney System as reference standard. Twenty studies with a total of 4241 subjects assessed the performance of serum panel test for the diagnosis of atrophic gastritis regardless of the site in the stomach. The summary sensitivity was 74.7% (95% confidence interval (CI), 62.0-84.3) and the specificity was 95.6% (95%CI, 92.6-97.4). With a prevalence of atrophic gastritis of 27% (median prevalence across the studies), the negative predictive value was 91%. Few studies with small sample size assessed the performance of the test in detecting the site of atrophic gastritis. The combination of pepsinogen, gastrin-17 and anti-H. pylori antibodies serological assays appears to be a reliable tool for the diagnosis of atrophic gastritis. This test may be used for screening subjects or populations at high risk of gastric cancer for atrophic gastritis; however, a cost-effectiveness analysis is needed. © 2017 John Wiley & Sons Ltd.

Newly diagnosed childhood diabetes: a psychosocial transition for parents?

PubMed

Lowes, Lesley; Gregory, John W; Lyne, Patricia

2005-05-01

This paper reports a study to gain a new theoretical understanding of parental grief responses and the process of adaptation to a diagnosis of childhood diabetes. A diagnosis of childhood (type 1) diabetes is an anxious and distressing event for the whole family. Little is known about the experience of parents of newly diagnosed children as they cope with and adapt to their new situation. Parkes' Theory of Psychosocial Transition proposes that life-change events, or 'psychosocial transitions', require people to undertake a major revision of their assumptions about the world. The relevance of this theory to adjusting to a diagnosis of childhood diabetes has not been explored. Forty audio taped in-depth interviews were undertaken with 38 parents of 20 newly-diagnosed children. The data were subsequently examined using the framework of the Theory of Psychosocial Transition. Before diagnosis, most parents associated their child's symptoms with normal childhood illnesses. The unexpectedness and speed of the diagnosis left all parents ill-prepared to deal with the situation. Their world suddenly changed, leaving them insecure and uncertain about the future. Diabetes intruded emotionally and practically upon all of their lives. Parents successfully adjusted and adapted their lives and rebuilt a new model of the world to accommodate their child's diabetes. However, this dynamic process has no guaranteed endpoint for parents. A diagnosis of childhood diabetes leads to a psychosocial transition for parents. The concept of transition provides a logical explanation of parents' responses to loss, and allows increased understanding of the grieving and adaptation processes experienced by parents of children diagnosed with a chronic condition such as diabetes. This knowledge should help health care professionals to assist parents in the period of transition.

Lived experiences of breast cancer survivors after diagnosis, treatment and beyond: qualitative study.

PubMed

Williams, Faustine; Jeanetta, Stephen C

2016-06-01

The number of breast cancer survivors has increased since 1990 due to advances in biomedical technology that lead to an increase in early diagnosis and treatment. Research on survivorship has focused on the psychological and treatment aspects of the disease. The goal of this study was focused on exploring the lived experiences of breast cancer survivors from diagnosis, treatment and beyond. To understand the lived experiences of women who are breast cancer survivors. A purposive sampling strategy was used to recruit participants from two Missouri cancer centres. A total of 15 women breast cancer survivors were interviewed. Three major themes emerged that described the lived experiences of the women. These were factors from the diagnosis and treatment management impacting survivorship, relationship and support system and implication of survivorship. Participants noted that coping with the diagnosis and treatment was a stressful journey and required lots of adjustment and changes. Some developed various techniques such as journaling their activities which provided comfort. In addition, support from family was shared as the key which gave them strength and courage through the different stages of treatment. However, they found it difficult to articulate what survivorship meant. Using in-depth interview techniques, this study shed light on the experiences of women who were diagnosed with breast cancer and have completed treatment. They acknowledged frustration with their diagnosis and body changes. Support received from family and friends helped them cope through their treatment. However, they felt abandoned once the treatment phase was over and were uncertain what survivorhood meant to them. © 2015 The Authors Health Expectations Published by John Wiley & Sons Ltd.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grantham, K; Santanam, L; Goddu, S

Purpose: We retrospectively evaluate the dosimetric impact of a 3.5% range uncertainty on CTV coverage and normal organ toxicity for a cohort of brain patients. Methods: Twenty treatment plans involving 20 brain cancer patients treated with Mevions S250 were reviewed. Forty uncertain plans were made by changing the ranges in original plans by ±3.5% while keeping all devices unchanged. Fidelity to the original plans was evaluated with gamma index. Changes in generalized equivalent uniform dose (gEUD) were reported for the following structures: CTV coverage, brainstem, optic chiasm, and optic nerves. Comparisons were made by plotting the relevant endpoints from themore » uncertain plans as a function of the same endpoints from the original clinical plan. Results: Gamma-index analysis resulted in a 50% pass rate of the uncertain plans using a 90% passing rate and 3%/3mm criterion. A 9.5% decrease in the slope of gEUD plot for the CTV was observed for the 3.5% downward range shift. However, the change in slope did not result in a gEUD change greater than 1.1% for the CTV. The slopes of the gEUD plots for normal structures increased by 3.1% 3.9% 2.4% and 0.2% for the chiasm, brainstem, left optic nerve and right optic nerve respectively. The maximum deviation from the gEUD of the clinical plan for normal structures was: 64% in the chiasm, 31% for the brainstem, and 19% for both optic nerves. Conclusion: A retrospective review shows moderate radiobiological impact of range uncertainty in passively scattered proton therapy with sporadic catastrophe. The linear regression analysis on the statistical data indicates a systematic deviation of gEUD from treatment planning in the light of range uncertainty.« less

Randomized comparison of Zotarolimus-Eluting Endeavor Sprint versus bare-metal stent implantation in uncertain drug-eluting stent candidates: rationale, design, and characterization of the patient population for the Zotarolimus-eluting Endeavor Sprint stent in uncertain DES candidates study.

PubMed

Valgimigli, Marco; Patialiakas, Athanasios; Thury, Attila; Colangelo, Salvatore; Campo, Gianluca; Tebaldi, Matteo; Ungi, Imre; Tondi, Stefano; Roffi, Marco; Menozzi, Alberto; de Cesare, Nicoletta; Garbo, Roberto; Meliga, Emanuele; Testa, Luca; Gabriel, Henrique M; Airoldi, Flavio; Ferlini, Marco; Liistro, Francesco; Dellavalle, Antonio; Vranckx, Pascal; Briguori, Carlo

2013-11-01

The use of drug-eluting stent (DES) instead of bare-metal stent (BMS) in patients at high stent thrombosis or bleeding risk as well as in those at low restenosis risk (ie, uncertain DES candidates) remains a matter of debate. Zotarolimus-Eluting Endeavor Sprint stent (E-ZES) (Santa Rosa, CA) is a hydrophilic polymer-based second-generation device with unique drug fast-release profile, which may allow for a shorter dual antiplatelet therapy (DAPT) duration without safety concerns. The primary objective is to assess whether E-ZES implantation followed by a shorter than currently recommended course of DAPT will decrease the incidence of 12-month major adverse cardiovascular events as compared with BMS in undefined DES recipients. Actual duration of DAPT regimen will be dictated by patients' characteristics and not by stent type and, as such, can be as short as 30 days after intervention in both stent groups. The ZEUS study is an open-label randomized clinical trial conducted at 20 clinical sites in Italy, Switzerland, Portugal, and Hungary. With 1,600 individuals, this study will have 85% power to detect a 33% difference in the primary end point consisting of the composite of death, nonfatal myocardial infarction, or target vessel revascularization. The ZEUS trial aims to assess whether the use of E-ZES, followed by a DAPT duration regimen based on patients' characteristics and not by stent type, is superior to conventional BMS implantation in undefined DES recipients who qualify for the presence of high thrombosis, bleeding, or low restenosis risk criteria. © 2013.

Atypical rearrangement involving 3′-IGH@ and a breakpoint at least 400 Kb upstream of an intact MYC in a CLL patient with an apparently balanced t(8;14)(q24.1;q32) and negative MYC expression

PubMed Central

2013-01-01

The t(8;14)(q24.1;q32), the cytogenetic hallmark of Burkitt’s lymphoma, is also found, but rarely, in cases of chronic lymphocytic leukemia (CLL). Such translocation typically results in a MYC-IGH@ fusion subsequently deregulating and overexpressing MYC on der 14q32. In CLL, atypical rearrangements resulting in its gain or loss, within or outside of IGH@ or MYC locus, have been reported, but their clinical significance remains uncertain. Herein, we report a 67 year-old male with complex cytogenetic findings of apparently balanced t(8;14) and unreported complex rearrangements of IGH@ and MYC loci. His clinical, morphological and immunophenotypic features were consistent with the diagnosis of CLL. Interphase FISH studies revealed deletions of 11q22.3 and 13q14.3, and an extra copy of IGH@, indicative of rearrangement. Karyotype analysis showed an apparently balanced t(8;14)(q24.1;q32). Sequential GPG-metaphase FISH studies revealed abnormal signal patterns: rearrangement of IGH break apart probe with the 5’-IGH@ on derivative 8q24.1 and the 3’-IGH@ retained on der 14q; absence of MYC break apart-specific signal on der 8q; and, the presence of unsplit 5’-MYC-3’ break apart probe signals on der 14q. The breakpoint on 8q24.1 was found to be at least 400 Kb upstream of 5’ of MYC. In addition, FISH studies revealed two abnormal clones; one with 13q14.3 deletion, and the other, with concurrent 11q deletion and atypical rearrangements. Chromosome microarray analysis (CMA) detected a 7.1 Mb deletion on 11q22.3-q23.3 including ATM, a finding consistent with FISH results. While no significant copy number gain or loss observed on chromosomes 8, 12 and 13, a 455 Kb microdeletion of uncertain clinical significance was detected on 14q32.33. Immunohistochemistry showed co-expression of CD19, CD5, and CD23, positive ZAP-70 expression and absence of MYC expression. Overall findings reveal an apparently balanced t(8;14) and atypical complex rearrangements involving 3’-IGH@ and a breakpoint at least 400 Kb upstream of MYC, resulting in the relocation of the intact 5’-MYC-3’ from der 8q, and apposition to 3’-IGH@ at der 14q. This case report provides unique and additional cytogenetic data that may be of clinical significance in such a rare finding in CLL. It also highlights the utility of conventional and sequential metaphase FISH in understanding complex chromosome anomalies and their association with other clinical findings in patients with CLL. To the best of our knowledge, this is the first CLL reported case with such an atypical rearrangement in a patient with a negative MYC expression. PMID:23369149

Clinical presentation of retinoblastoma in Alexandria: A step toward earlier diagnosis.

PubMed

Soliman, Sameh E; Eldomiaty, Wesam; Goweida, Mohamed B; Dowidar, Amgad

2017-01-01

To evaluate the clinical presentation of retinoblastoma in Alexandria, Egypt, correlate the timing of accurate diagnosis with the presence of advanced disease and identify causes of delayed presentation. Retrospective noncomparative single institution study reviews demographic and clinical data of all new children with retinoblastoma presenting to Alexandria Main University ocular oncology clinic (OOC) from January 2012 to June 2014. Diagnosis time was from initial parental complaint to retinoblastoma diagnosis and referral time was from retinoblastoma diagnosis to presentation to the Alexandria OCC. Delayed Diagnosis and referral were counted if >2 weeks. Advanced presentation is defined as clinical TNMH (8th edition) staging of cT2 or cT3 (international intraocular retinoblastoma classification group D or E) in at least one eye or the presence of extra-ocular disease (cT4). Seventy eyes of 47 children were eligible: 52% unilateral, 7% with family history and 96% presented with leukocorea. Sixty-four percent of children had advanced intraocular disease and none had extra-ocular disease. Delayed presentation occurred in 58% of children and was significantly associated with advanced disease in both unilaterally and bilaterally affected children (p = 0.003, 0.002 respectively). The delay in diagnosis was more in unilateral cases while the delay in referral was more in bilateral cases. The main cause of delayed presentation in unilateral retinoblastoma was misdiagnosis (30%) while parental shopping for second medical opinion (30%) was the main cause in bilateral children. Delayed diagnosis is a problem affecting retinoblastoma management. Better medical education and training, health education and earlier screening are recommended to achieve earlier diagnosis.

Lichenoid keratosis is frequently misdiagnosed as basal cell carcinoma.

PubMed

Maor, D; Ondhia, C; Yu, L L; Chan, J J

2017-08-01

Lichenoid keratosis (LK), also known as benign lichenoid keratosis or lichen planus-like keratosis, is a solitary, pink to red-brown scaly plaque representing a host immunological response to a variety of precursor lesions. LK is often misdiagnosed as a dermatological malignancy owing to its clinical resemblance to basal cell carcinoma (BCC) or Bowen disease. We performed a retrospective analysis of the pathology records of a series of LK lesions with reference to the demographic features and accuracy of clinical diagnosis. The pathology records from 2008 to 2009 of 263 consecutive patients with a histological diagnosis of LK from a specialized skin laboratory were retrieved. Data relating to clinical diagnosis, age, sex, anatomical location, time of year of presentation and any coexistent pathological lesions adjacent to the LK were recorded. Mean age at presentation was 64 years (range 34-96), and 58% of patients were female. The most common anatomical site was the chest/anterior torso, followed by the back and legs. The most common coexisting lesion was solar keratosis at 14%, followed by seborrhoeic keratosis (SK) at 7.8%. The correct clinical diagnosis of LK was made in 29.5% of cases. The most common clinical diagnosis was BCC (47%), while SK was the preferred diagnosis in 18%. A clinical diagnosis was not given in 5.5% of cases. In conclusion, it appears that LK is frequently misdiagnosed, with misdiagnosis occurring in > 70% of cases in this study. © 2017 British Association of Dermatologists.

A comprehensive laboratory-based program for classification of variants of uncertain significance in hereditary cancer genes.

PubMed

Eggington, J M; Bowles, K R; Moyes, K; Manley, S; Esterling, L; Sizemore, S; Rosenthal, E; Theisen, A; Saam, J; Arnell, C; Pruss, D; Bennett, J; Burbidge, L A; Roa, B; Wenstrup, R J

2014-09-01

Genetic testing has the potential to guide the prevention and treatment of disease in a variety of settings, and recent technical advances have greatly increased our ability to acquire large amounts of genetic data. The interpretation of this data remains challenging, as the clinical significance of genetic variation detected in the laboratory is not always clear. Although regulatory agencies and professional societies provide some guidance regarding the classification, reporting, and long-term follow-up of variants, few protocols for the implementation of these guidelines have been described. Because the primary aim of clinical testing is to provide results to inform medical management, a variant classification program that offers timely, accurate, confident and cost-effective interpretation of variants should be an integral component of the laboratory process. Here we describe the components of our laboratory's current variant classification program (VCP), based on 20 years of experience and over one million samples tested, using the BRCA1/2 genes as a model. Our VCP has lowered the percentage of tests in which one or more BRCA1/2 variants of uncertain significance (VUSs) are detected to 2.1% in the absence of a pathogenic mutation, demonstrating how the coordinated application of resources toward classification and reclassification significantly impacts the clinical utility of testing. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

CT measurement of central pulmonary arteries to diagnose pulmonary hypertension (PHTN): more reliable than valid?

PubMed

Terpenning, Silanath; Deng, Matthew; Hong-Zohlman, Susie N; Lin, Cheng Ting; Kligerman, Seth J; Jeudy, Jean; Ketai, Loren H

2016-01-01

The association between main pulmonary artery (MPA) size and pulmonary arterial hypertension (PAHTN) is well established; however, the clinical utility of routine measurement of MPA is uncertain due to considerable overlap between normal patients and those with pulmonary hypertension. The lack of diagnostic accuracy could be further degraded by variability among the radiologists. It is unknown whether the addition of right and left pulmonary artery measurements would improve accuracy or further impair it. The purposes of this study are to verify the accuracy of a proposed cutoff value for the size of MPA in the diagnosis PAHTN, to determine the interrater agreement for this measurement, and to determine whether addition of right pulmonary artery (RPA) and left pulmonary artery (LPA) measurement or simple assessment of patient comorbidities can improve the accuracy. Patients undergoing both cardiac catheterization and chest computed tomography (CT) within 3 months of each other at a large university hospital between January 2010 and December 2012 were identified. Patients with prior cardiac surgery or congenital heart disease and critically ill patients were excluded from the study population. Patients with pericardial disease or severe lung disease documented on CT examinations were also excluded. From the remaining patients, 45 patients with normal pulmonary artery pressure and 50 patients with proven pulmonary hypertension were selected. Demographic data and clinical information was collected from medical records of these patients. Three radiologists with different years of experience in cardiothoracic imaging measured the MPA, RPA, and LPA diameters on axial images using an electronic ruler on 3D work stations independently and were masked to the patient clinical symptoms, diagnosis, and each other's measurement to prevent bias. Association between MPA diameter (MPAD) and patient characteristics assessed by one-way analysis of variance for scalar measures. Each reader's measurements were used to construct a separate receiver operating curve (ROC) to assess optimal MPA threshold. The ability of an MPA measurement threshold to correctly identify PAHTN was assessed using chi-squared. Chi-squared was also used to assess the effect of categorical comorbidities on false positive diagnosis. None of the demographic data or patients' factors (age, gender, height, weight, body surface area, and body mass index) were related to the size of MPAD. The distribution of the MPAD was normal in both groups. Based on prior literature, MPAD (≥3.15cm) was selected as the cutoff value to diagnose PAHTN. Review of ROCs did not suggest a superior cutoff value for any reader. Using this threshold per case interrater agreement was good, kappa values >0.65. Based on an average measurement for all three readers, MPAD was 82% sensitive and 62% specific for PAHTN. Limiting positive diagnosis to those subjects with both MPAD ≥3.15 and either enlarged RPA diameter (RPAD) or LPAD diminished sensitivity but did not improve specificity. Defining positive study as the presence of any dilated artery (MPAD, RPAD, or LPAD) increased sensitivity to 94% but decreased specificity to 27%. Comorbidities that might cause fluctuating mean pulmonary artery pressures could not be shown to account for false positive studies. The 29 true negative patients and 16 false positive patients did not differ in the prevalence of obstructive sleep apnea/home oxygen use or documented congestive heart failure/low ejection fraction. Previously proposed threshold of MPAD ≥3.15cm is likely optimal but is not specific for identifying patient with PAHTN. Interobserver differences in MPAD measurement do not account this inaccuracy. Incorporation or RPA and LPA measurement does not improve diagnostic accuracy of PAHTN, and assessment of comorbidities does not easily identify likely false positive cases. Diagnosis of PAHTN based solely on CT examinations of the chest may not be sufficiently accurate for clinical use. Published by Elsevier Inc.

Burning mouth syndrome: a review on diagnosis and treatment.

PubMed

Coculescu, E C; Radu, A; Coculescu, B I

2014-01-01

Burning mouth syndrome (BMS) is defined as a chronic pain condition characterized by a burning sensation in the clinically healthy oral mucosa. It is difficult to diagnose BMS because there is a discrepancy between the severity, extensive objective pain felt by the patient and the absence of any clinical changes of the oral mucosa. This review presents some aspects of BMS, including its clinical diagnosis, classification, differential diagnosis, general treatment, evolution and prognosis.

A comparison between modified Alvarado score and RIPASA score in the diagnosis of acute appendicitis.

PubMed

Singla, Anand; Singla, Satpaul; Singh, Mohinder; Singla, Deeksha

2016-12-01

Acute appendicitis is a common but elusive surgical condition and remains a diagnostic dilemma. It has many clinical mimickers and diagnosis is primarily made on clinical grounds, leading to the evolution of clinical scoring systems for pin pointing the right diagnosis. The modified Alvarado and RIPASA scoring systems are two important scoring systems, for diagnosis of acute appendicitis. We prospectively compared the two scoring systems for diagnosing acute appendicitis in 50 patients presenting with right iliac fossa pain. The RIPASA score correctly classified 88 % of patients with histologically confirmed acute appendicitis compared with 48.0 % with modified Alvarado score, indicating that RIPASA score is more superior to Modified Alvarado score in our clinical settings.

Dermoscopy improves diagnosis of tinea nigra: a study of 50 cases.

PubMed

Piliouras, Peter; Allison, Scott; Rosendahl, Cliff; Buettner, Petra G; Weedon, David

2011-08-01

Tinea nigra is a relatively uncommon dematiaceous fungal infection of the palms and soles, which clinically may mimic a melanocytic lesion. We sought to ascertain how frequently misdiagnosis of this infection occurred and whether the use of dermoscopy helped in its diagnosis. Fifty consecutive cases of tinea nigra diagnosed at a dermatopathology laboratory were examined with regard to the clinical diagnosis, use of dermoscopy and the mode of management. Of the 50 cases, 21 (42.0%) were treated by shave or surgical excision. The clinical diagnosis of tinea nigra was made in five cases (10.0%) and suggested along with other diagnoses in a further two cases (4.0%). The dermatologists (n = 9) gave the correct diagnosis in four patients (44.4%), the general practitioners (n = 38) gave the correct diagnosis in one patient (2.6%) and the three surgeons involved did not give the correct diagnosis. When dermoscopy was used, in seven of 13 (53.8%) cases tinea nigra was suggested as a probable diagnosis but when dermoscopy was not used (n = 37) tinea nigra was not clinically diagnosed (P < 0.001). The diagnosis of tinea nigra is significantly improved by dermoscopy, the disease should be considered as a cause of palmar or plantar pigmentation. © 2011 The Authors; Australasian Journal of Dermatology © 2011 The Australasian College of Dermatologists.

Diagnostic and prognostic value of microRNA-628 for cancers.

PubMed

Li, Jing-Hua; Sun, Shan-Shan; Fu, Chang-Jin; Zhang, An-Qi; Wang, Chen; Xu, Rong; Xie, Shu-Yang; Wang, Ping-Yu

2018-01-01

Background: Many studies manifested miRNA-628 (miR-628) was deregulated in various cancers, indicating that miR-628 might serve as a novel biomarker of cancer diagnosis and prognosis, but it's role was still uncertain. This study aimed to evaluate the value of miR-628 in various cancers for diagnosis and prognosis, as well as its predictive power in combination biomarkers. Materials and Methods: A literature search was performed using Medline (via PubMed), Embase, Web of Science databases, and Ovid platform up to November 2017. Meta-analysis was performed to provide summative outcomes. Quality assessment of each included study was performed. Results: Twelve articles with 20 studies were included in our meta-analysis, including 8 articles with 15 studies for diagnostic meta-analysis and 4 articles with 5 studies for prognostic meta-analysis. For the diagnostic meta-analysis of miR-628 alone, the overall pooled results for sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the area under the summary receiver operating characteristic (SROC) curve (AUC) were 0.81 (95% CI: 0.62-0.91), 0.72 (95% CI: 0.48-0.88), 2.90 (95% CI: 1.50-5.40), 0.27 (95% CI: 0.14-0.50), 11.0 (95% CI: 4.00-25.00), and 0.84 (95% CI: 0.80-0.87), respectively. For the diagnostic meta-analysis of miR-628-related combination biomarkers, the above six parameters were 0.89 (95% CI: 0.84-0.92), 0.93 (95% CI: 0.82-0.97), 12.30 (95% CI: 4.70-32.50), 0.12 (95% CI: 0.08-0.19), and 100.00 (95% CI: 28.00-354.00), 0.93 (95% CI: 0.90-0.95), respectively. For the prognostic meta-analysis, patients with lower miR-628 had significant shorter overall survival than high expression of miR-628 (HR = 1.553, 95% CI: 1.041-2.318, z = 2.16, P = 0.031). Conclusions: This study confirms that miR-628 may be a promising biomarker for cancer diagnosis and prognosis. Expertly, microRNAs combination biomarkers could be a new alternative for clinical application.

Reducing low-value care in endometriosis between limited evidence and unresolved issues: a proposal.

PubMed

Vercellini, Paolo; Giudice, Linda C; Evers, Johannes L H; Abrao, Mauricio S

2015-09-01

Quantification of benefits and harms of medical interventions should be based on high-quality evidence, which is not always the case in the endometriosis field. In many clinical circumstances, healthcare decisions in women with endometriosis are taken based on suboptimal evidence or on evidence of coexistence of benefits and harms that must be balanced. In these conditions, it is important to avoid or reduce the use of low-value care, i.e. interventions with defined harms and uncertain benefits, or whose effectiveness is comparable with less expensive alternatives. In particular, we suggest that: (i) non-surgical diagnosis based on symptoms, physical findings and transvaginal ultrasonography is possible in most women with symptomatic endometriosis. Thus, except in doubtful cases, laparoscopy should be intended for surgical treatment, not for diagnostic purposes: early diagnosis and diagnostic laparoscopy are not synonymous; (ii) future trials on new drugs for endometriosis should address those outcomes that are most important to patients, should be designed as superiority trials and should include a progestin or an estrogen-progestin as a comparator. Moreover, limitation of repetitive surgery for recurrent endometriosis is among the objectives of long-term medical treatment; (iii) indications for surgery should be the result of a balance between demonstrated benefits in terms of fertility enhancement and pain relief, specific risks associated with excision of different types of endometriotic lesions, cost-effectiveness and patient preference after detailed information; (iv) physicians, health professionals and policy makers should discriminate between screening for and diagnosis of endometriosis. Limited peritoneal foci, which are frequently observed also in asymptomatic women, regress or remain stable in about two thirds of cases. Therefore, the theoretical premises for a screening campaign are currently unclear; (v) physicians should develop the ability to effectively communicate quantitative information based on international guidelines and systematic literature reviews. This will assist a woman's understanding of the interaction between the evidence and her priorities, facilitating the transition towards value-based medicine. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Early Diagnostic Performance of Heart-Type Fatty Acid Binding Protein in Suspected Acute Myocardial Infarction: Evidence From a Meta-Analysis of Contemporary Studies.

PubMed

Xu, Li-Qian; Yang, Yun-Mei; Tong, Hong; Xu, Chang-Fu

2018-04-01

Although cardiac troponin is the cornerstone in diagnosis of acute myocardial infarction (AMI), the accuracy is still suboptimal in the early hours after chest pain onset. Due to its small size, heart-type fatty acid-binding protein (H-FABP) has been reported accurate in diagnosis of AMI, however, this remains undetermined. The aim is to investigate the diagnostic performance of H-FABP alone and in conjunction with high-sensitivity troponin (hs-Tn) within 6 hours of symptom onset. Furthermore, accuracy in 0h/3h algorithm was also assessed. Medline and EMBASE databases were searched; sensitivity, specificity and area under ROC curve (AUC) were used as measures of the diagnostic accuracy. We pooled data on bivariate modelling, threshold effect and publication bias was applied for heterogeneity analysis. Twenty-two studies with 6602 populations were included, pooled sensitivity, specificity and AUC of H-FABP were 0.75 (0.68-0.81), 0.81 (0.75-0.86) and 0.85 (0.82-0.88) within 6 hours. Similar sensitivity (0.76, 0.69-0.82), specificity (0.80, 0.71-0.87) and AUC (0.85, 0.82-0.88) of H-FABP were observed in 4185 (63%) patients in 0h/3h algorithm. The additional use of H-FABP improved the sensitivity of hs-Tn alone but worsened its specificity (all p<0.001), and resulted in no improvement of AUC (p>0.99). There was no threshold effect (p=0.18) and publication bias (p=0.31) in this study. H-FABP has modest accuracy for early diagnosis of AMI within 3 and 6 hours of symptom onset. The incremental value of H-FABP seemed much smaller and was of uncertain clinical significance in addition to hs-Tn in patients with suspected AMI. Routine use of H-FABP in early presentation does not seem warranted. Copyright © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.