[Pathological features of myositis with myositis -specific autoantibodies].

PubMed

Shimizu, Jun; Mimori, Tsuneyo

2014-01-01

Myositis is a heterogeneous group of systemic autoimmune disorders characterized by inflammation of skeletal muscle. Historically, myositis has been defined using clinical features including muscle weakness, skin disease, internal organ involvement, and an association with cancer in adults. From a clinicopathologic approach, myositis has been classified into pathologically distinct subsets, polymyositis, dermatomyositis(DM), necrotizing autoimmune myositis, amyopathic DM, and non-specific myositis. Although the characteristic pathological changes are believed to be important in pathological mechanisms of each subset of myositis, in clinical practices, the percentages of the patients with typical pathological findings are usually not high. On the other hand, with the recent discovery of new myositis-specific autoantibodies (MSAs), it has been revealed that around 60% of patients with IIMs have been shown to have a anti-myositis-specific autoantibody, including anti-synthetase, anti-Mi-2, anti-MDA5, anti-TIF1 and anti-SRP antibodies. Because of striking association between unique MSAs and distinct clinical phenotypes, these antibodies are thought to be important not only for classifications of IIMs, but also as factors involved in the mechanism underlying their pathogenesis. This review reports recent progress in understanding of pathological features of myositis with MSAs.

Noonan syndrome - a new survey.

PubMed

Tafazoli, Alireza; Eshraghi, Peyman; Koleti, Zahra Kamel; Abbaszadegan, Mohammadreza

2017-02-01

Noonan syndrome (NS) is an autosomal dominant disorder with vast heterogeneity in clinical and genetic features. Various symptoms have been reported for this abnormality such as short stature, unusual facial characteristics, congenital heart abnormalities, developmental complications, and an elevated tumor incidence rate. Noonan syndrome shares clinical features with other rare conditions, including LEOPARD syndrome, cardio-facio-cutaneous syndrome, Noonan-like syndrome with loose anagen hair, and Costello syndrome. Germline mutations in the RAS-MAPK (mitogen-activated protein kinase) signal transduction pathway are responsible for NS and other related disorders. Noonan syndrome diagnosis is primarily based on clinical features, but molecular testing should be performed to confirm it in patients. Due to the high number of genes associated with NS and other RASopathy disorders, next-generation sequencing is the best choice for diagnostic testing. Patients with NS also have higher risk for leukemia and specific solid tumors. Age-specific guidelines for the management of NS are available.

Noonan syndrome – a new survey

PubMed Central

Tafazoli, Alireza; Eshraghi, Peyman; Koleti, Zahra Kamel

2016-01-01

Noonan syndrome (NS) is an autosomal dominant disorder with vast heterogeneity in clinical and genetic features. Various symptoms have been reported for this abnormality such as short stature, unusual facial characteristics, congenital heart abnormalities, developmental complications, and an elevated tumor incidence rate. Noonan syndrome shares clinical features with other rare conditions, including LEOPARD syndrome, cardio-facio-cutaneous syndrome, Noonan-like syndrome with loose anagen hair, and Costello syndrome. Germline mutations in the RAS-MAPK (mitogen-activated protein kinase) signal transduction pathway are responsible for NS and other related disorders. Noonan syndrome diagnosis is primarily based on clinical features, but molecular testing should be performed to confirm it in patients. Due to the high number of genes associated with NS and other RASopathy disorders, next-generation sequencing is the best choice for diagnostic testing. Patients with NS also have higher risk for leukemia and specific solid tumors. Age-specific guidelines for the management of NS are available. PMID:28144274

Adenoid cystic carcinoma of breast: Recent advances

PubMed Central

Miyai, Kosuke; Schwartz, Mary R; Divatia, Mukul K; Anton, Rose C; Park, Yong Wook; Ayala, Alberto G; Ro, Jae Y

2014-01-01

Adenoid cystic carcinoma (ACC) of the breast is a rare special subtype of breast cancer characterized by the presence of a dual cell population of luminal and basaloid cells arranged in specific growth patterns. Most breast cancers with triple-negative, basal-like breast features (i.e., tumors that are devoid of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression, and express basal cell markers) are generally high-grade tumors with an aggressive clinical course. Conversely, while ACCs also display a triple-negative, basal-like phenotype, they are usually low-grade and exhibit an indolent clinical behavior. Many discoveries regarding the molecular and genetic features of the ACC, including a specific chromosomal translocation t(6;9) that results in a MYB-NFIB fusion gene, have been made in recent years. This comprehensive review provides our experience with the ACC of the breast, as well as an overview of clinical, histopathological, and molecular genetic features. PMID:25516849

Adult and juvenile dermatomyositis: are the distinct clinical features explained by our current understanding of serological subgroups and pathogenic mechanisms?

PubMed Central

2013-01-01

Adult and juvenile dermatomyositis share the hallmark features of pathognomic skin rash and muscle inflammation, but are heterogeneous disorders with a range of additional disease features and complications. The frequency of important clinical features such as calcinosis, interstitial lung disease and malignancy varies markedly between adult and juvenile disease. These differences may reflect different disease triggers between children and adults, but whilst various viral and other environmental triggers have been implicated, results are so far conflicting. Myositis-specific autoantibodies can be detected in both adults and children with idiopathic inflammatory myopathies. They are associated with specific disease phenotypes and complications, and divide patients into clinically homogenous subgroups. Interestingly, whilst the same autoantibodies are found in both adults and children, the disease features remain different within autoantibody subgroups, particularly with regard to life-threatening disease associations, such as malignancy and rapidly progressive interstitial lung disease. Our understanding of the mechanisms that underlie these differences is limited by a lack of studies directly comparing adults and children. Dermatomyositis is an autoimmune disease, which is believed to develop as a result of an environmental trigger in a genetically predisposed individual. Age-specific host immune responses and muscle physiology may be additional complicating factors that have significant impact on disease presentation. Further study into this area may produce new insights into disease pathogenesis. PMID:23566358

SU-F-R-46: Predicting Distant Failure in Lung SBRT Using Multi-Objective Radiomics Model

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

Zhou, Z; Folkert, M; Iyengar, P

2016-06-15

Purpose: To predict distant failure in lung stereotactic body radiation therapy (SBRT) in early stage non-small cell lung cancer (NSCLC) by using a new multi-objective radiomics model. Methods: Currently, most available radiomics models use the overall accuracy as the objective function. However, due to data imbalance, a single object may not reflect the performance of a predictive model. Therefore, we developed a multi-objective radiomics model which considers both sensitivity and specificity as the objective functions simultaneously. The new model is used to predict distant failure in lung SBRT using 52 patients treated at our institute. Quantitative imaging features of PETmore » and CT as well as clinical parameters are utilized to build the predictive model. Image features include intensity features (9), textural features (12) and geometric features (8). Clinical parameters for each patient include demographic parameters (4), tumor characteristics (8), treatment faction schemes (4) and pretreatment medicines (6). The modelling procedure consists of two steps: extracting features from segmented tumors in PET and CT; and selecting features and training model parameters based on multi-objective. Support Vector Machine (SVM) is used as the predictive model, while a nondominated sorting-based multi-objective evolutionary computation algorithm II (NSGA-II) is used for solving the multi-objective optimization. Results: The accuracy for PET, clinical, CT, PET+clinical, PET+CT, CT+clinical, PET+CT+clinical are 71.15%, 84.62%, 84.62%, 85.54%, 82.69%, 84.62%, 86.54%, respectively. The sensitivities for the above seven combinations are 41.76%, 58.33%, 50.00%, 50.00%, 41.67%, 41.67%, 58.33%, while the specificities are 80.00%, 92.50%, 90.00%, 97.50%, 92.50%, 97.50%, 97.50%. Conclusion: A new multi-objective radiomics model for predicting distant failure in NSCLC treated with SBRT was developed. The experimental results show that the best performance can be obtained by combining all features.« less

Clinical significance of specific autoantibodies in juvenile dermatomyositis.

PubMed

Feldman, B M; Reichlin, M; Laxer, R M; Targoff, I N; Stein, L D; Silverman, E D

1996-10-01

To determine the prevalence and clinical association of myositis specific antibodies in an unselected group of patients with juvenile dermatomyositis (DM). The sera of 42 subjects, representing an unselected group of patients from a single center, with juvenile DM and 7 others with idiopathic inflammatory myopathy (IIM) were examined for the presence of myositis specific antibodies by immunodiffusion against calf thymus extract and immunoprecipitation with HeLa extract. Of the subjects with juvenile DM, only 2 had evidence of antibodies specific to myositis (anti-Mi2). Three other patients with juvenile DM had defined autoantibodies not usually considered to be specific to myositis. Two of the 3 subjects had anti-PM-Scl; both developed features of scleroderma after the juvenile DM remitted. The 5 subjects with defined autoantibodies did not differ clinically from the remainder of the subjects with the exception of the late development of scleroderma features in 2. Fourteen other subjects with juvenile DM had unidentified bands on immunoprecipitation, which may represent as yet undiscovered myositis specific antibodies. No myositis specific antibodies were detected in any of the 7 subjects with other IIM syndromes. Based on our findings, we do not recommend routine clinical testing for these antibodies in children with typical juvenile DM. Further study of the unidentified bands seen in our subjects may lead to better understanding of the clinical groupings and etiopathogenesis of childhood myositis.

The clinical expression of primary biliary cirrhosis.

PubMed

Heathcote, J

1997-02-01

Primary biliary cirrhosis (PBC) is likely an autoimmune disease that destroys the interlobular bile ducts. Although the term PBC implies cirrhosis, this is not always present. The condition may be entirely silent clinically, save for the hallmark mitochondrial antibodies in serum. The clinical spectrum of PBC ranges from asymptomatic anicteric cholestasis with or without extrahepatic manifestations to severe cholestasis with decompensated cirrhosis. It is uncertain whether or not the course of this disease is universally fatal. Currently, no specific features have been identified which predict progression from asymptomatic to symptomatic disease, although once hyperbilirubinemia is present, a rising level indicates a poor prognosis. The liver-specific complications include pruritus, abdominal pain, xantholasma, and portal hypertension. The latter is often an early feature, as the portal hypertension is presinusoidal in nature and, when present, does not always reflect the presence of cirrhosis. There are many extrahepatic features of PBC, the most common being metabolic, chiefly hypothyroidism and metabolic bone disease. Other common associations are rheumatologic, renal, pulmonary, neuromuscular, and dermatologic. The non-specific yet distressing symptom of fatigue affects up to two-thirds of PBC subjects, but its etiology remains obscure.

A Clinical Decision Support System Using Ultrasound Textures and Radiologic Features to Distinguish Metastasis From Tumor-Free Cervical Lymph Nodes in Patients With Papillary Thyroid Carcinoma.

PubMed

Abbasian Ardakani, Ali; Reiazi, Reza; Mohammadi, Afshin

2018-03-30

This study investigated the potential of a clinical decision support approach for the classification of metastatic and tumor-free cervical lymph nodes (LNs) in papillary thyroid carcinoma on the basis of radiologic and textural analysis through ultrasound (US) imaging. In this research, 170 metastatic and 170 tumor-free LNs were examined by the proposed clinical decision support method. To discover the difference between the groups, US imaging was used for the extraction of radiologic and textural features. The radiologic features in the B-mode scans included the echogenicity, margin, shape, and presence of microcalcification. To extract the textural features, a wavelet transform was applied. A support vector machine classifier was used to classify the LNs. In the training set data, a combination of radiologic and textural features represented the best performance with sensitivity, specificity, accuracy, and area under the curve (AUC) values of 97.14%, 98.57%, 97.86%, and 0.994, respectively, whereas the classification based on radiologic and textural features alone yielded lower performance, with AUCs of 0.964 and 0.922. On testing the data set, the proposed model could classify the tumor-free and metastatic LNs with an AUC of 0.952, which corresponded to sensitivity, specificity, and accuracy of 93.33%, 96.66%, and 95.00%. The clinical decision support method based on textural and radiologic features has the potential to characterize LNs via 2-dimensional US. Therefore, it can be used as a supplementary technique in daily clinical practice to improve radiologists' understanding of conventional US imaging for characterizing LNs. © 2018 by the American Institute of Ultrasound in Medicine.

[Granulomatous lobular mastitis: a clinicopathologic study of 68 cases].

PubMed

Cheng, Juan; Du, Yu-tang; Ding, Hua-ye

2010-10-01

To study the clinical and pathologic features of granulomatous lobular mastitis (GLM). Sixty-eight cases of GLM were retrieved from the archival file. The clinical data and histologic features were retrospectively reviewed. Sixty-eight patients presented with breast mass. Ulceration in overlying breast skin was seen in 9 cases. Most of the patients had history of breast feeding. None of them had evidence of specific infections involving the breast. The clinical and radiologic features mimicked malignancy. Histologically, GLM was characterized by the presence of non-necrotizing granulomas, usually admixed with neutrophils and associated with benign ductolobular units. The ductolobular architecture was still preserved. The duration of follow up ranged from 6 to 36 months. Four patients suffered from disease recurrence. GLM shows clinical and radiologic features reminiscent of breast cancer. Correct diagnosis requires histologic examination of the biopsy specimens.

Atypical depression is more common than melancholic in fibromyalgia: an observational cohort study.

PubMed

Ross, Rebecca L; Jones, Kim D; Ward, Rachel L; Wood, Lisa J; Bennett, Robert M

2010-06-14

It has been postulated that atypical and melancholic depression subtypes exist in depressed fibromyalgia (FM) patients, yet no study has empirically tested this hypothesis. The purpose of this study is to determine whether major depressive disorder (MDD) with atypical features and MDD with melancholic features occurs in a FM sample and to describe their demographic, clinical and diagnostic characteristics. An observational cohort study using a descriptive cross-sectional design recruited a convenience sample of 76 outpatients with FM from an academic rheumatology clinic and a community mental health practice. Diagnoses of FM were confirmed using the 1990 ACR classification guidelines. Diagnoses of MDD and diagnostic subtypes were determined using the DSM-IV-TR criteria. Clinical characteristics were measured using the Fibromyalgia Impact Questionnaire, Structured Interview Guide for the Hamilton Depression Rating Scale with Atypical Depression Supplement and other standardized instruments. Odds ratios were computed on subtype-specific diagnostic criteria. Correlations assessed associations between subtype diagnoses and diagnostic criteria. Of the 76 subjects with FM, 11.8% (n = 9) were euthymic, 52.6% (n = 40) met diagnostic criteria for MDD with atypical features and 35.6% (n = 27) for MDD with melancholic features. Groups did not differ on demographic characteristics except for gender (p = 0.01). The non-depressed and atypical groups trended toward having a longer duration of FM symptoms (18.05 yrs. +/- 12.83; 20.36 yrs. +/- 15.07) compared to the melancholic group (14.11 yrs. +/- 8.82; p = 0.09). The two depressed groups experienced greater severity on all clinical features compared to the non-depressed group. The atypical group did not differ clinically from the melancholic group except the latter experienced greater depression severity (p = 0.001). The atypical group demonstrated the highest prevalence and correlations with atypical-specific diagnostic criteria: (e.g., weight gain/ increased appetite: OR = 3.5, p = 0.02), as did the melancholic group for melancholic-specific criteria: (e.g., anhedonia: OR = 20, p < 0.001). Depressed fibromyalgia patients commonly experience both atypical and melancholic depressive features; however, in this study, atypical depression was 1.5 times more common than melancholic depression. This finding may have significant research and clinical implications.

Breast cancer - one term, many entities?

PubMed

Bertos, Nicholas R; Park, Morag

2011-10-01

Breast cancer, rather than constituting a monolithic entity, comprises heterogeneous tumors with different clinical characteristics, disease courses, and responses to specific treatments. Tumor-intrinsic features, including classical histological and immunopathological classifications as well as more recently described molecular subtypes, separate breast tumors into multiple groups. Tumor-extrinsic features, including microenvironmental configuration, also have prognostic significance and further expand the list of tumor-defining variables. A better understanding of the features underlying heterogeneity, as well as of the mechanisms and consequences of their interactions, is essential to improve targeting of existing therapies and to develop novel agents addressing specific combinations of features.

Cognitive and noncognitive neurological features of young-onset dementia.

PubMed

Kelley, Brendan J; Boeve, Bradley F; Josephs, Keith A

2009-01-01

The rarity of young-onset dementia (YOD), the broad differential diagnosis and unusual clinical presentations present unique challenges to correctly recognize the condition and establish an accurate diagnosis. Limited data exist regarding clinical features associated with dementia prior to the age of 45. We retrospectively assessed cognitive and noncognitive neurological characteristics of 235 patients who presented for evaluation of YOD to investigate the clinical characteristics of YOD compared to later-onset dementias and to identify clinical features associated with specific etiologies that may aid in the evaluation of YOD. Multiple cognitive domains were affected in most patients, and no significant differences in affected domains existed between groups. Early psychiatric and behavioral features occurred at very high frequencies. Nearly 80% of this YOD cohort had additional noncognitive symptoms or signs as a feature of their disease. Chorea was strongly associated with Huntington disease. Parkinsonism was not seen in patients having an autoimmune/inflammatory etiology. The rarity of YOD and the high frequency of early psychiatric features led to frequent misdiagnosis early in the clinical course. The high frequency of noncognitive symptoms and signs may aid clinicians in distinguishing patients requiring a more extensive evaluation for YOD.

Aggressive behavior and poor prognosis of endometrial stromal sarcomas with YWHAE-FAM22 rearrangement indicate the clinical importance to recognize this subset.

PubMed

Kruse, Arnold-Jan; Croce, Sabrina; Kruitwagen, Roy F P M; Riedl, Robert G; Slangen, Brigitte F M; Van Gorp, Toon; Van de Vijver, Koen K

2014-11-01

Although the World Health Organization (WHO) in 2003 defined endometrial stromal sarcomas (ESSs) in general have a good prognosis, considerable differences in clinical behavior and prognosis may exist between different patients with ESS. The ESSs of the type associated with YWHAE-NUTM2 (previously named YWHAE-FAM22) fusion have a more aggressive clinical behavior and poorer prognosis than conventional ESS. Recently, the WHO 2014 classification recognizes this subset of ESS as a separate entity and classifies these as high-grade ESSs. Recognition of this subset has therefore an important clinical impact. We performed a review of the literature to delineate the clinicopathologic features of ESS patients with an YWHAE-NUTM2 rearrangement, with the goal to recognize this subset of ESS. We report a case of a woman with WHO 2014-defined high-grade ESS. Furthermore, published English literature was reviewed for YWHAE-FAM22 ESS and uterus. Twenty patients were identified, with a median age of 50 (range, 28-67) years. There were no clinical features able to recognize YWHAE-NUTM2 ESS. However, they characteristically contain specific histopathological features. Furthermore, YWHAE-NUTM2 ESSs are strongly cyclin D1 positive in contrast to conventional low-grade ESSs. YWHAE-NUTM2 ESSs represent a subset of ESSs with an aggressive clinical behavior and poor prognosis. Specific histopathological features may indicate the presence of YWHAE-NUTM2 rearrangement, which subsequently can be confirmed by cyclin D1 immunostaining.

Classification of clinically useful sentences in clinical evidence resources.

PubMed

Morid, Mohammad Amin; Fiszman, Marcelo; Raja, Kalpana; Jonnalagadda, Siddhartha R; Del Fiol, Guilherme

2016-04-01

Most patient care questions raised by clinicians can be answered by online clinical knowledge resources. However, important barriers still challenge the use of these resources at the point of care. To design and assess a method for extracting clinically useful sentences from synthesized online clinical resources that represent the most clinically useful information for directly answering clinicians' information needs. We developed a Kernel-based Bayesian Network classification model based on different domain-specific feature types extracted from sentences in a gold standard composed of 18 UpToDate documents. These features included UMLS concepts and their semantic groups, semantic predications extracted by SemRep, patient population identified by a pattern-based natural language processing (NLP) algorithm, and cue words extracted by a feature selection technique. Algorithm performance was measured in terms of precision, recall, and F-measure. The feature-rich approach yielded an F-measure of 74% versus 37% for a feature co-occurrence method (p<0.001). Excluding predication, population, semantic concept or text-based features reduced the F-measure to 62%, 66%, 58% and 69% respectively (p<0.01). The classifier applied to Medline sentences reached an F-measure of 73%, which is equivalent to the performance of the classifier on UpToDate sentences (p=0.62). The feature-rich approach significantly outperformed general baseline methods. This approach significantly outperformed classifiers based on a single type of feature. Different types of semantic features provided a unique contribution to overall classification performance. The classifier's model and features used for UpToDate generalized well to Medline abstracts. Copyright © 2016 Elsevier Inc. All rights reserved.

The clinical syndrome of specific antibody deficiency in children.

PubMed

Boyle, R J; Le, C; Balloch, A; Tang, M L-K

2006-12-01

Specific antibody deficiency (SAD) is an immune deficiency which has been reported in adults and children with recurrent respiratory tract infections; however, the clinical features of SAD are not well described. This study evaluated formally the clinical syndrome of SAD, by comparing the clinical features of children with SAD and those of children with recurrent infection but normal immune function tests. SAD was defined as an adequate IgG antibody response to less than 50% of 12 pneumococcal serotypes tested following 23-valent unconjugated pneumococcal immunization. An adequate IgG antibody response was defined as a post-immunization titre of >or= 1.3 microg/ml or >or= four times the preimmunization value. Seventy-four children with recurrent infection were evaluated where immune deficiencies other than SAD had been excluded. Eleven (14.9%) of these children had SAD. Clinical features differed between the group with SAD and the group with normal antibody responses. A history of otitis media, particularly in association with chronic otorrhoea was associated with SAD [relative risk (RR) of SAD in those with chronic otorrhoea 4.64 (P = 0.02)]. SAD was associated with allergic disease, particularly allergic rhinitis [RR of SAD in those with allergic rhinitis 3.77 (P = 0.04)]. These two clinical associations of SAD were independent in this study [RR of chronic otorrhoea in those with allergic rhinitis 0.85 (P = 0.28)]. SAD was not an age-related phenomenon in this population. SAD has a distinct clinical phenotype, presenting as recurrent infection associated with chronic otorrhoea and/or allergic disease, and the condition should be sought in children with these features.

The measurement of retardation in depression.

PubMed

Dantchev, N; Widlöcher, D J

1998-01-01

The description of clinical features helps to distinguish between depressive illness and nondepressive psychic pain and enables the clinician to decide whether prescription of an antidepressant is beneficial. Psychomotor retardation is probably a central feature of depression, and this review discusses the methods available for measuring it. The Salpêtrière Retardation Rating Scale (SRRS) specifically measures psychomotor retardation; the scale and applications are described. Means of measuring motor and speech activity and an experimental approach for understanding the process underlying psychomotor retardation are reviewed. Comparison of the SRRS and other rating scale scores demonstrates that retardation is related to depression severity and therapeutic change and is a good criterion for prediction of therapeutic effect. The SRRS has been used to show that selective antidepressants target specific clinical dimensions of depression depending on the patient subgroup treated. Measures of motor and speech activity are sensitive to therapeutic response. Choice Reaction Time and Simple Reaction Time tasks are particularly suited for examining psychomotor retardation because they test the decision process while avoiding motivation and attention interference. Psychomotor retardation is a constant and probably central feature of depression. Means available for measuring it can be used to assess the effects of antidepressants on specific clinical dimensions.

WE-D-204-01: Site-Specific Clinical Rotation: Into the Minds of the Radiation Oncologists

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

Hendrickson, K.

2016-06-15

Speakers in this session will present overview and details of a specific rotation or feature of their Medical Physics Residency Program that is particularly exceptional and noteworthy. The featured rotations include foundational topics executed with exceptional acumen and innovative educational rotations perhaps not commonly found in Medical Physics Residency Programs. A site-specific clinical rotation will be described, where the medical physics resident follows the physician and medical resident for two weeks into patient consultations, simulation sessions, target contouring sessions, planning meetings with dosimetry, patient follow up visits, and tumor boards, to gain insight into the thought processes of the radiationmore » oncologist. An incident learning rotation will be described where the residents learns about and practices evaluating clinical errors and investigates process improvements for the clinic. The residency environment at a Canadian medical physics residency program will be described, where the training and interactions with radiation oncology residents is integrated. And the first month rotation will be described, where the medical physics resident rotates through the clinical areas including simulation, dosimetry, and treatment units, gaining an overview of the clinical flow and meeting all the clinical staff to begin the residency program. This session will be of particular interest to residency programs who are interested in adopting or adapting these curricular ideas into their programs and to residency candidates who want to learn about programs already employing innovative practices. Learning Objectives: To learn about exceptional and innovative clinical rotations or program features within existing Medical Physics Residency Programs. To understand how to adopt/adapt innovative curricular designs into your own Medical Physics Residency Program, if appropriate.« less

ANALYSIS OF CLINICAL AND DERMOSCOPIC FEATURES FOR BASAL CELL CARCINOMA NEURAL NETWORK CLASSIFICATION

PubMed Central

Cheng, Beibei; Stanley, R. Joe; Stoecker, William V; Stricklin, Sherea M.; Hinton, Kristen A.; Nguyen, Thanh K.; Rader, Ryan K.; Rabinovitz, Harold S.; Oliviero, Margaret; Moss, Randy H.

2012-01-01

Background Basal cell carcinoma (BCC) is the most commonly diagnosed cancer in the United States. In this research, we examine four different feature categories used for diagnostic decisions, including patient personal profile (patient age, gender, etc.), general exam (lesion size and location), common dermoscopic (blue-gray ovoids, leaf-structure dirt trails, etc.), and specific dermoscopic lesion (white/pink areas, semitranslucency, etc.). Specific dermoscopic features are more restricted versions of the common dermoscopic features. Methods Combinations of the four feature categories are analyzed over a data set of 700 lesions, with 350 BCCs and 350 benign lesions, for lesion discrimination using neural network-based techniques, including Evolving Artificial Neural Networks and Evolving Artificial Neural Network Ensembles. Results Experiment results based on ten-fold cross validation for training and testing the different neural network-based techniques yielded an area under the receiver operating characteristic curve as high as 0.981 when all features were combined. The common dermoscopic lesion features generally yielded higher discrimination results than other individual feature categories. Conclusions Experimental results show that combining clinical and image information provides enhanced lesion discrimination capability over either information source separately. This research highlights the potential of data fusion as a model for the diagnostic process. PMID:22724561

Recognition of Delirium Features in Clinical Practice: Data from the "Delirium Day 2015" National Survey.

PubMed

Mossello, Enrico; Tesi, Francesca; Di Santo, Simona G; Mazzone, Andrea; Torrini, Monica; Cherubini, Antonio; Bo, Mario; Musicco, Massimo; Bianchetti, Angelo; Ferrari, Alberto; Ferrara, Nicola; Trabucchi, Marco; Morandi, Alessandro; Bellelli, Giuseppe

2018-02-01

Delirium is underrecognized in clinical practice. The primary aim of the present multicenter study was to compare the ability of nurses to identify delirium features with a standardized assessment. The secondary aim was to identify predictors of missed or incorrect identifications of delirium by nurses. Point prevalence study in 120 wards across Italy. "Delirium Day 2015." Inpatients aged 65 and older (N = 1,867). Participants and nurses were asked specific questions to investigate their perceptions of the presence of delirium features (acute cognitive change, inattention, cognitive fluctuations, impaired arousal). Delirium was identified according to the results of the Assessment Test for Delirium and Cognitive Impairment (4AT), completed by a physician. Comorbidities including dementia, disability, drug treatments, and delirium motor subtype according to the Delirium Motor Subtype Scale were recorded. Delirium was present in 429 subjects (23%) according to the 4AT. Cognitive fluctuations was the delirium feature that the nurses most often recognized. Nurses' perceptions of acute cognitive change, cognitive fluctuations, or impaired arousal had 84% sensitivity and 81% specificity for delirium. The nonmotor subtype of delirium was less likely to be recognized (80%) than the hyperactive (97%), mixed (92%), and hypoactive (90%) subtypes. Incorrect perception of delirium was more frequent in subjects with dementia (specificity 64%). The delirium feature that nurses were best able to recognize was cognitive fluctuations. The nonmotor subtype was associated with a lower recognition rate. Routine observation and registration of delirium features by nurses in clinical practice might be helpful to increase formal diagnosis of delirium. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

Phonologic errors as a clinical marker of the logopenic variant of PPA.

PubMed

Leyton, Cristian E; Ballard, Kirrie J; Piguet, Olivier; Hodges, John R

2014-05-06

To disentangle the clinical heterogeneity of nonsemantic variants of primary progressive aphasia (PPA) and to identify a coherent linguistic-anatomical marker for the logopenic variant of PPA (lv-PPA). Key speech and language features of 14 cases of lv-PPA and 18 cases of nonfluent/agrammatic variant of PPA were systematically evaluated and scored by an independent rater blinded to diagnosis. Every case underwent a structural MRI and a Pittsburgh compound B (PiB)-PET scan, a putative biomarker of Alzheimer disease. Key speech and language features that showed association with the PiB-PET status were entered into a hierarchical cluster analysis. The linguistic features and patterns of cortical thinning in each resultant cluster were analyzed. The cluster analysis revealed 3 coherent clinical groups, each of which was linked to a specific PiB-PET status. The first cluster was linked to high PiB retention and characterized by phonologic errors and cortical thinning focused on the left superior temporal gyrus. The second and third clusters were characterized by grammatical production errors and motor speech disorders, respectively, and were associated with low PiB brain retention. A fourth cluster, however, demonstrated nonspecific language deficits and unpredictable PiB-PET status. These findings suggest that despite the clinical and pathologic heterogeneity of nonsemantic variants, discrete clinical syndromes can be distinguished and linked to specific likelihood of PiB-PET status. Phonologic errors seem to be highly predictive of high amyloid burden in PPA and can provide a specific clinical marker for lv-PPA.

An Optimal Mean Based Block Robust Feature Extraction Method to Identify Colorectal Cancer Genes with Integrated Data.

PubMed

Liu, Jian; Cheng, Yuhu; Wang, Xuesong; Zhang, Lin; Liu, Hui

2017-08-17

It is urgent to diagnose colorectal cancer in the early stage. Some feature genes which are important to colorectal cancer development have been identified. However, for the early stage of colorectal cancer, less is known about the identity of specific cancer genes that are associated with advanced clinical stage. In this paper, we conducted a feature extraction method named Optimal Mean based Block Robust Feature Extraction method (OMBRFE) to identify feature genes associated with advanced colorectal cancer in clinical stage by using the integrated colorectal cancer data. Firstly, based on the optimal mean and L 2,1 -norm, a novel feature extraction method called Optimal Mean based Robust Feature Extraction method (OMRFE) is proposed to identify feature genes. Then the OMBRFE method which introduces the block ideology into OMRFE method is put forward to process the colorectal cancer integrated data which includes multiple genomic data: copy number alterations, somatic mutations, methylation expression alteration, as well as gene expression changes. Experimental results demonstrate that the OMBRFE is more effective than previous methods in identifying the feature genes. Moreover, genes identified by OMBRFE are verified to be closely associated with advanced colorectal cancer in clinical stage.

Folded concave penalized learning in identifying multimodal MRI marker for Parkinson’s disease

PubMed Central

Liu, Hongcheng; Du, Guangwei; Zhang, Lijun; Lewis, Mechelle M.; Wang, Xue; Yao, Tao; Li, Runze; Huang, Xuemei

2016-01-01

Background Brain MRI holds promise to gauge different aspects of Parkinson’s disease (PD)-related pathological changes. Its analysis, however, is hindered by the high-dimensional nature of the data. New method This study introduces folded concave penalized (FCP) sparse logistic regression to identify biomarkers for PD from a large number of potential factors. The proposed statistical procedures target the challenges of high-dimensionality with limited data samples acquired. The maximization problem associated with the sparse logistic regression model is solved by local linear approximation. The proposed procedures then are applied to the empirical analysis of multimodal MRI data. Results From 45 features, the proposed approach identified 15 MRI markers and the UPSIT, which are known to be clinically relevant to PD. By combining the MRI and clinical markers, we can enhance substantially the specificity and sensitivity of the model, as indicated by the ROC curves. Comparison to existing methods We compare the folded concave penalized learning scheme with both the Lasso penalized scheme and the principle component analysis-based feature selection (PCA) in the Parkinson’s biomarker identification problem that takes into account both the clinical features and MRI markers. The folded concave penalty method demonstrates a substantially better clinical potential than both the Lasso and PCA in terms of specificity and sensitivity. Conclusions For the first time, we applied the FCP learning method to MRI biomarker discovery in PD. The proposed approach successfully identified MRI markers that are clinically relevant. Combining these biomarkers with clinical features can substantially enhance performance. PMID:27102045

Rhinovirus species and clinical features in children hospitalised with pneumonia from Mozambique.

PubMed

Annamalay, Alicia A; Lanaspa, Miguel; Khoo, Siew-Kim; Madrid, Lola; Acácio, Sozinho; Zhang, Guicheng; Laing, Ingrid A; Gern, James; Goldblatt, Jack; Bizzintino, Joelene; Lehmann, Deborah; Le Souëf, Peter N; Bassat, Quique

2016-09-01

To describe the prevalence of human rhinovirus (RV) species in children hospitalised with pneumonia in Manhiça, Mozambique, and the associations between RV species and demographic, clinical and laboratory features. Nasopharyngeal aspirates were collected from children 0 to 10 years of age (n = 277) presenting to Manhiça District Hospital with clinical pneumonia. Blood samples were collected for HIV and malaria testing, blood culture and full blood counts, and a chest X-ray was performed. A panel of common respiratory viruses was investigated using two independent multiplex RT-PCR assays with primers specific for each virus and viral type. RV species and genotypes were identified by seminested PCR assays, sequencing and phylogenetic tree analyses. At least one respiratory virus was identified in 206 (74.4%) children hospitalised with clinical pneumonia. RV was the most common virus identified in both HIV-infected (17 of 38, 44.7%) and HIV-uninfected (74 of 237, 31.2%; P = 0.100) children. RV-A was the most common RV species identified (47 of 275, 17.0%), followed by RV-C (35/275, 12.6%) and RV-B (8/275, 2.9%). Clinical presentation of the different RV species was similar and overlapping, with no particular species being associated with specific clinical features. RV-A and RV-C were the most common respiratory viruses identified in children hospitalised with clinical pneumonia in Manhiça. Clinical presentation of RV-A and RV-C was similar and overlapping. © 2016 John Wiley & Sons Ltd.

Adrenal cortical oncocytoma mimicking pheochromocytoma.

PubMed

Kiriakopoulos, Andreas; Papaioannou, Dimitrios; Linos, Dimitrios

2011-01-01

Adrenal tumors present with clinical features and signs unique to their specific hormonal hypersecretion. However, there have been cases in which the clinical expression has been in conflict with the histologic features of the tumor. In this communication we report an unusual clinical presentation of an adrenal cortical tumor with histologic features of an oncocytoma that clinically mimicked a pheochromocytoma. A 49-year old man was referred to our Unit due to type B aortic dissection and a mass of the left adrenal gland. Computed tomography and magnetic resonance imaging confirmed the presence of aortic dissection extending from the left subclavian artery to both iliac arteries and also revealed a 6 cm tumor on the left adrenal gland. Preoperative endocrine evaluation showed a near tenfold increase of urinary vanillylmandelic acid (VMA) and metanephrine values. Transperitoneal laparoscopic adrenalectomy was successfully performed. The adrenal tumor proved to be an adrenal cortical neoplasm with histologic features of oncocytoma. Although the case of an adrenal cortical adenoma clinically mimicking a pheochromocytoma has been described in the literature, to the best of our knowledge, there has been no previous report of an adrenal cortical neoplasm with predominant features of oncocytoma.

Clinical and radiological features of Marchiafava–Bignami disease

PubMed Central

Dong, Xiaoyu; Bai, Chaobo; Nao, Jianfei

2018-01-01

Abstract Marchiafava–Bignami disease (MBD) is a rare neurological disease usually associated with chronic alcoholism and characterized by demyelination and necrosis. Our aims were to describe the clinicoradiological features and identify factors that may affect the prognosis of patients with MBD. We examined clinical manifestations, laboratory results, and neuroradiological features of 9 patients with MBD. The patients were classified into 2 subgroups (favorable and poor outcome subgroups) based on the Modified Oxford Handicap Scale (MOSH). In addition, we compared the clinical and neuroimaging features between the 2 subgroups. Nine adult male patients (age of onset range 37–62 years, with a mean age of 47.00 ± 14.50 years) were included in this study. According to MOSH, 4 patients were placed in the poor outcome subgroup (MOHS ≥ 3), 5 patients were placed in the favorable outcome subgroup (MOHS ≤ 2). Relatively high score of MAST-C (≥6) (P = .008), extracallosal lesions (P = .048), GCS (P = .026), cerebral lobe impairment (P = .048) was significantly more common in the poor outcome subgroup. Clinical manifestations of MBD are variable and lack specificity. Early diagnosis by relatively specific performance of bisymmetric lesions in corpus callosum of diffusion-weighted imaging (DWI) may affect the prognosis. The prognosis of patients with severe disturbance of consciousness, heavy alcohol consumption, extracallosal lesions, cerebral lobe impairment is probably unfavorable. PMID:29384842

Guillain-Barre syndrome following specific viral infections--an appraisal.

PubMed

Murthy, J M

1994-01-01

Fifteen cases of Gullian-Barre syndrome (GBS) following specific infection are reported. The infections include varicella, 7 infective hepatitis, 4 measles, 2 and mumps, 2. There are no specific clinical or electrophysiological features which serve to distinguish GBS seen in association of these infections from those seen in other clinical settings. There is epidemiological evidence to suggest the association between GBS and hepatitis A, and non A non B hepatitis is more of a chance occurrence. Detailed epidemiological studies are needed to established a clear relationship between other specific viral infections and GBS.

Subtyping depression by clinical features: the Australasian database.

PubMed

Parker, G; Roy, K; Hadzi-Pavlovic, D; Mitchell, P; Wilhelm, K; Menkes, D B; Snowdon, J; Loo, C; Schweitzer, I

2000-01-01

To distinguish psychotic, melancholic and a residual non-melancholic class on the basis of clinical features alone. Previous studies at our Mood Disorders Unit (MDU) favour a hierarchical model, with the classes able to be distinguished by two specific clinical features, but any such intramural study risks rater bias and requires external replication. This replication study involved 27 Australasian psychiatrist raters, thus extending the sample and raters beyond the MDU facility. They collected clinical feature data using a standardized assessment with precoded rating options. A psychotic depression (PD) class was derived by respecting DSM-IV decision rules while a cluster analysis distinguished melancholic (MEL) and non-melancholic classes. The MELs were distinguished virtually entirely by the presence of significant psychomotor disturbance (PMD), as rated by the observationally based CORE measure, with over-representation on only three of an extensive set of 'endogeneity symptoms'. In comparison to PMD, endogeneity symptoms appear to be poor indicators of 'melancholic' type, confounding typology with severity. Results again support the hierarchical model.

Survey of Current Practice in the Fitting and Fine-Tuning of Common Signal-Processing Features in Hearing Aids for Adults.

PubMed

Anderson, Melinda C; Arehart, Kathryn H; Souza, Pamela E

2018-02-01

Current guidelines for adult hearing aid fittings recommend the use of a prescriptive fitting rationale with real-ear verification that considers the audiogram for the determination of frequency-specific gain and ratios for wide dynamic range compression. However, the guidelines lack recommendations for how other common signal-processing features (e.g., noise reduction, frequency lowering, directional microphones) should be considered during the provision of hearing aid fittings and fine-tunings for adult patients. The purpose of this survey was to identify how audiologists make clinical decisions regarding common signal-processing features for hearing aid provision in adults. An online survey was sent to audiologists across the United States. The 22 survey questions addressed four primary topics including demographics of the responding audiologists, factors affecting selection of hearing aid devices, the approaches used in the fitting of signal-processing features, and the strategies used in the fine-tuning of these features. A total of 251 audiologists who provide hearing aid fittings to adults completed the electronically distributed survey. The respondents worked in a variety of settings including private practice, physician offices, university clinics, and hospitals/medical centers. Data analysis was based on a qualitative analysis of the question responses. The survey results for each of the four topic areas (demographics, device selection, hearing aid fitting, and hearing aid fine-tuning) are summarized descriptively. Survey responses indicate that audiologists vary in the procedures they use in fitting and fine-tuning based on the specific feature, such that the approaches used for the fitting of frequency-specific gain differ from other types of features (i.e., compression time constants, frequency lowering parameters, noise reduction strength, directional microphones, feedback management). Audiologists commonly rely on prescriptive fitting formulas and probe microphone measures for the fitting of frequency-specific gain and rely on manufacturers' default settings and recommendations for both the initial fitting and the fine-tuning of signal-processing features other than frequency-specific gain. The survey results are consistent with a lack of published protocols and guidelines for fitting and adjusting signal-processing features beyond frequency-specific gain. To streamline current practice, a transparent evidence-based tool that enables clinicians to prescribe the setting of other features from individual patient characteristics would be desirable. American Academy of Audiology

Genotype-phenotype analysis of recombinant chromosome 4 syndrome: an array-CGH study and literature review

PubMed Central

2013-01-01

Background Recombinant chromosome 4, a rare constitutional rearrangement arising from pericentric inversion, comprises a duplicated segment of 4p13~p15→4pter and a deleted segment of 4q35→4qter. To date, 10 cases of recombinant chromosome 4 have been reported. Result We describe the second case in which array-CGH was used to characterize recombinant chromosome 4 syndrome. The patient was a one-year old boy with consistent clinical features. Conventional cytogenetics and FISH documented a recombinant chromosome 4, derived from a paternal pericentric inversion, leading to partial trisomy 4p and partial monosomy of 4q. Array-CGH, performed to further characterize the rearranged chromosome 4 and delineate the breakpoints, documented a small (4.36 Mb) 4q35.1 terminal deletion and a large (23.81 Mb) 4p15.1 terminal duplication. Genotype-phenotype analysis of 10 previously reported cases and the present case indicated relatively consistent clinical features and breakpoints. This consistency was more evident in our case and another characterized by array-CGH, where both showed the common breakpoints of p15.1 and q35.1. A genotype-phenotype correlation study between rec(4), dup(4p), and del(4q) syndromes revealed that urogenital and cardiac defects are probably due to the deletion of 4q whereas the other clinical features are likely due to 4p duplication. Conclusion Our findings support that the clinical features of patients with rec(4) are relatively consistent and specific to the regions of duplication or deletion. Recombinant chromosome 4 syndrome thus appears to be a discrete entity that can be suspected on the basis of clinical features or specific deleted and duplicated chromosomal regions. PMID:23639048

Genotype-phenotype analysis of recombinant chromosome 4 syndrome: an array-CGH study and literature review.

PubMed

Hemmat, Morteza; Hemmat, Omid; Anguiano, Arturo; Boyar, Fatih Z; El Naggar, Mohammed; Wang, Jia-Chi; Wang, Borris T; Sahoo, Trilochan; Owen, Renius; Haddadin, Mary

2013-05-02

Recombinant chromosome 4, a rare constitutional rearrangement arising from pericentric inversion, comprises a duplicated segment of 4p13~p15→4pter and a deleted segment of 4q35→4qter. To date, 10 cases of recombinant chromosome 4 have been reported. We describe the second case in which array-CGH was used to characterize recombinant chromosome 4 syndrome. The patient was a one-year old boy with consistent clinical features. Conventional cytogenetics and FISH documented a recombinant chromosome 4, derived from a paternal pericentric inversion, leading to partial trisomy 4p and partial monosomy of 4q. Array-CGH, performed to further characterize the rearranged chromosome 4 and delineate the breakpoints, documented a small (4.36 Mb) 4q35.1 terminal deletion and a large (23.81 Mb) 4p15.1 terminal duplication. Genotype-phenotype analysis of 10 previously reported cases and the present case indicated relatively consistent clinical features and breakpoints. This consistency was more evident in our case and another characterized by array-CGH, where both showed the common breakpoints of p15.1 and q35.1. A genotype-phenotype correlation study between rec(4), dup(4p), and del(4q) syndromes revealed that urogenital and cardiac defects are probably due to the deletion of 4q whereas the other clinical features are likely due to 4p duplication. Our findings support that the clinical features of patients with rec(4) are relatively consistent and specific to the regions of duplication or deletion. Recombinant chromosome 4 syndrome thus appears to be a discrete entity that can be suspected on the basis of clinical features or specific deleted and duplicated chromosomal regions.

76 FR 22404 - Analgesic Clinical Trials Innovation, Opportunities, and Networks (ACTION) Initiative

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-21

..., but not limited to, specific research designs and methodological features so as to inform the future... clinical trials. Many experts in analgesic drug development believe that it is the design of the clinical trials that is at fault in this situation and that better trial designs will yield more successful...

Does the choice of display system influence perception and visibility of clinically relevant features in digital pathology images?

NASA Astrophysics Data System (ADS)

Kimpe, Tom; Rostang, Johan; Avanaki, Ali; Espig, Kathryn; Xthona, Albert; Cocuranu, Ioan; Parwani, Anil V.; Pantanowitz, Liron

2014-03-01

Digital pathology systems typically consist of a slide scanner, processing software, visualization software, and finally a workstation with display for visualization of the digital slide images. This paper studies whether digital pathology images can look different when presenting them on different display systems, and whether these visual differences can result in different perceived contrast of clinically relevant features. By analyzing a set of four digital pathology images of different subspecialties on three different display systems, it was concluded that pathology images look different when visualized on different display systems. The importance of these visual differences is elucidated when they are located in areas of the digital slide that contain clinically relevant features. Based on a calculation of dE2000 differences between background and clinically relevant features, it was clear that perceived contrast of clinically relevant features is influenced by the choice of display system. Furthermore, it seems that the specific calibration target chosen for the display system has an important effect on the perceived contrast of clinically relevant features. Preliminary results suggest that calibrating to DICOM GSDF calibration performed slightly worse than sRGB, while a new experimental calibration target CSDF performed better than both DICOM GSDF and sRGB. This result is promising as it suggests that further research work could lead to better definition of an optimized calibration target for digital pathology images resulting in a positive effect on clinical performance.

Incorporating clinical metadata with digital image features for automated identification of cutaneous melanoma.

PubMed

Liu, Z; Sun, J; Smith, M; Smith, L; Warr, R

2013-11-01

Computer-assisted diagnosis (CAD) of malignant melanoma (MM) has been advocated to help clinicians to achieve a more objective and reliable assessment. However, conventional CAD systems examine only the features extracted from digital photographs of lesions. Failure to incorporate patients' personal information constrains the applicability in clinical settings. To develop a new CAD system to improve the performance of automatic diagnosis of melanoma, which, for the first time, incorporates digital features of lesions with important patient metadata into a learning process. Thirty-two features were extracted from digital photographs to characterize skin lesions. Patients' personal information, such as age, gender and, lesion site, and their combinations, was quantified as metadata. The integration of digital features and metadata was realized through an extended Laplacian eigenmap, a dimensionality-reduction method grouping lesions with similar digital features and metadata into the same classes. The diagnosis reached 82.1% sensitivity and 86.1% specificity when only multidimensional digital features were used, but improved to 95.2% sensitivity and 91.0% specificity after metadata were incorporated appropriately. The proposed system achieves a level of sensitivity comparable with experienced dermatologists aided by conventional dermoscopes. This demonstrates the potential of our method for assisting clinicians in diagnosing melanoma, and the benefit it could provide to patients and hospitals by greatly reducing unnecessary excisions of benign naevi. This paper proposes an enhanced CAD system incorporating clinical metadata into the learning process for automatic classification of melanoma. Results demonstrate that the additional metadata and the mechanism to incorporate them are useful for improving CAD of melanoma. © 2013 British Association of Dermatologists.

Relational Network for Knowledge Discovery through Heterogeneous Biomedical and Clinical Features

PubMed Central

Chen, Huaidong; Chen, Wei; Liu, Chenglin; Zhang, Le; Su, Jing; Zhou, Xiaobo

2016-01-01

Biomedical big data, as a whole, covers numerous features, while each dataset specifically delineates part of them. “Full feature spectrum” knowledge discovery across heterogeneous data sources remains a major challenge. We developed a method called bootstrapping for unified feature association measurement (BUFAM) for pairwise association analysis, and relational dependency network (RDN) modeling for global module detection on features across breast cancer cohorts. Discovered knowledge was cross-validated using data from Wake Forest Baptist Medical Center’s electronic medical records and annotated with BioCarta signaling signatures. The clinical potential of the discovered modules was exhibited by stratifying patients for drug responses. A series of discovered associations provided new insights into breast cancer, such as the effects of patient’s cultural background on preferences for surgical procedure. We also discovered two groups of highly associated features, the HER2 and the ER modules, each of which described how phenotypes were associated with molecular signatures, diagnostic features, and clinical decisions. The discovered “ER module”, which was dominated by cancer immunity, was used as an example for patient stratification and prediction of drug responses to tamoxifen and chemotherapy. BUFAM-derived RDN modeling demonstrated unique ability to discover clinically meaningful and actionable knowledge across highly heterogeneous biomedical big data sets. PMID:27427091

Relational Network for Knowledge Discovery through Heterogeneous Biomedical and Clinical Features

NASA Astrophysics Data System (ADS)

Chen, Huaidong; Chen, Wei; Liu, Chenglin; Zhang, Le; Su, Jing; Zhou, Xiaobo

2016-07-01

Biomedical big data, as a whole, covers numerous features, while each dataset specifically delineates part of them. “Full feature spectrum” knowledge discovery across heterogeneous data sources remains a major challenge. We developed a method called bootstrapping for unified feature association measurement (BUFAM) for pairwise association analysis, and relational dependency network (RDN) modeling for global module detection on features across breast cancer cohorts. Discovered knowledge was cross-validated using data from Wake Forest Baptist Medical Center’s electronic medical records and annotated with BioCarta signaling signatures. The clinical potential of the discovered modules was exhibited by stratifying patients for drug responses. A series of discovered associations provided new insights into breast cancer, such as the effects of patient’s cultural background on preferences for surgical procedure. We also discovered two groups of highly associated features, the HER2 and the ER modules, each of which described how phenotypes were associated with molecular signatures, diagnostic features, and clinical decisions. The discovered “ER module”, which was dominated by cancer immunity, was used as an example for patient stratification and prediction of drug responses to tamoxifen and chemotherapy. BUFAM-derived RDN modeling demonstrated unique ability to discover clinically meaningful and actionable knowledge across highly heterogeneous biomedical big data sets.

Detection of Clinical Depression in Adolescents’ Speech During Family Interactions

PubMed Central

Low, Lu-Shih Alex; Maddage, Namunu C.; Lech, Margaret; Sheeber, Lisa B.; Allen, Nicholas B.

2013-01-01

The properties of acoustic speech have previously been investigated as possible cues for depression in adults. However, these studies were restricted to small populations of patients and the speech recordings were made during patients’ clinical interviews or fixed-text reading sessions. Symptoms of depression often first appear during adolescence at a time when the voice is changing, in both males and females, suggesting that specific studies of these phenomena in adolescent populations are warranted. This study investigated acoustic correlates of depression in a large sample of 139 adolescents (68 clinically depressed and 71 controls). Speech recordings were made during naturalistic interactions between adolescents and their parents. Prosodic, cepstral, spectral, and glottal features, as well as features derived from the Teager energy operator (TEO), were tested within a binary classification framework. Strong gender differences in classification accuracy were observed. The TEO-based features clearly outperformed all other features and feature combinations, providing classification accuracy ranging between 81%–87% for males and 72%–79% for females. Close, but slightly less accurate, results were obtained by combining glottal features with prosodic and spectral features (67%–69% for males and 70%–75% for females). These findings indicate the importance of nonlinear mechanisms associated with the glottal flow formation as cues for clinical depression. PMID:21075715

Catatonia as presenting clinical feature of subacute sclerosing panencephalitis

PubMed Central

Dayal, Prabhoo; Balhara, Yatan Pal Singh

2014-01-01

Catatonia is not a usual clinical presentation of subacute sclerosing panencephalitis (SSPE), especially in the initial stages of illness. However, there is only one reported case of SSPE presenting as catatonia among children. In this report, however, there were SSPE-specific changes on EEG and the catatonia failed to respond to lorazepam. We describe a case of SSPE in a child presenting as catatonia that presented with clinical features of catatonia and did not have typical EEG findings when assessed at first contact. He responded to lorazepam and EEG changes emerged during the course of follow-up. PMID:24891908

Peripheral hypoechoic spaces in consolidated lung: a specific diagnostic sonographic finding for necrotizing pneumonia in children.

PubMed

Chiu, Chih-Yung; Wong, Kin-Sun; Lai, Shen-Hao; Huang, Yu-Hsuan; Tsai, Ming-Han; Lin, Yu-Ching

2008-01-01

The aim of this study was to investigate the diagnostic usefulness and clinical values of the sonographic feature of peripheral hypoechoic spaces (PHES) in children with necrotizing pneumonia (NP). Between July 2002 and July 2004, 23 consecutive children with NP in whom we performed real-time chest ultrasound were enrolled into our study. Details of demographics, clinical characteristics, laboratory data, causative pathogens, complications and outcomes of these children were recorded and analyzed. PHES in ultrasonography (US) were defined as peripheral cavitations seen as hypoechoic areas in consolidated lung. The sonographic feature of PHES was correlated with the diagnosis of NP and was also used to correlate with the clinical characteristics, complications and outcomes in children with NP. Sensitivity, specificity, and positive predictive value of this sonographic finding for the diagnosis of NP were 35%, 100%, and 100%, respectively. Pneumothorax was seen more commonly in children who presented PHES in US, with a significant difference (p < 0.05). In conclusion, the sonographic feature of PHES appears to be more specific for detecting NP in childhood pneumonia. In children with pneumonia with PHES in consolidated lung, the diagnosis of NP can be suggested with confidence, and it is important to be aware of the life-threatening complication of pneumothorax to decrease morbidity.

Asthma-like Features and Clinical Course of Chronic Obstructive Pulmonary Disease. An Analysis from the Hokkaido COPD Cohort Study.

PubMed

Suzuki, Masaru; Makita, Hironi; Konno, Satoshi; Shimizu, Kaoruko; Kimura, Hiroki; Kimura, Hirokazu; Nishimura, Masaharu

2016-12-01

Some patients with chronic obstructive pulmonary disease (COPD) have asthma-like features, such as significant bronchodilator reversibility, blood eosinophilia, and/or atopy, even if they are not clinically diagnosed as having asthma. However, the clinical significance of asthma-like features overlapping with COPD remains unclear. The aim of this study was to assess the effect of asthma-like features on the clinical course of patients with COPD who were adequately treated and followed-up over 10 years. A total of 268 patients with COPD who had been clinically considered as not having asthma by respiratory specialists were included in this study. The asthma-like features included in this study were bronchodilator reversibility (ΔFEV 1 , ≥12% and ≥200 ml), blood eosinophilia (≥300 cells/μl), and atopy (positive specific IgE for any inhaled antigen). The annual changes in post-bronchodilator FEV 1 and COPD exacerbations were monitored during the first 5 years, and mortality was followed during the entire 10 years of the study. Fifty-seven subjects (21%) had bronchodilator reversibility, 52 (19%) had blood eosinophilia, and 67 (25%) had atopy. Subjects with blood eosinophilia had significantly slower annual post-bronchodilator FEV 1 decline; bronchodilator reversibility and atopy did not affect the annual post-bronchodilator FEV 1 decline, and none of the asthma-like features was associated with development of COPD exacerbation. Even if subjects had two or more asthma-like features, they displayed annual post-bronchodilator FEV 1 declines and exacerbation rates similar to those of subjects with one or zero asthma-like features, as well as a lower 10-year mortality rate (P = 0.02). The presence of asthma-like features was associated with better clinical course in patients with COPD receiving appropriate treatment.

Stinging and biting insect allergy: an Australian experience.

PubMed

Solley, Graham O

2004-12-01

Stings and bites from various insects are responsible for many anaphylactic events. To document the clinical features of specific forms of anaphylaxis and investigate clinical concerns regarding stinging and biting insect allergy. All patients presenting for evaluation of adverse reactions to insect stings or bites between December 1980 and December 1997 had the clinical details of their reactions recorded and their reactions classified. The spectrum of clinical symptoms and signs is similar to that seen in anaphylaxis from other sources; stings on the head or neck are not more likely to cause life-threatening reactions than stings elsewhere on the body; a lesser reaction will not necessarily lead to a more serious reaction from a future sting; asthmatic patients do appear to have an increased risk of asthma as a feature of their anaphylactic response; anaphylaxis is usually confined to a particular insect species for the individual patient; patients who have had multiple stings at one time may have experienced true anaphylaxis and not a "toxic" response; and patients who have had anaphylaxis from other sources are at no greater risk than that of the general population of reacting similarly to insect stings or bites. Anaphylactic events from insect stings show the same clinical features as those from other sources. Systemic reactions seem confined to a specific insect species. Patients who experience RXN3 reactions from multiple stings at one time should undergo specific venom testing, because many have experienced true anaphylaxis and not a toxic response. Future consideration should be given to the role of beta-adrenergic antagonists and ACE inhibitors in patients with systemic reactions.

Clinical- and imaging-based prediction of stroke risk after transient ischemic attack: the CIP model.

PubMed

Ay, Hakan; Arsava, E Murat; Johnston, S Claiborne; Vangel, Mark; Schwamm, Lee H; Furie, Karen L; Koroshetz, Walter J; Sorensen, A Gregory

2009-01-01

Predictive instruments based on clinical features for early stroke risk after transient ischemic attack suffer from limited specificity. We sought to combine imaging and clinical features to improve predictions for 7-day stroke risk after transient ischemic attack. We studied 601 consecutive patients with transient ischemic attack who had MRI within 24 hours of symptom onset. A logistic regression model was developed using stroke within 7 days as the response criterion and diffusion-weighted imaging findings and dichotomized ABCD(2) score (ABCD(2) >/=4) as covariates. Subsequent stroke occurred in 25 patients (5.2%). Dichotomized ABCD(2) score and acute infarct on diffusion-weighted imaging were each independent predictors of stroke risk. The 7-day risk was 0.0% with no predictor, 2.0% with ABCD(2) score >/=4 alone, 4.9% with acute infarct on diffusion-weighted imaging alone, and 14.9% with both predictors (an automated calculator is available at http://cip.martinos.org). Adding imaging increased the area under the receiver operating characteristic curve from 0.66 (95% CI, 0.57 to 0.76) using the ABCD(2) score to 0.81 (95% CI, 0.74 to 0.88; P=0.003). The sensitivity of 80% on the receiver operating characteristic curve corresponded to a specificity of 73% for the CIP model and 47% for the ABCD(2) score. Combining acute imaging findings with clinical transient ischemic attack features causes a dramatic boost in the accuracy of predictions with clinical features alone for early risk of stroke after transient ischemic attack. If validated in relevant clinical settings, risk stratification by the CIP model may assist in early implementation of therapeutic measures and effective use of hospital resources.

[The specific features of the clinical course of acute suppurative otitis media of viral and mixed viral-bacterial etiology in the children of the preschool age].

PubMed

Radtsig, E Yu; Bugaichuk, O V

The objective of the present study was to elucidate the spectrum of the pathogenic agents responsible for the development of acute suppurative otitis media in the children of the preschool age and to reveal the specific clinical features of this disease depending on its etiological factors. The study involved 138 patients (186 ears) of either sex at the age from 1 year to 84 months who presented with acute suppurative otitis media. The following methods were employed for the purpose of the study: analysis of the patients' complaints and the past medical histories, examination of the ENT organs, microbiological (bacteriological and virological) studies of secretion from the tympanic cavity, diagnostic endoscopy of the nasal cavity and nasopharynx, laboratory investigations. The study allowed to reveal the characteristic clinical manifestations of the pathology of interest depending on its etiology.

Current research on pycnodysostosis.

PubMed

Turan, Serap

2014-08-01

Pycnodysostosis is a rare autosomal recessive disorder caused by an inactivating mutation in cathepsin K (CTSK) and characterized by dysmorphic facial features, a short stature, acroosteolysis, osteosclerosis with increased bone fragility, and delayed closure of cranial sutures. Patients usually present with short stature or dysmorphic features the Pediatric Endocrinology or Genetics clinics, with atypical fractures to the orthopedics clinics or hematological abnormalities to the hematology clinics. However, under-diagnosis or misdiagnosis of this condition is a major issue. Pycnodysostosis is not a life threatening condition, but craniosynostosis, frequent fractures, respiratory-sleep problems, and dental problems may cause significant morbidity. Although no specific treatment for this disorder has been described, patients should be followed for complications and treated accordingly. A specific treatment for the disorder must be established in the future to prevent complications and improve quality of life for patients in the current era of advanced molecular research.

Neuron-specific enolase levels in drug-naïve young adults with major depressive disorder.

PubMed

Wiener, Carolina David; Molina, Mariane Lopez; Passos, Miguel; Moreira, Fernanda Pedrotti; Bittencourt, Guilherme; de Mattos Souza, Luciano Dias; da Silva, Ricardo Azevedo; Jansen, Karen; Oses, Jean Pierre

2016-05-04

The aim of this study is to assess neuron-specific enolase (NSE) levels and clinical features in subjects with major depressive disorder (MDD). This is a cross-sectional study with drug-naïve young adults with MDD (aged 18-29 years). Serum levels of NSE were assessed using the electrochemiluminescence method. MDD diagnosis, suicidal ideation, and time of disease were assessed using the Structured Clinical Interview for DSM-IV (SCID). The Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Rating Scale (HARS) were used to assess depressive and anxiety symptoms. No relationship was observed between NSE levels and severity of depressive and anxiety symptoms, time of disease, and suicidal ideation. These results suggest that NSE serum levels were not associated with clinical features of MDD among drug-naïve young adults. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

[Clinical practice guidelines: juridical and medico legal issues in health care malpractice liability].

PubMed

Moreschi, Carlo; Broi, Ugo Da

2014-01-01

Clinical Practice Guidelines are clinical tools addressed to medical and health professionals and are normally employed to improve quality and safety of diagnostic and therapeutical procedures but may sometimes limit the autonomy of medical and other health care professionals. The adherence to Clinical Practice Guidelines should not be an exclusive step to evaluate the liability and respect of standards of care in case of medico-legal investigations being each clinical case very specific. Medical liability and respect of standards of care should be evaluated with the support of Clinical Practice Guidelines and the extensive examination of all specific features, professional background and experience requested to treat each single patient.

Histopathology and immunohistochemistry in the diagnosis of bioterrorism agents.

PubMed

Guarner, Jeannette; Zaki, Sherif R

2006-01-01

From October to November 2001, the inhalational and cutaneous anthrax cases that occurred in the U.S. underscored the importance of recognizing the clinical and pathological features of infectious agents that can be used in acts of terrorism. Early confirmation of bio-terrorist acts can only be performed by making organism-specific diagnosis of cases with clinical and pathologic syndromes that could be caused by possible bioterrorism weapons. Recognition and diagnosis of these cases is central to establish adequate responses. This review will examine the events that occurred during the anthrax bio-terrorist attack with specific emphasis on the role of pathology and immunohistochemistry and will describe the histopathologic features of category A bioterrorism agents (anthrax, plague, tularemia, botulism, smallpox, and viral hemorrhagic fevers).

The effects of clinical supervision on supervisees and patients in cognitive behavioral therapy: a systematic review.

PubMed

Alfonsson, Sven; Parling, Thomas; Spännargård, Åsa; Andersson, Gerhard; Lundgren, Tobias

2018-05-01

Clinical supervision is a central part of psychotherapist training but the empirical support for specific supervision theories or features is unclear. The aims of this study were to systematically review the empirical research literature regarding the effects of clinical supervision on therapists' competences and clinical outcomes within Cognitive Behavior Therapy (CBT). A comprehensive database search resulted in 4103 identified publications. Of these, 133 were scrutinized and in the end 5 studies were included in the review for data synthesis. The five studies were heterogeneous in scope and quality and only one provided firm empirical support for the positive effects of clinical supervision on therapists' competence. The remaining four studies suffered from methodological weaknesses, but provided some preliminary support that clinical supervision may be beneficiary for novice therapists. No study could show benefits from supervision for patients. The research literature suggests that clinical supervision may have some potential effects on novice therapists' competence compared to no supervision but the effects on clinical outcomes are still unclear. While bug-in-the-eye live supervision may be more effective than standard delayed supervision, the effects of specific supervision models or features are also unclear. There is a continued need for high-quality empirical studies on the effects of clinical supervision in psychotherapy.

Evolution of certain typical and atypical features in a case of subacute sclerosing panencephalitis

PubMed Central

Raut, Tushar Premraj; Singh, Maneesh Kumar; Garg, Ravindra Kumar; Rai, Dheeraj

2012-01-01

Subacute sclerosing panencephalitis (SSPE) is a slowly progressive inflammatory disease of the central nervous system caused by a persistent measles virus usually affecting the childhood and adolescent age group. Clinical features at onset are very subtle and non-specific. Certain atypical features can occur at onset or during the course of illness which can be misleading. Neuroimaging features often are non-specific. Features like myoclonic jerks, cognitive decline and typical EEG findings lead to a strong suspicion of SSPE. Here, we describe the stagewise progression of a case of SSPE in a 14-year-old girl who had myoclonic jerks and cognitive decline at onset. During the course of disease, the patient developed cortical vision loss, atypical extrapyramidal features like segmental and hemifacial dystonia ultimately leading to a bedbound vegetative state. EEG showed typical periodic discharges along with positive cerebrospinal fluid serology for measles. PMID:23266775

Evolution of certain typical and atypical features in a case of subacute sclerosing panencephalitis.

PubMed

Raut, Tushar Premraj; Singh, Maneesh Kumar; Garg, Ravindra Kumar; Rai, Dheeraj

2012-12-23

Subacute sclerosing panencephalitis (SSPE) is a slowly progressive inflammatory disease of the central nervous system caused by a persistent measles virus usually affecting the childhood and adolescent age group. Clinical features at onset are very subtle and non-specific. Certain atypical features can occur at onset or during the course of illness which can be misleading. Neuroimaging features often are non-specific. Features like myoclonic jerks, cognitive decline and typical EEG findings lead to a strong suspicion of SSPE. Here, we describe the stagewise progression of a case of SSPE in a 14-year-old girl who had myoclonic jerks and cognitive decline at onset. During the course of disease, the patient developed cortical vision loss, atypical extrapyramidal features like segmental and hemifacial dystonia ultimately leading to a bedbound vegetative state. EEG showed typical periodic discharges along with positive cerebrospinal fluid serology for measles.

Obstructive Sleep Apnea in Women: Study of Speech and Craniofacial Characteristics

PubMed Central

Tyan, Marina; Fernández Pozo, Rubén; Toledano, Doroteo; Lopez Gonzalo, Eduardo; Alcazar Ramirez, Jose Daniel; Hernandez Gomez, Luis Alfonso

2017-01-01

Background Obstructive sleep apnea (OSA) is a common sleep disorder characterized by frequent cessation of breathing lasting 10 seconds or longer. The diagnosis of OSA is performed through an expensive procedure, which requires an overnight stay at the hospital. This has led to several proposals based on the analysis of patients’ facial images and speech recordings as an attempt to develop simpler and cheaper methods to diagnose OSA. Objective The objective of this study was to analyze possible relationships between OSA and speech and facial features on a female population and whether these possible connections may be affected by the specific clinical characteristics in OSA population and, more specifically, to explore how the connection between OSA and speech and facial features can be affected by gender. Methods All the subjects are Spanish subjects suspected to suffer from OSA and referred to a sleep disorders unit. Voice recordings and photographs were collected in a supervised but not highly controlled way, trying to test a scenario close to a realistic clinical practice scenario where OSA is assessed using an app running on a mobile device. Furthermore, clinical variables such as weight, height, age, and cervical perimeter, which are usually reported as predictors of OSA, were also gathered. Acoustic analysis is centered in sustained vowels. Facial analysis consists of a set of local craniofacial features related to OSA, which were extracted from images after detecting facial landmarks by using the active appearance models. To study the probable OSA connection with speech and craniofacial features, correlations among apnea-hypopnea index (AHI), clinical variables, and acoustic and facial measurements were analyzed. Results The results obtained for female population indicate mainly weak correlations (r values between .20 and .39). Correlations between AHI, clinical variables, and speech features show the prevalence of formant frequencies over bandwidths, with F2/i/ being the most appropriate formant frequency for OSA prediction in women. Results obtained for male population indicate mainly very weak correlations (r values between .01 and .19). In this case, bandwidths prevail over formant frequencies. Correlations between AHI, clinical variables, and craniofacial measurements are very weak. Conclusions In accordance with previous studies, some clinical variables are found to be good predictors of OSA. Besides, strong correlations are found between AHI and some clinical variables with speech and facial features. Regarding speech feature, the results show the prevalence of formant frequency F2/i/ over the rest of features for the female population as OSA predictive feature. Although the correlation reported is weak, this study aims to find some traces that could explain the possible connection between OSA and speech in women. In the case of craniofacial measurements, results evidence that some features that can be used for predicting OSA in male patients are not suitable for testing female population. PMID:29109068

Anonymization of electronic medical records for validating genome-wide association studies

PubMed Central

Loukides, Grigorios; Gkoulalas-Divanis, Aris; Malin, Bradley

2010-01-01

Genome-wide association studies (GWAS) facilitate the discovery of genotype–phenotype relations from population-based sequence databases, which is an integral facet of personalized medicine. The increasing adoption of electronic medical records allows large amounts of patients’ standardized clinical features to be combined with the genomic sequences of these patients and shared to support validation of GWAS findings and to enable novel discoveries. However, disseminating these data “as is” may lead to patient reidentification when genomic sequences are linked to resources that contain the corresponding patients’ identity information based on standardized clinical features. This work proposes an approach that provably prevents this type of data linkage and furnishes a result that helps support GWAS. Our approach automatically extracts potentially linkable clinical features and modifies them in a way that they can no longer be used to link a genomic sequence to a small number of patients, while preserving the associations between genomic sequences and specific sets of clinical features corresponding to GWAS-related diseases. Extensive experiments with real patient data derived from the Vanderbilt's University Medical Center verify that our approach generates data that eliminate the threat of individual reidentification, while supporting GWAS validation and clinical case analysis tasks. PMID:20385806

[Pathogenesis of hypophosphatemia].

PubMed

Takeuchi, Yasuhiro

2016-02-01

Chronic hypophosphatemia is seriously involved in several disorders of musculoskeletal system. Symptoms of patients are usually non-specific, such as pain with or without muscle weakness on lower extremities and are often hard to be correctly diagnosed. It is clinically important for physicians to understand pathogenesis and clinical features of hypophosphatemia and its related diseases.

Light-induced autofluorescence and diffuse reflectance spectroscopy in clinical diagnosis of skin cancer

NASA Astrophysics Data System (ADS)

Borisova, E.; Pavlova, E.; Kundurjiev, T.; Troyanova, P.; Genova, Ts.; Avramov, L.

2014-05-01

We investigated more than 500 clinical cases to receive the spectral properties of basal cell (136 patients) and squamous cell carcinoma (28), malignant melanoma (41) and different cutaneous dysplastic and benign cutaneous lesions. Excitation at 365, 385 and 405 nm using LEDs sources is applied to obtain autofluorescence spectra, and broad-band illumination in the region of 400-900 nm is used to detect diffuse reflectance spectra of all pathologies investigated. USB4000 microspectrometer (Ocean Optics Inc, USA) is applied as a detector and fiber-optic probe is used for delivery of the light. In the case of in vivo tumor measurements spectral shape and intensity changes are observed that are specific for a given type of lesion. Autofluorescence origins of the signals coming from skin tissues are mainly due to proteins, such as collagen, elastin, keratin, their cross-links, co-enzimes - NADH and flavins and endogenous porphyrins. Spectral features significant into diffuse spectroscopy diagnosis are related to the effects of re-absorption of hemoglobin and its forms, as well as melanin and its concentration in different pathologies. We developed significant database and revealed specific features for a large class of cutaneous neoplasia, using about 30 different spectral peculiarities to differentiate cutaneous tumors. Sensitivity and specificity obtained exceed 90%, which make optical biopsy very useful tool for clinical practice. These results are obtained in the frames of clinical investigations for development of significant "spectral features" database for the most common cutaneous malignant, dysplastic and benign lesions. In the forthcoming plans, our group tries to optimize the existing experimental system for optical biopsy of skin, and to introduce it and the diagnostic algorithms developed into clinical practice, based on the high diagnostic accuracy achieved.

Scrub typhus and spotted fever among hospitalised children in South India: Clinical profile and serological epidemiology.

PubMed

Kalal, B S; Puranik, P; Nagaraj, S; Rego, S; Shet, A

2016-01-01

Rickettsial infections are re-emerging. In India, they are now being reported from several areas where they were previously unknown. The objective of this study was to describe the epidemiology, clinical profile and outcome of serologically-confirmed scrub typhus and spotted fever among children in a tertiary care hospital in Bengaluru. Hospitalised children aged <18 years, with clinical features suggestive of rickettsial disease admitted between January 2010 and October 2012 were included prospectively. Diagnosis was based on scrub typhus and spotted fever-specific IgM and IgG by enzyme-linked immunosorbent assay (ELISA). Of 103 children with clinical features suggestive of rickettsial illness, ELISA test confirmed 53 cases for scrub typhus, 23 cases for spotted fever group and 14 with mixed infection. The average age was 7.3 (±3.9) years and 44 (71.0%) children were male. Majority of cases were from Karnataka (50%), Andhra Pradesh (32.3%) and Tamil Nadu (17.7%). Common clinical features included fever (100%, average duration 11 days), nausea and vomiting (44%), rash (36%); eschar was rare. Compared to the ELISA test, Weil-Felix test (OX-K titre of 1:80) had a sensitivity and specificity of 88.7% and 43.9%, respectively. Treatment with chloramphenicol or doxycycline was given to the majority of the children. Complications included meningoencephalitis (28%), shock (10%), retinal vasculitis (10%) and purpura fulminans (7%). These findings suggest that the burden of rickettsial infection among children in India is high, with a substantially high complication rate. Rickettsial-specific ELISA tests can help in early diagnosis and early institution of appropriate treatment that may prevent life-threatening complications.

When fear of cancer recurrence becomes a clinical issue: a qualitative analysis of features associated with clinical fear of cancer recurrence.

PubMed

Mutsaers, Brittany; Jones, Georden; Rutkowski, Nicole; Tomei, Christina; Séguin Leclair, Caroline; Petricone-Westwood, Danielle; Simard, Sébastien; Lebel, Sophie

2016-10-01

Fear of cancer recurrence (FCR) is a common experience for cancer survivors. However, it remains unclear what characteristics differentiate non-clinical from clinical levels of FCR. The goal of this study was to investigate the potential hallmarks of clinical FCR. A convenience sample of 40 participants (n = 19 female) was drawn from another study (Lebel et al. in Qual Life Res 25:311-321. doi: 10.1007/s11136-015-1088-2 , 2016). The semi-structured interview for fear of cancer recurrence (Simard and Savard in J Cancer Surviv 9:481-491. doi: 10.1007/s11764-015-0424-4 , 2015) was used to identify participants with non-clinical and clinical FCR and qualitative analysis of these interviews was performed. Individuals with clinical FCR reported the following features: death-related thoughts, feeling alone, belief that the cancer would return, experiencing intolerance of uncertainty, having cancer-related thoughts and imagery that were difficult to control, daily and recurrent, lasted 30 minutes or more, increased over time, caused distress and impacted their daily life. Triggers of FCR and coping strategies did not appear to be features of clinical FCR as they were reported by participants with a range of FCR scores. While features of clinical FCR found in this analysis such as intrusive thoughts, distress and impact on functioning confirmed previous FCR research, other features spontaneously emerged from the interviews including "death-related thoughts," "feeling alone," and "belief that the cancer will return." The participants' descriptions of cancer-specific fear and worry suggest that FCR is a distinct phenomenon related to cancer survivorship, despite similarities with psychological disorders (e.g., Anxiety Disorders). Future research investigating the construct of FCR, and the distinguishing features of clinical FCR across a range of cancer types and gender is required.

Review of quantitative ultrasound: envelope statistics and backscatter coefficient imaging and contributions to diagnostic ultrasound

PubMed Central

Oelze, Michael L.; Mamou, Jonathan

2017-01-01

Conventional medical imaging technologies, including ultrasound, have continued to improve over the years. For example, in oncology, medical imaging is characterized by high sensitivity, i.e., the ability to detect anomalous tissue features, but the ability to classify these tissue features from images often lacks specificity. As a result, a large number of biopsies of tissues with suspicious image findings are performed each year with a vast majority of these biopsies resulting in a negative finding. To improve specificity of cancer imaging, quantitative imaging techniques can play an important role. Conventional ultrasound B-mode imaging is mainly qualitative in nature. However, quantitative ultrasound (QUS) imaging can provide specific numbers related to tissue features that can increase the specificity of image findings leading to improvements in diagnostic ultrasound. QUS imaging techniques can encompass a wide variety of techniques including spectral-based parameterization, elastography, shear wave imaging, flow estimation and envelope statistics. Currently, spectral-based parameterization and envelope statistics are not available on most conventional clinical ultrasound machines. However, in recent years QUS techniques involving spectral-based parameterization and envelope statistics have demonstrated success in many applications, providing additional diagnostic capabilities. Spectral-based techniques include the estimation of the backscatter coefficient, estimation of attenuation, and estimation of scatterer properties such as the correlation length associated with an effective scatterer diameter and the effective acoustic concentration of scatterers. Envelope statistics include the estimation of the number density of scatterers and quantification of coherent to incoherent signals produced from the tissue. Challenges for clinical application include correctly accounting for attenuation effects and transmission losses and implementation of QUS on clinical devices. Successful clinical and pre-clinical applications demonstrating the ability of QUS to improve medical diagnostics include characterization of the myocardium during the cardiac cycle, cancer detection, classification of solid tumors and lymph nodes, detection and quantification of fatty liver disease, and monitoring and assessment of therapy. PMID:26761606

Data standards for clinical research data collection forms: current status and challenges.

PubMed

Richesson, Rachel L; Nadkarni, Prakash

2011-05-01

Case report forms (CRFs) are used for structured-data collection in clinical research studies. Existing CRF-related standards encompass structural features of forms and data items, content standards, and specifications for using terminologies. This paper reviews existing standards and discusses their current limitations. Because clinical research is highly protocol-specific, forms-development processes are more easily standardized than is CRF content. Tools that support retrieval and reuse of existing items will enable standards adoption in clinical research applications. Such tools will depend upon formal relationships between items and terminological standards. Future standards adoption will depend upon standardized approaches for bridging generic structural standards and domain-specific content standards. Clinical research informatics can help define tools requirements in terms of workflow support for research activities, reconcile the perspectives of varied clinical research stakeholders, and coordinate standards efforts toward interoperability across healthcare and research data collection.

[The specific microbiological and clinical features of acute otitis media].

PubMed

Gurov, A V; Levina, Yu V; Guseva, A L; Elchueva, Z G; Efimova, S P; Gordienko, M V

The objective of the present study was to elucidate the specific features of the clinical course of acute otitis media as well as the peculiarities of the vestibular function and the microbial paysage associated with this pathological condition under the present-day conditions. The study included 135 patients presenting with acute otitis media (AOM) at different stages of the disease. The discharge obtained from the tympanic cavity of all the patients was examined with the use of polymerase chain reaction in real time, audiological and vestibulogical methods. The distinctive features of acute otitis medium associated with Streptococcus pneumoniae infection were found to be the intense pain syndrome with the symptoms of intoxication, well apparent inflammatory changes in the tympanic membrane as revealed by otoscopy, the increased frequency of sensorineural impairment of hearing, and the characteristic type B tympanometric curve. Typical of AOM associated with Haemophilus influenza infection are the mild pain syndrome, weak changes in the tympanic membrane as revealed by otoscopy, conductive hearing loss, and the type C tympanometric curve.

Electroconvulsive therapy in treatment-resistant schizophrenia: prediction of response and the nature of symptomatic improvement.

PubMed

Chanpattana, Worrawat; Sackeim, Harold A

2010-12-01

The clinical features of patients with schizophrenia who respond to electroconvulsive therapy (ECT) are uncertain. There is a longstanding belief that the duration of illness and/or the presence of affective symptoms associate with good prognosis. There is also little information on the nature of symptomatic improvement with this treatment. We examined the demographic and clinical history features associated with response, the symptom profile predictive of response, and the profile of symptomatic improvement. Using a standardized protocol, 253 patients with treatment-resistant schizophrenia were prospectively treated with a combination of ECT and flupenthixol. Of this group, 138 patients (54.5%) met the response criteria. Independence of sex, longer duration of current episode, and greater severity of baseline negative symptoms were predictive of poorer outcome. Duration of illness had weak relations with outcome only among females. There were marked sex differences in other clinical features and symptoms associated with response. In contrast, no sex differences were observed in the nature of symptomatic improvement. Treatment resulted in marked improvement in specific positive symptoms, with an intermediate effect on affective symptoms and no effect or worsening of specific negative symptoms. The findings challenge recommendations that long duration of illness or absence of affective symptoms portends poor response to ECT in patients with treatment-resistant schizophrenia. Sex may play a critical role in determining the features of the illness that predict outcome.

WE-D-204-04: Learning the Ropes: Clinical Immersion in the First Month of Residency

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

Dieterich, S.

Speakers in this session will present overview and details of a specific rotation or feature of their Medical Physics Residency Program that is particularly exceptional and noteworthy. The featured rotations include foundational topics executed with exceptional acumen and innovative educational rotations perhaps not commonly found in Medical Physics Residency Programs. A site-specific clinical rotation will be described, where the medical physics resident follows the physician and medical resident for two weeks into patient consultations, simulation sessions, target contouring sessions, planning meetings with dosimetry, patient follow up visits, and tumor boards, to gain insight into the thought processes of the radiationmore » oncologist. An incident learning rotation will be described where the residents learns about and practices evaluating clinical errors and investigates process improvements for the clinic. The residency environment at a Canadian medical physics residency program will be described, where the training and interactions with radiation oncology residents is integrated. And the first month rotation will be described, where the medical physics resident rotates through the clinical areas including simulation, dosimetry, and treatment units, gaining an overview of the clinical flow and meeting all the clinical staff to begin the residency program. This session will be of particular interest to residency programs who are interested in adopting or adapting these curricular ideas into their programs and to residency candidates who want to learn about programs already employing innovative practices. Learning Objectives: To learn about exceptional and innovative clinical rotations or program features within existing Medical Physics Residency Programs. To understand how to adopt/adapt innovative curricular designs into your own Medical Physics Residency Program, if appropriate.« less

Exploring cognitive integration of basic science and its effect on diagnostic reasoning in novices.

PubMed

Lisk, Kristina; Agur, Anne M R; Woods, Nicole N

2016-06-01

Integration of basic and clinical science knowledge is increasingly being recognized as important for practice in the health professions. The concept of 'cognitive integration' places emphasis on the value of basic science in providing critical connections to clinical signs and symptoms while accounting for the fact that clinicians may not spontaneously articulate their use of basic science knowledge in clinical reasoning. In this study we used a diagnostic justification test to explore the impact of integrated basic science instruction on novices' diagnostic reasoning process. Participants were allocated to an integrated basic science or clinical science training group. The integrated basic science group was taught the clinical features along with the underlying causal mechanisms of four musculoskeletal pathologies while the clinical science group was taught only the clinical features. Participants completed a diagnostic accuracy test immediately after initial learning, and one week later a diagnostic accuracy and justification test. The results showed that novices who learned the integrated causal mechanisms had superior diagnostic accuracy and better understanding of the relative importance of key clinical features. These findings further our understanding of cognitive integration by providing evidence of the specific changes in clinical reasoning when basic and clinical sciences are integrated during learning.

Evaluation of Voice Acoustics as Predictors of Clinical Depression Scores.

PubMed

Hashim, Nik Wahidah; Wilkes, Mitch; Salomon, Ronald; Meggs, Jared; France, Daniel J

2017-03-01

The aim of the present study was to determine if acoustic measures of voice, characterizing specific spectral and timing properties, predict clinical ratings of depression severity measured in a sample of patients using the Hamilton Depression Rating Scale (HAMD) and Beck Depression Inventory (BDI-II). This is a prospective study. Voice samples and clinical depression scores were collected prospectively from consenting adult patients who were referred to psychiatry from the adult emergency department or primary care clinics. The patients were audio-recorded as they read a standardized passage in a nearly closed-room environment. Mean Absolute Error (MAE) between actual and predicted depression scores was used as the primary outcome measure. The average MAE between predicted and actual HAMD scores was approximately two scores for both men and women, and the MAE for the BDI-II scores was approximately one score for men and eight scores for women. Timing features were predictive of HAMD scores in female patients while a combination of timing features and spectral features was predictive of scores in male patients. Timing features were predictive of BDI-II scores in male patients. Voice acoustic features extracted from read speech demonstrated variable effectiveness in predicting clinical depression scores in men and women. Voice features were highly predictive of HAMD scores in men and women, and BDI-II scores in men, respectively. The methodology is feasible for diagnostic applications in diverse clinical settings as it can be implemented during a standard clinical interview in a normal closed room and without strict control on the recording environment. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Texture-specific bag of visual words model and spatial cone matching-based method for the retrieval of focal liver lesions using multiphase contrast-enhanced CT images.

PubMed

Xu, Yingying; Lin, Lanfen; Hu, Hongjie; Wang, Dan; Zhu, Wenchao; Wang, Jian; Han, Xian-Hua; Chen, Yen-Wei

2018-01-01

The bag of visual words (BoVW) model is a powerful tool for feature representation that can integrate various handcrafted features like intensity, texture, and spatial information. In this paper, we propose a novel BoVW-based method that incorporates texture and spatial information for the content-based image retrieval to assist radiologists in clinical diagnosis. This paper presents a texture-specific BoVW method to represent focal liver lesions (FLLs). Pixels in the region of interest (ROI) are classified into nine texture categories using the rotation-invariant uniform local binary pattern method. The BoVW-based features are calculated for each texture category. In addition, a spatial cone matching (SCM)-based representation strategy is proposed to describe the spatial information of the visual words in the ROI. In a pilot study, eight radiologists with different clinical experience performed diagnoses for 20 cases with and without the top six retrieved results. A total of 132 multiphase computed tomography volumes including five pathological types were collected. The texture-specific BoVW was compared to other BoVW-based methods using the constructed dataset of FLLs. The results show that our proposed model outperforms the other three BoVW methods in discriminating different lesions. The SCM method, which adds spatial information to the orderless BoVW model, impacted the retrieval performance. In the pilot trial, the average diagnosis accuracy of the radiologists was improved from 66 to 80% using the retrieval system. The preliminary results indicate that the texture-specific features and the SCM-based BoVW features can effectively characterize various liver lesions. The retrieval system has the potential to improve the diagnostic accuracy and the confidence of the radiologists.

Age specific fast breathing in under-five diarrheal children in an urban hospital: Acidosis or pneumonia?

PubMed

Nuzhat, Sharika; Ahmed, Tahmeed; Kawser, Chowdhury Ali; Khan, Azharul Islam; Islam, S M Rafiqul; Shahrin, Lubaba; Shahunja, K M; Shahid, Abu S M S B; Al Imran, Abdullah; Chisti, Mohammod Jobayer

2017-01-01

Children with diarrhea often present with fast breathing due to metabolic acidosis from dehydration. On the other hand, age specific fast breathing is the cornerstone for the diagnosis of pneumonia following classification of pneumonia recommended by the World Health Organization (WHO). Correction of metabolic acidosis by rehydrating the diarrheal children requires time, which delays early initiation of appropriate antimicrobials for pneumonia and thereby increases the risk of deaths. We need to further investigate the simple clinical features other than fast breathing which might help us in earliest diagnosis of pneumonia in children with diarrhea Thus, the objective of our study was to identify other contributing clinical features that may independently help for early diagnosis of pneumonia in diarrheal children who present with age specific fast breathing. This was an unmatched case-control study. Diarrheal children aged 0-59 months, admitted to Dhaka Hospital of the International Centre for Diarrheal Disease Research, Bangladesh (icddr,b) during January 2014 to December 2014 having age specific fast breathing (<2 month ≥60 breath/min, 2-11 months ≥50 breaths/min, >11-59 months ≥40 breaths/min) were studied. The study children with clinical and radiological pneumonia constituted the cases (n = 276) and those without pneumonia constituted the controls (n = 446). Comparison of clinical features and outcomes between the cases and the controls was made. The distribution of acidosis among the cases and the controls was comparable (35% vs. 41%, p = 0.12). The cases had proportionately higher deaths compared to the controls, however, the difference was not statistically significant (3% vs. 1%; p = 0.23). In logistic regression analysis after adjusting for potential confounders, the cases were independently associated with cough (OR = 62.19, 95% CI = 27.79-139.19; p<0.01) and chest wall indrawing (OR = 31.05, 95%CI = 13.43-71.82; p<0.01) and less often had severe acute malnutrition (OR = 0.33, 95%CI = 0.13-0.79; p<0.01). The sensitivity and specificity of cough were 83% (78-87%) and 93% (91-96%). The sensitivity and specificity for lower chest wall indrawing were 65% (59-71%) and 95% (93-97%). However, the sensitivity and specificity of cough and lower chest wall indrawing combined were 94% (89-97%) and 99% (97-100%). Thus, diarrheal children having fast breathing who present with cough and/or lower chest wall indrawing, irrespective of presence or absence of metabolic acidosis, are more likely to have radiological pneumonia. The results underscore the importance of early identification of these simple clinical features that may help to minimize potential delay due to rehydration in initiating prompt treatment of pneumonia in order to reduce fatal consequences in such children.

Diagnosis of Polycystic Ovary Syndrome: AMH in combination with clinical symptoms.

PubMed

Sahmay, Sezai; Aydin, Yavuz; Oncul, Mahmut; Senturk, Levent M

2014-02-01

We assessed the utility of using anti-Müllerian hormone (AMH) and clinical features of polycystic ovary syndrome (PCOS), polycystic ovarian morphology (PCOM), oligo/amenorrhea (OA), and hyperandrogenism (HA) for diagnosing PCOS, and compared their diagnostic accuracy with those of classical diagnostic systems. A total of 606 females were admitted to a university hospital with menstrual irregularities or symptoms of hyperandrogenism were enrolled in this cross-sectional study. Fasting blood samples were collected. Pelvic and/or abdominal ultrasonography and clinical examination were performed. Patients were evaluated for the presence of PCOS according to conventional diagnostic criteria. The diagnostic performance of using serum AMH levels alone and in various combinations with the clinical features of PCOM, OA, and HA were investigated. For the diagnosis of PCOS, the combination of OA and/or HA with AMH showed 83% sensitivity and 100% specificity according to the Rotterdam criteria; 83% sensitivity and 89% specificity according to the National Institutes of Health (NIH) criteria; and 82% sensitivity and 93.5% specificity according to the Androgen Excess Society (AES) criteria. The serum AMH level is a useful diagnostic marker for PCOS and is correlated with conventional diagnostic criteria. The combination of AMH level with OA and/or HA markedly increased the clinical scope for PCOS diagnosis and can be introduced as a possible objective criterion for the diagnosis of this disease.

[Discriminant analysis to predict the clinical diagnosis of primary immunodeficiencies: a preliminary report].

PubMed

Murata, Chiharu; Ramírez, Ana Belén; Ramírez, Guadalupe; Cruz, Alonso; Morales, José Luis; Lugo-Reyes, Saul Oswaldo

2015-01-01

The features in a clinical history from a patient with suspected primary immunodeficiency (PID) direct the differential diagnosis through pattern recognition. PIDs are a heterogeneous group of more than 250 congenital diseases with increased susceptibility to infection, inflammation, autoimmunity, allergy and malignancy. Linear discriminant analysis (LDA) is a multivariate supervised classification method to sort objects of study into groups by finding linear combinations of a number of variables. To identify the features that best explain membership of pediatric PID patients to a group of defect or disease. An analytic cross-sectional study was done with a pre-existing database with clinical and laboratory records from 168 patients with PID, followed at the National Institute of Pediatrics during 1991-2012, it was used to build linear discriminant models that would explain membership of each patient to the different group defects and to the most prevalent PIDs in our registry. After a preliminary run only 30 features were included (4 demographic, 10 clinical, 10 laboratory, 6 germs), with which the training models were developed through a stepwise regression algorithm. We compared the automatic feature selection with a selection made by a human expert, and then assessed the diagnostic usefulness of the resulting models (sensitivity, specificity, prediction accuracy and kappa coefficient), with 95% confidence intervals. The models incorporated 6 to 14 features to explain membership of PID patients to the five most abundant defect groups (combined, antibody, well-defined, dysregulation and phagocytosis), and to the four most prevalent PID diseases (X-linked agammaglobulinemia, chronic granulomatous disease, common variable immunodeficiency and ataxiatelangiectasia). In practically all cases of feature selection the machine outperformed the human expert. Diagnosis prediction using the equations created had a global accuracy of 83 to 94%, with sensitivity of 60 to 100%, specificity of 83 to 95% and kappa coefficient of 0.37 to 0.76. In general, the selection of features has clinical plausibility, and the practical advantage of utilizing only clinical attributes, infecting germs and routine lab results (blood cell counts and serum immunoglobulins). The performance of the model as a diagnostic tool was acceptable. The study's main limitations are a limited sample size and a lack of cross validation. This is only the first step in the construction of a machine learning system, with a wider approach that includes a larger database and different methodologies, to assist the clinical diagnosis of primary immunodeficiencies.

[Malabsorption is a leading clinical sign of small bowel disease].

PubMed

Parfenov, A I; Krums, L M

The paper presents a variety of clinical manifestations of malabsorption syndrome (MAS) in celiac disease, collagenous sprue, Whipple's disease, Crohn's disease, intestinal lymphangiectasia, amyloidosis, common variable immune deficiency, and treatment of short bowel syndrome. It shows the specific features of the pathophysiology, diagnosis, and treatment of MAS in small bowel diseases.

Legionella (Legionnaires' Disease and Pontiac Fever): Treatment and Complications

MedlinePlus

... and Trends Fast Facts For Clinicians Disease Specifics Clinical Features Diagnosis, Treatment, & Prevention For Health Departments Surveillance & Reporting Resources Case Definitions CDC Surveillance Classifications How to Report Cases Case ...

Pediatric Eosinophilic Esophagitis Symptom Scores (PEESS® v2.0) identify histologic and molecular correlates of the key clinical features of disease

PubMed Central

Martin, Lisa J.; Franciosi, James P.; Collins, Margaret H.; Abonia, J. Pablo; Lee, James J.; Hommel, Kevin A.; Varni, James W.; Grotjan, J. Tommie; Eby, Michael; He, Hua; Marsolo, Keith; Putnam, Philip E.; Garza, Jose M.; Kaul, Ajay; Wen, Ting; Rothenberg, Marc E.

2015-01-01

Background The Pediatric Eosinophilic Esophagitis Symptom Score (PEESS® v2.0) measures patient-relevant outcomes. However, whether patient-identified domains (dysphagia, gastrointestinal reflux disease (GERD), nausea/vomiting, and pain) align with clinical symptomology and histopathologic and molecular features of eosinophilic esophagitis (EoE) is unclear. Objective The purpose of this study was to determine if clinical features of EoE, measured through the PEESS® v2.0, associate with histopathologic and molecular features of EoE. This represents a novel approach for analysis of allergic diseases, given the availability of allergic tissue biopsy specimens. Methods We systematically recruited treated and untreated, pediatric patients with EoE (aged 2–18 years) and examined parent proxy–reported symptoms using the PEESS® v2.0. Clinical symptomology was collected by questionnaire. Esophageal biopsy samples were quantified for levels of eosinophils, eosinophil peroxidase (EPX) immunohistochemical staining, and mast cells. Molecular features were assessed by the EoE Diagnostic Panel (94 EoE-related gene transcripts). Associations between domain scores and clinical symptoms and biologic features were analyzed using Wilcoxon Rank Sum and Spearman correlation. Results The PEESS® v2.0 domains correlated to specific parent-reported symptoms: dysphagia (p = 0.0012), GERD (p = 0.0001), and nausea/vomiting (p < 0.0001). Pain correlated with multiple symptoms (p < 0.0005). Dysphagia correlated most strongly with overall histopathology, particularly in the proximal esophagus (p ≤ 0.0049). Markers of esophageal activity (EPX) were significantly associated with dysphagia (strongest r = .37; p = 0.02). Eosinophil levels were more associated with pain (r = 0.27; p=0.06) than for dysphagia (r = 0.24; p = 0.13). The dysphagia domain correlated the most with esophageal gene transcript levels, predominantly with mast cell–specific genes. Conclusion We have 1) established a validated, parent proxy–report measure for pediatric EoE — the PEESS® v2.0; 2) verified that parent-proxy effectively captures symptoms; 3) determined that the dysphagia domain most closely aligns with symptoms and tissue-based molecular biomarkers; 4) established that symptoms correlate EPX staining; and 5) observed association between mast cells and dysphagia. PMID:26051952

Word sense disambiguation in the clinical domain: a comparison of knowledge-rich and knowledge-poor unsupervised methods

PubMed Central

Chasin, Rachel; Rumshisky, Anna; Uzuner, Ozlem; Szolovits, Peter

2014-01-01

Objective To evaluate state-of-the-art unsupervised methods on the word sense disambiguation (WSD) task in the clinical domain. In particular, to compare graph-based approaches relying on a clinical knowledge base with bottom-up topic-modeling-based approaches. We investigate several enhancements to the topic-modeling techniques that use domain-specific knowledge sources. Materials and methods The graph-based methods use variations of PageRank and distance-based similarity metrics, operating over the Unified Medical Language System (UMLS). Topic-modeling methods use unlabeled data from the Multiparameter Intelligent Monitoring in Intensive Care (MIMIC II) database to derive models for each ambiguous word. We investigate the impact of using different linguistic features for topic models, including UMLS-based and syntactic features. We use a sense-tagged clinical dataset from the Mayo Clinic for evaluation. Results The topic-modeling methods achieve 66.9% accuracy on a subset of the Mayo Clinic's data, while the graph-based methods only reach the 40–50% range, with a most-frequent-sense baseline of 56.5%. Features derived from the UMLS semantic type and concept hierarchies do not produce a gain over bag-of-words features in the topic models, but identifying phrases from UMLS and using syntax does help. Discussion Although topic models outperform graph-based methods, semantic features derived from the UMLS prove too noisy to improve performance beyond bag-of-words. Conclusions Topic modeling for WSD provides superior results in the clinical domain; however, integration of knowledge remains to be effectively exploited. PMID:24441986

Towards automated processing of clinical Finnish: sublanguage analysis and a rule-based parser.

PubMed

Laippala, Veronika; Ginter, Filip; Pyysalo, Sampo; Salakoski, Tapio

2009-12-01

In this paper, we present steps taken towards more efficient automated processing of clinical Finnish, focusing on daily nursing notes in a Finnish Intensive Care Unit (ICU). First, we analyze ICU Finnish as a sublanguage, identifying its specific features facilitating, for example, the development of a specialized syntactic analyser. The identified features include frequent omission of finite verbs, limitations in allowed syntactic structures, and domain-specific vocabulary. Second, we develop a formal grammar and a parser for ICU Finnish, thus providing better tools for the development of further applications in the clinical domain. The grammar is implemented in the LKB system in a typed feature structure formalism. The lexicon is automatically generated based on the output of the FinTWOL morphological analyzer adapted to the clinical domain. As an additional experiment, we study the effect of using Finnish constraint grammar to reduce the size of the lexicon. The parser construction thus makes efficient use of existing resources for Finnish. The grammar currently covers 76.6% of ICU Finnish sentences, producing highly accurate best-parse analyzes with F-score of 91.1%. We find that building a parser for the highly specialized domain sublanguage is not only feasible, but also surprisingly efficient, given an existing morphological analyzer with broad vocabulary coverage. The resulting parser enables a deeper analysis of the text than was previously possible.

Early Detection of Ureteropelvic Junction Obstruction Using Signal Analysis and Machine Learning: A Dynamic Solution to a Dynamic Problem.

PubMed

Blum, Emily S; Porras, Antonio R; Biggs, Elijah; Tabrizi, Pooneh R; Sussman, Rachael D; Sprague, Bruce M; Shalaby-Rana, Eglal; Majd, Massoud; Pohl, Hans G; Linguraru, Marius George

2017-10-21

We sought to define features that describe the dynamic information in diuresis renograms for the early detection of clinically significant hydronephrosis caused by ureteropelvic junction obstruction. We studied the diuresis renogram of 55 patients with a mean ± SD age of 75 ± 66 days who had congenital hydronephrosis at initial presentation. Five patients had bilaterally affected kidneys for a total of 60 diuresis renograms. Surgery was performed on 35 kidneys. We extracted 45 features based on curve shape and wavelet analysis from the drainage curves recorded after furosemide administration. The optimal features were selected as the combination that maximized the ROC AUC obtained from a linear support vector machine classifier trained to classify patients as with or without obstruction. Using these optimal features we performed leave 1 out cross validation to estimate the accuracy, sensitivity and specificity of our framework. Results were compared to those obtained using post-diuresis drainage half-time and the percent of clearance after 30 minutes. Our framework had 93% accuracy, including 91% sensitivity and 96% specificity, to predict surgical cases. This was a significant improvement over the same accuracy of 82%, including 71% sensitivity and 96% specificity obtained from half-time and 30-minute clearance using the optimal thresholds of 24.57 minutes and 55.77%, respectively. Our machine learning framework significantly improved the diagnostic accuracy of clinically significant hydronephrosis compared to half-time and 30-minute clearance. This aids in the clinical decision making process by offering a tool for earlier detection of severe cases and it has the potential to reduce the number of diuresis renograms required for diagnosis. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

WE-D-204-00: Session in Memory of Franca Kuchnir: Excellence in Medical Physics Residency Education

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

NONE

Speakers in this session will present overview and details of a specific rotation or feature of their Medical Physics Residency Program that is particularly exceptional and noteworthy. The featured rotations include foundational topics executed with exceptional acumen and innovative educational rotations perhaps not commonly found in Medical Physics Residency Programs. A site-specific clinical rotation will be described, where the medical physics resident follows the physician and medical resident for two weeks into patient consultations, simulation sessions, target contouring sessions, planning meetings with dosimetry, patient follow up visits, and tumor boards, to gain insight into the thought processes of the radiationmore » oncologist. An incident learning rotation will be described where the residents learns about and practices evaluating clinical errors and investigates process improvements for the clinic. The residency environment at a Canadian medical physics residency program will be described, where the training and interactions with radiation oncology residents is integrated. And the first month rotation will be described, where the medical physics resident rotates through the clinical areas including simulation, dosimetry, and treatment units, gaining an overview of the clinical flow and meeting all the clinical staff to begin the residency program. This session will be of particular interest to residency programs who are interested in adopting or adapting these curricular ideas into their programs and to residency candidates who want to learn about programs already employing innovative practices. Learning Objectives: To learn about exceptional and innovative clinical rotations or program features within existing Medical Physics Residency Programs. To understand how to adopt/adapt innovative curricular designs into your own Medical Physics Residency Program, if appropriate.« less

WE-D-204-03: CAMPEP Residencies in a Canadian Context: Comprehensive Cancer Centers and Integrated Learning Environments

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

Parker, W.

Speakers in this session will present overview and details of a specific rotation or feature of their Medical Physics Residency Program that is particularly exceptional and noteworthy. The featured rotations include foundational topics executed with exceptional acumen and innovative educational rotations perhaps not commonly found in Medical Physics Residency Programs. A site-specific clinical rotation will be described, where the medical physics resident follows the physician and medical resident for two weeks into patient consultations, simulation sessions, target contouring sessions, planning meetings with dosimetry, patient follow up visits, and tumor boards, to gain insight into the thought processes of the radiationmore » oncologist. An incident learning rotation will be described where the residents learns about and practices evaluating clinical errors and investigates process improvements for the clinic. The residency environment at a Canadian medical physics residency program will be described, where the training and interactions with radiation oncology residents is integrated. And the first month rotation will be described, where the medical physics resident rotates through the clinical areas including simulation, dosimetry, and treatment units, gaining an overview of the clinical flow and meeting all the clinical staff to begin the residency program. This session will be of particular interest to residency programs who are interested in adopting or adapting these curricular ideas into their programs and to residency candidates who want to learn about programs already employing innovative practices. Learning Objectives: To learn about exceptional and innovative clinical rotations or program features within existing Medical Physics Residency Programs. To understand how to adopt/adapt innovative curricular designs into your own Medical Physics Residency Program, if appropriate.« less

WE-D-204-02: Errors and Process Improvements in Radiation Therapy

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

Fontenla, D.

2016-06-15

Speakers in this session will present overview and details of a specific rotation or feature of their Medical Physics Residency Program that is particularly exceptional and noteworthy. The featured rotations include foundational topics executed with exceptional acumen and innovative educational rotations perhaps not commonly found in Medical Physics Residency Programs. A site-specific clinical rotation will be described, where the medical physics resident follows the physician and medical resident for two weeks into patient consultations, simulation sessions, target contouring sessions, planning meetings with dosimetry, patient follow up visits, and tumor boards, to gain insight into the thought processes of the radiationmore » oncologist. An incident learning rotation will be described where the residents learns about and practices evaluating clinical errors and investigates process improvements for the clinic. The residency environment at a Canadian medical physics residency program will be described, where the training and interactions with radiation oncology residents is integrated. And the first month rotation will be described, where the medical physics resident rotates through the clinical areas including simulation, dosimetry, and treatment units, gaining an overview of the clinical flow and meeting all the clinical staff to begin the residency program. This session will be of particular interest to residency programs who are interested in adopting or adapting these curricular ideas into their programs and to residency candidates who want to learn about programs already employing innovative practices. Learning Objectives: To learn about exceptional and innovative clinical rotations or program features within existing Medical Physics Residency Programs. To understand how to adopt/adapt innovative curricular designs into your own Medical Physics Residency Program, if appropriate.« less

Obstructive Sleep Apnea in Women: Study of Speech and Craniofacial Characteristics.

PubMed

Tyan, Marina; Espinoza-Cuadros, Fernando; Fernández Pozo, Rubén; Toledano, Doroteo; Lopez Gonzalo, Eduardo; Alcazar Ramirez, Jose Daniel; Hernandez Gomez, Luis Alfonso

2017-11-06

Obstructive sleep apnea (OSA) is a common sleep disorder characterized by frequent cessation of breathing lasting 10 seconds or longer. The diagnosis of OSA is performed through an expensive procedure, which requires an overnight stay at the hospital. This has led to several proposals based on the analysis of patients' facial images and speech recordings as an attempt to develop simpler and cheaper methods to diagnose OSA. The objective of this study was to analyze possible relationships between OSA and speech and facial features on a female population and whether these possible connections may be affected by the specific clinical characteristics in OSA population and, more specifically, to explore how the connection between OSA and speech and facial features can be affected by gender. All the subjects are Spanish subjects suspected to suffer from OSA and referred to a sleep disorders unit. Voice recordings and photographs were collected in a supervised but not highly controlled way, trying to test a scenario close to a realistic clinical practice scenario where OSA is assessed using an app running on a mobile device. Furthermore, clinical variables such as weight, height, age, and cervical perimeter, which are usually reported as predictors of OSA, were also gathered. Acoustic analysis is centered in sustained vowels. Facial analysis consists of a set of local craniofacial features related to OSA, which were extracted from images after detecting facial landmarks by using the active appearance models. To study the probable OSA connection with speech and craniofacial features, correlations among apnea-hypopnea index (AHI), clinical variables, and acoustic and facial measurements were analyzed. The results obtained for female population indicate mainly weak correlations (r values between .20 and .39). Correlations between AHI, clinical variables, and speech features show the prevalence of formant frequencies over bandwidths, with F2/i/ being the most appropriate formant frequency for OSA prediction in women. Results obtained for male population indicate mainly very weak correlations (r values between .01 and .19). In this case, bandwidths prevail over formant frequencies. Correlations between AHI, clinical variables, and craniofacial measurements are very weak. In accordance with previous studies, some clinical variables are found to be good predictors of OSA. Besides, strong correlations are found between AHI and some clinical variables with speech and facial features. Regarding speech feature, the results show the prevalence of formant frequency F2/i/ over the rest of features for the female population as OSA predictive feature. Although the correlation reported is weak, this study aims to find some traces that could explain the possible connection between OSA and speech in women. In the case of craniofacial measurements, results evidence that some features that can be used for predicting OSA in male patients are not suitable for testing female population. ©Marina Tyan, Fernando Espinoza-Cuadros, Rubén Fernández Pozo, Doroteo Toledano, Eduardo Lopez Gonzalo, Jose Daniel Alcazar Ramirez, Luis Alfonso Hernandez Gomez. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 06.11.2017.

Breast Cancer Subtypes: Morphologic and Biologic Characterization

PubMed Central

2016-01-01

Advances in basic science, technology and translational research have created a revolution in breast cancer diagnosis and therapy. Researchers' discoveries of genes defining variability in response to therapy and heterogeneity in clinical presentations and tumor biology are the foundation of the path to personalized medicine. The success of personalized breast cancer care depends on access to pertinent clinical information and risk factors, optimal imaging findings, well-established morphologic features, and traditional and contemporary prognostic/predictive testing. The integration of these entities provides an opportunity to identify patients who can benefit from specific therapies, and demonstrates the link between breast cancer subtypes and their association with different tumor biology. It is critical to recognize specific types of breast cancer in individual patients and design optimal personalized therapy. This article will highlight the roles of morphologic features and established tumor biomarkers on patient outcome. PMID:26756229

What to consider when pseudohypoparathyroidism is ruled out: iPPSD and differential diagnosis.

PubMed

Pereda, Arrate; Garin, Intza; Perez de Nanclares, Guiomar

2018-03-02

Pseudohypoparathyroidism (PHP) is a rare disease whose phenotypic features are rather difficult to identify in some cases. Thus, although these patients may present with the Albright's hereditary osteodystrophy (AHO) phenotype, which is characterized by small stature, obesity with a rounded face, subcutaneous ossifications, mental retardation and brachydactyly, its manifestations are somewhat variable. Indeed, some of them present with a complete phenotype, whereas others show only subtle manifestations. In addition, the features of the AHO phenotype are not specific to it and a similar phenotype is also commonly observed in other syndromes. Brachydactyly type E (BDE) is the most specific and objective feature of the AHO phenotype, and several genes have been associated with syndromic BDE in the past few years. Moreover, these syndromes have a skeletal and endocrinological phenotype that overlaps with AHO/PHP. In light of the above, we have developed an algorithm to aid in genetic testing of patients with clinical features of AHO but with no causative molecular defect at the GNAS locus. Starting with the feature of brachydactyly, this algorithm allows the differential diagnosis to be broadened and, with the addition of other clinical features, can guide genetic testing. We reviewed our series of patients (n = 23) with a clinical diagnosis of AHO and with brachydactyly type E or similar pattern, who were negative for GNAS anomalies, and classify them according to the diagnosis algorithm to finally propose and analyse the most probable gene(s) in each case. A review of the clinical data for our series of patients, and subsequent analysis of the candidate gene(s), allowed detection of the underlying molecular defect in 12 out of 23 patients: five patients harboured a mutation in PRKAR1A, one in PDE4D, four in TRPS1 and two in PTHLH. This study confirmed that the screening of other genes implicated in syndromes with BDE and AHO or a similar phenotype is very helpful for establishing a correct genetic diagnosis for those patients who have been misdiagnosed with "AHO-like phenotype" with an unknown genetic cause, and also for better describing the characteristic and differential features of these less common syndromes.

Clinical aspects of the fragile X syndrome.

PubMed

Brown, W Ted

2012-01-01

Fragile X syndrome patients express a wide array of cognitive and other gender-specific phenotypic features. These manifestations result not only from molecular mechanisms that are altered as a result of the expansion of a CGG-repeat region in the FMR1 promoter, but also genetic factors such as founder effects and mosaicism. In this chapter, I will summarize the many and varied features of fragile X syndrome as they present themselves in a clinical setting and describe the procedures that are used to diagnose patients. Finally, I will briefly touch on recent developments that will affect patient screening in the future.

Using classification models for the generation of disease-specific medications from biomedical literature and clinical data repository.

PubMed

Wang, Liqin; Haug, Peter J; Del Fiol, Guilherme

2017-05-01

Mining disease-specific associations from existing knowledge resources can be useful for building disease-specific ontologies and supporting knowledge-based applications. Many association mining techniques have been exploited. However, the challenge remains when those extracted associations contained much noise. It is unreliable to determine the relevance of the association by simply setting up arbitrary cut-off points on multiple scores of relevance; and it would be expensive to ask human experts to manually review a large number of associations. We propose that machine-learning-based classification can be used to separate the signal from the noise, and to provide a feasible approach to create and maintain disease-specific vocabularies. We initially focused on disease-medication associations for the purpose of simplicity. For a disease of interest, we extracted potentially treatment-related drug concepts from biomedical literature citations and from a local clinical data repository. Each concept was associated with multiple measures of relevance (i.e., features) such as frequency of occurrence. For the machine purpose of learning, we formed nine datasets for three diseases with each disease having two single-source datasets and one from the combination of previous two datasets. All the datasets were labeled using existing reference standards. Thereafter, we conducted two experiments: (1) to test if adding features from the clinical data repository would improve the performance of classification achieved using features from the biomedical literature only, and (2) to determine if classifier(s) trained with known medication-disease data sets would be generalizable to new disease(s). Simple logistic regression and LogitBoost were two classifiers identified as the preferred models separately for the biomedical-literature datasets and combined datasets. The performance of the classification using combined features provided significant improvement beyond that using biomedical-literature features alone (p-value<0.001). The performance of the classifier built from known diseases to predict associated concepts for new diseases showed no significant difference from the performance of the classifier built and tested using the new disease's dataset. It is feasible to use classification approaches to automatically predict the relevance of a concept to a disease of interest. It is useful to combine features from disparate sources for the task of classification. Classifiers built from known diseases were generalizable to new diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

Correlation between Clinical Features and Magnetic Resonance Imaging Findings in Lumbar Disc Prolapse.

PubMed

Thapa, S S; Lakhey, R B; Sharma, P; Pokhrel, R K

2016-05-01

Magnetic resonance imaging is routinely done for diagnosis of lumbar disc prolapse. Many abnormalities of disc are observed even in asymptomatic patient.This study was conducted tocorrelate these abnormalities observed on Magnetic resonance imaging and clinical features of lumbar disc prolapse. A This prospective analytical study includes 57 cases of lumbar disc prolapse presenting to Department of Orthopedics, Tribhuvan University Teaching Hospital from March 2011 to August 2012. All patientshad Magnetic resonance imaging of lumbar spine and the findings regarding type, level and position of lumbar disc prolapse, any neural canal or foraminal compromise was recorded. These imaging findings were then correlated with clinical signs and symptoms. Chi-square test was used to find out p-value for correlation between clinical features and Magnetic resonance imaging findings using SPSS 17.0. This study included 57 patients, with mean age 36.8 years. Of them 41(71.9%) patients had radicular leg pain along specific dermatome. Magnetic resonance imaging showed 104 lumbar disc prolapselevel. Disc prolapse at L4-L5 and L5-S1 level constituted 85.5%.Magnetic resonance imaging findings of neural foramina compromise and nerve root compression were fairly correlated withclinical findings of radicular pain and neurological deficit. Clinical features and Magnetic resonance imaging findings of lumbar discprolasehad faircorrelation, but all imaging abnormalities do not have a clinical significance.

Polycystic ovary syndrome: perceptions and attitudes of women and primary health care physicians on features of PCOS and renaming the syndrome.

PubMed

Teede, Helena; Gibson-Helm, Melanie; Norman, Robert J; Boyle, Jacqueline

2014-01-01

Polycystic ovary syndrome (PCOS) is an under-recognized, common, and complex endocrinopathy. The name PCOS is a misnomer, and there have been calls for a change to reflect the broader clinical syndrome. The aim of the study was to determine perceptions held by women and primary health care physicians around key clinical features of PCOS and attitudes toward current and alternative names for the syndrome. We conducted a cross-sectional study utilizing a devised questionnaire. Participants were recruited throughout Australia via professional associations, women's health organizations, and a PCOS support group. Fifty-seven women with PCOS and 105 primary care physicians participated in the study. Perceptions of key clinical PCOS features and attitudes toward current and alternative syndrome names were investigated. Irregular periods were identified as a key clinical feature of PCOS by 86% of the women with PCOS and 90% of the primary care physicians. In both groups, 60% also identified hormone imbalance as a key feature. Among women with PCOS, 47% incorrectly identified ovarian cysts as key, 48% felt the current name is confusing, and 51% supported a change. Most primary care physicians agreed that the name is confusing (74%) and needs changing (81%); however, opinions on specific alternative names were divided. The name "polycystic ovary syndrome" is perceived as confusing, and there is general support for a change to reflect the broader clinical syndrome. Engagement of primary health care physicians and consumers is strongly recommended to ensure that an alternative name enhances understanding and recognition of the syndrome and its complex features.

Stem cell biobanks.

PubMed

Bardelli, Silvana

2010-04-01

Stem cells contribute to innate healing and harbor a promising role for regenerative medicine. Stem cell banking through long-term storage of different stem cell platforms represents a fundamental source to preserve original features of stem cells for patient-specific clinical applications. Stem cell research and clinical translation constitute fundamental and indivisible modules catalyzed through biobanking activity, generating a return of investment.

What is misophonia and how can we treat it?

PubMed

Cavanna, Andrea E

2014-04-01

Selective sound sensitivity syndrome or misophonia is a chronic condition characterized by unpleasant emotional experiences and autonomic arousal in response to specific sounds. Over the last few years there have been a few reports detailing the clinical features associated with this condition. These focused reports raise interesting questions about the nosological status of this potentially disabling clinical entity.

Freezing of Gait Detection in Parkinson's Disease: A Subject-Independent Detector Using Anomaly Scores.

PubMed

Pham, Thuy T; Moore, Steven T; Lewis, Simon John Geoffrey; Nguyen, Diep N; Dutkiewicz, Eryk; Fuglevand, Andrew J; McEwan, Alistair L; Leong, Philip H W

2017-11-01

Freezing of gait (FoG) is common in Parkinsonian gait and strongly relates to falls. Current clinical FoG assessments are patients' self-report diaries and experts' manual video analysis. Both are subjective and yield moderate reliability. Existing detection algorithms have been predominantly designed in subject-dependent settings. In this paper, we aim to develop an automated FoG detector for subject independent. After extracting highly relevant features, we apply anomaly detection techniques to detect FoG events. Specifically, feature selection is performed using correlation and clusterability metrics. From a list of 244 feature candidates, 36 candidates were selected using saliency and robustness criteria. We develop an anomaly score detector with adaptive thresholding to identify FoG events. Then, using accuracy metrics, we reduce the feature list to seven candidates. Our novel multichannel freezing index was the most selective across all window sizes, achieving sensitivity (specificity) of (). On the other hand, freezing index from the vertical axis was the best choice for a single input, achieving sensitivity (specificity) of () for ankle and () for back sensors. Our subject-independent method is not only significantly more accurate than those previously reported, but also uses a much smaller window (e.g., versus ) and/or lower tolerance (e.g., versus ).Freezing of gait (FoG) is common in Parkinsonian gait and strongly relates to falls. Current clinical FoG assessments are patients' self-report diaries and experts' manual video analysis. Both are subjective and yield moderate reliability. Existing detection algorithms have been predominantly designed in subject-dependent settings. In this paper, we aim to develop an automated FoG detector for subject independent. After extracting highly relevant features, we apply anomaly detection techniques to detect FoG events. Specifically, feature selection is performed using correlation and clusterability metrics. From a list of 244 feature candidates, 36 candidates were selected using saliency and robustness criteria. We develop an anomaly score detector with adaptive thresholding to identify FoG events. Then, using accuracy metrics, we reduce the feature list to seven candidates. Our novel multichannel freezing index was the most selective across all window sizes, achieving sensitivity (specificity) of (). On the other hand, freezing index from the vertical axis was the best choice for a single input, achieving sensitivity (specificity) of () for ankle and () for back sensors. Our subject-independent method is not only significantly more accurate than those previously reported, but also uses a much smaller window (e.g., versus ) and/or lower tolerance (e.g., versus ).

Competitive Advantage of PET/MRI

PubMed Central

Jadvar, Hossein; Colletti, Patrick M.

2013-01-01

Multimodality imaging has made great strides in the imaging evaluation of patients with a variety of diseases. Positron emission tomography/computed tomography (PET/CT) is now established as the imaging modality of choice in many clinical conditions, particularly in oncology. While the initial development of combined PET/magnetic resonance imaging (PET/MRI) was in the preclinical arena, hybrid PET/MR scanners are now available for clinical use. PET/MRI combines the unique features of MRI including excellent soft tissue contrast, diffusion-weighted imaging, dynamic contrast-enhanced imaging, fMRI and other specialized sequences as well as MR spectroscopy with the quantitative physiologic information that is provided by PET. Most evidence for the potential clinical utility of PET/MRI is based on studies performed with side-by-side comparison or software-fused MRI and PET images. Data on distinctive utility of hybrid PET/MRI are rapidly emerging. There are potential competitive advantages of PET/MRI over PET/CT. In general, PET/MRI may be preferred over PET/CT where the unique features of MRI provide more robust imaging evaluation in certain clinical settings. The exact role and potential utility of simultaneous data acquisition in specific research and clinical settings will need to be defined. It may be that simultaneous PET/MRI will be best suited for clinical situations that are disease-specific, organ-specific, related to diseases of the children or in those patients undergoing repeated imaging for whom cumulative radiation dose must be kept as low as reasonably achievable. PET/MRI also offers interesting opportunities for use of dual modality probes. Upon clear definition of clinical utility, other important and practical issues related to business operational model, clinical workflow and reimbursement will also be resolved. PMID:23791129

Competitive advantage of PET/MRI.

PubMed

Jadvar, Hossein; Colletti, Patrick M

2014-01-01

Multimodality imaging has made great strides in the imaging evaluation of patients with a variety of diseases. Positron emission tomography/computed tomography (PET/CT) is now established as the imaging modality of choice in many clinical conditions, particularly in oncology. While the initial development of combined PET/magnetic resonance imaging (PET/MRI) was in the preclinical arena, hybrid PET/MR scanners are now available for clinical use. PET/MRI combines the unique features of MRI including excellent soft tissue contrast, diffusion-weighted imaging, dynamic contrast-enhanced imaging, fMRI and other specialized sequences as well as MR spectroscopy with the quantitative physiologic information that is provided by PET. Most evidence for the potential clinical utility of PET/MRI is based on studies performed with side-by-side comparison or software-fused MRI and PET images. Data on distinctive utility of hybrid PET/MRI are rapidly emerging. There are potential competitive advantages of PET/MRI over PET/CT. In general, PET/MRI may be preferred over PET/CT where the unique features of MRI provide more robust imaging evaluation in certain clinical settings. The exact role and potential utility of simultaneous data acquisition in specific research and clinical settings will need to be defined. It may be that simultaneous PET/MRI will be best suited for clinical situations that are disease-specific, organ-specific, related to diseases of the children or in those patients undergoing repeated imaging for whom cumulative radiation dose must be kept as low as reasonably achievable. PET/MRI also offers interesting opportunities for use of dual modality probes. Upon clear definition of clinical utility, other important and practical issues related to business operational model, clinical workflow and reimbursement will also be resolved. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Pathological Gleason prediction through gland ring morphometry in immunofluorescent prostate cancer images

NASA Astrophysics Data System (ADS)

Scott, Richard; Khan, Faisal M.; Zeineh, Jack; Donovan, Michael; Fernandez, Gerardo

2016-03-01

The Gleason score is the most common architectural and morphological assessment of prostate cancer severity and prognosis. There have been numerous quantitative techniques developed to approximate and duplicate the Gleason scoring system. Most of these approaches have been developed in standard H and E brightfield microscopy. Immunofluorescence (IF) image analysis of tissue pathology has recently been proven to be extremely valuable and robust in developing prognostic assessments of disease, particularly in prostate cancer. There have been significant advances in the literature in quantitative biomarker expression as well as characterization of glandular architectures in discrete gland rings. In this work we leverage a new method of segmenting gland rings in IF images for predicting the pathological Gleason; both the clinical and the image specific grade, which may not necessarily be the same. We combine these measures with nuclear specific characteristics as assessed by the MST algorithm. Our individual features correlate well univariately with the Gleason grades, and in a multivariate setting have an accuracy of 85% in predicting the Gleason grade. Additionally, these features correlate strongly with clinical progression outcomes (CI of 0.89), significantly outperforming the clinical Gleason grades (CI of 0.78). This work presents the first assessment of morphological gland unit features from IF images for predicting the Gleason grade.

Review of Quantitative Ultrasound: Envelope Statistics and Backscatter Coefficient Imaging and Contributions to Diagnostic Ultrasound.

PubMed

Oelze, Michael L; Mamou, Jonathan

2016-02-01

Conventional medical imaging technologies, including ultrasound, have continued to improve over the years. For example, in oncology, medical imaging is characterized by high sensitivity, i.e., the ability to detect anomalous tissue features, but the ability to classify these tissue features from images often lacks specificity. As a result, a large number of biopsies of tissues with suspicious image findings are performed each year with a vast majority of these biopsies resulting in a negative finding. To improve specificity of cancer imaging, quantitative imaging techniques can play an important role. Conventional ultrasound B-mode imaging is mainly qualitative in nature. However, quantitative ultrasound (QUS) imaging can provide specific numbers related to tissue features that can increase the specificity of image findings leading to improvements in diagnostic ultrasound. QUS imaging can encompass a wide variety of techniques including spectral-based parameterization, elastography, shear wave imaging, flow estimation, and envelope statistics. Currently, spectral-based parameterization and envelope statistics are not available on most conventional clinical ultrasound machines. However, in recent years, QUS techniques involving spectral-based parameterization and envelope statistics have demonstrated success in many applications, providing additional diagnostic capabilities. Spectral-based techniques include the estimation of the backscatter coefficient (BSC), estimation of attenuation, and estimation of scatterer properties such as the correlation length associated with an effective scatterer diameter (ESD) and the effective acoustic concentration (EAC) of scatterers. Envelope statistics include the estimation of the number density of scatterers and quantification of coherent to incoherent signals produced from the tissue. Challenges for clinical application include correctly accounting for attenuation effects and transmission losses and implementation of QUS on clinical devices. Successful clinical and preclinical applications demonstrating the ability of QUS to improve medical diagnostics include characterization of the myocardium during the cardiac cycle, cancer detection, classification of solid tumors and lymph nodes, detection and quantification of fatty liver disease, and monitoring and assessment of therapy.

Computational neuroscience approach to biomarkers and treatments for mental disorders.

PubMed

Yahata, Noriaki; Kasai, Kiyoto; Kawato, Mitsuo

2017-04-01

Psychiatry research has long experienced a stagnation stemming from a lack of understanding of the neurobiological underpinnings of phenomenologically defined mental disorders. Recently, the application of computational neuroscience to psychiatry research has shown great promise in establishing a link between phenomenological and pathophysiological aspects of mental disorders, thereby recasting current nosology in more biologically meaningful dimensions. In this review, we highlight recent investigations into computational neuroscience that have undertaken either theory- or data-driven approaches to quantitatively delineate the mechanisms of mental disorders. The theory-driven approach, including reinforcement learning models, plays an integrative role in this process by enabling correspondence between behavior and disorder-specific alterations at multiple levels of brain organization, ranging from molecules to cells to circuits. Previous studies have explicated a plethora of defining symptoms of mental disorders, including anhedonia, inattention, and poor executive function. The data-driven approach, on the other hand, is an emerging field in computational neuroscience seeking to identify disorder-specific features among high-dimensional big data. Remarkably, various machine-learning techniques have been applied to neuroimaging data, and the extracted disorder-specific features have been used for automatic case-control classification. For many disorders, the reported accuracies have reached 90% or more. However, we note that rigorous tests on independent cohorts are critically required to translate this research into clinical applications. Finally, we discuss the utility of the disorder-specific features found by the data-driven approach to psychiatric therapies, including neurofeedback. Such developments will allow simultaneous diagnosis and treatment of mental disorders using neuroimaging, thereby establishing 'theranostics' for the first time in clinical psychiatry. © 2016 The Authors. Psychiatry and Clinical Neurosciences © 2016 Japanese Society of Psychiatry and Neurology.

Single neuropsychological test scores associated with rate of cognitive decline in early Alzheimer disease.

PubMed

Parikh, Mili; Hynan, Linda S; Weiner, Myron F; Lacritz, Laura; Ringe, Wendy; Cullum, C Munro

2014-01-01

Alzheimer disease (AD) characteristically begins with episodic memory impairment followed by other cognitive deficits; however, the course of illness varies, with substantial differences in the rate of cognitive decline. For research and clinical purposes it would be useful to distinguish between persons who will progress slowly from persons who will progress at an average or faster rate. Our objective was to use neurocognitive performance features and disease-specific and health information to determine a predictive model for the rate of cognitive decline in participants with mild AD. We reviewed the records of a series of 96 consecutive participants with mild AD from 1995 to 2011 who had been administered selected neurocognitive tests and clinical measures. Based on Clinical Dementia Rating (CDR) of functional and cognitive decline over 2 years, participants were classified as Faster (n = 45) or Slower (n = 51) Progressors. Stepwise logistic regression analyses using neurocognitive performance features, disease-specific, health, and demographic variables were performed. Neuropsychological scores that distinguished Faster from Slower Progressors included Trail Making Test - A, Digit Symbol, and California Verbal Learning Test (CVLT) Total Learned and Primacy Recall. No disease-specific, health, or demographic variable predicted rate of progression; however, history of heart disease showed a trend. Among the neuropsychological variables, Trail Making Test - A best distinguished Faster from Slower Progressors, with an overall accuracy of 68%. In an omnibus model including neuropsychological, disease-specific, health, and demographic variables, only Trail Making Test - A distinguished between groups. Several neuropsychological performance features were associated with the rate of cognitive decline in mild AD, with baseline Trail Making Test - A performance best separating those who declined at an average or faster rate from those who showed slower progression.

Spondyloenchondrodysplasia: a rare cause of short stature.

PubMed

Yeşiltepe-Mutlu, Gül; Ozsu, Elif; Cizmecioğlu, Filiz Mine; Alanay, Yasemin; Hatun, Sükrü

2011-01-01

Skeletal dysplasias (osteochondrodysplasias) are a group of diseases that must be included in the differential diagnosis of disproportionate short stature. History, clinical and radiologic findings and consanguinity are important features to be considered when a specific diagnosis is investigated. Spondyloenchondrodysplasia is a very rare skeletal dysplasia characterized with enchondromas in the long bones and platyspondyly. Manifestation of the disorder may include neurological involvement (spasticity, intracranial calcifications and mental retardation) and immune dysfunction. Herein, we report a 12-year-old boy who admitted to our clinic with short stature, who was born to consanguineous parents. He presented clinical (significant widening of wrists, ankles and knees) and radiologic (enchondromatous lesions in the metaphysis of long bones) features of spondyloenchondrodysplasia but did not yet have neurologic or immunologic involvement.

Long-term outcomes of adults with features of VACTERL association

PubMed Central

Raam, Manu S.; Pineda-Alvarez, Daniel E.; Hadley, Donald W.; Solomon, Benjamin D.

2010-01-01

VACTERL association involves the presence of specific congenital, multi-organ malformations that tend to co-occur. Clinical and research efforts typically center on pediatric patients, and there is a scarcity of information in the literature regarding VACTERL-related issues and outcomes in adulthood. We describe here 11 adults with features of VACTERL association ascertained through our research study on the condition. In our cohort of adult patients, approximately 25% of medically significant malformations that are component features of VACTERL association, including 40% of vertebral, 50% of cardiac, and 50% of renal anomalies, were not identified during childhood. Additionally, medical sequelae of many of the primary malformations identified in infancy or early childhood persist or are first reported in adulthood. These sequelae can involve challenging medical and surgical management in adulthood. As most adults with VACTERL association are not specifically followed for VACTERL-related issues, a more uniform diagnostic work-up and a low threshold for investigation of medical sequelae of the primary disorder may enhance the quality of clinical management in these patients. PMID:20888933

Unravelling the myotonic dystrophy type 1 clinical spectrum: A systematic registry-based study with implications for disease classification.

PubMed

De Antonio, M; Dogan, C; Hamroun, D; Mati, M; Zerrouki, S; Eymard, B; Katsahian, S; Bassez, G

2016-10-01

The broad clinical spectrum of myotonic dystrophy type 1 (DM1) creates particular challenges for both medical care and design of clinical trials. Clinical onset spans a continuum from birth to late adulthood, with symptoms that are highly variable in both severity and nature of the affected organ systems. In the literature, this complex phenotype is divided into three grades (mild, classic, and severe) and four or five main clinical categories (congenital, infantile/juvenile, adult-onset and late-onset forms), according to symptom severity and age of onset, respectively. However, these classifications are still under discussion with no consensus thus far. While some specific clinical features have been primarily reported in some forms of the disease, there are no clear distinctions. As a consequence, no modifications in the management of healthcare or the design of clinical studies have been proposed based on the clinical form of DM1. The present study has used the DM-Scope registry to assess, in a large cohort of DM1 patients, the robustness of a classification divided into five clinical forms. Our main aim was to describe the disease spectrum and investigate features of each clinical form. The five subtypes were compared by distribution of CTG expansion size, and the occurrence and onset of the main symptoms of DM1. Analyses validated the relevance of a five-grade model for DM1 classification. Patients were classified as: congenital (n=93, 4.5%); infantile (n=303, 14.8%); juvenile (n=628, 30.7%); adult (n=694, 34.0%); and late-onset (n=326, 15.9%). Our data show that the assumption of a continuum from congenital to the late-onset form is valid, and also highlights disease features specific to individual clinical forms of DM1 in terms of symptom occurrence and chronology throughout the disease course. These results support the use of the five-grade model for disease classification, and the distinct clinical profiles suggest that age of onset and clinical form may be key criteria in the design of clinical trials when considering DM1 health management and research. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

The clinical and cultural factors in classifying low back pain patients within Greece: a qualitative exploration of Greek health professionals.

PubMed

Billis, Evdokia V; McCarthy, Christopher J; Stathopoulos, Ioannis; Kapreli, Eleni; Pantzou, Paulina; Oldham, Jacqueline A

2007-06-01

Identifying homogenous subgroups of low back pain (LBP) patients is considered a priority in musculoskeletal rehabilitation and is believed to enhance clinical outcomes. In order to achieve this, the specific features of each subgroup need to be identified. The aim of this study was to develop a list of clinical and cultural features that are included in the assessment of LBP patients in Greece, among health professionals. This 'list' will be, utilized in a clinical study for developing LBP subgroups. Three focus groups were conducted, each one comprising health professionals with homogenous characteristics and all coordinated by a single moderator. There were: 11 physiotherapists (PTs) with clinical experience in LBP patients, seven PTs specialized in LBP management, and five doctors with a particular spinal interest. The focus of discussions was to develop a list of clinical and cultural features that were important in the examination of LBP. Content analysis was performed by two researchers. Clinicians and postgraduates developed five categories within the History (Present Symptoms, History of Symptoms, Function, Psychosocial, Medical History) and six categories within the Physical Examination (Observation, Neurological Examination, Active and Passive Movements, Muscle Features and Palpation). The doctors identified four categories in History (Symptomatology, Function, Psychosocial, Medical History) and an additional in Physical Examination (Special Tests). All groups identified three cultural categories; Attitudes of Health Professionals, Patients' Attitudes and Health System influences. An extensive Greek 'list' of clinical and cultural features was developed from the groups' analysis. Although similarities existed in most categories, there were several differences across the three focus groups which will be discussed.

Is Early-onset in Major Depression a Predictor of Specific Clinical Features with More Impaired Social Function?

PubMed Central

Liu, Yan-Hong; Chen, Lin; Su, Yun-Ai; Fang, Yi-Ru; Srisurapanont, Manit; Hong, Jin Pyo; Hatim, Ahmad; Chua, Hong Choon; Bautista, Dianne; Si, Tian-Mei

2015-01-01

Background: Early-onset major depressive disorder (MDD) (EOD) is often particularly malignant due to its special clinical features, accompanying impaired social function, protracted recovery time, and frequent recurrence. This study aimed to observe the effects of age onset on clinical characteristics and social function in MDD patients in Asia. Methods: In total, 547 out-patients aged 18–65 years who were from 13 study sites in five Asian countries were included. These patients had MDD diagnose according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria. Clinical features and social function were assessed using Symptom Checklist-90-revised (SCL-90-R) and Sheehan Disability Scale (SDS). Quality of life was assessed by a 36-item Short-form Health Survey (SF-36). Analyses were performed using a continuous or dichotomous (cut-off: 30 years) age-of-onset indicator. Results: Early-onset MDD (EOD, <30 years) was associated with longer illness (P = 0.003), unmarried status (P < 0.001), higher neuroticism (P ≤ 0.002) based on the SCL-90-R, and more limited social function and mental health (P = 0.006, P = 0.007) based on the SF-36 and SDS. The impairment of social function and clinical severity were more prominent at in-patients with younger onset ages. Special clinical features and more impaired social function and quality of life were associated with EOD, as in western studies. Conclusions: EOD often follows higher levels of neuroticism. Age of onset of MDD may be a predictor of clinical features and impaired social function, allowing earlier diagnosis and treatment. PMID:25758278

Identification of Location Specific Feature Points in a Cardiac Cycle Using a Novel Seismocardiogram Spectrum System.

PubMed

Lin, Wen-Yen; Chou, Wen-Cheng; Chang, Po-Cheng; Chou, Chung-Chuan; Wen, Ming-Shien; Ho, Ming-Yun; Lee, Wen-Chen; Hsieh, Ming-Jer; Lin, Chung-Chih; Tsai, Tsai-Hsuan; Lee, Ming-Yih

2018-03-01

Seismocardiogram (SCG) or mechanocardiography is a noninvasive cardiac diagnostic method; however, previous studies used only a single sensor to detect cardiac mechanical activities that will not be able to identify location-specific feature points in a cardiac cycle corresponding to the four valvular auscultation locations. In this study, a multichannel SCG spectrum measurement system was proposed and examined for cardiac activity monitoring to overcome problems like, position dependency, time delay, and signal attenuation, occurring in traditional single-channel SCG systems. ECG and multichannel SCG signals were simultaneously recorded in 25 healthy subjects. Cardiac echocardiography was conducted at the same time. SCG traces were analyzed and compared with echocardiographic images for feature point identification. Fifteen feature points were identified in the corresponding SCG traces. Among them, six feature points, including left ventricular lateral wall contraction peak velocity, septal wall contraction peak velocity, transaortic peak flow, transpulmonary peak flow, transmitral ventricular relaxation flow, and transmitral atrial contraction flow were identified. These new feature points were not observed in previous studies because the single-channel SCG could not detect the location-specific signals from other locations due to time delay and signal attenuation. As the results, the multichannel SCG spectrum measurement system can record the corresponding cardiac mechanical activities with location-specific SCG signals and six new feature points were identified with the system. This new modality may help clinical diagnoses of valvular heart diseases and heart failure in the future.

Clinical features for diagnosis of pneumonia in children younger than 5 years: a systematic review and meta-analysis.

PubMed

Rambaud-Althaus, Clotilde; Althaus, Fabrice; Genton, Blaise; D'Acremont, Valérie

2015-04-01

Pneumonia is the biggest cause of deaths in young children in developing countries, but early diagnosis and intervention can effectively reduce mortality. We aimed to assess the diagnostic value of clinical signs and symptoms to identify radiological pneumonia in children younger than 5 years and to review the accuracy of WHO criteria for diagnosis of clinical pneumonia. We searched Medline (PubMed), Embase (Ovid), the Cochrane Database of Systematic Reviews, and reference lists of relevant studies, without date restrictions, to identify articles assessing clinical predictors of radiological pneumonia in children. Selection was based on: design (diagnostic accuracy studies), target disease (pneumonia), participants (children aged <5 years), setting (ambulatory or hospital care), index test (clinical features), and reference standard (chest radiography). Quality assessment was based on the 2011 Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) criteria. For each index test, we calculated sensitivity and specificity and, when the tests were assessed in four or more studies, calculated pooled estimates with use of bivariate model and hierarchical summary receiver operation characteristics plots for meta-analysis. We included 18 articles in our analysis. WHO-approved signs age-related fast breathing (six studies; pooled sensitivity 0·62, 95% CI 0·26-0·89; specificity 0·59, 0·29-0·84) and lower chest wall indrawing (four studies; 0·48, 0·16-0·82; 0·72, 0·47-0·89) showed poor diagnostic performance in the meta-analysis. Features with the highest pooled positive likelihood ratios were respiratory rate higher than 50 breaths per min (1·90, 1·45-2·48), grunting (1·78, 1·10-2·88), chest indrawing (1·76, 0·86-3·58), and nasal flaring (1·75, 1·20-2·56). Features with the lowest pooled negative likelihood ratio were cough (0·30, 0·09-0·96), history of fever (0·53, 0·41-0·69), and respiratory rate higher than 40 breaths per min (0·43, 0·23-0·83). Not one clinical feature was sufficient to diagnose pneumonia definitively. Combination of clinical features in a decision tree might improve diagnostic performance, but the addition of new point-of-care tests for diagnosis of bacterial pneumonia would help to attain an acceptable level of accuracy. Swiss National Science Foundation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Hallucinations: A Systematic Review of Points of Similarity and Difference Across Diagnostic Classes

PubMed Central

Waters, Flavie; Fernyhough, Charles

2017-01-01

Hallucinations constitute one of the 5 symptom domains of psychotic disorders in DSM-5, suggesting diagnostic significance for that group of disorders. Although specific featural properties of hallucinations (negative voices, talking in the third person, and location in external space) are no longer highlighted in DSM, there is likely a residual assumption that hallucinations in schizophrenia can be identified based on these candidate features. We investigated whether certain featural properties of hallucinations are specifically indicative of schizophrenia by conducting a systematic review of studies showing direct comparisons of the featural and clinical characteristics of (auditory and visual) hallucinations among 2 or more population groups (one of which included schizophrenia). A total of 43 articles were reviewed, which included hallucinations in 4 major groups (nonclinical groups, drug- and alcohol-related conditions, medical and neurological conditions, and psychiatric disorders). The results showed that no single hallucination feature or characteristic uniquely indicated a diagnosis of schizophrenia, with the sole exception of an age of onset in late adolescence. Among the 21 features of hallucinations in schizophrenia considered here, 95% were shared with other psychiatric disorders, 85% with medical/neurological conditions, 66% with drugs and alcohol conditions, and 52% with the nonclinical groups. Additional differences rendered the nonclinical groups somewhat distinctive from clinical disorders. Overall, when considering hallucinations, it is inadvisable to give weight to the presence of any featural properties alone in making a schizophrenia diagnosis. It is more important to focus instead on the co-occurrence of other symptoms and the value of hallucinations as an indicator of vulnerability. PMID:27872259

Clinical exam of the shoulder.

PubMed

Clarnette, R G; Miniaci, A

1998-04-01

This paper outlines the important features of the clinical assessment of the shoulder in a systematic and thorough manner. We highlight the key symptoms, particularly pain and instability, and describe how they may be associated with the various different pathologies. The physical examination is detailed in order of inspection, palpation, and motion, and then considerable emphasis is given to specific shoulder tests looking for evidence of rotator cuff weakness, impingement, biceps pathology, and instability. A number of specific tests of instability are outlined including an examination technique for posterior instability that has not previously been described.

3D brain tumor segmentation in multimodal MR images based on learning population- and patient-specific feature sets.

PubMed

Jiang, Jun; Wu, Yao; Huang, Meiyan; Yang, Wei; Chen, Wufan; Feng, Qianjin

2013-01-01

Brain tumor segmentation is a clinical requirement for brain tumor diagnosis and radiotherapy planning. Automating this process is a challenging task due to the high diversity in appearance of tumor tissue among different patients and the ambiguous boundaries of lesions. In this paper, we propose a method to construct a graph by learning the population- and patient-specific feature sets of multimodal magnetic resonance (MR) images and by utilizing the graph-cut to achieve a final segmentation. The probabilities of each pixel that belongs to the foreground (tumor) and the background are estimated by global and custom classifiers that are trained through learning population- and patient-specific feature sets, respectively. The proposed method is evaluated using 23 glioma image sequences, and the segmentation results are compared with other approaches. The encouraging evaluation results obtained, i.e., DSC (84.5%), Jaccard (74.1%), sensitivity (87.2%), and specificity (83.1%), show that the proposed method can effectively make use of both population- and patient-specific information. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

[Mixed depressions: clinical and neurophysiological biomarkers].

PubMed

Micoulaud Franchi, J-A; Geoffroy, P-A; Vion-Dury, J; Balzani, C; Belzeaux, R; Maurel, M; Cermolacce, M; Fakra, E; Azorin, J-M

2013-12-01

Epidemiological studies of major depressive episodes (MDE) highlighted the frequent association of symptoms or signs of mania or hypomania with depressive syndrome. Beyond the strict definition of DSM-IV, epidemiological recognition of a subset of MDE characterized by the presence of symptoms or signs of the opposite polarity is clinically important because it is associated with pejorative prognosis and therapeutic response compared to the subgroup of "typical MDE". The development of DSM-5 took into account the epidemiological data. DSM-5 opted for a more dimensional perspective in implementing the concept of "mixed features" from an "episode" to a "specification" of mood disorder. As outlined in the DSM-5: "Mixed features associated with a major depressive episode have been found to be a significant risk factor for the development of bipolar I and II disorder. As a result, it is clinically useful to note the presence of this specifier for treatment planning and monitoring of response to therapeutic". However, the mixed features are sometimes difficult to identify, and neurophysiological biomarkers would be useful to make a more specific diagnosis. Two neurophysiological models make it possible to better understand MDE with mixed features : i) the emotional regulation model that highlights a tendency to hyper-reactive and unstable emotion response, and ii) the vigilance regulation model that highlights, through EEG recording, a tendency to unstable vigilance. Further research is required to better understand relationships between these two models. These models provide the opportunity of a neurophysiological framework to better understand the mixed features associated with MDE and to identify potential neurophysiological biomarkers to guide therapeutic strategies. Copyright © 2013 L’Encéphale. Published by Elsevier Masson SAS.. All rights reserved.

Genetic Factors in Systemic Lupus Erythematosus: Contribution to Disease Phenotype

PubMed Central

Ceccarelli, Fulvia; Perricone, Carlo; Borgiani, Paola; Ciccacci, Cinzia; Rufini, Sara; Cipriano, Enrica; Alessandri, Cristiano; Spinelli, Francesca Romana; Sili Scavalli, Antonio; Novelli, Giuseppe; Valesini, Guido; Conti, Fabrizio

2015-01-01

Genetic factors exert an important role in determining Systemic Lupus Erythematosus (SLE) susceptibility, interplaying with environmental factors. Several genetic studies in various SLE populations have identified numerous susceptibility loci. From a clinical point of view, SLE is characterized by a great heterogeneity in terms of clinical and laboratory manifestations. As widely demonstrated, specific laboratory features are associated with clinical disease subset, with different severity degree. Similarly, in the last years, an association between specific phenotypes and genetic variants has been identified, allowing the possibility to elucidate different mechanisms and pathways accountable for disease manifestations. However, except for Lupus Nephritis (LN), no studies have been designed to identify the genetic variants associated with the development of different phenotypes. In this review, we will report data currently known about this specific association. PMID:26798662

Articular dysfunction patterns in patients with mechanical low back pain: A clinical algorithm to guide specific mobilization and manipulation techniques.

PubMed

Dewitte, V; Cagnie, B; Barbe, T; Beernaert, A; Vanthillo, B; Danneels, L

2015-06-01

Recent systematic reviews have demonstrated reasonable evidence that lumbar mobilization and manipulation techniques are beneficial. However, knowledge on optimal techniques and doses, and its clinical reasoning is currently lacking. To address this, a clinical algorithm is presented so as to guide therapists in their clinical reasoning to identify patients who are likely to respond to lumbar mobilization and/or manipulation and to direct appropriate technique selection. Key features in subjective and clinical examination suggestive of mechanical nociceptive pain probably arising from articular structures, can categorize patients into distinct articular dysfunction patterns. Based on these patterns, specific mobilization and manipulation techniques are suggested. This clinical algorithm is merely based on empirical clinical expertise and complemented through knowledge exchange between international colleagues. The added value of the proposed articular dysfunction patterns should be considered within a broader perspective. Copyright © 2014 Elsevier Ltd. All rights reserved.

Acquired Auditory Verbal Agnosia and Seizures in Childhood

ERIC Educational Resources Information Center

Cooper, Judith A.; Ferry, Peggy C.

1978-01-01

The paper presents a review of cases of children with acquired aphasia with convulsive disorder and discusses clinical features of three additional children in whom the specific syndrome of auditory verbal agnosia was identified. (Author/CL)

Sotos Syndrome. Clinical Exchange.

ERIC Educational Resources Information Center

Shuey, Elaine M.; Jamison, Kristen

1996-01-01

Sotos syndrome is characterized by high birth length, rapid bone growth, distinctive facial features, and possible verbal and motor delays. It is more common in males than females. Developmental deficits, specific learning problems, and speech/language delays may also occur. (DB)

Elderly patients and inflammatory bowel disease

PubMed Central

Nimmons, Danielle; Limdi, Jimmy K

2016-01-01

The incidence and prevalence of inflammatory bowel disease (IBD) is increasing globally. Coupled with an ageing population, the number of older patients with IBD is set to increase. The clinical features and therapeutic options in young and elderly patients are comparable but there are some significant differences. The wide differential diagnosis of IBD in elderly patients may result in a delay in diagnosis. The relative dearth of data specific to elderly IBD patients often resulting from their exclusion from pivotal clinical trials and the lack of consensus guidelines have made clinical decisions somewhat challenging. In addition, age specific concerns such as co-morbidity; loco-motor and cognitive function, poly-pharmacy and its consequences need to be taken into account. In applying modern treatment paradigms to the elderly, the clinician must consider the potential for more pronounced adverse effects in this vulnerable group and set appropriate boundaries maximising benefit and minimising harm. Meanwhile, clinicians need to make personalised decisions but as evidence based as possible in the holistic, considered and optimal management of IBD in elderly patients. In this review we will cover the clinical features and therapeutic options of IBD in the elderly; as well as addressing common questions and challenges posed by its management. PMID:26855812

Occurrence and clinical features of sensitization to Pityrosporum orbiculare and other allergens in children with atopic dermatitis.

PubMed

Lindgren, L; Wahlgren, C F; Johansson, S G; Wiklund, I; Nordvall, S L

1995-07-01

One hundred and nineteen consecutive cases of children with atopic dermatitis aged 4-16 years (73 girls) from a pediatric dermatology outpatient clinic were included in a study of atopic sensitization. Structured interviews and clinical investigations were performed. IgE antibodies to common inhalant allergens, Pityrosporum orbiculare, Candida albicans, Tricophyton rubrum and Staphylococcus aureus were detected. Specific IgE antibodies frequently occurred to pollens, animal epithelia, C. albicans, house dust mites and moulds, whereas specific IgE antibodies to potential skin allergens were less prevalent. Twenty-six children (21.8%) had IgE antibodies to P. orbiculare, 14 (11.8%) to T. rubrum and 3 (2.5%) to S. aureus. Atopic dermatitis in children with one or several RAST positivities was worse, with a more chronic course, higher total eczema score, more frequent distribution in the head-neck-face regions and more itch compared to the children without serum detectable IgE antibodies. Severe itch disturbing nightly sleep was the only clinical feature that characterised P. orbiculare-positive cases. Allergy to P. orbiculare appears to be of little importance in early childhood atopic dermatitis but is likely to carry a poor prognosis.

[Genetic mutation and clinical features of osteogenesis imperfecta type V].

PubMed

Guan, Shizhen; Bai, Xue; Wang, Yi; Liu, Zhigang; Ren, Xiuzhi; Zhang, Tianke; Ju, Mingyan; Li, Keqiu; Li, Guang

2017-12-10

To explore genetic mutations and clinical features of osteogenesis imperfecta type V. Clinical record of five patients (including one familial case) with osteogenesis imperfecta type V were retrospectively analyzed. Peripheral blood samples of the patients, one family member, as well as healthy controls were collected. Mutation of IFITM5 gene was identified by PCR amplification and Sanger sequencing. A heterozygous mutation (c.-14C>T) in the 5-UTR of the IFITM5 gene was identified in all of the patients and one mother. The clinical findings included frequent fractures and spine and/or extremities deformities, absence of dentinogenesis imperfecta, absence of hearing impairment, and blue sclera in 1 case. Radiographic findings revealed calcification of the interosseous membrane between the radius-ulna in all cases. Hyperplastic callus formation was found in 3 cases. Four had radial-head dislocation. A single heterozygous mutation c.-14C>T was found in the 5-UTR of the IFITM5 gene in 5 patients with osteogensis imperfecta type V. The patients showed specific radiological features including calcification of interosseous membrane, hyperplastic callus formation, and radial-head dislocation.

Confetti-like Sparing

PubMed Central

Fitzpatrick, Richard E.; Goldman, Mitchel P.

2016-01-01

Diagnostic uncertainty when a patient presents with melasma-like Undings can lead to suboptimal treatment and inaccurate prognostic expectations. In this study, the authors present a unique clinical feature of melasma that they term the “Fitzpatrick macule” and test its Utility in establishing diagnostic certainty. The “Fitzpatrick macule” is a confetti-like macule of regularly pigmented skin located within a larger patch of melasma hyperpigmentation. To test its diagnostic Utility, the authors compared clinical photography of known cases of melasma with common mimickers, such as poikiloderma of Civatte and solar lentiginosis, and determined the positivity rate of the Fitzpatrick macule in each scenario. Their results show that 89.1 percent of clinical photographs of melasma were positive for the presence of Fitzpatrick macules compared to 1.1 percent that were negative. In contrast, 37.5 and 56.3 percent of clinical photographs of poikiloderma of Civatte were positive and negative for Fitzpatrick macules, respectively. Solar lentiginosis showed a 5.6 percent positivity and a 77.8 percent negativity for Fitzpatrick macules. The sensitivity and specificity of Fitzpatrick macules for melasma was 99 and 83 percent, respectively. In summary, the authors report a highly sensitive and specific clinical feature of melasma. In cases of diagnostic uncertainty, the presence of Fitzpatrick macules may aid in establishing a diagnosis of melasma. PMID:27047632

Clinical Diagnostics in Human Genetics with Semantic Similarity Searches in Ontologies

PubMed Central

Köhler, Sebastian; Schulz, Marcel H.; Krawitz, Peter; Bauer, Sebastian; Dölken, Sandra; Ott, Claus E.; Mundlos, Christine; Horn, Denise; Mundlos, Stefan; Robinson, Peter N.

2009-01-01

The differential diagnostic process attempts to identify candidate diseases that best explain a set of clinical features. This process can be complicated by the fact that the features can have varying degrees of specificity, as well as by the presence of features unrelated to the disease itself. Depending on the experience of the physician and the availability of laboratory tests, clinical abnormalities may be described in greater or lesser detail. We have adapted semantic similarity metrics to measure phenotypic similarity between queries and hereditary diseases annotated with the use of the Human Phenotype Ontology (HPO) and have developed a statistical model to assign p values to the resulting similarity scores, which can be used to rank the candidate diseases. We show that our approach outperforms simpler term-matching approaches that do not take the semantic interrelationships between terms into account. The advantage of our approach was greater for queries containing phenotypic noise or imprecise clinical descriptions. The semantic network defined by the HPO can be used to refine the differential diagnosis by suggesting clinical features that, if present, best differentiate among the candidate diagnoses. Thus, semantic similarity searches in ontologies represent a useful way of harnessing the semantic structure of human phenotypic abnormalities to help with the differential diagnosis. We have implemented our methods in a freely available web application for the field of human Mendelian disorders. PMID:19800049

Hidden flexion injury of the cervical spine.

PubMed

Webb, J K; Broughton, R B; McSweeney, T; Park, W M

1976-08-01

This paper describes seven patients who developed late vertebral deformity after flexion injuries of the cervical spine. In four the clinical and radiological features were subtle and because the patients walked into an emergency department the severity of the injury was not initially appreciated. Certain specific clinical and radiological features of flexion injury are described and emphasis is placed on the importance of correct management. A radiological tetrad is described which should alert the surgeon to the possibility of damage to the posterior interspinous complex of the cervical spine and so lead to further radiological investigations. Despite the frequency of flexion injuries the alarming complications described in this paper are rare.

Distinct phenotype clusters in childhood inflammatory brain diseases: implications for diagnostic evaluation.

PubMed

Cellucci, Tania; Tyrrell, Pascal N; Twilt, Marinka; Sheikh, Shehla; Benseler, Susanne M

2014-03-01

To identify distinct clusters of children with inflammatory brain diseases based on clinical, laboratory, and imaging features at presentation, to assess which features contribute strongly to the development of clusters, and to compare additional features between the identified clusters. A single-center cohort study was performed with children who had been diagnosed as having an inflammatory brain disease between June 1, 1989 and December 31, 2010. Demographic, clinical, laboratory, neuroimaging, and histologic data at diagnosis were collected. K-means cluster analysis was performed to identify clusters of patients based on their presenting features. Associations between the clusters and patient variables, such as diagnoses, were determined. A total of 147 children (50% female; median age 8.8 years) were identified: 105 with primary central nervous system (CNS) vasculitis, 11 with secondary CNS vasculitis, 8 with neuronal antibody syndromes, 6 with postinfectious syndromes, and 17 with other inflammatory brain diseases. Three distinct clusters were identified. Paresis and speech deficits were the most common presenting features in cluster 1. Children in cluster 2 were likely to present with behavior changes, cognitive dysfunction, and seizures, while those in cluster 3 experienced ataxia, vision abnormalities, and seizures. Lesions seen on T2/fluid-attenuated inversion recovery sequences of magnetic resonance imaging were common in all clusters, but unilateral ischemic lesions were more prominent in cluster 1. The clusters were associated with specific diagnoses and diagnostic test results. Children with inflammatory brain diseases presented with distinct phenotypical patterns that are associated with specific diagnoses. This information may inform the development of a diagnostic classification of childhood inflammatory brain diseases and suggest that specific pathways of diagnostic evaluation are warranted. Copyright © 2014 by the American College of Rheumatology.

The role of magnetic resonance imaging and ultrasound in patients with adnexal masses.

PubMed

Sohaib, S A; Mills, T D; Sahdev, A; Webb, J A W; Vantrappen, P O; Jacobs, I J; Reznek, R H

2005-03-01

To evaluate the accuracy of ultrasonography (US) and magnetic resonance imaging (MRI) in characterizing adnexal masses, and to determine which patients may benefit from MRI. We prospectively studied 72 women (mean age 53 years, range 19 to 86 years) with clinically suspected adnexal masses. A single experienced sonographer performed transabdominal and transvaginal greyscale spectral and colour Doppler examinations. MRI was carried out on a 1.5T system using T1, T2 and fat-suppressed T1-weighted sequences before and after intravenous injection of gadolinium. The adnexal masses were categorized as benign or malignant without knowledge of clinical details, according to the imaging features which were compared with the surgical and pathological findings. For characterizing lesions as malignant, the sensitivity, specificity and accuracy of MRI were 96.6%, 83.7% and 88.9%, respectively, and of US were 100%, 39.5% and 63.9%, respectively. MRI was more specific (p<0.05) than US. Both MRI and US correctly diagnosed 17 (24%) cases with benign and 28 (39%) cases with malignant masses. MRI correctly diagnosed 19 (26%) cases with benign lesion(s), which on US were thought to be malignant. The age, menopausal status and CA-125 levels in these women made benign disease likely, but US features were suggestive of malignancy (large masses and solid-cystic lesions with nodules). MRI is more specific and accurate than US and Doppler assessment for characterizing adnexal masses. Women who clinically have a relatively low risk of malignancy but who have complex sonographic features may benefit from MRI.

Specific features of cytological and colposcopical pattern in pregnant women with benign cervix uteri pathology in anamnesis.

PubMed

Bysaha, Nataliya Yu

2016-01-01

a tendency of increasing incidence of the cervix uteri precancer and cancer in women of reproductive age is noticed recently being related to the growth of number of the sexually-transmitted infections. The cervix uteri pathology incidence in women of fertile age is 20-25%. to study the specific features of the cytological and colposcopical pattern in pregnant patients with benign cervix uteri pathology in the anamnesis and the character of its change post partum. we have examined 195 women during their pregnancy and 3-5 months post partum. All pregnant women, alongside with generally accepted clinical and laboratory examinations, were subjected to the simple and extended colposcopy, cytology of the targeted smears and, according to indications, the histological studies of bioptate. according to the results of the colcoscopical studies and the signs of the cervix uteri pathology found, the patients were divided into several groups. A control group included 49 pregnant women. The clinical and instrumental examination of 146 women with cervix uteri pathology has been carried out both during pregnancy and post partum. the structure of the clinical forms of benign and premalignant changes in the cervix uteri epithelium in pregnant patients has been found. Specific features of the cytological and colposcopical pattern in pregnant patients with benign cervix uteri pathology in anamnesis have been studied. The relationship between the parity of pregnancy, delivery, route of delivery and regress of both benign and premalignant changes in the cervix uteri epithelium 3-5 months post partum has been determined.

Clinical state assessment in bipolar patients by means of HRV features obtained with a sensorized T-shirt.

PubMed

Mariani, Sara; Migliorini, Matteo; Tacchino, Giulia; Gentili, Claudio; Bertschy, Gilles; Werner, Sandra; Bianchi, Anna M

2012-01-01

The aim of this study is to identify parameters extracted from the Heart Rate Variability (HRV) signal that correlate to the clinical state in patients affected by bipolar disorder. 25 ECG and activity recordings from 12 patients were obtained by means of a sensorized T-shirt and the clinical state of the subjects was assessed by a psychiatrist. Features in the time and frequency domain were extracted from each signal. HRV features were also used to automatically compute the sleep profile of each subject by means of an Artificial Neural Network, trained on a control group of healthy subjects. From the hypnograms, sleep-specific parameters were computed. All the parameters were compared with those computed on the control group, in order to highlight significant differences in their values during different stages of the pathology. The analysis was performed by grouping the subjects first on the basis of the depression-mania level and then on the basis of the anxiety level.

Biochemical recurrence after radical prostatectomy: what does it mean?

PubMed Central

Tourinho-Barbosa, Rafael; Srougi, Victor; Nunes-Silva, Igor; Baghdadi, Mohammed; Rembeyo, Gregory; Eiffel, Sophie S.; Barret, Eric; Rozet, Francois; Galiano, Marc; Cathelineau, Xavier; Sanchez-Salas, Rafael

2018-01-01

ABSTRACT Background Radical prostatectomy (RP) has been used as the main primary treatment for prostate cancer (PCa) for many years with excellent oncologic results. However, approximately 20-40% of those patients has failed to RP and presented biochemical recurrence (BCR). Prostatic specific antigen (PSA) has been the pivotal tool for recurrence diagnosis, but there is no consensus about the best PSA threshold to define BCR until this moment. The natural history of BCR after surgical procedure is highly variable, but it is important to distinguish biochemical and clinical recurrence and to find the correct timing to start multimodal treatment strategy. Also, it is important to understand the role of each clinical and pathological feature of prostate cancer in BCR, progression to metastatic disease and cancer specific mortality (CSM). Review design A simple review was made in Medline for articles written in English language about biochemical recurrence after radical prostatectomy. Objective To provide an updated assessment of BCR definition, its meaning, PCa natural history after BCR and the weight of each clinical/pathological feature and risk group classifications in BCR, metastatic disease and CSM. PMID:29039897

Clinical and laboratory features of murine typhus in central Tunisia: a report of seven cases.

PubMed

Letaïef, A Omezzine; Kaabia, N; Chakroun, M; Khalifa, M; Bouzouaia, N; Jemni, L

2005-11-01

Murine or endemic typhus, caused by Rickettsia typhi, has been reported in all continents. In the 1970s, no cases of murine typhus were diagnosed in Tunisia. The clinico-epidemiological characteristics of seven cases of murine typhus diagnosed at our hospitals since 1993 are reported. Diagnosis was confirmed by indirect fluorescence assay detecting specific R. typhi antibodies. Murine typhus occurred in all ages from 18-80 years during the hot season in rural areas. Clinical features were: sudden onset of fever and absence of eschar in all cases, with maculo-papular rash (five cases), prostration (four cases), meningism (three cases) and pneumonia (four cases). Frequent laboratory findings were moderate thrombopenia (four cases) and elevated transaminases (four cases). Before the results of serology, clinical diagnoses were Mediterranean Spotted Fever (four cases), Q fever (one case), pneumonia (one case), and lymphocytic meningitis (one case). Serology confirmed all diagnoses with cross-reactivity with Rickettsia conorii. Murine typhus exists in Tunisia and its prevalence is underestimated. Further, more specific studies are needed to evaluate the true prevalence.

Clinical features and risk factors for development of urinary tract infections in cats.

PubMed

Martinez-Ruzafa, Ivan; Kruger, John M; Miller, RoseAnn; Swenson, Cheryl L; Bolin, Carole A; Kaneene, John B

2012-10-01

The clinical and diagnostic features of 155 cats with urinary tract infection (UTI) and 186 controls with negative urine culture/s were characterized retrospectively (signalment, clinical signs, urinalysis, urine culture, concurrent diseases, lower urinary tract diagnostic/therapeutic procedures). Multivariable logistic regression was used to identify risk factors associated with UTI. Cats of all ages were affected by UTI with no sex/breed predisposition. Lower urinary tract signs were absent in 35.5% of cats with UTI. Pyuria and bacteriuria had sensitivities of 52.9% and 72.9%, and specificities of 85.5% and 67.7% for detection of UTI, respectively. Risk factors significantly associated with increased odds of UTI were urinary incontinence [odds ratio (OR)=10.78, P=0.0331], transurethral procedures (OR=8.37, P<0.0001), urogenital surgery (OR=6.03, P=0.0385), gastrointestinal disease (OR=2.62, P=0.0331), decreased body weight (OR=0.81, P=0.0259) and decreased urine specific gravity (OR=0.78, P=0.0055). Whilst not independently significant, renal disease and lower urinary tract anatomic abnormalities improved statistical model performance and contributed to UTI.

Genomic DNA Methylation Signatures Enable Concurrent Diagnosis and Clinical Genetic Variant Classification in Neurodevelopmental Syndromes.

PubMed

Aref-Eshghi, Erfan; Rodenhiser, David I; Schenkel, Laila C; Lin, Hanxin; Skinner, Cindy; Ainsworth, Peter; Paré, Guillaume; Hood, Rebecca L; Bulman, Dennis E; Kernohan, Kristin D; Boycott, Kym M; Campeau, Philippe M; Schwartz, Charles; Sadikovic, Bekim

2018-01-04

Pediatric developmental syndromes present with systemic, complex, and often overlapping clinical features that are not infrequently a consequence of Mendelian inheritance of mutations in genes involved in DNA methylation, establishment of histone modifications, and chromatin remodeling (the "epigenetic machinery"). The mechanistic cross-talk between histone modification and DNA methylation suggests that these syndromes might be expected to display specific DNA methylation signatures that are a reflection of those primary errors associated with chromatin dysregulation. Given the interrelated functions of these chromatin regulatory proteins, we sought to identify DNA methylation epi-signatures that could provide syndrome-specific biomarkers to complement standard clinical diagnostics. In the present study, we examined peripheral blood samples from a large cohort of individuals encompassing 14 Mendelian disorders displaying mutations in the genes encoding proteins of the epigenetic machinery. We demonstrated that specific but partially overlapping DNA methylation signatures are associated with many of these conditions. The degree of overlap among these epi-signatures is minimal, further suggesting that, consistent with the initial event, the downstream changes are unique to every syndrome. In addition, by combining these epi-signatures, we have demonstrated that a machine learning tool can be built to concurrently screen for multiple syndromes with high sensitivity and specificity, and we highlight the utility of this tool in solving ambiguous case subjects presenting with variants of unknown significance, along with its ability to generate accurate predictions for subjects presenting with the overlapping clinical and molecular features associated with the disruption of the epigenetic machinery. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Models of clinical reasoning with a focus on general practice: A critical review.

PubMed

Yazdani, Shahram; Hosseinzadeh, Mohammad; Hosseini, Fakhrolsadat

2017-10-01

Diagnosis lies at the heart of general practice. Every day general practitioners (GPs) visit patients with a wide variety of complaints and concerns, with often minor but sometimes serious symptoms. General practice has many features which differentiate it from specialty care setting, but during the last four decades little attention was paid to clinical reasoning in general practice. Therefore, we aimed to critically review the clinical reasoning models with a focus on the clinical reasoning in general practice or clinical reasoning of general practitioners to find out to what extent the existing models explain the clinical reasoning specially in primary care and also identity the gaps of the model for use in primary care settings. A systematic search to find models of clinical reasoning were performed. To have more precision, we excluded the studies that focused on neurobiological aspects of reasoning, reasoning in disciplines other than medicine decision making or decision analysis on treatment or management plan. All the articles and documents were first scanned to see whether they include important relevant contents or any models. The selected studies which described a model of clinical reasoning in general practitioners or with a focus on general practice were then reviewed and appraisal or critics of other authors on these models were included. The reviewed documents on the model were synthesized. Six models of clinical reasoning were identified including hypothetic-deductive model, pattern recognition, a dual process diagnostic reasoning model, pathway for clinical reasoning, an integrative model of clinical reasoning, and model of diagnostic reasoning strategies in primary care. Only one model had specifically focused on general practitioners reasoning. A Model of clinical reasoning that included specific features of general practice to better help the general practitioners with the difficulties of clinical reasoning in this setting is needed.

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.

Patient-specific instruments: advantages and pitfalls

PubMed Central

Hafez, Mahmoud A.; Moholkar, Kirti

2017-01-01

Patient-specific instruments (PSI) aim to improve the accuracy of total knee replacement (TKR) based on computer-assisted preoperative planning. In this work, the authors describe the advantages and pitfalls of PSI based on their clinical experience. The main conclusion of this work is that PSI has direct impact on the logistical and technical features of TKR with some advantages and pitfalls. PMID:29227785

[Clinical features and comorbidities of Asperger syndrome in children].

PubMed

Fu, Xiao-Yan; Xie, Xiao-Tian; Mei, Zhu; Cheng, Wen-Hong

2013-09-01

To investigate and summarize the clinical features and comorbidities of Asperger syndrome (AS) in children and to provide a theoretical basis for improving the understanding and diagnosis of AS. Inquiry of medical history, physical examination, behavioral observation, psychiatric examination, questionnaire survey, and the Wechsler Intelligence Scale were used to summarize and analyse the clinical data of 95 children with AS, including chief complaint, symptoms, perinatal and familial conditions, family genetic history, and common comorbidities. AS was more common in male children, with hyperactivity, inattention, and social withdrawal as frequent chief complaints. The main clinical manifestations included poor communication skills (95%), restricted interest (82%), repetitive and stereotyped patterns of behavior (77%), semantic comprehension deficit (74%), and indiscipline (68%). Verbal IQ was higher than performance IQ in most patients. The comorbidities of AS included attention deficit hyperactivity disorder (ADHD) (39%), emotional disorder (18%), and schizophrenia (2%); emotional disorder was more common in patients aged 13-16 years, while ADHD was more common in patients aged 7-16 years. Among these patients, 61% had fathers with introverted personality, 43% had mothers with introverted personality, and 19% had a family history of mental illness. AS has specific clinical manifestations. It is essential to know more about the clinical features and comorbidities of AS, which is helpful for early identification and diagnosis of AS.

[Difference in target antigens between central tolerance and peripheral tolerance deficiencies].

PubMed

Chida, Natsuko; Kobayashi, Ichiro

2015-01-01

Failure of the immunotolerance mechanisms causes multiple organ-specific autoimmune disorders. Mutations of autoimmune regulator (AIRE) gene result in central immunotolerance deficiency named autoimmune polyendocrinopathy, candidiasis, ectodermal dystrophy (APECED). Mutations of FOXP3 genes cause regulatory T cell (Treg) deficiency named immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. Because T cell tolerance influences B cell tolerance, autoantibodies seem to reflect the presence of autoreactive T cells with the same antigen specificity. To date many differences in both clinical features and autoantibody profiles have been described between APECED and IPEX syndrome. In addition to the differences in target organs, we have found differences in the target antigens in the same organ, small intestine, between both disorders; anti-autoimmune enteropathy-related 75 kDa antigen (AIE-75) antibodies are specific to IPEX syndrome, whereas anti-tryptophan hydroxylase-1 (TPH-1) antibodies are specific to APECED. These facts suggest that immunotolerance to AIE-75 depends on the Treg, whereas the tolerance to TPH-1 depends on the central mechanisms. Furthermore, given the earlier onset and more serious clinical features of IPEX syndrome than APECED, physiological roles of Aire on the selection of Treg may be, if present, limited.

Clinical Effectiveness of Prospectively Reported Sonographic Twinkling Artifact for the Diagnosis of Renal Calculus in Patients Without Known Urolithiasis.

PubMed

Masch, William R; Cohan, Richard H; Ellis, James H; Dillman, Jonathan R; Rubin, Jonathan M; Davenport, Matthew S

2016-02-01

The purpose of this study was to determine the clinical effectiveness of prospectively reported sonographic twinkling artifact for the diagnosis of renal calculus in patients without known urolithiasis. All ultrasound reports finalized in one health system from June 15, 2011, to June 14, 2014, that contained the words "twinkle" or "twinkling" in reference to suspected renal calculus were identified. Patients with known urolithiasis or lack of a suitable reference standard (unenhanced abdominal CT with ≤ 2.5-mm slice thickness performed ≤ 30 days after ultrasound) were excluded. The sensitivity, specificity, and positive likelihood ratio of sonographic twinkling artifact for the diagnosis of renal calculus were calculated by renal unit and stratified by two additional diagnostic features for calcification (echogenic focus, posterior acoustic shadowing). Eighty-five patients formed the study population. Isolated sonographic twinkling artifact had sensitivity of 0.78 (82/105), specificity of 0.40 (26/65), and a positive likelihood ratio of 1.30 for the diagnosis of renal calculus. Specificity and positive likelihood ratio improved and sensitivity declined when the following additional diagnostic features were present: sonographic twinkling artifact and echogenic focus (sensitivity, 0.61 [64/105]; specificity, 0.65 [42/65]; positive likelihood ratio, 1.72); sonographic twinkling artifact and posterior acoustic shadowing (sensitivity, 0.31 [33/105]; specificity, 0.95 [62/65]; positive likelihood ratio, 6.81); all three features (sensitivity, 0.31 [33/105]; specificity, 0.95 [62/65]; positive likelihood ratio, 6.81). Isolated sonographic twinkling artifact has a high false-positive rate (60%) for the diagnosis of renal calculus in patients without known urolithiasis.

Brain damage resembling acute necrotizing encephalopathy as a specific manifestation of haemophagocytic lymphohistiocytosis - induced by hypersensitivity.

PubMed

Dai, Dongling; Wen, Feiqiu; Liu, Sixi; Zhou, Shaoming

2016-08-31

Both haemophagocytic lymphohistiocytosis and acute necrotizing encephalopathy are life-threatening condition. It presents major diagnostic difficulties, since it may have a diversity in clinical picture and with many conditions leading to the same clinical presentation. So it is key important to understand the disorders. We report a pediatric case of haemophagocytic lymphohistiocytosis with specific presentation which predominantly featured as acute necrotizing encephalopathy of childhood. We discuss the diagnosis and differential diagnosis, and speculate the etiology of haemophagocytic lymphohistiocytosis is due to hypersensitivity. Haemophagocytic lymphohistiocytosis and brain damage in this case may be induced by hypersensitivity, which have good clinical outcome if diagnosed and treated early.

PubMed-supported clinical term weighting approach for improving inter-patient similarity measure in diagnosis prediction.

PubMed

Chan, Lawrence Wc; Liu, Ying; Chan, Tao; Law, Helen Kw; Wong, S C Cesar; Yeung, Andy Ph; Lo, K F; Yeung, S W; Kwok, K Y; Chan, William Yl; Lau, Thomas Yh; Shyu, Chi-Ren

2015-06-02

Similarity-based retrieval of Electronic Health Records (EHRs) from large clinical information systems provides physicians the evidence support in making diagnoses or referring examinations for the suspected cases. Clinical Terms in EHRs represent high-level conceptual information and the similarity measure established based on these terms reflects the chance of inter-patient disease co-occurrence. The assumption that clinical terms are equally relevant to a disease is unrealistic, reducing the prediction accuracy. Here we propose a term weighting approach supported by PubMed search engine to address this issue. We collected and studied 112 abdominal computed tomography imaging examination reports from four hospitals in Hong Kong. Clinical terms, which are the image findings related to hepatocellular carcinoma (HCC), were extracted from the reports. Through two systematic PubMed search methods, the generic and specific term weightings were established by estimating the conditional probabilities of clinical terms given HCC. Each report was characterized by an ontological feature vector and there were totally 6216 vector pairs. We optimized the modified direction cosine (mDC) with respect to a regularization constant embedded into the feature vector. Equal, generic and specific term weighting approaches were applied to measure the similarity of each pair and their performances for predicting inter-patient co-occurrence of HCC diagnoses were compared by using Receiver Operating Characteristics (ROC) analysis. The Areas under the curves (AUROCs) of similarity scores based on equal, generic and specific term weighting approaches were 0.735, 0.728 and 0.743 respectively (p < 0.01). In comparison with equal term weighting, the performance was significantly improved by specific term weighting (p < 0.01) but not by generic term weighting. The clinical terms "Dysplastic nodule", "nodule of liver" and "equal density (isodense) lesion" were found the top three image findings associated with HCC in PubMed. Our findings suggest that the optimized similarity measure with specific term weighting to EHRs can improve significantly the accuracy for predicting the inter-patient co-occurrence of diagnosis when compared with equal and generic term weighting approaches.

Monogenic diabetes in children and young adults: Challenges for researcher, clinician and patient

PubMed Central

2006-01-01

Monogenic diabetes results from one or more mutations in a single gene which might hence be rare but has great impact leading to diabetes at a very young age. It has resulted in great challenges for researchers elucidating the aetiology of diabetes and related features in other organ systems, for clinicians specifying a diagnosis that leads to improved genetic counselling, predicting of clinical course and changes in treatment, and for patients to altered treatment that has lead to coming off insulin and injections with no alternative (Glucokinase mutations), insulin injections being replaced by tablets (e.g. low dose in HNFα or high dose in potassium channel defects -Kir6.2 and SUR1) or with tablets in addition to insulin (e.g. metformin in insulin resistant syndromes). Genetic testing requires guidance to test for what gene especially given limited resources. Monogenic diabetes should be considered in any diabetic patient who has features inconsistent with their current diagnosis (unspecified neonatal diabetes, type 1 or type 2 diabetes) and clinical features of a specific subtype of monogenic diabetes (neonatal diabetes, familial diabetes, mild hyperglycaemia, syndromes). Guidance is given by clinical and physiological features in patient and family and the likelihood of the proposed mutation altering clinical care. In this article, I aimed to provide insight in the genes and mutations involved in insulin synthesis, secretion, and resistance, and to provide guidance for genetic testing by showing the clinical and physiological features and tests for each specified diagnosis as well as the opportunities for treatment. PMID:17186387

Neuropsychiatric disorders in persons with severe traumatic brain injury: prevalence, phenomenology, and relationship with demographic, clinical, and functional features.

PubMed

Ciurli, Paola; Formisano, Rita; Bivona, Umberto; Cantagallo, Anna; Angelelli, Paola

2011-01-01

To characterize neuropsychiatric symptoms in a large group of individuals with severe traumatic brain injury (TBI) and to correlate these symptoms with demographic, clinical, and functional features. The Neuropsychiatric Inventory (NPI), a frequently used scale to assess behavioral, emotional, and motivational disorders in persons with neurological diseases, was administered to a sample of 120 persons with severe TBI. Controls were 77 healthy subjects. A wide range of neuropsychiatric symptoms was found in the population with severe TBI: apathy (42%), irritability (37%), dysphoria/depressed mood (29%), disinhibition (28%), eating disturbances (27%), and agitation (24%). A clear relationship was also found with other demographic and clinical variables. Neuropsychiatric disorders constitute an important part of the comorbidity in populations with severe TBI. Our study emphasizes the importance of integrating an overall assessment of cognitive disturbances with a specific neuropsychiatric evaluation to improve clinical understanding and treatment of persons with TBI.

[Integration of clinical and biological data in clinical practice using bioinformatics].

PubMed

Coltell, Oscar; Arregui, María; Fabregat, Antonio; Portolés, Olga

2008-05-01

The aim of our work is to describe essential aspects of Medical Informatics, Bioinformatics and Biomedical Informatics, that are used in biomedical research and clinical practice. These disciplines have emerged from the need to find new scientific and technical approaches to manage, store, analyze and report data generated in clinical practice and molecular biology and other medical specialties. It can be also useful to integrate research information generated in different areas of health care. Moreover, these disciplines are interdisciplinary and integrative, two key features not shared by other areas of medical knowledge. Finally, when Bioinformatics and Biomedical Informatics approach to medical investigation and practice are applied, a new discipline, called Clinical Bioinformatics, emerges. The latter requires a specific training program to create a new professional profile. We have not been able to find a specific training program in Clinical Bioinformatics in Spain.

Responsibility after the apparent end: 'following-up' in clinical ethics consultation.

PubMed

Finder, Stuart G; Bliton, Mark J

2011-09-01

Clinical ethics literature typically presents ethics consultations as having clear beginnings and clear ends. Experience in actual clinical ethics practice, however, reflects a different characterization, particularly when the moral experiences of ethics consultants are included in the discussion. In response, this article emphasizes listening and learning about moral experience as core activities associated with clinical ethics consultation. This focus reveals that responsibility in actual clinical ethics practice is generated within the moral scope of an ethics consultant's activities as she or he encounters the unique and specific features that emerge from interactions with a specific patient, or family, or practitioner within a given situation and over time. A long-form narrative about an ethics consultant's interactions is interwoven with a more didactic discussion to highlight the theme of responsibility and to probe questions that arise regarding follow-up within the practice of clinical ethics consultation. © 2011 Blackwell Publishing Ltd.

Are manic symptoms that 'dip' into depression the essence of mixed features?

PubMed

Malhi, Gin S; Fritz, Kristina; Allwang, Christine; Burston, Nicole; Cocks, Chris; Devlin, Jill; Harper, Margaret; Hoadley, Ben; Kearney, Brian; Klug, Peter; Meagher, Linton; Rowe, Mark; Samir, Hany; Way, Raymond; Wilson, Craig; Lyndon, William

2016-03-01

Three symptoms of (hypo)mania that clinically represent mood disorders mixed states have been omitted from the DSM-5 mixed features specifier because 'they fail to discriminate between manic and depressive syndromes'. Therefore, the present study examined the role of distractibility, irritability and psychomotor agitation (DIP) in characterising mixed depressive states. Fifty in-patients at a specialist mood disorders unit underwent a detailed longitudinal clinical evaluation (3-6 weeks) and were assessed on a range of standardized measures to characterise their illness according to depression subtype, duration of illness and clinical features-including specifically depressive and manic symptoms and the context in which these occur. 49 patients met criteria for major depressive episode, and of these, 34 experienced at least one dip symptom. Patients who endorsed distractibility were more likely to be diagnosed with Bipolar Disorder than Major Depressive Disorder; patients who endorsed irritable mood were more likely to have non-melancholic depression (admixture of depressive and anxiety symptoms), and patients who reported psychomotor agitation experienced a significantly greater number of distinct periods of (hypo)manic symptoms compared with those who did not. The present study used a modest sample size and did not control for medication or comorbid illness. Although this is inevitable when examining real-world patients in a naturalistic setting, future research needs to allow for comorbidity and its impact, specifically anxiety. The present findings suggest that all 3 symptoms that have been excluded from DSM-5 may be cardinal features of mixed states, as they 'dip' into depressive symptoms to create a mixed state. Copyright © 2015 Elsevier B.V. All rights reserved.

[Phenotypic variability in 47, XXX patients: Clinical report of four new cases].

PubMed

Goldschmidt, Ernesto; Márquez, Marisa; Solari, Andrea; Ziembar, María I; Laudicina, Alejandro

2010-08-01

The 47, XXX karyotype has a frequency of 1 in 1000 female newborns. However, this karyotype is not usually suspected at birth or childhood. These patients are usually diagnosed during adulthood when they develop premature ovarian failure or infertility, because the early phenotype doesn t have any specific features. The study describes four cases and the clinical variability of the 47, XXX karyotype.

Cerebro-facio-thoracic dysplasia (Pascual-Castroviejo syndrome): Identification of a novel mutation, use of facial recognition analysis, and review of the literature.

PubMed

Tender, Jennifer A F; Ferreira, Carlos R

2018-04-13

Cerebro-facio-thoracic dysplasia (CFTD) is a rare, autosomal recessive disorder characterized by facial dysmorphism, cognitive impairment and distinct skeletal anomalies and has been linked to the TMCO1 defect syndrome. To describe two siblings with features consistent with CFTD with a novel homozygous p.Arg114* pathogenic variant in the TMCO1 gene. We conducted a literature review and summarized the clinical features and laboratory results of two siblings with a novel pathogenic variant in the TMCO1 gene. Facial recognition analysis was utilized to assess the specificity of facial traits. The novel homozygous p.Arg114* pathogenic variant in the TMCO1 gene is responsible for the clinical features of CFTD in two siblings. Facial recognition analysis allows unambiguous distinction of this syndrome against controls.

GABA(A) Receptor Alpha5 Subunit as a Candidate Gene for Autism and Bipolar Disorder: A Proposed Endophenotype with Parent-of-Origin and Gain-of-Function Features, with or without Oculocutaneous Albinism

ERIC Educational Resources Information Center

Delong, Robert

2007-01-01

Our earlier family history studies of individuals with autism found a high incidence of major affective disorder, especially bipolar disorder, and unusual talents or intellectual abilities among family members. We now describe a subgroup of such families, selected from a large clinical experience, illustrating specific features of major affective…

Activation of Type I Interferon Pathway in Systemic Lupus Erythematosus: Association with Distinct Clinical Phenotypes

PubMed Central

Karageorgas, Theophanis P.; Tseronis, Dimitrios D.; Mavragani, Clio P.

2011-01-01

Growing evidence over the last few years suggests a central role of type I IFN pathway in the pathogenesis of systemic autoimmune disorders. Data from clinical and genetic studies in patients with systemic lupus erythematosus (SLE) and lupus-prone mouse models, indicates that the type I interferon system may play a pivotal role in the pathogenesis of several lupus and associated clinical features, such as nephritis, neuropsychiatric and cutaneous lupus, premature atherosclerosis as well as lupus-specific autoantibodies particularly against ribonucleoproteins. In the current paper, our aim is to summarize the latest findings supporting the association of type I IFN pathway with specific clinical manifestations in the setting of SLE providing insights on the potential use of type I IFN as a therapeutic target. PMID:22162633

Hallucinations: A Systematic Review of Points of Similarity and Difference Across Diagnostic Classes.

PubMed

Waters, Flavie; Fernyhough, Charles

2017-01-01

Hallucinations constitute one of the 5 symptom domains of psychotic disorders in DSM-5, suggesting diagnostic significance for that group of disorders. Although specific featural properties of hallucinations (negative voices, talking in the third person, and location in external space) are no longer highlighted in DSM, there is likely a residual assumption that hallucinations in schizophrenia can be identified based on these candidate features. We investigated whether certain featural properties of hallucinations are specifically indicative of schizophrenia by conducting a systematic review of studies showing direct comparisons of the featural and clinical characteristics of (auditory and visual) hallucinations among 2 or more population groups (one of which included schizophrenia). A total of 43 articles were reviewed, which included hallucinations in 4 major groups (nonclinical groups, drug- and alcohol-related conditions, medical and neurological conditions, and psychiatric disorders). The results showed that no single hallucination feature or characteristic uniquely indicated a diagnosis of schizophrenia, with the sole exception of an age of onset in late adolescence. Among the 21 features of hallucinations in schizophrenia considered here, 95% were shared with other psychiatric disorders, 85% with medical/neurological conditions, 66% with drugs and alcohol conditions, and 52% with the nonclinical groups. Additional differences rendered the nonclinical groups somewhat distinctive from clinical disorders. Overall, when considering hallucinations, it is inadvisable to give weight to the presence of any featural properties alone in making a schizophrenia diagnosis. It is more important to focus instead on the co-occurrence of other symptoms and the value of hallucinations as an indicator of vulnerability. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

Diagnosis of treponemal co-infection in HIV-infected West Africans.

PubMed

Mamoojee, Yaasir; Tan, Grace; Gittins, Sandra; Sarfo, Stephen; Stephenson, Lisa; Carrington, David; Bedu-Addo, George; Phillips, Richard; Appiah, Lambert T; Chadwick, David

2012-12-01

To evaluate the performance of two enzyme immunoassays (EIA), Murex and ICE, and the Determine TP point-of-care test (POCT) in diagnosing treponemal infection (syphilis or yaws) in patients attending a large HIV clinic in Ghana; to determine the prevalence of treponemal co-infections; and to characterise demographic and clinical features of patients with infection. Samples were tested with EIAs and rapid plasma reagin (RPR), then POCT and reference assays for Treponema pallidum to determine prevalence of active and past infection. Sensitivity and specificity of each assay were calculated and demographic and clinical characteristics of patients compared. Data were collected from case notes of patients retrospectively. Overall, 45/284 patient samples (14.8%, 95% CI, 11.1-19.4%) were Treponema pallidum particle agglutination (TPPA) positive, and of these, 27 (64.3%) were RPR positive and 4 (8.9%) were treponemal IgM positive. Both EIAs and Determine TP POCT showed high sensitivities and specificities for identifying infection although RPR was less reliable. Clinical features of syphilis or yaws were rarely identified in TPPA-positive patients suggesting most had previous or late latent infection. Treatment of various intercurrent infections using short courses of antibiotics active against T. pallidum was common in the clinic. A high proportion of this HIV-infected cohort showed evidence of treponemal infection. Both EIAs as well as the POCT were practical and effective at diagnosing treponemal co-infection in this setting. RPR alone was unreliable at identifying active treponemal co-infection, however might be useful in some settings where treponemal-specific assays are unaffordable. © 2012 Blackwell Publishing Ltd.

[Clinical features and therapeutic response of our anti-SRP positive patients with myositis].

PubMed

Botos, Balázs; Nagy-Vincze, Melinda; Dankó, Katalin

2017-09-01

Idiopathic inflammatory myopathies are a group of clinically heterogeneous diseases, which have been classified by myositis specific antibodies recently. The anti-SRP positive subset of this group is characterized by more severe clinical prognosis than other myositis specific antibody positive types. Our goal was to compare 16 anti-SRP positive patients in the Division of Clinical Immunology, Department of Internal Medicine, University of Debrecen with 16 antibody negative ones. Muscle strength validated in both groups by the manual muscle test proved to be significantly decreased both before and after therapy (χ 2 = 0.006 and 0.019) in the anti-SRP positive group. Muscle-specific inflammatory laboratory parameters showed significant difference only in case of LDH-levels after therapy. Both groups showed good clinical response to first line steroid treatment, yet the significantly higher rate of second line administration suggests worse therapeutic response of the antibody positive group. Based on these facts we determined poor clinical prognosis and therapeutic response of the anti-SRP positive group. Orv Hetil. 2017; 158(35): 1382-1389.

Adrenal haemangioblastoma presenting as phaeochromocytoma: a rare manifestation of extraneural hemangioblastoma.

PubMed

Deb, Prabal; Pal, Seerat; Dutta, Vibha; Srivastava, Anand; Bhargava, Akshay; Yadav, Krishan Kumar

2012-09-01

Adrenal haemangioblastoma presenting clinically as pheochromocytoma is a rare manifestation of extraneural haemangioblastoma. We present an unusual case of von Hippel-Lindau (VHL) disease that had adrenal and cerebellar haemangioblastoma with multiple renal cysts, and a review of the literature. Unlike the usual manifestations of secondary polycythemia or increased intracranial pressure and hydrocephalus due to cerebellar lesion, this 36-year-old male presented with hypertension. Investigations revealed right suprarenal mass with raised urinary catecholamines and serum vanillylmandelic acid (VMA) levels, apparently confirming the clinical diagnosis of phaeochromocytoma. Histopathology of the biopsy specimen showed features of haemangioblastoma, which was confirmed by immunohistochemistry using antibodies to neuron specific enolase and aquaporin-1. Based on this, the patient was screened for possible features of VHL, which revealed cerebellar haemangioblastoma and multiple renal cysts with angiomatous lesion. Postoperative follow-up showed normal levels of catecholamines without any symptoms of phaeochromocytoma. Adrenal haemangioblastoma is a rare entity with only four cases reported in the literature. Surgical removal is the treatment of choice. However, screening for other possible features of VHL, even in the absence of clinical features, is essential to exclude other potential lesions.

Dental Implant Macro-Design Features Can Impact the Dynamics of Osseointegration.

PubMed

Vivan Cardoso, Marcio; Vandamme, Katleen; Chaudhari, Amol; De Rycker, Judith; Van Meerbeek, Bart; Naert, Ignace; Duyck, Joke

2015-08-01

The purpose of this study was to compare the clinical performance of two dental implant types possessing a different macro-design in the in vivo pig model. Titanium Aadva(TM) implants (GC, Tokyo, Japan) were compared with OsseoSpeed(TM) implants (Astra, Mölndal, Sweden), with the Aadva implant displaying significant larger inter-thread dimensions than the OsseoSpeed implant. Implants were installed in the parietal bone of 12 domestic pigs and left for healing for either 1 or 3 months. Implant osseointegration was evaluated by quantitative histology (bone volume relative to the tissue volume [BV/TV]; bone-to-implant contact [BIC]) for distinct implant regions (collar, body, total implant length) with specific implant thread features. The Wilcoxon-Mann-Whitney nonparametric test with α = 0.05 was performed. An inferior amount of bone enveloping the Aadva implant compared with the OsseoSpeed implant was observed, in particular at the implant body part with its considerable inter-thread gaps (p < .05). Concomitantly, the Aadva macro-design negatively affected the amount of bone in direct contact with the implant for this specific implant part (p < .05), and resulted in an overall impaired implant osseointegration at the initial healing stage (total implant length; 1-month healing; p < .05). Although the Aadva implant displayed a clinically acceptable level of osseointegration, the findings demonstrate that implant macro-design features can impact the dynamics of implant osseointegration. Consideration of specific implant macro-design features should be made relative to the biological and mechanical microenvironment. © 2013 Wiley Periodicals, Inc.

A Data Base Management System for Clinical and Epidemiologic Studies In Systemic Lupus Erythematosus: Design and Maintenance

PubMed Central

Kosmides, Victoria S.; Hochberg, Marc C.

1984-01-01

This report describes the development, design specifications, features and implementation of a data base management system (DBMS) for clinical and epidemiologic studies in SLE. The DBMS is multidimensional with arrays formulated across patients, studies and variables. The major impact of this DBMS has been to increase the efficiency of managing and analyzing vast amounts of clinical and laboratory data and, as a result, to allow for continued growth in research productivity in areas related to SLE.

Clinical prediction of Gardnerella vaginalis in general practice

PubMed Central

O'Dowd, T.C.; West, R.R.

1987-01-01

In a study of 162 women with vaginal symptoms the clinical features of increased discharge, yellow discharge, 'high cheese' odour and pH greater than 5 were statistically strongly associated with the presence of Gardnerella vaginalis, confirmed by microbiological culture. The sensitivities and specificities of these clinical tests, although not as high as those of previously described sideroom tests using the amine test and microscopy for 'clue cells' nevertheless allow the clinician to predict G. vaginalis reliably and initiate treatment at first consultation. PMID:3499508

Automatic detection and classification of artifacts in single-channel EEG.

PubMed

Olund, Thomas; Duun-Henriksen, Jonas; Kjaer, Troels W; Sorensen, Helge B D

2014-01-01

Ambulatory EEG monitoring can provide medical doctors important diagnostic information, without hospitalizing the patient. These recordings are however more exposed to noise and artifacts compared to clinically recorded EEG. An automatic artifact detection and classification algorithm for single-channel EEG is proposed to help identifying these artifacts. Features are extracted from the EEG signal and wavelet subbands. Subsequently a selection algorithm is applied in order to identify the best discriminating features. A non-linear support vector machine is used to discriminate among different artifact classes using the selected features. Single-channel (Fp1-F7) EEG recordings are obtained from experiments with 12 healthy subjects performing artifact inducing movements. The dataset was used to construct and validate the model. Both subject-specific and generic implementation, are investigated. The detection algorithm yield an average sensitivity and specificity above 95% for both the subject-specific and generic models. The classification algorithm show a mean accuracy of 78 and 64% for the subject-specific and generic model, respectively. The classification model was additionally validated on a reference dataset with similar results.

[Gastroesophageal reflux disease associated with duodenogastroesophageal reflux in patients with biliary pathology: the specific features of the course and esophagogastroduodenal microbial biocenosis].

PubMed

Dzhulai, G S; Sekareva, E V; Chervinets, V M; Mikhailova, E S; Dzhulai, T E

2014-01-01

To study the specific features of the clinical course of gastroesophageal reflux disease (GERD) associated with duodenogastroesophageal reflux (DGER) in patients with chronic acalculous cholecystitis (CAC) and cholelithiasis (CL), as well as qualitative and quantitative characteristics. The clinical, morphological, motor tonic characteristics of the esophagogastroduodenal area, mucosal microbial biocenosis in the esophagus, stomach, and duodenum were studied in detail in 83 patients with GERD that was associated with DGER and ran concurrently with CAC or CL. Impaired duodenal propulsive activity as a concomitance of the signs of gastrostasis and duodenal dyskinesia with dyscoordination of both anthroduodenal and duodenojejunal propulsion and with the development of duodenogastric reflux and DGER, which in turn determine esophageal and gastric pH values is shown to be of importance in CAC and CL, which match GERD. Abnormal microbiocenosis in the upper digestive tract is characterized by the higher quantitative and qualitative content of the mucous microflora. Opportunistic microorganisms exhibit cytotoxic, hemolytic, lecithinase, caseinolytic, urease, and RNAase activities. The found specific features of the course of GERD associated with DGER in patients with biliary tract abnormalities lead us to search for novel therapeutic approaches based on the correction of digestive motor tonic disorders and abnormal microbiocenoses of the mucous flora in the esophagus, stomach, and duodenum.

Articular dysfunction patterns in patients with mechanical neck pain: a clinical algorithm to guide specific mobilization and manipulation techniques.

PubMed

Dewitte, Vincent; Beernaert, Axel; Vanthillo, Bart; Barbe, Tom; Danneels, Lieven; Cagnie, Barbara

2014-02-01

In view of a didactical approach for teaching cervical mobilization and manipulation techniques to students as well as their use in daily practice, it is mandatory to acquire sound clinical reasoning to optimally apply advanced technical skills. The aim of this Masterclass is to present a clinical algorithm to guide (novice) therapists in their clinical reasoning to identify patients who are likely to respond to mobilization and/or manipulation. The presented clinical reasoning process is situated within the context of pain mechanisms and is narrowed to and applicable in patients with a dominant input pain mechanism. Based on key features in subjective and clinical examination, patients with mechanical nociceptive pain probably arising from articular structures can be categorized into specific articular dysfunction patterns. Pending on these patterns, specific mobilization and manipulation techniques are warranted. The proposed patterns are illustrated in 3 case studies. This clinical algorithm is the corollary of empirical expertise and is complemented by in-depth discussions and knowledge exchange with international colleagues. Consequently, it is intended that a carefully targeted approach contributes to an increase in specificity and safety in the use of cervical mobilizations and manipulation techniques as valuable adjuncts to other manual therapy modalities. Copyright © 2013 Elsevier Ltd. All rights reserved.

Evaluation of the Goldmann-Witmer coefficient in the immunological diagnosis of ocular toxocariasis.

PubMed

Wang, Zhu Jian; Zhou, Min; Cao, Wen Jun; Ji, Jian; Bi, Ying Wen; Huang, Xin; Xu, Ge Zhi

2016-06-01

Ocular toxocariasis (OT) is a zoonotic parasitic infection mainly caused by the intraocular tissue invasion of second-stage Toxocara canis or Toxocara cati larva. Measuring specific anti-T. canis antibodies in the intraocular fluid (IF) can increase OT diagnosis accuracy using Goldmann-Witmer coefficient (GWC). However, there is no systemic evaluation of GWC application in the immunological diagnosis of OT. To assess GWC for the immunodiagnosis of ocular toxocariasis, paired IF and serum samples from 72 patients diagnosed with OT were retrospectively analyzed for specific anti-T. canis IgG by enzyme linked immunosorbent assay (ELISA). GWC values were calculated to determine intraocular specific IgG production. Clinical features and other laboratory data were recorded, and their correlations with GWC evaluated. Of the 72 OT patients, 60 (83.33%) showed intraocular specific IgG production confirmed by GWC, while intraocular nonspecific IgE production was found in 64/69 (92.75%) cases. No significant correlation was found among clinical features and IF specific IgG production. Values for peripheral blood samples were lower than those of intraocular fluid regarding OT screening, and vitreous humor samples showed increased local specific IgG and nonspecific IgE production compared with aqueous humor samples. Overall, our results indicate that GWC and intraocular IgE production have referential values in diagnosing ocular toxocariasis. Copyright © 2016 Elsevier B.V. All rights reserved.

The Characteristics of Herpes Simplex Virus Type 1 Infection in Rhesus Macaques and the Associated Pathological Features.

PubMed

Fan, Shengtao; Cai, Hongzhi; Xu, Xingli; Feng, Min; Wang, Lichun; Liao, Yun; Zhang, Ying; He, Zhanlong; Yang, Fengmei; Yu, Wenhai; Wang, Jingjing; Zhou, Jumin; Li, Qihan

2017-01-30

As one of the major pathogens for human herpetic diseases, herpes simplex virus type 1 (HSV1) causes herpes labialis, genital herpes and herpetic encephalitis. Our aim here was to investigate the infectious process of HSV1 in rhesus macaques and the pathological features induced during this infection. Clinical symptoms that manifested in the rhesus macaque during HSV1 infection included vesicular lesions and their pathological features. Viral distribution in the nervous tissues and associated pathologic changes indicated the typical systematic pathological processes associated with viral distribution of HSV1.Interestingly, vesicular lesions recurred in oral skin or in mucosa associated with virus shedding in macaques within four to five months post-infection,and viral latency-associated transcript (LAT) mRNA was found in the trigeminal ganglia (TG)on day 365 post-infection. Neutralization testing and enzyme-linked immunospot (ELISpot) detection of specific T cell responses confirmed the specific immunity induced by HSV1 infection. Thus, rhesus macaques could serve as an infectious model for HSV1 due to their typical clinical symptoms and the pathological recurrence associated with viral latency in nervous tissues.

Characteristics of U.S. Veteran Patients with Major Depressive Disorder who require "next-step" treatments: A VAST-D report.

PubMed

Zisook, Sidney; Tal, Ilanit; Weingart, Kimberly; Hicks, Paul; Davis, Lori L; Chen, Peijun; Yoon, Jean; Johnson, Gary R; Vertrees, Julia E; Rao, Sanjai; Pilkinton, Patricia D; Wilcox, James A; Sapra, Mamta; Iranmanesh, Ali; Huang, Grant D; Mohamed, Somaia

2016-12-01

Finding effective and lasting treatments for patients with Major Depressive Disorder (MDD) that fail to respond optimally to initial standard treatment is a critical public health imperative. Understanding the nature and characteristics of patients prior to initiating "next-step" treatment is an important component of identifying which specific treatments are best suited for individual patients. We describe clinical features and demographic characteristics of a sample of Veterans who enrolled in a "next-step" clinical trial after failing to achieve an optimal outcome from at least one well-delivered antidepressant trial. 1522 Veteran outpatients with nonpsychotic MDD completed assessments prior to being randomized to study treatment. Data is summarized and presented in terms of demographic, social, historical and clinical features and compared to a similar, non-Veteran sample. Participants were largely male and white, with about half unmarried and half unemployed. They were moderately severely depressed, with about one-third reporting recent suicidal ideation. More than half had chronic and/or recurrent depression. General medical and psychiatric comorbidities were highly prevalent, particularly PTSD. Many had histories of childhood adversity and bereavement. Participants were impaired in multiple domains of their lives and had negative self-worth. These results may not be generalizable to females, and some characteristics may be specific to Veterans of US military service. There was insufficient data on age of clinical onset and depression subtypes, and three novel measures were not psychometrically validated. Characterizing VAST-D participants provides important information to help clinicians understand features that may optimize "next-step" MDD treatments. Published by Elsevier B.V.

Comparison of patellofemoral outcomes after TKA using two prostheses with different patellofemoral design features.

PubMed

Bae, Dae Kyung; Baek, Jong Hun; Yoon, Kyung Tack; Son, Hyuck Sung; Song, Sang Jun

2017-12-01

The purpose of the present study was to compare the clinical and radiographic results after TKA using two prostheses with different sagittal patellofemoral design features, including outcomes related to compatibility of the patellofemoral joint. The clinical and radiographic results of 81 patients (100 knees) who underwent TKA using the specific prosthesis (group A) were compared with those in a control group who underwent TKA using the other prosthesis (group B). The presence of anterior knee joint pain, patellar crepitation, and patellar clunk syndrome was also checked. The function score and maximum flexion angle at the last follow-up were slightly better in group A than those in group B (92.0 ± 2.3 vs. 90.6 ± 4.2) (133.6° ± 8.4° vs. 129.6° ± 11.4°). Anterior knee pain was observed in 6 knees and patellar crepitation in four knees in group A. In group B, these symptoms were observed in 22 knees and 18 knees, respectively. There was no patellar clunk syndrome in either group. The alignment was corrected with satisfactory positioning of components. The patellar height remained unchanged after TKA in the two groups. The differences between preoperative and postoperative patellar tilt angle and patellar translation were small. When comparing the clinical and radiographic results after TKA using two prostheses with different sagittal patellofemoral design features, TKA using the specific prosthesis provided satisfactory results with less clinical symptoms related to the patellofemoral kinematics with TKA using the other prosthesis. III.

Optic nerve coloboma, Dandy-Walker malformation, microglossia, tongue hamartomata, cleft palate and apneic spells: an existing oral-facial-digital syndrome or a new variant?

PubMed

Toriello, Helga V; Lemire, Edmond G

2002-01-01

We report on a female infant with postaxial polydactyly of the hands, preaxial polydactyly of the right foot, cleft palate, microglossia and tongue hamartomata consistent with an oral-facial-digital syndrome (OFDS). The patient also had optic nerve colobomata, a Dandy-Walker malformation, micrognathia and apneic spells. This combination of clinical features has not been previously reported. This patient either expands the clinical features of one of the existing OFDS or represents a new variant. A review of the literature highlights the difficulties in making a specific diagnosis because of the different classification systems that exist in the literature.

Clinical and microbiological characterization of Clostridium difficile infection in a tertiary care hospital in Shanghai, China.

PubMed

Dong, Danfeng; Peng, Yibing; Zhang, Lihua; Jiang, Cen; Wang, Xuefeng; Mao, Enqiang

2014-01-01

Over the last decade, Clostridium difficile infection (CDI) has emerged as a significant nosocomial infection, yet little has been reported from China. This study aimed to characterize the clinical and microbiological features of CDI from a hospital in Shanghai. Patients with CDI seen between December 2010 and March 2013 were included in this study, of which clinical data were retrospectively collected. The microbiological features of corresponding isolates were analyzed including genotype by multi-locus sequence typing (MLST), antimicrobial susceptibility, toxin production, sporulation capacity, biofilm formation, and motility. Ninety-four cases of CDI were included during this study period, 12 of whom were severe cases. By reviewing the clinical data, all patients were treated empirically with proton pump inhibitor or antibiotics or both, and they were distributed widely across various wards, most frequently to the digestive ward (28/94, 29.79%). Comparing the severe with mild cases, no significant differences were found in the basic epidemiological data or the microbiological features. Among the 94 isolates, 31 were toxin A-negative toxin B-positive all genotyped as ST37. They generated fewer toxins and spores, as well as similar amounts of biofilm and motility percentages, but exhibited highest drug resistance to cephalosporins, quinolones, macrolide-lincosamide and streptogramin (MLSB), and tetracycline. No specific clinical genotype or microbiological features were found in severe cases; antimicrobial resistance could be the primary reason for epidemic strains leading to the dissemination and persistence of CDI.

Williams syndrome-specific neuroanatomical profile and its associations with behavioral features.

PubMed

Fan, Chun Chieh; Brown, Timothy T; Bartsch, Hauke; Kuperman, Joshua M; Hagler, Donald J; Schork, Andrew; Searcy, Yvonne; Bellugi, Ursula; Halgren, Eric; Dale, Anders M

2017-01-01

Williams Syndrome (WS) is a rare genetic disorder with unique behavioral features. Yet the rareness of WS has limited the number and type of studies that can be conducted in which inferences are made about how neuroanatomical abnormalities mediate behaviors. In this study, we extracted a WS-specific neuroanatomical profile from structural magnetic resonance imaging (MRI) measurements and tested its association with behavioral features of WS. Using a WS adult cohort (22 WS, 16 healthy controls), we modeled a sparse representation of a WS-specific neuroanatomical profile. The predictive performances are robust within the training cohort (10-fold cross-validation, AUC = 1.0) and accurately identify all WS individuals in an independent child WS cohort (seven WS, 59 children with diverse developmental status, AUC = 1.0). The WS-specific neuroanatomical profile includes measurements in the orbitofrontal cortex, superior parietal cortex, Sylvian fissures, and basal ganglia, and variability within these areas related to the underlying size of hemizygous deletion in patients with partial deletions. The profile intensity mediated the overall cognitive impairment as well as personality features related to hypersociability. Our results imply that the unique behaviors in WS were mediated through the constellation of abnormalities in cortical-subcortical circuitry consistent in child WS and adult WS. The robustness of the derived WS-specific neuroanatomical profile also demonstrates the potential utility of our approach in both clinical and research applications.

Stereotaxical Infusion of Rotenone: A Reliable Rodent Model for Parkinson's Disease

PubMed Central

Xiong, Nian; Huang, Jinsha; Zhang, Zhentao; Zhang, Zhaowen; Xiong, Jing; Liu, Xingyuan; Jia, Min; Wang, Fang; Chen, Chunnuan; Cao, Xuebing; Liang, Zhihou; Sun, Shenggang; Lin, Zhicheng; Wang, Tao

2009-01-01

A clinically-related animal model of Parkinson's disease (PD) may enable the elucidation of the etiology of the disease and assist the development of medications. However, none of the current neurotoxin-based models recapitulates the main clinical features of the disease or the pathological hallmarks, such as dopamine (DA) neuron specificity of degeneration and Lewy body formation, which limits the use of these models in PD research. To overcome these limitations, we developed a rat model by stereotaxically (ST) infusing small doses of the mitochondrial complex-I inhibitor, rotenone, into two brain sites: the right ventral tegmental area and the substantia nigra. Four weeks after ST rotenone administration, tyrosine hydroxylase (TH) immunoreactivity in the infusion side decreased by 43.7%, in contrast to a 75.8% decrease observed in rats treated systemically with rotenone (SYS). The rotenone infusion also reduced the DA content, the glutathione and superoxide dismutase activities, and induced alpha-synuclein expression, when compared to the contralateral side. This ST model displays neither peripheral toxicity or mortality and has a high success rate. This rotenone-based ST model thus recapitulates the slow and specific loss of DA neurons and better mimics the clinical features of idiopathic PD, representing a reliable and more clinically-related model for PD research. PMID:19924288

The diagnosis of idiopathic pulmonary fibrosis: current and future approaches

PubMed Central

Martinez, Fernando J; Chisholm, Alison; Collard, Harold R; Flaherty, Kevin R; Myers, Jeffrey; Raghu, Ganesh; Walsh, Simon LF; White, Eric S; Richeldi, Luca

2017-01-01

With the recent development of two effective treatments for patients with idiopathic pulmonary fibrosis, an accurate diagnosis is crucial. The traditional approach to diagnosis emphasises the importance of thorough clinical and laboratory evaluations to exclude secondary causes of disease. High-resolution CT is a critical initial diagnostic test and acts as a tool to identify patients who should undergo surgical lung biopsy to secure a definitive histological diagnosis of usual interstitial pneumonia pattern. This diagnostic approach faces several challenges. Many patients with suspected idiopathic pulmonary fibrosis present with atypical high-resolution CT characteristics but are unfit for surgical lung biopsy, therefore preventing a confident diagnosis. The state of the art suggests an iterative, multidisciplinary process that incorporates available clinical, laboratory, imaging, and histological features. Recent research has explored genomic techniques to molecularly phenotype patients with interstitial lung disease. In the future, clinicians will probably use blood-specific or lung-specific molecular markers in combination with other clinical, physiological, and imaging features to enhance diagnostic efforts, refine prognostic recommendations, and influence the initial or subsequent treatment options. There is an urgent and increasing need for well designed, large, prospective studies measuring the effect of different diagnostic approaches. Ultimately, this will help to inform the development of guidelines and tailor clinical practice for the benefit of patients. PMID:27932290

Patient-specific analysis of post-operative aortic hemodynamics: a focus on thoracic endovascular repair (TEVAR)

NASA Astrophysics Data System (ADS)

Auricchio, F.; Conti, M.; Lefieux, A.; Morganti, S.; Reali, A.; Sardanelli, F.; Secchi, F.; Trimarchi, S.; Veneziani, A.

2014-10-01

The purpose of this study is to quantitatively evaluate the impact of endovascular repair on aortic hemodynamics. The study addresses the assessment of post-operative hemodynamic conditions of a real clinical case through patient-specific analysis, combining accurate medical image analysis and advanced computational fluid-dynamics (CFD). Although the main clinical concern was firstly directed to the endoluminal protrusion of the prosthesis, the CFD simulations have demonstrated that there are two other important areas where the local hemodynamics is impaired and a disturbed blood flow is present: the first one is the ostium of the subclavian artery, which is partially closed by the graft; the second one is the stenosis of the distal thoracic aorta. Besides the clinical relevance of these specific findings, this study highlights how CFD analyses allow to observe important flow effects resulting from the specific features of patient vessel geometries. Consequently, our results demonstrate the potential impact of computational biomechanics not only on the basic knowledge of physiopathology, but also on the clinical practice, thanks to a quantitative extraction of knowledge made possible by merging medical data and mathematical models.

Quantitative Stratification of Diffuse Parenchymal Lung Diseases

PubMed Central

Raghunath, Sushravya; Rajagopalan, Srinivasan; Karwoski, Ronald A.; Maldonado, Fabien; Peikert, Tobias; Moua, Teng; Ryu, Jay H.; Bartholmai, Brian J.; Robb, Richard A.

2014-01-01

Diffuse parenchymal lung diseases (DPLDs) are characterized by widespread pathological changes within the pulmonary tissue that impair the elasticity and gas exchange properties of the lungs. Clinical-radiological diagnosis of these diseases remains challenging and their clinical course is characterized by variable disease progression. These challenges have hindered the introduction of robust objective biomarkers for patient-specific prediction based on specific phenotypes in clinical practice for patients with DPLD. Therefore, strategies facilitating individualized clinical management, staging and identification of specific phenotypes linked to clinical disease outcomes or therapeutic responses are urgently needed. A classification schema consistently reflecting the radiological, clinical (lung function and clinical outcomes) and pathological features of a disease represents a critical need in modern pulmonary medicine. Herein, we report a quantitative stratification paradigm to identify subsets of DPLD patients with characteristic radiologic patterns in an unsupervised manner and demonstrate significant correlation of these self-organized disease groups with clinically accepted surrogate endpoints. The proposed consistent and reproducible technique could potentially transform diagnostic staging, clinical management and prognostication of DPLD patients as well as facilitate patient selection for clinical trials beyond the ability of current radiological tools. In addition, the sequential quantitative stratification of the type and extent of parenchymal process may allow standardized and objective monitoring of disease, early assessment of treatment response and mortality prediction for DPLD patients. PMID:24676019

[Features and forensic-psychiatric significance of psychogenic jealousy in psychopathies in women].

PubMed

Kozlova, A M

1985-01-01

Examination of 37 cases of psychogenic nonpsychotic jealousy in women with psychopathies revealed specific features of the clinical picture of psychogenic emotions in relation to the premorbid characteristics of the personality and showed differences between psychogenic jealousy in women and an analogous state in males. Peculiarities of law offences committed by such individuals for jealousy motives were elicited and approaches to the prevention of socially dangerous actions of such individuals are outlined.

INHERITED NEUROPATHIES: CLINICAL OVERVIEW AND UPDATE

PubMed Central

KLEIN, CHRISTOPHER J.; DUAN, XIAOHUI; SHY, MICHAEL E.

2014-01-01

Inherited neuropathy is a group of common neurologic disorders with heterogeneous clinical presentations and genetic causes. Detailed neuromuscular evaluations, including nerve conduction studies, laboratory testing, and histopathologic examination, can assist in identification of the inherited component beyond family history. Genetic testing increasingly enables definitive diagnosis of specific inherited neuropathies. Diagnosis, however, is often complex, and neurologic disability may have both genetic and acquired components in individual patients. The decision of which genetic test to order or whether to order genetic tests is often complicated, and the strategies to maximize the value of testing are evolving. Apart from rare inherited metabolic neuropathies, treatment approaches remain largely supportive. We provide a clinical update of the various types of inherited neuropathies, their differential diagnoses, and distinguishing clinical features (where available). A framework is provided for clinical evaluations, including the inheritance assessment, electrophysiologic examinations, and specific genetic tests. PMID:23801417

Giant cell angiofibroma misdiagnosed as a vascular malformation and treated with absolute alcohol for one year: a case report and review of the literature.

PubMed

He, Yue; Zhang, Chenping; Liu, Guanglong; Tian, Zhuowei; Wang, Lizhen; Kalfarentzos, Evagelos

2014-04-24

To present the clinical, imaging, pathological and immunohistochemical features of giant cell angiofibroma (GCA). In this paper we report an atypical case of a GCA extending from the parotid to the parapharyngeal space. The lesion was being treated as a vascular malformation for one year prior to surgical removal. We summarize the clinical manifestations, imaging, pathological and molecular features of this rare disease.After complete surgical removal of the tumor, immunohistochemical analysis revealed strong positivity for the mesenchymal markers vimentin, CD34, CD31 and CD99 in neoplastic cells. Tumor proliferation antigen marker Ki67 was partly positive (<5% of cells). Tumor cells were negative for muscle-specific actin, epithelial membrane antigen, smooth muscle actin, cytokeratin pan, S100, desmin, glial fibrillary acidic protein, myogenin, MyoD1 and F8. The morphological and immunohistochemical profile was consistent with the diagnosis of GCA. GCA is a rare soft tissue tumor that can easily be misdiagnosed in the clinical preoperative setting. In view of the clinical, pathological and molecular features of the tumor, complete surgical removal is the current optimal treatment option, providing accurate diagnosis and low to minimal recurrence rate.

Predicting clinical outcome of neuroblastoma patients using an integrative network-based approach.

PubMed

Tranchevent, Léon-Charles; Nazarov, Petr V; Kaoma, Tony; Schmartz, Georges P; Muller, Arnaud; Kim, Sang-Yoon; Rajapakse, Jagath C; Azuaje, Francisco

2018-06-07

One of the main current challenges in computational biology is to make sense of the huge amounts of multidimensional experimental data that are being produced. For instance, large cohorts of patients are often screened using different high-throughput technologies, effectively producing multiple patient-specific molecular profiles for hundreds or thousands of patients. We propose and implement a network-based method that integrates such patient omics data into Patient Similarity Networks. Topological features derived from these networks were then used to predict relevant clinical features. As part of the 2017 CAMDA challenge, we have successfully applied this strategy to a neuroblastoma dataset, consisting of genomic and transcriptomic data. In particular, we observe that models built on our network-based approach perform at least as well as state of the art models. We furthermore explore the effectiveness of various topological features and observe, for instance, that redundant centrality metrics can be combined to build more powerful models. We demonstrate that the networks inferred from omics data contain clinically relevant information and that patient clinical outcomes can be predicted using only network topological data. This article was reviewed by Yang-Yu Liu, Tomislav Smuc and Isabel Nepomuceno.

Primary progressive aphasia and the evolving neurology of the language network

PubMed Central

Mesulam, M.-Marsel; Rogalski, Emily J.; Wieneke, Christina; Hurley, Robert S.; Geula, Changiz; Bigio, Eileen H.; Thompson, Cynthia K.; Weintraub, Sandra

2014-01-01

Primary progressive aphasia (PPA) is caused by selective neurodegeneration of the language-dominant cerebral hemisphere; a language deficit initially arises as the only consequential impairment and remains predominant throughout most of the course of the disease. Agrammatic, logopenic and semantic subtypes, each reflecting a characteristic pattern of language impairment and corresponding anatomical distribution of cortical atrophy, represent the most frequent presentations of PPA. Such associations between clinical features and the sites of atrophy have provided new insights into the neurology of fluency, grammar, word retrieval, and word comprehension, and have necessitated modification of concepts related to the functions of the anterior temporal lobe and Wernicke’s area. The underlying neuropathology of PPA is, most commonly, frontotemporal lobar degeneration in the agrammatic and semantic forms, and Alzheimer disease (AD) pathology in the logopenic form; the AD pathology often displays atypical and asymmetrical anatomical features consistent with the aphasic phenotype. The PPA syndrome reflects complex interactions between disease-specific neuropathological features and patient-specific vulnerability. A better understanding of these interactions might help us to elucidate the biology of the language network and the principles of selective vulnerability in neurodegenerative diseases. We review these aspects of PPA, focusing on advances in our understanding of the clinical features and neuropathology of PPA and what they have taught us about the neural substrates of the language network. PMID:25179257

Sonographic features of thyroid nodules that may help distinguish clinically atypical subacute thyroiditis from thyroid malignancy.

PubMed

Pan, Fu-shun; Wang, Wei; Wang, Yan; Xu, Ming; Liang, Jin-yu; Zheng, Yan-ling; Xie, Xiao-yan; Li, Xiao-xi

2015-04-01

The purpose of this study was to evaluate sonographic features for distinguishing clinically atypical subacute thyroiditis from malignant thyroid nodules. A total of 165 hypoechoic thyroid nodules without calcification in 135 patients with histologic diagnosis were included in this study. These nodules were classified into 2 groups: a thyroiditis group (55 nodules in 36 patients) and a malignancy group (110 nodules in 99 patients). The sonographic features of the groups were retrospectively reviewed. No significant differences were detected for the variables of marked echogenicity, a taller-than-wide shape, and mixed vascularity. However, a poorly defined margin was detected more frequently in the thyroiditis group than the malignancy group (P < .05); it yielded a high capability for differential diagnosis of atypical subacute thyroiditis, with sensitivity and specificity of 87.3% and 80.9%, respectively. Centripetal reduction echogenicity was observed exclusively in the thyroiditis group, with high specificity (100%) but low sensitivity (21.8%) for atypical subacute thyroiditis diagnosis. All of the thyroiditis nodules with a positive color signal showed noninternal vascularity (negative predictive value, 100%). There is a considerable overlap between the sonographic features of atypical subacute thyroiditis and thyroid malignancy. However, the margin, echogenicity, and vascularity type are helpful indicators for differential diagnosis of atypical subacute thyroiditis. © 2015 by the American Institute of Ultrasound in Medicine.

Primary progressive aphasia and the evolving neurology of the language network.

PubMed

Mesulam, M-Marsel; Rogalski, Emily J; Wieneke, Christina; Hurley, Robert S; Geula, Changiz; Bigio, Eileen H; Thompson, Cynthia K; Weintraub, Sandra

2014-10-01

Primary progressive aphasia (PPA) is caused by selective neurodegeneration of the language-dominant cerebral hemisphere; a language deficit initially arises as the only consequential impairment and remains predominant throughout most of the course of the disease. Agrammatic, logopenic and semantic subtypes, each reflecting a characteristic pattern of language impairment and corresponding anatomical distribution of cortical atrophy, represent the most frequent presentations of PPA. Such associations between clinical features and the sites of atrophy have provided new insights into the neurology of fluency, grammar, word retrieval, and word comprehension, and have necessitated modification of concepts related to the functions of the anterior temporal lobe and Wernicke's area. The underlying neuropathology of PPA is, most commonly, frontotemporal lobar degeneration in the agrammatic and semantic forms, and Alzheimer disease (AD) pathology in the logopenic form; the AD pathology often displays atypical and asymmetrical anatomical features consistent with the aphasic phenotype. The PPA syndrome reflects complex interactions between disease-specific neuropathological features and patient-specific vulnerability. A better understanding of these interactions might help us to elucidate the biology of the language network and the principles of selective vulnerability in neurodegenerative diseases. We review these aspects of PPA, focusing on advances in our understanding of the clinical features and neuropathology of PPA and what they have taught us about the neural substrates of the language network.

Exome Sequencing Discerns Syndromes in Patients from Consanguineous Families with Congenital Anomalies of the Kidneys and Urinary Tract

PubMed Central

Vivante, Asaf; Hwang, Daw-Yang; Kohl, Stefan; Chen, Jing; Shril, Shirlee; Schulz, Julian; van der Ven, Amelie; Daouk, Ghaleb; Soliman, Neveen A.; Kumar, Aravind Selvin; Senguttuvan, Prabha; Kehinde, Elijah O.; Tasic, Velibor

2017-01-01

Congenital anomalies of the kidneys and urinary tract (CAKUT) are the leading cause of CKD in children, featuring a broad variety of malformations. A monogenic cause can be detected in around 12% of patients. However, the morphologic clinical phenotype of CAKUT frequently does not indicate specific genes to be examined. To determine the likelihood of detecting causative recessive mutations by whole-exome sequencing (WES), we analyzed individuals with CAKUT from 33 different consanguineous families. Using homozygosity mapping and WES, we identified the causative mutations in nine of the 33 families studied (27%). We detected recessive mutations in nine known disease–causing genes: ZBTB24, WFS1, HPSE2, ATRX, ASPH, AGXT, AQP2, CTNS, and PKHD1. Notably, when mutated, these genes cause multiorgan syndromes that may include CAKUT as a feature (syndromic CAKUT) or cause renal diseases that may manifest as phenocopies of CAKUT. None of the above monogenic disease–causing genes were suspected on clinical grounds before this study. Follow-up clinical characterization of those patients allowed us to revise and detect relevant new clinical features in a more appropriate pathogenetic context. Thus, applying WES to the diagnostic approach in CAKUT provides opportunities for an accurate and early etiology–based diagnosis and improved clinical management. PMID:27151922

Diagnosis of Richter transformation in chronic lymphocytic leukemia: histology tips the scales.

PubMed

Federmann, Birgit; Mueller, Martin R; Steinhilber, Julia; Horger, Marius S; Fend, Falko

2018-06-12

Development of diffuse large B-cell lymphoma in chronic lymphocytic leukemia, so-called Richter transformation (RT), occurs in 2-5% of patients and is associated with poor outcome. The clinical features of RT are fairly non-specific and unable to discriminate transformation from other mimics. In case of clinically suspected RT, a CT/MRT is recommended, and FDG-PET/CT may help to select the site of biopsy. Radiological features suggestive of RT have been defined, but there are only limited data about their predictive value, and histological confirmation is still considered the gold standard for RT diagnosis. We retrospectively analyzed 34 patients with clinically suspected RT and available radiological and histological data. A histopathological diagnosis of RT with concordant clinical and radiological findings was obtained in 13 patients. In 18 patients, CT did not show features of transformation, concordant with lack of RT in the biopsy. Of interest, a distinct lymphoma other than DLBCL was identified in two of these cases. A false-positive radiological diagnosis of RT was rendered in two patients, including a case of Herpes simplex virus lymphadenitis. In conclusion, our findings confirm the central role of tissue biopsy in the diagnostic work up in case of clinically suspected RT.

The myositis autoantibody phenotypes of the juvenile idiopathic inflammatory myopathies.

PubMed

Rider, Lisa G; Shah, Mona; Mamyrova, Gulnara; Huber, Adam M; Rice, Madeline Murguia; Targoff, Ira N; Miller, Frederick W

2013-07-01

The juvenile idiopathic inflammatory myopathies (JIIM) are systemic autoimmune diseases characterized by skeletal muscle weakness, characteristic rashes, and other systemic features. In follow-up to our study defining the major clinical subgroup phenotypes of JIIM, we compared demographics, clinical features, laboratory measures, and outcomes among myositis-specific autoantibody (MSA) subgroups, as well as with published data on adult idiopathic inflammatory myopathy patients enrolled in a separate natural history study. In the present study, of 430 patients enrolled in a nationwide registry study who had serum tested for myositis autoantibodies, 374 had either a single specific MSA (n = 253) or no identified MSA (n = 121) and were the subject of the present report. Following univariate analysis, we used random forest classification and exact logistic regression modeling to compare autoantibody subgroups. Anti-p155/140 autoantibodies were the most frequent subgroup, present in 32% of patients with juvenile dermatomyositis (JDM) or overlap myositis with JDM, followed by anti-MJ autoantibodies, which were seen in 20% of JIIM patients, primarily in JDM. Other MSAs, including anti-synthetase, anti-signal recognition particle (SRP), and anti-Mi-2, were present in only 10% of JIIM patients. Features that characterized the anti-p155/140 autoantibody subgroup included Gottron papules, malar rash, "shawl-sign" rash, photosensitivity, cuticular overgrowth, lowest creatine kinase (CK) levels, and a predominantly chronic illness course. The features that differed for patients with anti-MJ antibodies included muscle cramps, dysphonia, intermediate CK levels, a high frequency of hospitalization, and a monocyclic disease course. Patients with anti-synthetase antibodies had higher frequencies of interstitial lung disease, arthralgia, and "mechanic's hands," and had an older age at diagnosis. The anti-SRP group, which had exclusively juvenile polymyositis, was characterized by high frequencies of black race, severe onset, distal weakness, falling episodes, Raynaud phenomenon, cardiac involvement, high CK levels, chronic disease course, frequent hospitalization, and wheelchair use. Characteristic features of the anti-Mi-2 subgroup included Hispanic ethnicity, classic dermatomyositis and malar rashes, high CK levels, and very low mortality. Finally, the most common features of patients without any currently defined MSA or myositis-associated autoantibodies included linear extensor erythema, arthralgia, and a monocyclic disease course. Several demographic and clinical features were shared between juvenile and adult idiopathic inflammatory myopathy subgroups, but with several important differences. We conclude that juvenile myositis is a heterogeneous group of illnesses with distinct autoantibody phenotypes defined by varying clinical and demographic characteristics, laboratory features, and outcomes.

The Myositis Autoantibody Phenotypes of the Juvenile Idiopathic Inflammatory Myopathies

PubMed Central

Shah, Mona; Mamyrova, Gulnara; Huber, Adam M.; Rice, Madeline Murguia; Targoff, Ira N.; Miller, Frederick W.

2013-01-01

Abstract The juvenile idiopathic inflammatory myopathies (JIIM) are systemic autoimmune diseases characterized by skeletal muscle weakness, characteristic rashes, and other systemic features. In follow-up to our study defining the major clinical subgroup phenotypes of JIIM, we compared demographics, clinical features, laboratory measures, and outcomes among myositis-specific autoantibody (MSA) subgroups, as well as with published data on adult idiopathic inflammatory myopathy patients enrolled in a separate natural history study. In the present study, of 430 patients enrolled in a nationwide registry study who had serum tested for myositis autoantibodies, 374 had either a single specific MSA (n = 253) or no identified MSA (n = 121) and were the subject of the present report. Following univariate analysis, we used random forest classification and exact logistic regression modeling to compare autoantibody subgroups. Anti-p155/140 autoantibodies were the most frequent subgroup, present in 32% of patients with juvenile dermatomyositis (JDM) or overlap myositis with JDM, followed by anti-MJ autoantibodies, which were seen in 20% of JIIM patients, primarily in JDM. Other MSAs, including anti-synthetase, anti-signal recognition particle (SRP), and anti-Mi-2, were present in only 10% of JIIM patients. Features that characterized the anti-p155/140 autoantibody subgroup included Gottron papules, malar rash, “shawl-sign” rash, photosensitivity, cuticular overgrowth, lowest creatine kinase (CK) levels, and a predominantly chronic illness course. The features that differed for patients with anti-MJ antibodies included muscle cramps, dysphonia, intermediate CK levels, a high frequency of hospitalization, and a monocyclic disease course. Patients with anti-synthetase antibodies had higher frequencies of interstitial lung disease, arthralgia, and “mechanic’s hands,” and had an older age at diagnosis. The anti-SRP group, which had exclusively juvenile polymyositis, was characterized by high frequencies of black race, severe onset, distal weakness, falling episodes, Raynaud phenomenon, cardiac involvement, high CK levels, chronic disease course, frequent hospitalization, and wheelchair use. Characteristic features of the anti-Mi-2 subgroup included Hispanic ethnicity, classic dermatomyositis and malar rashes, high CK levels, and very low mortality. Finally, the most common features of patients without any currently defined MSA or myositis-associated autoantibodies included linear extensor erythema, arthralgia, and a monocyclic disease course. Several demographic and clinical features were shared between juvenile and adult idiopathic inflammatory myopathy subgroups, but with several important differences. We conclude that juvenile myositis is a heterogeneous group of illnesses with distinct autoantibody phenotypes defined by varying clinical and demographic characteristics, laboratory features, and outcomes. PMID:23877355

What every teacher needs to know about clinical reasoning.

PubMed

Eva, Kevin W

2005-01-01

One of the core tasks assigned to clinical teachers is to enable students to sort through a cluster of features presented by a patient and accurately assign a diagnostic label, with the development of an appropriate treatment strategy being the end goal. Over the last 30 years there has been considerable debate within the health sciences education literature regarding the model that best describes how expert clinicians generate diagnostic decisions. The purpose of this essay is to provide a review of the research literature on clinical reasoning for frontline clinical teachers. The strengths and weaknesses of different approaches to clinical reasoning will be examined using one of the core divides between various models (that of analytic (i.e. conscious/controlled) versus non-analytic (i.e. unconscious/automatic) reasoning strategies) as an orienting framework. Recent work suggests that clinical teachers should stress the importance of both forms of reasoning, thereby enabling students to marshal reasoning processes in a flexible and context-specific manner. Specific implications are drawn from this overview for clinical teachers.

The utility of a classificatory decision tree approach to assist clinical differentiation of melancholic and non-melancholic depression.

PubMed

Parker, G; McCraw, S; Hadzi-Pavlovic, D

2015-07-15

Studies suggest that differentiating melancholic from non-melancholic depressive disorders is advanced by use of illness course as well as symptom variables but, in practice, potentially differentiating variables are generally positioned as having equal value. Judging that differentiating features are more likely to vary in their signal intensity, we sought to determine the number of features required to effect differentiation and their hierarchical order. The 24-item clinician-rated Sydney Melancholia Prototype Index (SMPI-CR) was completed for 364 unipolar depressed patients. The sample was divided into two cohorts according to the recruitment period. An RPART classification tree analysis identified the most discriminating SMPI items in the development sample of 197 patients, and examined the sensitivity and specificity of the diagnostic decisions, then sought to replicate findings in a validation sample of 169 patients. Independent analyses of putative SMPI items identified only seven items as required to discriminate those with clinically-diagnosed melancholic or non-melancholic depression when the conditions were examined separately. An RPART analysis considering differentiation of melancholic and non-melancholic depression in the total samples retained five of those items in the classification tree, three of which were non-symptom items, and with 92% sensitivity and 80% specificity in the development sample. This reduced item set showed 93% sensitivity and 82% specificity in the validation sample. Our clinical judgment of melancholic or non-melancholic depression may not correspond with the clinical logic employed by other clinicians. Only five SMPI items were required to derive a succinct and efficient decision tree, comprising high sensitivity and specificity in differentiating melancholic and non-melancholic depression. Current study findings provide an empirical model that could enrich clinicians׳ approach to differentiating melancholic and non-melancholic depression. Copyright © 2015 Elsevier B.V. All rights reserved.

Intracranial hypotension and hypertension in children and adolescents.

PubMed

Ozge, Aynur; Bolay, Hayrunnisa

2014-07-01

The specific aim of this review is to report the features of intracranial pressure changes [spontaneous intracranial hypotension (SIH) and idiopathic intracranial hypertension (IIH)] in children and adolescents, with emphasis on the presentation, diagnosis, and treatment modalities. Headache associated with intracranial pressure changes are relatively rare and less known in children and adolescents. SIH is a specific syndrome involving reduced intracranial pressure with orthostatic headache, frequently encountered connective tissue disorders, and a good prognosis with medical management, initial epidural blood patching, and sometimes further interventions may be required. IIH is an uncommon condition in children and different from the disease in adults, not only with respect to clinical features (likely to present with strabismus and stiff neck rather than headache or pulsatile tinnitus) but also different in outcome. Consequently, specific ICP changes of pediatric ages required specific attention both of exact diagnosis and entire management.

Automatic diagnosis of lumbar disc herniation with shape and appearance features from MRI

NASA Astrophysics Data System (ADS)

Alomari, Raja'S.; Corso, Jason J.; Chaudhary, Vipin; Dhillon, Gurmeet

2010-03-01

Intervertebral disc herniation is a major reason for lower back pain (LBP), which is the second most common neurological ailment in the United States. Automation of herniated disc diagnosis reduces the large burden on radiologists who have to diagnose hundreds of cases each day using clinical MRI. We present a method for automatic diagnosis of lumbar disc herniation using appearance and shape features. We jointly use the intensity signal for modeling the appearance of herniated disc and the active shape model for modeling the shape of herniated disc. We utilize a Gibbs distribution for classification of discs using appearance and shape features. We use 33 clinical MRI cases of the lumbar area for training and testing both appearance and shape models. We achieve over 91% accuracy in detection of herniation in a cross-validation experiment with specificity of 91% and sensitivity of 94%.

Cerebro-facio-thoracic dysplasia (Pascual-Castroviejo syndrome): Identification of a novel mutation, use of facial recognition analysis, and review of the literature

PubMed Central

Tender, Jennifer A.F.; Ferreira, Carlos R.

2018-01-01

BACKGROUND: Cerebro-facio-thoracic dysplasia (CFTD) is a rare, autosomal recessive disorder characterized by facial dysmorphism, cognitive impairment and distinct skeletal anomalies and has been linked to the TMCO1 defect syndrome. OBJECTIVE: To describe two siblings with features consistent with CFTD with a novel homozygous p.Arg114* pathogenic variant in the TMCO1 gene. METHODS: We conducted a literature review and summarized the clinical features and laboratory results of two siblings with a novel pathogenic variant in the TMCO1 gene. Facial recognition analysis was utilized to assess the specificity of facial traits. CONCLUSION: The novel homozygous p.Arg114* pathogenic variant in the TMCO1 gene is responsible for the clinical features of CFTD in two siblings. Facial recognition analysis allows unambiguous distinction of this syndrome against controls. PMID:29682451

Predicting Relapse in Patients With Medulloblastoma by Integrating Evidence From Clinical and Genomic Features

PubMed Central

Tamayo, Pablo; Cho, Yoon-Jae; Tsherniak, Aviad; Greulich, Heidi; Ambrogio, Lauren; Schouten-van Meeteren, Netteke; Zhou, Tianni; Buxton, Allen; Kool, Marcel; Meyerson, Matthew; Pomeroy, Scott L.; Mesirov, Jill P.

2011-01-01

Purpose Despite significant progress in the molecular understanding of medulloblastoma, stratification of risk in patients remains a challenge. Focus has shifted from clinical parameters to molecular markers, such as expression of specific genes and selected genomic abnormalities, to improve accuracy of treatment outcome prediction. Here, we show how integration of high-level clinical and genomic features or risk factors, including disease subtype, can yield more comprehensive, accurate, and biologically interpretable prediction models for relapse versus no-relapse classification. We also introduce a novel Bayesian nomogram indicating the amount of evidence that each feature contributes on a patient-by-patient basis. Patients and Methods A Bayesian cumulative log-odds model of outcome was developed from a training cohort of 96 children treated for medulloblastoma, starting with the evidence provided by clinical features of metastasis and histology (model A) and incrementally adding the evidence from gene-expression–derived features representing disease subtype–independent (model B) and disease subtype–dependent (model C) pathways, and finally high-level copy-number genomic abnormalities (model D). The models were validated on an independent test cohort (n = 78). Results On an independent multi-institutional test data set, models A to D attain an area under receiver operating characteristic (au-ROC) curve of 0.73 (95% CI, 0.60 to 0.84), 0.75 (95% CI, 0.64 to 0.86), 0.80 (95% CI, 0.70 to 0.90), and 0.78 (95% CI, 0.68 to 0.88), respectively, for predicting relapse versus no relapse. Conclusion The proposed models C and D outperform the current clinical classification schema (au-ROC, 0.68), our previously published eight-gene outcome signature (au-ROC, 0.71), and several new schemas recently proposed in the literature for medulloblastoma risk stratification. PMID:21357789

Easily obtainable clinical features increase the diagnostic accuracy for latent autoimmune diabetes in adults: an evidence-based report.

PubMed

Lutgens, Maurice W M D; Meijer, Melanie; Peeters, Babette; Poulsen, Marie-Louise N F; Rutten, Marjet J; Bots, Michiel L; van der Heijden, Geert J M G; Soedamah-Muthu, Sabita S

2008-12-01

Latent autoimmune diabetes in adults (LADA) represents a subgroup of diabetes mellitus. LADA is characterised by adult-onset diabetes and circulating autoimmune antibodies. LADA patients may need a different therapeutic approach than the usual type 2 diabetes mellitus. When LADA is inadequately diagnosed as type 2 diabetes mellitus, LADA patients will mistakenly be exposed to a high dose of oral glucose lowering drugs and their possible side effects. To assess which clinical features predict the presence or absence of LADA in patients older than 25 years presenting with hyperglycemia. A structured Medline and Embase search was conducted. Titles and abstracts were screened using predetermined selection criteria. Critical appraisal was based on standardized validity criteria for diagnostic research. One-hundred and eighty-four papers were retrieved of which after assessment of relevance and validity 2 studies remained for further analysis. One study reported a probability of LADA of 0.99 with one or two out of the following five clinical features: age at onset <50 years; acute symptoms; BMI<25 kg/m(2); a history of autoimmune disease; a family history positive for diabetes mellitus. The other study reported a probability of LADA of zero with none of the following clinical features and of 0.32 with one out of three: fasting blood glucose> or =15 mmol/l and/or HbA(1c)> or =10%; 10% reduction in body weight in the previous 3 months; BMI<25 kg/m(2). Further testing for LADA by measurement of autoimmune antibodies appears to be unnecessary in the absence of a specific set of clinical features. Before initiating therapy applying the above criteria may help to separate LADA from usual type 2 diabetes.

Clinical and Molecular Genetic Analysis in Three Children with Wolfram Syndrome: A Novel WFS1 Mutation (c.2534T>A)

PubMed Central

Çelmeli, Gamze; Türkkahraman, Doğa; Çürek, Yusuf; Houghton, Jayne; Akçurin, Sema; Bircan, İffet

2017-01-01

Wolfram syndrome (WS) is an autosomal recessive disorder caused by mutations in WFS1 gene. The clinical features include diabetes insipidus, diabetes mellitus (DM), optic atrophy, deafness, and other variable clinical manifestations. In this paper, we present the clinical and genetic characteristics of 3 WS patients from 3 unrelated Turkish families. Clinical characteristics of the patients and the age of onset of symptoms were quite different in each pedigree. The first two cases developed all symptoms of the disease in their first decade of life. The heterozygous father of case 2 was symptomatic with bilateral deafness. The first ocular finding of one patient (patient 3) was bilateral cataract which was accompanying DM as a first feature of the syndrome. In this patient’s family, there were two members with features suggestive of WS. Previously known homozygous mutations, c.460+1G>A in intron 4 and c.1885C>T in exon 8, were identified in these cases. A novel homozygous c.2534T>A mutation was also detected in the exon 8 of WFS1 gene. Because of the rarity and heterogeneity of WS, detection of specific and nonspecific clinical signs including ocular findings and family history in non-autoimmune, insulinopenic diabetes cases should lead to a tentative diagnosis of WS. Genetic testing is required to confirm the diagnosis. PMID:27468121

Mining hidden data to predict patient prognosis: texture feature extraction and machine learning in mammography

NASA Astrophysics Data System (ADS)

Leighs, J. A.; Halling-Brown, M. D.; Patel, M. N.

2018-03-01

The UK currently has a national breast cancer-screening program and images are routinely collected from a number of screening sites, representing a wealth of invaluable data that is currently under-used. Radiologists evaluate screening images manually and recall suspicious cases for further analysis such as biopsy. Histological testing of biopsy samples confirms the malignancy of the tumour, along with other diagnostic and prognostic characteristics such as disease grade. Machine learning is becoming increasingly popular for clinical image classification problems, as it is capable of discovering patterns in data otherwise invisible. This is particularly true when applied to medical imaging features; however clinical datasets are often relatively small. A texture feature extraction toolkit has been developed to mine a wide range of features from medical images such as mammograms. This study analysed a dataset of 1,366 radiologist-marked, biopsy-proven malignant lesions obtained from the OPTIMAM Medical Image Database (OMI-DB). Exploratory data analysis methods were employed to better understand extracted features. Machine learning techniques including Classification and Regression Trees (CART), ensemble methods (e.g. random forests), and logistic regression were applied to the data to predict the disease grade of the analysed lesions. Prediction scores of up to 83% were achieved; sensitivity and specificity of the models trained have been discussed to put the results into a clinical context. The results show promise in the ability to predict prognostic indicators from the texture features extracted and thus enable prioritisation of care for patients at greatest risk.

Laboratory Biomarkers to Facilitate Differential Diagnosis between Measles and Kawasaki Disease in a Pediatric Emergency Room: A Retrospective Study.

PubMed

Buonsenso, Danilo; Macchiarulo, Giulia; Supino, Maria Chiara; La Penna, Francesco; Scateni, Simona; Marchesi, Alessandra; Reale, Antonino; Boccuzzi, Elena

2018-01-01

This retrospective study was conducted to analyze clinical and laboratoristic parameters to individuate specific differences and facilitate differential diagnosis between Measles and Kawasaki Disease (KD) at first evaluation in an emergency room. We found similar clinical features as duration of fever and number of KD criteria (p > 0.5) but significant differences in white blood cell count, neutrophils, CRP and LDH levels (p < 0.001). LDH value ≥ 800 mg/dl had sensibility of 89% and specificity of 90% for Measles while CRP ≥ 3 mg/dl had sensibility 89% and specificity of 85% for KD. The combined use of CRP, LDH and AST showed accuracy of 86.67%.

Evaluation of Imaging Methods in Tick-Borne Encephalitis.

PubMed

Zawadzki, Radosław; Garkowski, Adam; Kubas, Bożena; Zajkowska, Joanna; Hładuński, Marcin; Jurgilewicz, Dorota; Łebkowska, Urszula

2017-01-01

Tick-borne encephalitis (TBE) is caused by a virus that belongs to the Flaviviridae family and is transmitted by tick bites. The disease has a biphasic course. Diagnosis is based on laboratory examinations because of non-specific clinical features, which usually entails the detection of specific IgM antibodies in either blood or cerebrospinal fluid that appear in the second phase of the disease. Neurological symptoms, time course of the disease, and imaging findings are multifaceted. During the second phase of the disease, after the onset of neurological symptoms, magnetic resonance imaging (MRI) abnormalities are observed in a limited number of cases. However, imaging features may aid in predicting the prognosis of the disease.

Association between dynamic features of breast DCE-MR imaging and clinical response of neoadjuvant chemotherapy: a preliminary analysis

NASA Astrophysics Data System (ADS)

Huang, Lijuan; Fan, Ming; Li, Lihua; Zhang, Juan; Shao, Guoliang; Zheng, Bin

2016-03-01

Neoadjuvant chemotherapy (NACT) is being used increasingly in the management of patients with breast cancer for systemically reducing the size of primary tumor before surgery in order to improve survival. The clinical response of patients to NACT is correlated with reduced or abolished of their primary tumor, which is important for treatment in the next stage. Recently, the dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is used for evaluation of the response of patients to NACT. To measure this correlation, we extracted the dynamic features from the DCE- MRI and performed association analysis between these features and the clinical response to NACT. In this study, 59 patients are screened before NATC, of which 47 are complete or partial response, and 12 are no response. We segmented the breast areas depicted on each MR image by a computer-aided diagnosis (CAD) scheme, registered images acquired from the sequential MR image scan series, and calculated eighteen features extracted from DCE-MRI. We performed SVM with the 18 features for classification between patients of response and no response. Furthermore, 6 of the 18 features are selected to refine the classification by using Genetic Algorithm. The accuracy, sensitivity and specificity are 87%, 95.74% and 50%, respectively. The calculated area under a receiver operating characteristic (ROC) curve is 0.79+/-0.04. This study indicates that the features of DCE-MRI of breast cancer are associated with the response of NACT. Therefore, our method could be helpful for evaluation of NACT in treatment of breast cancer.

Acute gastrointestinal vaso-occlusive ischemia in sickle cell disease: CT imaging features and clinical outcome.

PubMed

Gardner, Carly S; Jaffe, Tracy A

2016-03-01

The purpose of this study was to determine the incidence, specific imaging features, and outcome of gastrointestinal vaso-occlusive ischemia (GVOI) in sickle cell patients undergoing CT for acute abdominal pain. This HIPAA-compliant, IRB-approved retrospective study evaluated sickle cell patients with an abdominal pain crisis and acute gastrointestinal abnormalities on CT from 1/2006 to 1/2014. CT findings were divided into those compatible and incompatible with bowel ischemia or clinical diagnosis of GVOI. Two abdominal radiologists (1, 13 years' experience) reviewed the CTs for specific imaging features of ischemia. Clinical laboratory values (lactate, WBC) and outcome were recorded. Descriptive statistics and Wilcoxon-Mann-Whitney two-sample rank-sum test were performed. Of 217 CTs, 33 had acute gastrointestinal abnormalities: 75% (25/33) consistent with ischemia and clinical GVOI. Complications of ischemia occurred in 16% (4/25): ileus (50%), perforation (25%), and pneumatosis (25%). In uncomplicated cases, all had bowel wall thickening: segmental 52% (11/21) or diffuse 48% (10/21). The colon was commonly involved (76%, 16/21), particularly the ascending (57%, 12/21). Most abnormalities (52%, 11/21) were in the superior mesenteric artery distribution. Average lactate (4.3 ± 4.0 mmol/L, p = 0.02) and WBC count (20.1 ± 10.4, ×1000 cells/μL, p = 0.01) were significantly higher in GVOI. Overall mortality in patients with GVOI was 17% (3/18). GVOI is an important feature of the acute abdominal crisis in patients with sickle cell disease and can be seen in up to 75% of patients with abnormal bowel findings on CT. The diagnosis should be strongly considered in sickle cell patients with CT findings of diffuse or segmental bowel wall thickening, particularly involving the colon.

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

The clinical reasoning process in randomized clinical trials with patients with non-specific neck pain is incomplete: A systematic review.

PubMed

Maissan, Francois; Pool, Jan; de Raaij, Edwin; Mollema, Jürgen; Ostelo, Raymond; Wittink, Harriet

2018-06-01

Primarily to evaluate the completeness of the description of the clinical reasoning process in RCTs with patients with non-specific neck pain with an argued or diagnosed cause i.e. an impairment or activity limitation. Secondly, to determine the association between the completeness of the clinical reasoning process and the degree of risk of bias. Pubmed, Cinahl and PEDro were systematically searched from inception to July 2016. RCTs (n = 122) with patients with non-specific neck pain receiving physiotherapy treatment published in English were included. Data extraction included study characteristics and important features of the clinical reasoning process based on the Hypothesis-Oriented Algorithm for Clinicians II (HOAC II)]. Thirty-seven studies (30%) had a complete clinical reasoning process of which 8 (6%) had a 'diagnosed cause' and 29 (24%) had an 'argued cause'. The Spearmans rho association between the extent of the clinical reasoning process and the risk of bias was -0.2. In the majority of studies (70%) the described clinical reasoning process was incomplete. A very small proportion (6%) had a 'diagnosed cause'. Therefore, a better methodological quality does not necessarily imply a better described clinical reasoning process. Copyright © 2018 Elsevier Ltd. All rights reserved.

Primary mediastinal large B-cell lymphoma: Clinical features, prognostic factors and survival with RCHOP in Arab patients in the PET scan era.

PubMed

Al Shemmari, Salem; Sankaranarayanan, Sreedharan P; Krishnan, Yamini

2014-07-01

PMBCL is a distinct type of nonhodgkins lymphoma with specific clinicopathological features. To clarify clinical features, treatment alternatives and outcomes, we evaluated 28 Arab patients treated with chemotherapy or radiotherapy between 2006 and 2011. PMBCL lymphoma patients identified according to WHO classification and treated at KCCC between 2006 and 2011 were included in this study. Demographic and clinical data are presented as means or medians. Overall survival was estimated using the Kaplan-Meier method. Survival rates were compared using the log-rank test. A P < 0.05 was considered significant. The median age of the patients was 31 years and the male to female ratio was 2:1. Majority of the patients (75%) presented with stage I/II disease. Most had features of local extension like pleural effusion (18%) and SVCO (39%). Only 11% of the patients had bone marrow involvement at presentation. 96% of the patients required biopsy from the mediastinal mass either by image guided core biopsy (75%) or by surgical biopsy. Most patients were treated by RCHOP and involved field radiotherapy. Patients with positive PET scan after RCHOP chemotherapy received salvage chemotherapy and BEAM autologous marrow transplant. The five year OS for the entire group was 85% while the PFS was 73%. Patients who had PET scan for response evaluation had better OS [P = 0.013] and PFS [P = 0.039] when compared with those patients who received only radiotherapy based on CT scan evaluation. PMBCL is a specific lymphoma entity seen in the young with good survival. The role of PET scan for response evaluation and the type of consolidation therapy needs to be further clarified.

Primary mediastinal large B-cell lymphoma: Clinical features, prognostic factors and survival with RCHOP in Arab patients in the PET scan era

PubMed Central

Al Shemmari, Salem; Sankaranarayanan, Sreedharan P.; Krishnan, Yamini

2014-01-01

Objective: PMBCL is a distinct type of nonhodgkins lymphoma with specific clinicopathological features. To clarify clinical features, treatment alternatives and outcomes, we evaluated 28 Arab patients treated with chemotherapy or radiotherapy between 2006 and 2011. Patients and Methods: PMBCL lymphoma patients identified according to WHO classification and treated at KCCC between 2006 and 2011 were included in this study. Demographic and clinical data are presented as means or medians. Overall survival was estimated using the Kaplan-Meier method. Survival rates were compared using the log-rank test. A P < 0.05 was considered significant. Results: The median age of the patients was 31 years and the male to female ratio was 2:1. Majority of the patients (75%) presented with stage I/II disease. Most had features of local extension like pleural effusion (18%) and SVCO (39%). Only 11% of the patients had bone marrow involvement at presentation. 96% of the patients required biopsy from the mediastinal mass either by image guided core biopsy (75%) or by surgical biopsy. Most patients were treated by RCHOP and involved field radiotherapy. Patients with positive PET scan after RCHOP chemotherapy received salvage chemotherapy and BEAM autologous marrow transplant. The five year OS for the entire group was 85% while the PFS was 73%. Patients who had PET scan for response evaluation had better OS [P = 0.013] and PFS [P = 0.039] when compared with those patients who received only radiotherapy based on CT scan evaluation. Conclusion: PMBCL is a specific lymphoma entity seen in the young with good survival. The role of PET scan for response evaluation and the type of consolidation therapy needs to be further clarified PMID:25125808

Clinical epidemiology.

PubMed

Martin, S W; Bonnett, B

1987-06-01

Rational clinical practice requires deductive particularization of diagnostic findings, prognoses, and therapeutic responses from groups of animals (herds) to the individual animal (herd) under consideration This process utilizes concepts, skills, and methods of epidemiology, as they relate to the study of the distribution and determinants of health and disease in populations, and casts them in a clinical perspective.We briefly outline diagnostic strategies and introduce a measure of agreement, called kappa, between clinical diagnoses. This statistic is useful not only as a measure of diagnostic accuracy, but also as a means of quantifying and understanding disagreement between diagnosticians. It is disconcerting to many, clinicians included, that given a general deficit of data on sensitivity and specificity, the level of agreement between many clinical diagnoses is only moderate at best with kappa values of 0.3 to 0.6.Sensitivity, specificity, pretest odds, and posttest probability of disease are defined and related to the interpretation of clinical findings and ancillary diagnostic test results. An understanding of these features and how they relate to ruling-in or ruling-out a diagnosis, or minimizzing diagnostic errors will greatly enhance the diagnostic accuracy of the practitioner, and reduce the frequency of clinical disagreement. The approach of running multiple tests on every patient is not only wasteful and expensive, it is unlikely to improve the ability of the clinician to establish the correct diagnosis.We conclude with a discussion of how to decide on the best therapy, a discussion which centers on, and outlines the key features of, the well designed clinical trial. Like a diagnosis, the results from a clinical trial may not always be definitive, nonetheless it is the best available method of gleaning information about treatment efficacy.

Influenza-associated Encephalitis/Encephalopathy Identified by the Australian Childhood Encephalitis Study 2013-2015.

PubMed

Britton, Philip N; Dale, Russell C; Blyth, Christopher C; Macartney, Kristine; Crawford, Nigel W; Marshall, Helen; Clark, Julia E; Elliott, Elizabeth J; Webster, Richard I; Cheng, Allen C; Booy, Robert; Jones, Cheryl A

2017-11-01

Influenza-associated encephalitis/encephalopathy (IAE) is an important cause of acute encephalitis syndrome in children. IAE includes a series of clinicoradiologic syndromes or acute encephalopathy syndromes that have been infrequently reported outside East Asia. We aimed to describe cases of IAE identified by the Australian Childhood Encephalitis study. Children ≤ 14 years of age with suspected encephalitis were prospectively identified in 5 hospitals in Australia. Demographic, clinical, laboratory, imaging, and outcome at discharge data were reviewed by an expert panel and cases were categorized by using predetermined case definitions. We extracted cases associated with laboratory identification of influenza virus for this analysis; among these cases, specific IAE syndromes were identified where clinical and radiologic features were consistent with descriptions in the published literature. We identified 13 cases of IAE during 3 southern hemisphere influenza seasons at 5 tertiary children's hospitals in Australia; 8 children with specific acute encephalopathy syndromes including: acute necrotizing encephalopathy, acute encephalopathy with biphasic seizures and late diffusion restriction, mild encephalopathy with reversible splenial lesion, and hemiconvulsion-hemiplegia syndrome. Use of influenza-specific antiviral therapy and prior influenza vaccination were infrequent. In contrast, death or significant neurologic morbidity occurred in 7 of the 13 children (54%). The conditions comprising IAE are heterogeneous with varied clinical features, magnetic resonance imaging changes, and outcomes. Overall, outcome of IAE is poor emphasizing the need for optimized prevention, early recognition, and empiric management.

Patient-specific system for prognosis of surgical treatment outcomes of human cardiovascular system

NASA Astrophysics Data System (ADS)

Golyadkina, Anastasiya A.; Kalinin, Aleksey A.; Kirillova, Irina V.; Kossovich, Elena L.; Kossovich, Leonid Y.; Menishova, Liyana R.; Polienko, Asel V.

2015-03-01

Object of study: Improvement of life quality of patients with high stroke risk ia the main goal for development of system for patient-specific modeling of cardiovascular system. This work is dedicated at increase of safety outcomes for surgical treatment of brain blood supply alterations. The objects of study are common carotid artery, internal and external carotid arteries and bulb. Methods: We estimated mechanical properties of carotid arteries tissues and patching materials utilized at angioplasty. We studied angioarchitecture features of arteries. We developed and clinically adapted computer biomechanical models, which are characterized by geometrical, physical and mechanical similarity with carotid artery in norm and with pathology (atherosclerosis, pathological tortuosity, and their combination). Results: Collaboration of practicing cardiovascular surgeons and specialists in the area of Mathematics and Mechanics allowed to successfully conduct finite-element modeling of surgical treatment taking into account various features of operation techniques and patching materials for a specific patient. Numerical experiment allowed to reveal factors leading to brain blood supply decrease and atherosclerosis development. Modeling of carotid artery reconstruction surgery for a specific patient on the basis of the constructed biomechanical model demonstrated the possibility of its application in clinical practice at approximation of numerical experiment to the real conditions.

How well do services for young people with long term conditions deliver features proposed to improve transition?

PubMed

Colver, A; Pearse, R; Watson, R M; Fay, M; Rapley, T; Mann, K D; Le Couteur, A; Parr, J R; McConachie, H

2018-05-08

For young people with long-term conditions, transition from child to adult-oriented health services is a critical period which, if not managed well, may lead to poor outcomes. There are features of transition services which guidance and research suggest improve outcomes. We studied nine such features, calling them 'proposed beneficial features': age-banded clinic; meet adult team before transfer; promotion of health self-efficacy; written transition plan; appropriate parent involvement; key worker; coordinated team; holistic life-skills training; transition manager for clinical team. We aimed to describe the extent to which service providers offer these nine features, and to compare this with young people's reported experience of them. A longitudinal, mixed methods study followed 374 young people as their care moved from child to adult health services. Participants had type 1 diabetes, cerebral palsy or autism spectrum disorder with additional mental health difficulties. Data are reported from the first two visits, one year apart. Three hundred four (81.3%) of the young people took part in the second visit (128 with diabetes, 91 with autism, 85 with cerebral palsy). Overall, the nine proposed beneficial features of transition services were poorly provided. Fewer than half of services stated they provided an age-banded clinic, written transition plan, transition manager for clinical team, a protocol for promotion of health self-efficacy, or holistic life-skills training. To varying degrees, young people reported that they had not experienced the features which services said they provided. For instance, the agreement for written transition plan, holistic life-skills training and key worker, was 30, 43 and 49% respectively. Agreement was better for appropriate parent involvement, age-banded clinic, promotion of health self-efficacy and coordinated team at 77, 77, 80 and 69% respectively. Variation in the meaning of the features as experienced by young people and families was evident from qualitative interviews and observations. UK services provide only some of the nine proposed beneficial features for supporting healthcare transition of young people with long term conditions. Observational studies or trials which examine the influence of features of transition services on outcomes should ensure that the experiences of young people and families are captured, and not rely on service specifications.

The development of a clinical outcomes survey research application: Assessment Center.

PubMed

Gershon, Richard; Rothrock, Nan E; Hanrahan, Rachel T; Jansky, Liz J; Harniss, Mark; Riley, William

2010-06-01

The National Institutes of Health sponsored Patient-Reported Outcome Measurement Information System (PROMIS) aimed to create item banks and computerized adaptive tests (CATs) across multiple domains for individuals with a range of chronic diseases. Web-based software was created to enable a researcher to create study-specific Websites that could administer PROMIS CATs and other instruments to research participants or clinical samples. This paper outlines the process used to develop a user-friendly, free, Web-based resource (Assessment Center) for storage, retrieval, organization, sharing, and administration of patient-reported outcomes (PRO) instruments. Joint Application Design (JAD) sessions were conducted with representatives from numerous institutions in order to supply a general wish list of features. Use Cases were then written to ensure that end user expectations matched programmer specifications. Program development included daily programmer "scrum" sessions, weekly Usability Acceptability Testing (UAT) and continuous Quality Assurance (QA) activities pre- and post-release. Assessment Center includes features that promote instrument development including item histories, data management, and storage of statistical analysis results. This case study of software development highlights the collection and incorporation of user input throughout the development process. Potential future applications of Assessment Center in clinical research are discussed.

Multivariate Protein Signatures of Pre-Clinical Alzheimer's Disease in the Alzheimer's Disease Neuroimaging Initiative (ADNI) Plasma Proteome Dataset

PubMed Central

Johnstone, Daniel; Milward, Elizabeth A.; Berretta, Regina; Moscato, Pablo

2012-01-01

Background Recent Alzheimer's disease (AD) research has focused on finding biomarkers to identify disease at the pre-clinical stage of mild cognitive impairment (MCI), allowing treatment to be initiated before irreversible damage occurs. Many studies have examined brain imaging or cerebrospinal fluid but there is also growing interest in blood biomarkers. The Alzheimer's Disease Neuroimaging Initiative (ADNI) has generated data on 190 plasma analytes in 566 individuals with MCI, AD or normal cognition. We conducted independent analyses of this dataset to identify plasma protein signatures predicting pre-clinical AD. Methods and Findings We focused on identifying signatures that discriminate cognitively normal controls (n = 54) from individuals with MCI who subsequently progress to AD (n = 163). Based on p value, apolipoprotein E (APOE) showed the strongest difference between these groups (p = 2.3×10−13). We applied a multivariate approach based on combinatorial optimization ((α,β)-k Feature Set Selection), which retains information about individual participants and maintains the context of interrelationships between different analytes, to identify the optimal set of analytes (signature) to discriminate these two groups. We identified 11-analyte signatures achieving values of sensitivity and specificity between 65% and 86% for both MCI and AD groups, depending on whether APOE was included and other factors. Classification accuracy was improved by considering “meta-features,” representing the difference in relative abundance of two analytes, with an 8-meta-feature signature consistently achieving sensitivity and specificity both over 85%. Generating signatures based on longitudinal rather than cross-sectional data further improved classification accuracy, returning sensitivities and specificities of approximately 90%. Conclusions Applying these novel analysis approaches to the powerful and well-characterized ADNI dataset has identified sets of plasma biomarkers for pre-clinical AD. While studies of independent test sets are required to validate the signatures, these analyses provide a starting point for developing a cost-effective and minimally invasive test capable of diagnosing AD in its pre-clinical stages. PMID:22485168

Relations of mindfulness facets with psychological symptoms among individuals with a diagnosis of obsessive-compulsive disorder, major depressive disorder, or borderline personality disorder.

PubMed

Didonna, Fabrizio; Rossi, Roberta; Ferrari, Clarissa; Iani, Luca; Pedrini, Laura; Rossi, Nicoletta; Xodo, Erica; Lanfredi, Mariangela

2018-03-25

To explore differences in mindfulness facets among patients with a diagnosis of either obsessive-compulsive disorder (OCD), major depressive disorder (MDD), or borderline personality disorder (BPD), and healthy controls (HC), and their associations with clinical features. One hundred and fifty-three patients and 50 HC underwent a clinical assessment including measures of mindfulness (Five Facets Mindfulness Questionnaire - FFMQ), psychopathological symptoms (Symptom Check List-90-R), dissociation (Dissociative Experience Scale), alexithymia (Alexithymia Scale 20), and depression (Beck Depression Inventory-II). Analysis of variance (ANOVA) and analysis of covariance (ANCOVA) were performed to assess differences in mindfulness scores and their associations with clinical features. The three diagnostic groups scored lower on all mindfulness facets (apart from FFMQobserving) compared to the HC group. OCD group had a significant higher FFMQ total score (FFMQ-TS) and FFMQacting with awareness compared to the BPD group, and scored higher on FFMQdescribing compared to BPD and MDD groups. The scores in non-judging facet were significantly lower in all the three diagnostic groups compared to the HC group. Interestingly, higher FFMQ-TS was inversely related to all psychological measures, regardless of diagnostic group. Deficits in mindfulness skills were present in all diagnostic groups. Furthermore, we found disease-specific relationships between some mindfulness facets and specific psychological variables. Clinical implications are discussed. The study showed deficits in mindfulness scores in all diagnostic groups compared to a healthy control group. Overall, mindfulness construct has a significantly negative association with indexes of global distress, dissociative symptoms, alexithymia, and depression. Mindfulness-based interventions in clinical settings should take into account different patterns of mindfulness skills and their impact on disease-specific maladaptive cognitive strategies or symptomatology. © 2018 The British Psychological Society.

Evidence-based decision-making as a practice-based learning skill: a pilot study.

PubMed

Falzer, Paul R; Garman, D Melissa

2012-03-01

As physicians are being trained to adapt their practices to the needs and experience of patients, initiatives to standardize care have been gaining momentum. The resulting conflict can be addressed through a practice-based learning and improvement (PBL) program that develops competency in using treatment guidelines as decision aids and incorporating patient-specific information into treatment recommendations. This article describes and tests a program that is consistent with the ACGME's multilevel competency-based approach, targets students at four levels of training, and features progressive learning objectives and assessments. The program was pilot-tested with 22 paid volunteer psychiatric residents and fellows. They were introduced to a schizophrenia treatment guideline and reviewed six case vignettes of varying complexity. PBL assessments were based on how treatment recommendations were influenced by clinical and patient-specific factors. The task permitted separate assessments of learning objectives all four training levels. Among the key findings at each level, most participants found the treatment guideline helpful in making treatment decisions. Recommendations were influenced by guideline-based assessment criteria and other clinical features. They were also influenced by patients' perceptions of their illness, patient-based progress assessments, and complications such as stressors and coping patterns. Recommendations were strongly influenced by incongruence between clinical facts and patient experience. Practical understanding of how patient experience joins with clinical knowledge can enhance the use of treatment guidelines as decision tools and enable clinicians to appreciate more fully how and why patients' perceptions of their illness should influence treatment recommendations. This PBL program can assist training facilities in preparing students to cope with contradictory demands to both standardize and adapt their practice. The program can be modified to accommodate various disorders and a range of clinical factors and patient-specific complications.

A detailed clinical analysis of 13 patients with AUTS2 syndrome further delineates the phenotypic spectrum and underscores the behavioural phenotype.

PubMed

Beunders, Gea; van de Kamp, Jiddeke; Vasudevan, Pradeep; Morton, Jenny; Smets, Katrien; Kleefstra, Tjitske; de Munnik, Sonja A; Schuurs-Hoeijmakers, Janneke; Ceulemans, Berten; Zollino, Marcella; Hoffjan, Sabine; Wieczorek, Stefan; So, Joyce; Mercer, Leanne; Walker, Tanya; Velsher, Lea; Parker, Michael J; Magee, Alex C; Elffers, Bart; Kooy, R Frank; Yntema, Helger G; Meijers-Heijboer, Elizabeth J; Sistermans, Erik A

2016-08-01

AUTS2 syndrome is an 'intellectual disability (ID) syndrome' caused by genomic rearrangements, deletions, intragenic duplications or mutations disrupting AUTS2. So far, 50 patients with AUTS2 syndrome have been described, but clinical data are limited and almost all cases involved young children. We present a detailed clinical description of 13 patients (including six adults) with AUTS2 syndrome who have a pathogenic mutation or deletion in AUTS2. All patients were systematically evaluated by the same clinical geneticist. All patients have borderline to severe ID/developmental delay, 83-100% have microcephaly and feeding difficulties. Congenital malformations are rare, but mild heart defects, contractures and genital malformations do occur. There are no major health issues in the adults; the oldest of whom is now 59 years of age. Behaviour is marked by it is a friendly outgoing social interaction. Specific features of autism (like obsessive behaviour) are seen frequently (83%), but classical autism was not diagnosed in any. A mild clinical phenotype is associated with a small in-frame 5' deletions, which are often inherited. Deletions and other mutations causing haploinsufficiency of the full-length AUTS2 transcript give a more severe phenotype and occur de novo. The 13 patients with AUTS2 syndrome with unique pathogenic deletions scattered around the AUTS2 locus confirm a phenotype-genotype correlation. Despite individual variations, AUTS2 syndrome emerges as a specific ID syndrome with microcephaly, feeding difficulties, dysmorphic features and a specific behavioural phenotype. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Could texture features from preoperative CT image be used for predicting occult peritoneal carcinomatosis in patients with advanced gastric cancer?

PubMed

Kim, Hae Young; Kim, Young Hoon; Yun, Gabin; Chang, Won; Lee, Yoon Jin; Kim, Bohyoung

2018-01-01

To retrospectively investigate whether texture features obtained from preoperative CT images of advanced gastric cancer (AGC) patients could be used for the prediction of occult peritoneal carcinomatosis (PC) detected during operation. 51 AGC patients with occult PC detected during operation from January 2009 to December 2012 were included as occult PC group. For the control group, other 51 AGC patients without evidence of distant metastasis including PC, and whose clinical T and N stage could be matched to those of the patients of the occult PC group, were selected from the period of January 2011 to July 2012. Each group was divided into test (n = 41) and validation cohort (n = 10). Demographic and clinical data of these patients were acquired from the hospital database. Texture features including average, standard deviation, kurtosis, skewness, entropy, correlation, and contrast were obtained from manually drawn region of interest (ROI) over the omentum on the axial CT image showing the omentum at its largest cross sectional area. After using Fisher's exact and Wilcoxon signed-rank test for comparison of the clinical and texture features between the two groups of the test cohort, conditional logistic regression analysis was performed to determine significant independent predictor for occult PC. Using the optimal cut-off value from receiver operating characteristic (ROC) analysis for the significant variables, diagnostic sensitivity and specificity were determined in the test cohort. The cut-off value of the significant variables obtained from the test cohort was then applied to the validation cohort. Bonferroni correction was used to adjust P value for multiple comparisons. Between the two groups, there was no significant difference in the clinical features. Regarding the texture features, the occult PC group showed significantly higher average, entropy, standard deviation, and significantly lower correlation (P value < 0.004 for all). Conditional logistic regression analysis demonstrated that entropy was significant independent predictor for occult PC. When the cut-off value of entropy (> 7.141) was applied to the validation cohort, sensitivity and specificity for the prediction of occult PC were 80% and 90%, respectively. For AGC patients whose PC cannot be detected with routine imaging such as CT, texture analysis may be a useful adjunct for the prediction of occult PC.

The hypothalamus and pituitary in cerebral gigantism. A clinicopathologic and immunocytochemical study.

PubMed

Whitaker, M D; Scheithauer, B W; Hayles, A B; Okazaki, H

1985-07-01

Cerebral gigantism, or Sotos' disease, is a rare disorder of unknown cause characterized by the early onset of excessive growth, acromegalic features, and some degree of mental retardation. Although several endocrinologic abnormalities have been described in such patients, none has been specific or sufficient to explain the clinical features. Our report of the endocrinologic and pathologic aspects in a young woman with Sotos' disease includes the first microanatomic study of the hypothalamus and immunocytochemical examination of the pituitary gland in this disorder.

Developing a clinical utility framework to evaluate prediction models in radiogenomics

NASA Astrophysics Data System (ADS)

Wu, Yirong; Liu, Jie; Munoz del Rio, Alejandro; Page, David C.; Alagoz, Oguzhan; Peissig, Peggy; Onitilo, Adedayo A.; Burnside, Elizabeth S.

2015-03-01

Combining imaging and genetic information to predict disease presence and behavior is being codified into an emerging discipline called "radiogenomics." Optimal evaluation methodologies for radiogenomics techniques have not been established. We aim to develop a clinical decision framework based on utility analysis to assess prediction models for breast cancer. Our data comes from a retrospective case-control study, collecting Gail model risk factors, genetic variants (single nucleotide polymorphisms-SNPs), and mammographic features in Breast Imaging Reporting and Data System (BI-RADS) lexicon. We first constructed three logistic regression models built on different sets of predictive features: (1) Gail, (2) Gail+SNP, and (3) Gail+SNP+BI-RADS. Then, we generated ROC curves for three models. After we assigned utility values for each category of findings (true negative, false positive, false negative and true positive), we pursued optimal operating points on ROC curves to achieve maximum expected utility (MEU) of breast cancer diagnosis. We used McNemar's test to compare the predictive performance of the three models. We found that SNPs and BI-RADS features augmented the baseline Gail model in terms of the area under ROC curve (AUC) and MEU. SNPs improved sensitivity of the Gail model (0.276 vs. 0.147) and reduced specificity (0.855 vs. 0.912). When additional mammographic features were added, sensitivity increased to 0.457 and specificity to 0.872. SNPs and mammographic features played a significant role in breast cancer risk estimation (p-value < 0.001). Our decision framework comprising utility analysis and McNemar's test provides a novel framework to evaluate prediction models in the realm of radiogenomics.

De Novo Truncating Variants in ASXL2 Are Associated with a Unique and Recognizable Clinical Phenotype.

PubMed

Shashi, Vandana; Pena, Loren D M; Kim, Katherine; Burton, Barbara; Hempel, Maja; Schoch, Kelly; Walkiewicz, Magdalena; McLaughlin, Heather M; Cho, Megan; Stong, Nicholas; Hickey, Scott E; Shuss, Christine M; Freemark, Michael S; Bellet, Jane S; Keels, Martha Ann; Bonner, Melanie J; El-Dairi, Maysantoine; Butler, Megan; Kranz, Peter G; Stumpel, Constance T R M; Klinkenberg, Sylvia; Oberndorff, Karin; Alawi, Malik; Santer, Rene; Petrovski, Slavé; Kuismin, Outi; Korpi-Heikkilä, Satu; Pietilainen, Olli; Aarno, Palotie; Kurki, Mitja I; Hoischen, Alexander; Need, Anna C; Goldstein, David B; Kortüm, Fanny

2016-10-06

The ASXL genes (ASXL1, ASXL2, and ASXL3) participate in body patterning during embryogenesis and encode proteins involved in epigenetic regulation and assembly of transcription factors to specific genomic loci. Germline de novo truncating variants in ASXL1 and ASXL3 have been respectively implicated in causing Bohring-Opitz and Bainbridge-Ropers syndromes, which result in overlapping features of severe intellectual disability and dysmorphic features. ASXL2 has not yet been associated with a human Mendelian disorder. In this study, we performed whole-exome sequencing in six unrelated probands with developmental delay, macrocephaly, and dysmorphic features. All six had de novo truncating variants in ASXL2. A careful review enabled the recognition of a specific phenotype consisting of macrocephaly, prominent eyes, arched eyebrows, hypertelorism, a glabellar nevus flammeus, neonatal feeding difficulties, hypotonia, and developmental disabilities. Although overlapping features with Bohring-Opitz and Bainbridge-Ropers syndromes exist, features that distinguish the ASXL2-associated condition from ASXL1- and ASXL3-related disorders are macrocephaly, absence of growth retardation, and more variability in the degree of intellectual disabilities. We were also able to demonstrate with mRNA studies that these variants are likely to exert a dominant-negative effect, given that both alleles are expressed in blood and the mutated ASXL2 transcripts escape nonsense-mediated decay. In conclusion, de novo truncating variants in ASXL2 underlie a neurodevelopmental syndrome with a clinically recognizable phenotype. This report expands the germline disorders that are linked to the ASXL genes. Copyright © 2016. Published by Elsevier Inc.

Clinical features of atopic keratoconjunctivitis.

PubMed

Tuft, S J; Kemeny, D M; Dart, J K; Buckley, R J

1991-02-01

The clinical spectrum of ocular disease in 37 patients with atopic keratoconjunctivitis (AKC) is described. Patients typically had a severe blepharoconjunctivitis. Associated corneal scarring, suppurative keratitis, or keratoconus were the major causes of visual loss. Serum and tear samples from these patients were analyzed to quantify total and specific IgE antibodies. The results were compared as a case control study with results from samples from 55 patients with other forms of atopic disease and 16 nonatopic volunteers. Although the mean values for total and specific IgEs in the serum of patients with atopic disease were markedly higher than the values from nonatopic controls (P less than 0.00002), a difference between the disease groups could not be demonstrated (P greater than 0.05). There were also differences between both the total IgE (P = 0.0002) and pollen-specific IgE (P = 0.015) in tears from patients with atopic disease and nonatopic controls, but not for house dust mite or cat dander-specific IgEs. These results suggest that clinical differences between groups of patients with chronic allergic external eye disease are not associated with specific patterns of IgE production.

Useful Information on...Alzheimer's Disease.

ERIC Educational Resources Information Center

Cohen, Gene D.

This brochure provides information on Alzheimer's disease by examining who gets Alzheimer's disease and what to expect when someone has Alzheimer's disease. Abnormal brain tissue findings are discussed and three clinical features of Alzheimer's disease are listed: dementia; insidious onset of symptoms; and exclusion of all other specific causes of…

[Prostate histopathology of NIH category IV prostatitis detected by sextant prostate needle biopsy from the patients with high prostatic specific antigen].

PubMed

Shimomura, Tatsuya; Kiyota, Hiroshi; Takahashi, Hiroyuki; Madarame, Jun; Kimura, Takahiro; Onodera, Shouichi

2003-08-01

Asymptomatic prostatitis is classified as category IV in NIH classification of prostatitis syndrome (1999). No report concerning this category has been present. We investigated this category histopathologically and clinically, in order to clarify the histopathological distribution and its correlation to the clinical features, in this study. Among 785 patients who were suspected prostate cancer because of their high prostatic specific antigen (PSA) values and to have a sextant prostate needle biopsy was performed between January, 1996 and December, 2000, 88 patients (11.2%) were diagnosed as NIH category IV prostatitis (asymptomatic prostatitis). We observed all pathological specimens stained with Hematoxylin-Eosine, and classified them into subtypes according to the classification criteria for prostatitis defined by True et al. (1999). We also investigated the relationship between histopathological distribution and clinical features such as PSA values, PSA density, the incidence of pyuria or bacteriuria. In the histopathological study, grade distributions were 12.5% (11/88) in mild, 71.6% (63/88) in moderate, and 15.9% (14/88) in severe. Location distributions were 2.3% (2/88) in glandular, 68.2% (60/88) in periglandular, and 29.5% (26/88) in stromal. No relationship between these subtypes and clinical features was recognized statistically. However, 7 patients (7.95%) were diagnosed as prostate cancers, later. Pyuria was found in 29.1% (23/79). Bacteriuria was present in 14.3% (11/77). Isolated bacteria were 4 strains of Enterococcus faccalis, 2 strains of each of Pseudomonas aeruginosa and Staphylococcus aureus, and one strain of each of Escherichia coli, Klebsiella oxytoca, Enterobacter cloacae, Enterobacter aerogenes, Staphylococcus haemolyticus, and Staphylococcus epidermidis. Gram positive rod, and Candida sp. No relationship between these subtypes and bacterial species was recognized. These results indicated that the incidence of NIII category IV prostatits was not low without correlation to any clinical features. However, we should pay attention to the presence of prostate cancer, because a small number of the patients were diagnosed as prostate cancer, later.

Pruritus is a common feature in sheep infected with the BSE agent

PubMed Central

Konold, Timm; Bone, Gemma; Vidal-Diez, Alberto; Tortosa, Raul; Davis, Andrew; Dexter, Glenda; Hill, Peter; Jeffrey, Martin; Simmons, Marion M; Chaplin, Melanie J; Bellworthy, Susan J; Berthelin-Baker, Christine

2008-01-01

Background The variability in the clinical or pathological presentation of transmissible spongiform encephalopathies (TSEs) in sheep, such as scrapie and bovine spongiform encephalopathy (BSE), has been attributed to prion protein genotype, strain, breed, clinical duration, dose, route and type of inoculum and the age at infection. The study aimed to describe the clinical signs in sheep infected with the BSE agent throughout its clinical course to determine whether the clinical signs were as variable as described for classical scrapie in sheep. The clinical signs were compared to BSE-negative sheep to assess if disease-specific clinical markers exist. Results Forty-seven (34%) of 139 sheep, which comprised 123 challenged sheep and 16 undosed controls, were positive for BSE. Affected sheep belonged to five different breeds and three different genotypes (ARQ/ARQ, VRQ/VRQ and AHQ/AHQ). None of the controls or BSE exposed sheep with ARR alleles were positive. Pruritus was present in 41 (87%) BSE positive sheep; the remaining six were judged to be pre-clinically infected. Testing of the response to scratching along the dorsum of a sheep proved to be a good indicator of clinical disease with a test sensitivity of 85% and specificity of 98% and usually coincided with weight loss. Clinical signs that were displayed significantly earlier in BSE positive cases compared to negative cases were behavioural changes, pruritic behaviour, a positive scratch test, alopecia, skin lesions, teeth grinding, tremor, ataxia, loss of weight and loss of body condition. The frequency and severity of each specific clinical sign usually increased with the progression of disease over a period of 16–20 weeks. Conclusion Our results suggest that BSE in sheep presents with relatively uniform clinical signs, with pruritus of increased severity and abnormalities in behaviour or movement as the disease progressed. Based on the studied sheep, these clinical features appear to be independent of breed, affected genotype, dose, route of inoculation and whether BSE was passed into sheep from cattle or from other sheep, suggesting that the clinical phenotype of BSE is influenced by the TSE strain more than by other factors. The clinical phenotype of BSE in the genotypes and breed studied was indistinguishable from that described for classical scrapie cases. PMID:18445253

A Virtual Mental Health Clinic for University Students: A Qualitative Study of End-User Service Needs and Priorities

PubMed Central

Gulliver, Amelia; Chan, Jade KY; Bennett, Kylie; Griffiths, Kathleen M

2015-01-01

Background Help seeking for mental health problems among university students is low, and Internet-based interventions such as virtual clinics have the potential to provide private, streamlined, and high quality care to this vulnerable group. Objective The objective of this study was to conduct focus groups with university students to obtain input on potential functions and features of a university-specific virtual clinic for mental health. Methods Participants were 19 undergraduate students from an Australian university between 19 and 24 years of age. Focus group discussion was structured by questions that addressed the following topics: (1) the utility and acceptability of a virtual mental health clinic for students, and (2) potential features of a virtual mental health clinic. Results Participants viewed the concept of a virtual clinic for university students favorably, despite expressing concerns about privacy of personal information. Participants expressed a desire to connect with professionals through the virtual clinic, for the clinic to provide information tailored to issues faced by students, and for the clinic to enable peer-to-peer interaction. Conclusions Overall, results of the study suggest the potential for virtual clinics to play a positive role in providing students with access to mental health support. PMID:26543908

A comparison of clinical characteristics of older adults treated with antidepressants in general and psychiatric hospitals in Asia.

PubMed

Wang, Yuan-Yuan; Xiang, Yu-Tao; Ungvari, Gabor S; Ng, Chee H; Chiu, Helen F K; Yim, Larina C L; Si, Tian-Mei; Chee, Kok-Yoon; Avasthi, Ajit; Grover, Sandeep; Chong, Mian-Yoon; Sim, Kang; Kanba, Shigenobu; He, Yan-Ling; Lee, Min-Soo; Yang, Shu-Yu; Udomratn, Pichet; Kallivayalil, Roy A; Tanra, Andi J; Maramis, Margarita M; Shen, Winston W; Sartorius, Norman; Mahendran, Rathi; Teng, Jia-Ying; Tan, Chay-Hoon; Shinfuku, Naotaka

2017-11-01

This study compared the demographics, clinical characteristics, and antidepressant prescription patterns between Asian patients aged 50 years and older attending psychiatric hospitals and those attending general hospitals. In total, 955 patients (604 in general hospitals, 351 in psychiatric hospitals) aged 50 years or older treated with antidepressants in 10 Asian countries and territories were examined. Patients' demographics, clinical features, and prescriptions of psychotropic drugs were recorded using a standardized protocol and data collection procedure. Binary logistic regression revealed that high income and diagnosis of schizophrenia were independently associated with psychiatric hospital treatment, whereas outpatient care, diagnosis of anxiety disorders, and multiple major medical conditions were independently associated with general hospital treatment. In addition, tetracyclic and noradrenergic and specific serotonergic antidepressants were more likely to be prescribed in general hospitals. Older adults treated with antidepressants showed different demographic and clinical features between general hospitals and psychiatric hospitals in Asia. © 2017 Japanese Psychogeriatric Society.

A rare case of acute presentation of trocar site hernia from robot-assisted laparoscopic partial nephrectomy.

PubMed

Ng, Zi Qin; Pemberton, Richard; Tan, Patrick

2018-02-15

Trocar site hernia is not a common acute complication encountered after robot-assisted surgery, especially in the urological cohort of patients. A few case reports of small bowel obstruction secondary to incarceration by trocar site hernia have been described in gynaecological surgery and prostatectomies. As the clinical presentation is non-specific, late diagnosis has significant implication on morbidity and mortality. Here, we present a rare case of a patient with recent robot-assisted laparoscopic partial nephrectomy for a renal cell carcinoma presented with features of impending bowel obstruction secondary to incarcerated small bowel in the trocar site. We also reviewed the literature focusing on clinical features of trocar site hernia and preventive measures.

Biologic Therapy and Asthma.

PubMed

Viswanathan, Ravi K; Busse, William W

2018-02-01

Although airway inflammation is an intrinsic and key feature of asthma, this response varies in its intensity and translation to clinical characteristics and responsiveness to treatment. The observations that clinical heterogeneity is an important aspect of asthma and a feature that likely dictates and determines responses to treatment in severe asthma, patient responsiveness to medication is incomplete, and risks for exacerbation are increased. The development of biologics, which target selected and specific components of inflammation, has been a promising advance to achieve asthma control in patients with severe disease. This article reviews the current biologics available and under development and how their use has affected asthma and which subpopulations appear to benefit the greatest. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Waldenstrom’s Macroglobulinemia: An Update

PubMed Central

Mazzucchelli, Maddalena; Frustaci, Anna Maria; Deodato, Marina; Cairoli, Roberto; Tedeschi, Alessandra

2018-01-01

Waldenstrom Macroglobulinemia is a rare lymphoproliferative disorder with distinctive clinical features. Diagnostic and prognostic characterisation in WM significantly changed with the discovery of two molecular markers: MYD88 and CXCR4. Mutational status of these latter influences both clinical presentation and prognosis and demonstrated therapeutic implications. Treatment choice in Waldenstrom disease is strictly guided by patients age and characteristics, specific goals of therapy, the necessity for rapid disease control, the risk of treatment-related neuropathy, disease features, the risk of immunosuppression or secondary malignancies and potential for future autologous stem cell transplantation. The therapeutic landscape has expanded during the last years and the approval of ibrutinib, the first drug approved for Waldenstrom Macroglobulinemia, represents a significant step forward for a better management of the disease. PMID:29326801

The relationship between impulse control disorders and obsessive-compulsive disorder: a current understanding and future research directions

PubMed Central

Potenza, Marc Nicholas; Koran, Lorrin Michael; Pallanti, Stefano

2009-01-01

Impulse control disorders (ICDs) constitute a heterogeneous group of conditions linked diagnostically by difficulties in resisting “the impulse, drive, or temptation to perform an act that is harmful to the person or to others.” Specific ICDs share clinical, phenomenological and biological features with obsessive-compulsive disorder (OCD) that have suggested that these disorders might be categorized together. However, other data suggest significant differences between OCD and ICDs. In this article, clinical, phenomenological and biological features of the formal ICDs are reviewed and compared and contrasted with those of OCD. Available data indicate substantial differences between ICDs and OCD that suggest independent categorizations. Existing research gaps are identified and avenues for future research suggested. PMID:19811840

A framework for treating DSM-5 alternative model for personality disorder features.

PubMed

Hopwood, Christopher J

2018-04-15

Despite its demonstrated empirical superiority over the DSM-5 Section 2 categorical model of personality disorders for organizing the features of personality pathology, limitations remain with regard to the translation of the DSM-5 Section 3 alternative model of personality disorders (AMPD) to clinical practice. The goal of this paper is to outline a general and preliminary framework for approaching treatment from the perspective of the AMPD. Specific techniques are discussed for the assessment and treatment of both Criterion A personality dysfunction and Criterion B maladaptive traits. A concise and step-by-step model is presented for clinical decision making with the AMPD, in the hopes of offering clinicians a framework for treating personality pathology and promoting further research on the clinical utility of the AMPD. Copyright © 2018 John Wiley & Sons, Ltd. Copyright © 2018 John Wiley & Sons, Ltd.

Enhance placebo, avoid nocebo: How contextual factors affect physiotherapy outcomes.

PubMed

Testa, Marco; Rossettini, Giacomo

2016-08-01

Placebo and nocebo represent complex and distinct psychoneurobiological phenomena in which behavioural and neurophysiological modifications occur together with the application of a treatment. Despite a better understanding of this topic in the medical field, little is known about their role in physiotherapy. The aim of this review is: a) to elucidate the neurobiology behind placebo and nocebo effects, b) to describe the role of the contextual factors as modulators of the clinical outcomes in rehabilitation and c) to provide clinical and research guidelines on their uses. The physiotherapist's features, the patient's features, the patient-physiotherapist relationship, the characteristics of the treatment and the overall healthcare setting are all contextual factors influencing clinical outcomes. Since every physiotherapy treatment determines a specific and a contextual effect, physiotherapists should manage the contextual factors as a boosting element of any manual therapy to improve placebo effects and avoid detrimental nocebo effects. Copyright © 2016 Elsevier Ltd. All rights reserved.

Seizures and EEG features in 74 patients with genetic-dysmorphic syndromes.

PubMed

Alfei, Enrico; Raviglione, Federico; Franceschetti, Silvana; D'Arrigo, Stefano; Milani, Donatella; Selicorni, Angelo; Riva, Daria; Zuffardi, Orsetta; Pantaleoni, Chiara; Binelli, Simona

2014-12-01

Epilepsy is one of the most common findings in chromosome aberrations. Types of seizures and severity may significantly vary both between different conditions and within the same aberration. Hitherto specific seizures and EEG patterns are identified for only few syndromes. We studied 74 patients with defined genetic-dysmorphic syndromes with and without epilepsy in order to assess clinical and electroencephalographic features, to compare our observation with already described electro-clinical phenotypes, and to identify putative electroencephalographic and/or seizure characteristics useful to address the diagnosis. In our population, 10 patients had chromosomal disorders, 19 microdeletion or microduplication syndromes, and 32 monogenic syndromes. In the remaining 13, syndrome diagnosis was assessed on clinical grounds. Our study confirmed the high incidence of epilepsy in genetic-dysmorphic syndromes. Moreover, febrile seizures and neonatal seizures had a higher incidence compared to general population. In addition, more than one third of epileptic patients had drug-resistant epilepsy. EEG study revealed poor background organization in 42 patients, an excess of diffuse rhythmic activities in beta, alpha or theta frequency bands in 34, and epileptiform patterns in 36. EEG was completely normal only in 20 patients. No specific electro-clinical pattern was identified, except for inv-dup15, Angelman, and Rett syndromes. Nevertheless some specific conditions are described in detail, because of notable differences from what previously reported. Regarding the diagnostic role of EEG, we found that--even without any epileptiform pattern--the generation of excessive rhythmic activities in different frequency bandwidths might support the diagnosis of a genetic syndrome. © 2014 Wiley Periodicals, Inc.

West Nile encephalitis outbreak in Kerala, India, 2011.

PubMed

Anukumar, B; Sapkal, Gajanan N; Tandale, Babasheb V; Balasubramanian, R; Gangale, Daya

2014-09-01

An outbreak of acute encephalitis syndrome (AES) was reported in Kerala in India in May 2011. The outbreak features were unusual in terms of seasonality, geographical distribution, age group, and clinical manifestations in comparison to the epidemiological features of Japanese Encephalitis. To detect the etiology of the acute encephalitis syndrome outbreak. Investigation of outbreak was undertaken by collection of brief clinical history and epidemiological details along with the specimens for viral diagnosis. The serum/CSF samples (patients=208) received from the sentinel hospitals were subjected to IgM capture ELISA and RT-PCR specific for Japanese encephalitis (JE) virus and West Nile virus (WNV). The JE/WN IgM positive samples were further tested by serum neutralization assay for the presence of JE and WNV specific neutralizing antibody. Most of the affected patients were aged above 15 years. No spatial clustering of the disease was noticed. Cases were observed in premonsoon and early monsoon season and in JE non-endemic area of Kerala. A total of 47 patient samples were positive for in-house JE IgM capture ELISA and WNV IgM capture ELISA. Serum neutralization assay result revealed that 32 of 42 (76.19%) sera were positive for WNV neutralization antibodies. WNV was isolated from a clinical specimen. Phylogenetic analysis of WNV envelope gene revealed 99% homology with Russian Lineage 1 WNV. West Nile virus (WNV) etiology was confirmed by virus isolation and detection of virus specific antibody from clinical specimen. Phylogenetic analysis grouped the current strain in lineage I West Nile virus. Copyright © 2014 Elsevier B.V. All rights reserved.

Models of clinical reasoning with a focus on general practice: A critical review

PubMed Central

YAZDANI, SHAHRAM; HOSSEINZADEH, MOHAMMAD; HOSSEINI, FAKHROLSADAT

2017-01-01

Introduction: Diagnosis lies at the heart of general practice. Every day general practitioners (GPs) visit patients with a wide variety of complaints and concerns, with often minor but sometimes serious symptoms. General practice has many features which differentiate it from specialty care setting, but during the last four decades little attention was paid to clinical reasoning in general practice. Therefore, we aimed to critically review the clinical reasoning models with a focus on the clinical reasoning in general practice or clinical reasoning of general practitioners to find out to what extent the existing models explain the clinical reasoning specially in primary care and also identity the gaps of the model for use in primary care settings. Methods: A systematic search to find models of clinical reasoning were performed. To have more precision, we excluded the studies that focused on neurobiological aspects of reasoning, reasoning in disciplines other than medicine decision making or decision analysis on treatment or management plan. All the articles and documents were first scanned to see whether they include important relevant contents or any models. The selected studies which described a model of clinical reasoning in general practitioners or with a focus on general practice were then reviewed and appraisal or critics of other authors on these models were included. The reviewed documents on the model were synthesized. Results: Six models of clinical reasoning were identified including hypothetic-deductive model, pattern recognition, a dual process diagnostic reasoning model, pathway for clinical reasoning, an integrative model of clinical reasoning, and model of diagnostic reasoning strategies in primary care. Only one model had specifically focused on general practitioners reasoning. Conclusion: A Model of clinical reasoning that included specific features of general practice to better help the general practitioners with the difficulties of clinical reasoning in this setting is needed. PMID:28979912

Clinical Characteristics and Outcome of Patients with Neuroblastoma Presenting Genomic Amplification of Loci Other than MYCN

PubMed Central

Guimier, Anne; Ferrand, Sandrine; Pierron, Gaëlle; Couturier, Jérôme; Janoueix-Lerosey, Isabelle; Combaret, Valérie; Mosseri, Véronique; Thebaud, Estelle; Gambart, Marion; Plantaz, Dominique; Marabelle, Aurélien; Coze, Carole; Rialland, Xavier; Fasola, Sylvie; Lapouble, Eve; Fréneaux, Paul; Peuchmaur, Michel; Michon, Jean; Delattre, Olivier; Schleiermacher, Gudrun

2014-01-01

Background Somatically acquired genomic alterations with MYCN amplification (MNA) are key features of neuroblastoma (NB), the most common extra-cranial malignant tumour of childhood. Little is known about the frequency, clinical characteristics and outcome of NBs harbouring genomic amplification(s) distinct from MYCN. Methods Genomic profiles of 1100 NBs from French centres studied by array-CGH were re-examined specifically to identify regional amplifications. Patients were included if amplifications distinct from the MYCN locus were seen. A subset of NBs treated at Institut Curie and harbouring MNA as determined by array-CGH without other amplification was also studied. Clinical and histology data were retrospectively collected. Results In total, 56 patients were included and categorised into 3 groups. Group 1 (n = 8) presented regional amplification(s) without MNA. Locus 12q13-14 was a recurrent amplified region (4/8 cases). This group was heterogeneous in terms of INSS stages, primary localisations and histology, with atypical clinical features. Group 2 (n = 26) had MNA as well as other regional amplifications. These patients shared clinical features of those of a group of NBs MYCN amplified (Group 3, n = 22). Overall survival for group 1 was better than that of groups 2 and 3 (5 year OS: 87.5%±11% vs 34.9%±7%, log-rank p<0.05). Conclusion NBs harbouring regional amplification(s) without MNA are rare and seem to show atypical features in clinical presentation and genomic profile. Further high resolution genetic explorations are justified in this heterogeneous group, especially when considering these alterations as predictive markers for targeted therapy. PMID:25013904

Angio-Architectural Features of High-Grade Intracranial Dural Arteriovenous Fistulas: Correlation With Aggressive Clinical Presentation and Hemorrhagic Risk.

PubMed

Della Pepa, Giuseppe Maria; Parente, Paolo; D'Argento, Francesco; Pedicelli, Alessandro; Sturiale, Carmelo Lucio; Sabatino, Giovanni; Albanese, Alessio; Puca, Alfredo; Fernandez, Eduardo; Olivi, Alessando; Marchese, Enrico

2017-08-01

High-grade dural arteriovenous fistulas (dAVFs) can present shunts with very different angio-architectural characteristics. Specific hemodynamic factors may affect clinical history and determine very different clinical courses. To evaluate the relationship between some venous angio-architectural features in high-grade dAVFs and clinical presentation. Specific indicators of moderate or severe venous hypertension were analyzed, such as altered configurations of the dural sinuses (by a single or a dual thrombosis), or overload of cortical vessels (restrictions of outflow, pseudophlebitic cortical vessels, and venous aneurysms). The institutional series was retrospectively reviewed (49 cases), and the pattern of venous drainage was analyzed in relationship with clinical presentation (benign/aggressive/hemorrhage). Thirty-five of 49 cases displayed cortical reflux (high-grade dAVFs). This subgroup displayed a benign presentation in 31.42% of cases, an aggressive in 31.42%, and hemorrhage in 37.14%. Our data confirm that within high-grade dAVFs, 2 distinct subpopulations exist according to severity of clinical presentation. Some indicators we examined showed correlation with aggressive nonhemorrhagic manifestations (outflow restriction and pseudophlebitic cortical vessels), while other showed a correlation with hemorrhage (dual thrombosis and venous aneurysms). Current classifications appear insufficient to identify a wide range of conditions that ultimately determine the organization of the cortical venous drainage. Intermediate degrees of venous congestion correlate better with the clinical risk than the simple definition of cortical reflux. The angiographic aspects of venous drainage presented in this study may prove useful to assess dAVF hemodynamic characteristics and identify conditions at higher clinical risk. Copyright © 2017 by the Congress of Neurological Surgeons

Paediatric autoimmune encephalopathies: clinical features, laboratory investigations and outcomes in patients with or without antibodies to known central nervous system autoantigens

PubMed Central

Hacohen, Yael; Wright, Sukhvir; Waters, Patrick; Agrawal, Shakti; Carr, Lucinda; Cross, Helen; De Sousa, Carlos; DeVile, Catherine; Fallon, Penny; Gupta, Rajat; Hedderly, Tammy; Hughes, Elaine; Kerr, Tim; Lascelles, Karine; Lin, Jean-Pierre; Philip, Sunny; Pohl, Keith; Prabahkar, Prab; Smith, Martin; Williams, Ruth; Clarke, Antonia; Hemingway, Cheryl; Wassmer, Evangeline; Vincent, Angela; Lim, Ming J

2013-01-01

Objective To report the clinical and investigative features of children with a clinical diagnosis of probable autoimmune encephalopathy, both with and without antibodies to central nervous system antigens. Method Patients with encephalopathy plus one or more of neuropsychiatric symptoms, seizures, movement disorder or cognitive dysfunction, were identified from 111 paediatric serum samples referred from five tertiary paediatric neurology centres to Oxford for antibody testing in 2007–2010. A blinded clinical review panel identified 48 patients with a diagnosis of probable autoimmune encephalitis whose features are described. All samples were tested/retested for antibodies to N-methyl-D-aspartate receptor (NMDAR), VGKC-complex, LGI1, CASPR2 and contactin-2, GlyR, D1R, D2R, AMPAR, GABA(B)R and glutamic acid decarboxylase. Results Seizures (83%), behavioural change (63%), confusion (50%), movement disorder (38%) and hallucinations (25%) were common. 52% required intensive care support for seizure control or profound encephalopathy. An acute infective organism (15%) or abnormal cerebrospinal fluid (32%), EEG (70%) or MRI (37%) abnormalities were found. One 14-year-old girl had an ovarian teratoma. Serum antibodies were detected in 21/48 (44%) patients: NMDAR 13/48 (27%), VGKC-complex 7/48(15%) and GlyR 1/48(2%). Antibody negative patients shared similar clinical features to those who had specific antibodies detected. 18/34 patients (52%) who received immunotherapy made a complete recovery compared to 4/14 (28%) who were not treated; reductions in modified Rankin Scale for children scores were more common following immunotherapies. Antibody status did not appear to influence the treatment effect. Conclusions Our study outlines the common clinical and paraclinical features of children and adolescents with probable autoimmune encephalopathies. These patients, irrespective of positivity for the known antibody targets, appeared to benefit from immunotherapies and further antibody targets may be defined in the future. PMID:23175854

Diagnosis of response and non-response to dry eye treatment using infrared thermography images

NASA Astrophysics Data System (ADS)

Acharya, U. Rajendra; Tan, Jen Hong; Vidya, S.; Yeo, Sharon; Too, Cheah Loon; Lim, Wei Jie Eugene; Chua, Kuang Chua; Tong, Louis

2014-11-01

The dry eye treatment outcome depends on the assessment of clinical relevance of the treatment effect. The potential approach to assess the clinical relevance of the treatment is to identify the symptoms responders and non-responders to the given treatments using the responder analysis. In our work, we have performed the responder analysis to assess the clinical relevance effect of the dry eye treatments namely, hot towel, EyeGiene®, and Blephasteam® twice daily and 12 min session of Lipiflow®. Thermography is performed at week 0 (baseline), at weeks 4 and 12 after treatment. The clinical parameters such as, change in the clinical irritations scores, tear break up time (TBUT), corneal staining and Schirmer's symptoms tests values are used to obtain the responders and non-responders groups. We have obtained the infrared thermography images of dry eye symptoms responders and non-responders to the three types of warming treatments. The energy, kurtosis, skewness, mean, standard deviation, and various entropies namely Shannon, Renyi and Kapoor are extracted from responders and non-responders thermograms. The extracted features are ranked based on t-values. These ranked features are fed to the various classifiers to get the highest performance using minimum features. We have used decision tree (DT), K nearest neighbour (KNN), Naves Bayesian (NB) and support vector machine (SVM) to classify the features into responder and non-responder classes. We have obtained an average accuracy of 99.88%, sensitivity of 99.7% and specificity of 100% using KNN classifier using ten-fold cross validation.

MO-AB-BRA-10: Cancer Therapy Outcome Prediction Based On Dempster-Shafer Theory and PET Imaging

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

Lian, C; University of Rouen, QuantIF - EA 4108 LITIS, 76000 Rouen; Li, H

2015-06-15

Purpose: In cancer therapy, utilizing FDG-18 PET image-based features for accurate outcome prediction is challenging because of 1) limited discriminative information within a small number of PET image sets, and 2) fluctuant feature characteristics caused by the inferior spatial resolution and system noise of PET imaging. In this study, we proposed a new Dempster-Shafer theory (DST) based approach, evidential low-dimensional transformation with feature selection (ELT-FS), to accurately predict cancer therapy outcome with both PET imaging features and clinical characteristics. Methods: First, a specific loss function with sparse penalty was developed to learn an adaptive low-rank distance metric for representing themore » dissimilarity between different patients’ feature vectors. By minimizing this loss function, a linear low-dimensional transformation of input features was achieved. Also, imprecise features were excluded simultaneously by applying a l2,1-norm regularization of the learnt dissimilarity metric in the loss function. Finally, the learnt dissimilarity metric was applied in an evidential K-nearest-neighbor (EK- NN) classifier to predict treatment outcome. Results: Twenty-five patients with stage II–III non-small-cell lung cancer and thirty-six patients with esophageal squamous cell carcinomas treated with chemo-radiotherapy were collected. For the two groups of patients, 52 and 29 features, respectively, were utilized. The leave-one-out cross-validation (LOOCV) protocol was used for evaluation. Compared to three existing linear transformation methods (PCA, LDA, NCA), the proposed ELT-FS leads to higher prediction accuracy for the training and testing sets both for lung-cancer patients (100+/−0.0, 88.0+/−33.17) and for esophageal-cancer patients (97.46+/−1.64, 83.33+/−37.8). The ELT-FS also provides superior class separation in both test data sets. Conclusion: A novel DST- based approach has been proposed to predict cancer treatment outcome using PET image features and clinical characteristics. A specific loss function has been designed for robust accommodation of feature set incertitude and imprecision, facilitating adaptive learning of the dissimilarity metric for the EK-NN classifier.« less

Dengue fever outbreak: a clinical management experience.

PubMed

Ahmed, Shahid; Ali, Nadir; Ashraf, Shahzad; Ilyas, Mohammad; Tariq, Waheed-Uz-Zaman; Chotani, Rashid A

2008-01-01

To determine the frequency of dengue as a cause of fever and compare the clinical and haematological characteristics of Dengue-probable and Dengue-proven cases. An observational study. The Combined Military Hospital, Malir Cantt., Karachi, from August 2005 to December 2006. All patients with age above 14 years, who were either hospitalized or treated in medical outdoor clinic due to acute febrile illness, were evaluated for clinical features of Dengue Fever (DF), Dengue haemorrhagic fever (DHF) and Dengue Shock Syndrome (DSS). Patients showing typical clinical features and haematological findings suggestive of Dengue fever (As per WHO criteria) were evaluated in detail for comparison of probable and confirmed cases of Dengue fever. All other cases of acute febrile illness, not showing clinical features or haematological abnormalities of Dengue fever, were excluded. The clinical and laboratory features were recorded on SPSS 11.0 programme and graded where required, for descriptive and statistical analysis. Out of 5200 patients with febrile illness, 107(2%) presented with typical features of DF, 40/107(37%) were Dengue-proven while 67/107(63%) were Dengue-probable. Out of Dengue-proven cases, 38 were of DF and 2 were of DHF. Day 1 temperature ranged from 99-1050C (mean 1010C). Chills and rigors were noticed in 86 (80%), myalgia in 67%, headache in 54%, pharyngitis in 35%, rash in 28%, and bleeding manifestations in 2% cases. Hepatomegaly in 1(0.5%), lymphadenopathy in 1(0.5%) and splenomegaly in 12 (11.2%) cases. Leucopoenia (count<4x109 /L) was noted in 73%, platelet count<150 x109 /L in 84% and ALT>40 U/L in 57% cases. Frequency of clinically suspected dengue virus infection was 107 (2%), while confirmed dengue fever cases were 40 (0.8%) out of 5200 fever cases. Fever with chills and rigors, body aches, headache, myalgia, rash, haemorrhagic manifestations, platelet count, total leukocyte count, and ALT, are parameters to screen the cases of suspected dengue virus infection; the diagnosis cannot be confirmed unless supported by molecular studies or dengue specific IgM .

Abnormal hepatic biochemistries and clinical liver disease in patients with primary Sjögren's syndrome.

PubMed

Montaño-Loza, Aldo J; Crispín-Acuña, José Carlos; Remes-Troche, José María; Uribe, Misael

2007-01-01

Patients with primary Sjögren's syndrome may present liver involvement. Our goals were to establish the prevalence of abnormal hepatic biochemistries and clinical liver disease in patients with primary Sjögren's syndrome and correlate their presence with other clinical and laboratory features. Ninety-five patients with diagnosis of primary Sjögren's syndrome were studied. Data on gender, age, clinical features, liver biochemistries, tests of inflammation and autoimmunity, and concomitant diseases were collected. Forty-two patients (44%) had abnormal hepatic biochemistries, and of these 19 patients (20%) had clinical liver disease. Patients with abnormal hepatic biochemistries had higher frequency of autoimmune hypotiroidism, arthritis, vasculitis, Raynaud's phenomenon, higher sedimentation rate,and higher frequency of antinuclear and antimitochondrial antibodies than patients with normal liver biochemistries (P < 0.05 for each). Patients with clinical liver disease had higher frequency of arthritis, vasculitis, and higher frequency of antimitochondrial antibodies than patients without clinical liver disease (P < 0.05 for each). Twenty-one patients had diagnosis of a specific liver disease, such as hepatitis C virus infection (n = 11), autoimmune hepatitis (n = 2), primary biliary cirrhosis (n =5),nonalcoholic fatty liver disease (n = 2), and hepatitis B virus infection (n = 1). In half of patients with liver involvement a definitive cause could not be identified. Liver involvement is frequently found in patients with primary Sjögren's syndrome, and its presence is associated with clinical features of systemic disease, and markers of autoimmunity and inflammation. There may be a subgroup of patients with liver involvement secondary to primary Sjögren's syndrome.

Cause and Effect: Testing a Mechanism and Method for the Cognitive Integration of Basic Science.

PubMed

Kulasegaram, Kulamakan; Manzone, Julian C; Ku, Cheryl; Skye, Aimee; Wadey, Veronica; Woods, Nicole N

2015-11-01

Methods of integrating basic science with clinical knowledge are still debated in medical training. One possibility is increasing the spatial and temporal proximity of clinical content to basic science. An alternative model argues that teaching must purposefully expose relationships between the domains. The authors compared different methods of integrating basic science: causal explanations linking basic science to clinical features, presenting both domains separately but in proximity, and simply presenting clinical features First-year undergraduate health professions students were randomized to four conditions: (1) science-causal explanations (SC), (2) basic science before clinical concepts (BC), (3) clinical concepts before basic science (CB), and (4) clinical features list only (FL). Based on assigned conditions, participants were given explanations for four disorders in neurology or rheumatology followed by a memory quiz and diagnostic test consisting of 12 cases which were repeated after one week. Ninety-four participants completed the study. No difference was found on memory test performance, but on the diagnostic test, a condition by time interaction was found (F[3,88] = 3.05, P < .03, ηp = 0.10). Although all groups had similar immediate performance, the SC group had a minimal decrease in performance on delayed testing; the CB and FL groups had the greatest decreases. These results suggest that creating proximity between basic science and clinical concepts may not guarantee cognitive integration. Although cause-and-effect explanations may not be possible for all domains, making explicit and specific connections between domains will likely facilitate the benefits of integration for learners.

Current developments in understanding of West Nile virus central nervous system disease.

PubMed

Tyler, Kenneth L

2014-06-01

West Nile virus (WNV) is the most important cause of epidemic encephalitis in the United States. We review articles published in the last 18 months related to the epidemiology, immunology, clinical features, and treatment of this disease. There was a resurgence in WNV disease in the United States in 2012. The WNV strain now predominant in the United States (NA/WN02) differs from the initial emergent isolate in 1999 (NY99). However, differences in the genetics of currently circulating United States WNV strains do not explain variations in epidemic magnitude or disease severity. Innate and acquired immunity are critical in control of WNV, and in some cases pathways are central nervous system specific. The clinical features of infection are now well understood, although nonconfirmed observations of chronic viral excretion in urine remain controversial. There is no specific antiviral therapy for WNV, but studies of antivirals specific for other flaviviruses may identify agents with promise against WNV. Phase I and II human WNV vaccine clinical trials have established that well tolerated and immunogenic WNV vaccines can be developed. WNV remains an important public health problem. Although recent studies have significantly increased our understanding of host immune and genetic factors involved in control of WNV infection, no specific therapy is yet available. Development of a well tolerated, immunogenic, and effective vaccine against WNV is almost certainly feasible, but economic factors and the lack of predictability of the magnitude and location of outbreaks are problematic for designing phase III trials and ultimate licensure.

Mixed, melancholic, and anxious features in depression: a cross-sectional study of sociodemographic and clinical correlates.

PubMed

Zaninotto, Leonardo; Souery, Daniel; Calati, Raffaella; Scudellari, Paolo; Janiri, Luigi; Montgomery, Stuart; Kasper, Siegfried; Zohar, Joseph; Mendlewicz, Julien; Serretti, Alessandro

2014-11-01

Major depression (MD) is currently viewed as a heterogeneous condition, characterized by different psychopathological dimensions. Our sample was composed of 1,289 nonpsychotic bipolar/unipolar depressed patients. Participants were divided into mixed (MXD), melancholic (MEL), and anxious (ANX) depressed, according to a hierarchical functional model. Sociodemographic and clinical variables were compared across depressive subtypes by χ2 test and analysis of variance. The Young Mania Rating Scale (YMRS) and 2 subscales (melancholic [MEL-S] and psychic-somatic anxiety [PSOM-ANX]) from the Hamilton Depression Rating Scale also served as continuous outcome measures. MXD patients more frequently had bipolar I disorder (BD I), younger age of onset, and a higher familial load for mood disorders. MEL and ANX patients were more frequently diagnosed with major depressive disorder and reported a higher suicide risk. YMRS scores in depression was associated with BD I diagnosis (P < .0001) and manic polarity of the last episode (P < .0001), while a depressive polarity of the last episode (P < .0001) was associated with higher MEL-S score. No specific predictor was associated with PSOM-ANX score. Overall, our findings suggest that mixed depressive features are associated with significant hallmarks of bipolarity, and melancholic features may be influenced by previous depressive polarity. The symptom domain of anxiety appears to have no specific predictor.

Mesomelic skeletal dysplasias.

PubMed

Kaitila, I; Leisti, J T; Rimoin, D L

1976-01-01

Mesomelic shortening of the extremities lends itself as a useful clinical and/or radiologic sign to characterize a group of hereditary bone dysplasias. Table 1 and Figure 4 are presented to facilitate the comparison between the many different types of mesomelic dwarfism. Differential diagnosis between these types is not difficult because of the specific bone changes and extraskeletal malformations present. As in many hereditary syndromes, however, there may be wide clinical variability within a single entity, and meticulous clinical and radiologic examination must be done to arrive at the correct diagnosis. Certain other forms of chondrodystrophies, such as achondroplasia, hypochondroplasia, pseudoachondroplasia and distrophic dwarfism, can be easily differentiated from the mesomelic dysplasias by their clinical features and skeletal radiographs. Nothing is known about the pathogenesis of the various forms of mesomelic dysplasias. There is no available specific treatment, although corrective surgery has benefited selected patients. The correct diagnosis is, however, important both for prognostication and accurate genetic counseling.

Miniscrews for orthodontic anchorage: a review of available systems.

PubMed

Alkadhimi, Aslam; Al-Awadhi, Ebrahim A

2018-03-15

In recent years, extensive research has introduced novel ways of reinforcing orthodontic anchorage using a variety of devices temporarily anchored in bone (miniscrews). Currently, there are numerous manufacturers with different miniscrew designs on the market. The aim of this paper is to discuss the key design features of different miniscrew systems on the market. Furthermore, to present clinical selection criteria of miniscrews in different settings taking into account the determinant factors. Review of the literature was carried out using the following search methods: MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL). The search was focused on studies published until January 2018. We studied each individual miniscrew from all the identified manufacturers in details. All the features were then summarised and presented as a clinical guideline for the selection of miniscrews. In this article, we reviewed the development of miniscrews and outlined the general design features of miniscrews as well as specific design features of the current miniscrews in the market. Extensive research of the current products was carried out to help clinicians better understand the difference between the various designs of miniscrews that can be used.

Cognition, Language, and Clinical Pathological Features of Non-Alzheimer's Dementias: An Overview

ERIC Educational Resources Information Center

Reilly, Jamie; Rodriguez, Amy D.; Lamy, Martine; Neils-Strunjas, Jean

2010-01-01

There are many distinct forms of dementia whose pharmacological and behavioral management differ. Differential diagnosis among the dementia variants currently relies upon a weighted combination of genetic and protein biomarkers, neuroanatomical integrity, and behavior. Diagnostic specificity is complicated by a high degree of overlap in the…

Heterogeneity in Learning Style in Asperger Syndrome and High-Functioning Autism

ERIC Educational Resources Information Center

Tsatsanis, Katharine D.

2004-01-01

Although children and adolescents with high-functioning autism and Asperger syndrome present with some similar clinical features and challenges, heterogeneity of learning style coupled with the predominance of specific "packages" of materials and methods tends to understate the need for individualization when designing an educational and/or a…

Copper toxicity in ruminant animals

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

Oehme, F.W.

This discussion includes clinical and post mortem features, metabolism of both normal and toxic quantities of copper, effect of copper upon the tissues, and control treatment and prevention of copper toxicity. These effects are discussed in regard to ruminants. Specific emphasis is placed on metabolism and biochemistry. 33 references, 3 figures.

Prototypes for Content-Based Image Retrieval in Clinical Practice

PubMed Central

Depeursinge, Adrien; Fischer, Benedikt; Müller, Henning; Deserno, Thomas M

2011-01-01

Content-based image retrieval (CBIR) has been proposed as key technology for computer-aided diagnostics (CAD). This paper reviews the state of the art and future challenges in CBIR for CAD applied to clinical practice. We define applicability to clinical practice by having recently demonstrated the CBIR system on one of the CAD demonstration workshops held at international conferences, such as SPIE Medical Imaging, CARS, SIIM, RSNA, and IEEE ISBI. From 2009 to 2011, the programs of CADdemo@CARS and the CAD Demonstration Workshop at SPIE Medical Imaging were sought for the key word “retrieval” in the title. The systems identified were analyzed and compared according to the hierarchy of gaps for CBIR systems. In total, 70 software demonstrations were analyzed. 5 systems were identified meeting the criterions. The fields of application are (i) bone age assessment, (ii) bone fractures, (iii) interstitial lung diseases, and (iv) mammography. Bridging the particular gaps of semantics, feature extraction, feature structure, and evaluation have been addressed most frequently. In specific application domains, CBIR technology is available for clinical practice. While system development has mainly focused on bridging content and feature gaps, performance and usability have become increasingly important. The evaluation must be based on a larger set of reference data, and workflow integration must be achieved before CBIR-CAD is really established in clinical practice. PMID:21892374

Exome Sequencing Discerns Syndromes in Patients from Consanguineous Families with Congenital Anomalies of the Kidneys and Urinary Tract.

PubMed

Vivante, Asaf; Hwang, Daw-Yang; Kohl, Stefan; Chen, Jing; Shril, Shirlee; Schulz, Julian; van der Ven, Amelie; Daouk, Ghaleb; Soliman, Neveen A; Kumar, Aravind Selvin; Senguttuvan, Prabha; Kehinde, Elijah O; Tasic, Velibor; Hildebrandt, Friedhelm

2017-01-01

Congenital anomalies of the kidneys and urinary tract (CAKUT) are the leading cause of CKD in children, featuring a broad variety of malformations. A monogenic cause can be detected in around 12% of patients. However, the morphologic clinical phenotype of CAKUT frequently does not indicate specific genes to be examined. To determine the likelihood of detecting causative recessive mutations by whole-exome sequencing (WES), we analyzed individuals with CAKUT from 33 different consanguineous families. Using homozygosity mapping and WES, we identified the causative mutations in nine of the 33 families studied (27%). We detected recessive mutations in nine known disease-causing genes: ZBTB24, WFS1, HPSE2, ATRX, ASPH, AGXT, AQP2, CTNS, and PKHD1 Notably, when mutated, these genes cause multiorgan syndromes that may include CAKUT as a feature (syndromic CAKUT) or cause renal diseases that may manifest as phenocopies of CAKUT. None of the above monogenic disease-causing genes were suspected on clinical grounds before this study. Follow-up clinical characterization of those patients allowed us to revise and detect relevant new clinical features in a more appropriate pathogenetic context. Thus, applying WES to the diagnostic approach in CAKUT provides opportunities for an accurate and early etiology-based diagnosis and improved clinical management. Copyright © 2016 by the American Society of Nephrology.

Recent Methods for Purification and Structure Determination of Oligonucleotides.

PubMed

Zhang, Qiulong; Lv, Huanhuan; Wang, Lili; Chen, Man; Li, Fangfei; Liang, Chao; Yu, Yuanyuan; Jiang, Feng; Lu, Aiping; Zhang, Ge

2016-12-18

Aptamers are single-stranded DNA or RNA oligonucleotides that can interact with target molecules through specific three-dimensional structures. The excellent features, such as high specificity and affinity for target proteins, small size, chemical stability, low immunogenicity, facile chemical synthesis, versatility in structural design and engineering, and accessible for site-specific modifications with functional moieties, make aptamers attractive molecules in the fields of clinical diagnostics and biopharmaceutical therapeutics. However, difficulties in purification and structural identification of aptamers remain a major impediment to their broad clinical application. In this mini-review, we present the recently attractive developments regarding the purification and identification of aptamers. We also discuss the advantages, limitations, and prospects for the major methods applied in purifying and identifying aptamers, which could facilitate the application of aptamers.

Rectal bleeding, fecal incontinence, and high stool frequency after conformal radiotherapy for prostate cancer: Normal tissue complication probability modeling

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

Peeters, Stephanie; Hoogeman, Mischa S.; Heemsbergen, Wilma D.

2006-09-01

Purpose: To analyze whether inclusion of predisposing clinical features in the Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) model improves the estimation of late gastrointestinal toxicity. Methods and Materials: This study includes 468 prostate cancer patients participating in a randomized trial comparing 68 with 78 Gy. We fitted the probability of developing late toxicity within 3 years (rectal bleeding, high stool frequency, and fecal incontinence) with the original, and a modified LKB model, in which a clinical feature (e.g., history of abdominal surgery) was taken into account by fitting subset specific TD50s. The ratio of these TD50s is the dose-modifyingmore » factor for that clinical feature. Dose distributions of anorectal (bleeding and frequency) and anal wall (fecal incontinence) were used. Results: The modified LKB model gave significantly better fits than the original LKB model. Patients with a history of abdominal surgery had a lower tolerance to radiation than did patients without previous surgery, with a dose-modifying factor of 1.1 for bleeding and of 2.5 for fecal incontinence. The dose-response curve for bleeding was approximately two times steeper than that for frequency and three times steeper than that for fecal incontinence. Conclusions: Inclusion of predisposing clinical features significantly improved the estimation of the NTCP. For patients with a history of abdominal surgery, more severe dose constraints should therefore be used during treatment plan optimization.« less

Clinical and pathological features of amyotrophic lateral sclerosis caused by mutation in the C9ORF72 gene on chromosome 9p.

PubMed

Stewart, Heather; Rutherford, Nicola J; Briemberg, Hannah; Krieger, Charles; Cashman, Neil; Fabros, Marife; Baker, Matt; Fok, Alice; DeJesus-Hernandez, Mariely; Eisen, Andrew; Rademakers, Rosa; Mackenzie, Ian R A

2012-03-01

Two studies recently identified a GGGGCC hexanucleotide repeat expansion in a non-coding region of the chromosome 9 open-reading frame 72 gene (C9ORF72) as the cause of chromosome 9p-linked amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). In a cohort of 231 probands with ALS, we identified the C9ORF72 mutation in 17 familial (27.4%) and six sporadic (3.6%) cases. Patients with the mutation presented with typical motor features of ALS, although subjects with the C9ORF72 mutation had more frequent bulbar onset, compared to those without this mutation. Dementia was significantly more common in ALS patients and families with the C9ORF72 mutation and was usually early-onset FTD. There was striking clinical heterogeneity among the members of individual families with the mutation. The associated neuropathology was a combination of ALS with TDP-ir inclusions and FTLD-TDP. In addition to TDP-43-immunoreactive pathology, a consistent and specific feature of cases with the C9ORF72 mutation was the presence of ubiquitin-positive, TDP-43-negative inclusions in a variety of neuroanatomical regions, such as the cerebellar cortex. These findings support the C9ORF72 mutation as an important newly recognized cause of ALS, provide a more detailed characterization of the associated clinical and pathological features and further demonstrate the clinical and molecular overlap between ALS and FTD.

27 The DiPEP (Diagnosis of PE in Pregnancy) study: can clinical assessment, d-dimer or chest x-ray be used to select pregnant or postpartum women with suspected PE for diagnostic imaging?

PubMed

Goodacre, Steve; Horspool, Kimberley; Nelson-Piercy, Catherine; Knight, Marian; Shephard, Neil; Lecky, Fiona; Thomas, Steven; Hunt, Beverley; Fuller, Gordon

2017-12-01

To determine whether clinical features (in the form of a clinical decision rule) or d-dimer can be used to select pregnant or postpartum women with suspected PE for diagnostic imaging. Observational cohort study augmented with additional cases. Consultant-led maternity units participating in the UK Obstetric Surveillance System (UKOSS) and emergency departments and maternity units at eleven prospectively recruiting sites. 198 pregnant or postpartum women with diagnosed PE identified through UKOSS and 324 pregnant or postpartum women with suspected PE from prospectively recruiting sites. Data were collected relating to clinical features, elements of clinical decision rules, d-dimer measurements, diagnostic imaging, treatment for PE and adverse outcomes. Women were classified as having or not having PE on the basis of diagnostic imaging, treatment and subsequent adverse outcomes. Primary analysis was limited to women with conclusive diagnostic imaging. Secondary analyses included women with clinically diagnosed or ruled out PE. The primary analysis included 181 women with PE and 259 without. Most clinical features showed no association with PE. The only exceptions were number of previous pregnancies over 24 weeks (p=0.017), no varicose veins (p=0.045), no recent long haul travel (p=0.006), recent surgery including caesarean section (p=0.001), increased temperature (p=0.003), low oxygen saturation (p<0.001), PE-related chest x-ray abnormality (p=0.01) and other chest x-ray abnormality (p=0.001).Clinical decision rules had areas under the receiver-operator characteristic curve ranging from 0.577 to 0.732. No clinically useful threshold for decision-making was identified for any rule. The sensitivities and specificities of d-dimer were 88.4% and 8.8% using the standard laboratory threshold and 69.8% and 32.8% using a pregnancy-specific threshold. Clinical decision rules, d-dimer and chest x-ray should not be used to select pregnant or postpartum women with suspected PE for diagnostic imaging. © 2017, 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.

Model-based and Model-free Machine Learning Techniques for Diagnostic Prediction and Classification of Clinical Outcomes in Parkinson's Disease.

PubMed

Gao, Chao; Sun, Hanbo; Wang, Tuo; Tang, Ming; Bohnen, Nicolaas I; Müller, Martijn L T M; Herman, Talia; Giladi, Nir; Kalinin, Alexandr; Spino, Cathie; Dauer, William; Hausdorff, Jeffrey M; Dinov, Ivo D

2018-05-08

In this study, we apply a multidisciplinary approach to investigate falls in PD patients using clinical, demographic and neuroimaging data from two independent initiatives (University of Michigan and Tel Aviv Sourasky Medical Center). Using machine learning techniques, we construct predictive models to discriminate fallers and non-fallers. Through controlled feature selection, we identified the most salient predictors of patient falls including gait speed, Hoehn and Yahr stage, postural instability and gait difficulty-related measurements. The model-based and model-free analytical methods we employed included logistic regression, random forests, support vector machines, and XGboost. The reliability of the forecasts was assessed by internal statistical (5-fold) cross validation as well as by external out-of-bag validation. Four specific challenges were addressed in the study: Challenge 1, develop a protocol for harmonizing and aggregating complex, multisource, and multi-site Parkinson's disease data; Challenge 2, identify salient predictive features associated with specific clinical traits, e.g., patient falls; Challenge 3, forecast patient falls and evaluate the classification performance; and Challenge 4, predict tremor dominance (TD) vs. posture instability and gait difficulty (PIGD). Our findings suggest that, compared to other approaches, model-free machine learning based techniques provide a more reliable clinical outcome forecasting of falls in Parkinson's patients, for example, with a classification accuracy of about 70-80%.

Sporadic periventricular nodular heterotopia: Classification, phenotype and correlation with Filamin A mutations.

PubMed

Liu, Wenyu; Yan, Bo; An, Dongmei; Xiao, Jiahe; Hu, Fayun; Zhou, Dong

2017-07-01

The purpose of this study was to better delineate the clinical spectrum of periventricular nodular heterotopia (PNH) in a large patient population after long term follow up. Specifically, this study aimed to relate PNH subtypes to clinical or epileptic outcomes, epileptic discharges and underlying Filamin A (FLNA) mutations by analyzing anatomical features. The study included 100 patients with radiologically confirmed nodular heterotopia. Patients' FLNA gene sequences and medical records were analyzed. Two-sided Chi-square test and Fisher's exact t-test were used to assess associations between the distribution of PNHs and specific clinical features. Based on imaging data, patients were subdivided into three groups: (a) classical (bilateral frontal and body, n=41 patients), (b) bilateral asymmetrical or posterior (n=16) and (c) unilateral heterotopia (n=43). Most patients with classical heterotopia were females (P=0.033) and were likely to have arachnoid cysts (P=0.025) and cardiac abnormalities (P=0.041), but were mostly seizure-free. Additionally, hippocampal abnormalities (P=0.022), neurological deficits (P=0.028) and cerebellar abnormalities (P=0.005) were more common in patients with bilateral asymmetrical heterotopia. Patients with unilateral heterotopia were prone to develop refractory epilepsy (P=0.041). FLNA mutations were identified in 8 patients. Each group's distinctive genetic mutations, epileptic discharge patterns and overall clinical outcomes confirm that the proposed classification system is reliable. These findings could not only be an indicator of a more severe morphological and clinical phenotype, but could also have clinical implications with respect to the epilepsy management and optimization of therapeutic options. Copyright © 2017 Elsevier B.V. All rights reserved.

Association of Systemic Lupus Erythematosus Clinical Features with European Population Genetic Substructure

PubMed Central

Calaza, Manuel; Witte, Torsten; Papasteriades, Chryssa; Marchini, Maurizio; Migliaresi, Sergio; Kovacs, Attila; Ordi-Ros, Josep; Bijl, Marc; Santos, Maria Jose; Ruzickova, Sarka; Pullmann, Rudolf; Carreira, Patricia; Skopouli, Fotini N.; D'Alfonso, Sandra; Sebastiani, Gian Domenico; Suarez, Ana; Blanco, Francisco J.; Gomez-Reino, Juan J.; Gonzalez, Antonio

2011-01-01

Systemic Lupus Erythematosus (SLE) is an autoimmune disease with a very varied spectrum of clinical manifestations that could be partly determined by genetic factors. We aimed to determine the relationship between prevalence of 11 clinical features and age of disease onset with European population genetic substructure. Data from 1413 patients of European ancestry recruited in nine countries was tested for association with genotypes of top ancestry informative markers. This analysis was done with logistic regression between phenotypes and genotypes or principal components extracted from them. We used a genetic additive model and adjusted for gender and disease duration. Three clinical features showed association with ancestry informative markers: autoantibody production defined as immunologic disorder (P = 6.8×10−4), oral ulcers (P = 6.9×10−4) and photosensitivity (P = 0.002). Immunologic disorder was associated with genotypes more common in Southern European ancestries, whereas the opposite trend was observed for photosensitivity. Oral ulcers were specifically more common in patients of Spanish and Portuguese self-reported ancestry. These results should be taken into account in future research and suggest new hypotheses and possible underlying mechanisms to be investigated. A first hypothesis linking photosensitivity with variation in skin pigmentation is suggested. PMID:22194982

Duodenal L cell density correlates with features of metabolic syndrome and plasma metabolites.

PubMed

van Baar, Annieke C G; Prodan, Andrei; Wahlgren, Camilla D; Poulsen, Steen S; Knop, Filip K; Groen, Albert K; Bergman, Jacques J; Nieuwdorp, Max; Levin, Evgeni

2018-05-01

Enteroendocrine cells are essential for the regulation of glucose metabolism, but it is unknown whether they are associated with clinical features of metabolic syndrome (MetS) and fasting plasma metabolites. We aimed to identify fasting plasma metabolites that associate with duodenal L cell, K cell and delta cell densities in subjects with MetS with ranging levels of insulin resistance. In this cross-sectional study, we evaluated L, K and delta cell density in duodenal biopsies from treatment-naïve males with MetS using machine-learning methodology. We identified specific clinical biomarkers and plasma metabolites associated with L cell and delta cell density. L cell density was associated with increased plasma metabolite levels including symmetrical dimethylarginine, 3-aminoisobutyric acid, kynurenine and glycine. In turn, these L cell-linked fasting plasma metabolites correlated with clinical features of MetS. Our results indicate a link between duodenal L cells, plasma metabolites and clinical characteristics of MetS. We conclude that duodenal L cells associate with plasma metabolites that have been implicated in human glucose metabolism homeostasis. Disentangling the causal relation between L cells and these metabolites might help to improve the (small intestinal-driven) pathophysiology behind insulin resistance in human obesity. © 2018 The authors.

Giant cell angiofibroma misdiagnosed as a vascular malformation and treated with absolute alcohol for one year: a case report and review of the literature

PubMed Central

2014-01-01

Purpose To present the clinical, imaging, pathological and immunohistochemical features of giant cell angiofibroma (GCA). Case presentation In this paper we report an atypical case of a GCA extending from the parotid to the parapharyngeal space. The lesion was being treated as a vascular malformation for one year prior to surgical removal. We summarize the clinical manifestations, imaging, pathological and molecular features of this rare disease. After complete surgical removal of the tumor, immunohistochemical analysis revealed strong positivity for the mesenchymal markers vimentin, CD34, CD31 and CD99 in neoplastic cells. Tumor proliferation antigen marker Ki67 was partly positive (<5% of cells). Tumor cells were negative for muscle-specific actin, epithelial membrane antigen, smooth muscle actin, cytokeratin pan, S100, desmin, glial fibrillary acidic protein, myogenin, MyoD1 and F8. The morphological and immunohistochemical profile was consistent with the diagnosis of GCA. Conclusion GCA is a rare soft tissue tumor that can easily be misdiagnosed in the clinical preoperative setting. In view of the clinical, pathological and molecular features of the tumor, complete surgical removal is the current optimal treatment option, providing accurate diagnosis and low to minimal recurrence rate. PMID:24758544

Stones, bones, and heredity.

PubMed

Milliner, Dawn S

2006-07-01

Genetic disorders of mineral metabolism cause urolithiasis, renal disease, and osteodystrophy. Most are rare, such that the full spectrum of clinical expression is difficult to appreciate. Diagnosis is further complicated by overlap of clinical features. Dent's disease and primary hyperoxaluria, inherited causes of calcium urolithiasis, are both associated with nephrocalcinosis and urolithiasis in early childhood and renal failure that can occur at any age but is seen more often in adulthood. Bone disease is an inconsistent feature of each. Dent's disease is caused by mutations of the CLCN-5 gene with impaired kidney-specific CLC-5 chloride channel expression in the proximal tubule, thick ascending limb of Henle, and the collecting ducts. Resulting hypercalciuria and proximal tubule dysfunction, including phosphate wasting, are primarily responsible for the clinical manifestations. Low-molecular-weight proteinuria is characteristic. Definitive diagnosis is made by DNA mutation analysis. Primary hyperoxaluria, type I, is due to mutations of the AGXT gene leading to deficient hepatic alanine-glyoxylate aminotransferase activity. Marked overproduction of oxalate by hepatic cells results in the hyperoxaluria responsible for clinical features. Definitive diagnosis is by liver biopsy with measurement of enzyme activity, with DNA mutation analysis used increasingly as mutations and their frequency are defined. These disorders of calcium urolithiasis illustrate the value of molecular medicine for diagnosis and the promise it provides for innovative and more effective future treatments.

Defining competency-based evaluation objectives in family medicine

PubMed Central

Lawrence, Kathrine; Allen, Tim; Brailovsky, Carlos; Crichton, Tom; Bethune, Cheri; Donoff, Michel; Laughlin, Tom; Wetmore, Stephen; Carpentier, Marie-Pierre; Visser, Shaun

2011-01-01

Abstract Objective To develop key features for priority topics previously identified by the College of Family Physicians of Canada that, together with skill dimensions and phases of the clinical encounter, broadly describe competence in family medicine. Design Modified nominal group methodology, which was used to develop key features for each priority topic through an iterative process. Setting The College of Family Physicians of Canada. Participants An expert group of 7 family physicians and 1 educational consultant, all of whom had experience in assessing competence in family medicine. Group members represented the Canadian family medicine context with respect to region, sex, language, community type, and experience. Methods The group used a modified Delphi process to derive a detailed operational definition of competence, using multiple iterations until consensus was achieved for the items under discussion. The group met 3 to 4 times a year from 2000 to 2007. Main findings The group analyzed 99 topics and generated 773 key features. There were 2 to 20 (average 7.8) key features per topic; 63% of the key features focused on the diagnostic phase of the clinical encounter. Conclusion This project expands previous descriptions of the process of generating key features for assessment, and removes this process from the context of written examinations. A key-features analysis of topics focuses on higher-order cognitive processes of clinical competence. The project did not define all the skill dimensions of competence to the same degree, but it clearly identified those requiring further definition. This work generates part of a discipline-specific, competency-based definition of family medicine for assessment purposes. It limits the domain for assessment purposes, which is an advantage for the teaching and assessment of learners. A validation study on the content of this work would ensure that it truly reflects competence in family medicine. PMID:21998245

[Sensitivity and specificity of optical coherence tomography in diagnosing polypoidal choroidal vasculopathy].

PubMed

Zhang, Yi; Yao, Jing; Wang, Xiao-Hua; Zhao, Lin; Wang, Li-Jun; Wang, Jian-Ming; Zhou, Ai-Yi

2016-02-20

To establish the diagnostic criteria for polypoidal choroidal vasculopathy (PCV) based on spectral-domain optical coherence tomography (SD OCT) by evaluating the sensitivity and specificity of SD OCT in differentiating PCV from wet age-related macular degeneration (wAMD). The clinical data were reviewed for 62 patients (63 eyes) with the initial diagnosis of PCV or wAMD between August, 2012 and June, 2016. Twenty-four patients (25 eyes) were diagnosed to have PCV and 38 (38 eyes) had wAMD based on findings by fundus photography, fluorescein angiography (FFA) and indocyanine green angiography (ICGA). Among the 6 features of SD OCT, namely a sharp RPED peak, double-layer sign, multiple RPED, an RPED notch, a hyporeflective lumen representing polyps, and hyperreflective intraretinal hard exudates, findings of the first two features and at least one of the other features sufficed the diagnosis of PCV; in the absence of the first two features, the diagnosis of PCV was also made when at least 3 of the other features were present simultaneously. The sensitivity and specificity of SD OCT-based diagnosis were estimated by comparison with the gold standard ICGA-based diagnosis. In the 25 eyes with an established diagnosis of PCV, 23 eyes (92.0%) met the diagnostic criteria based on SD OCT findings; in the 38 eyes with the diagnosis of wAMD, only 4 eyes (10.5%) met the criteria. The sensitivity and specificity of SD OCT-based diagnosis of PCV was 92.0% and 89.5%, respectively. s We established the diagnostic criteria for PCV based on SD OCT findings with a high sensitivity and specificity. SD OCT shows a strong capacity for differentiating PCV from wAMD.

Distinct Clinical Features and Outcomes in Motor Neuron Disease Associated with Behavioural Variant Frontotemporal Dementia.

PubMed

Cortés-Vicente, Elena; Turon-Sans, Janina; Gelpi, Ellen; Clarimón, Jordi; Borrego-Écija, Sergi; Dols-Icardo, Oriol; Illán-Gala, Ignacio; Lleó, Alberto; Illa, Isabel; Blesa, Rafael; Al-Chalabi, Ammar; Rojas-García, Ricard

2018-06-08

To determine the motor phenotype and outcome in a clinically ascertained group of patients with motor neuron disease (MND) and frontotemporal dementia (FTD). This is an observational retrospective clinical study of patients fulfilling the clinical criteria for MND-FTD. A contemporary series of patients with amyotrophic lateral sclerosis (ALS) without dementia were included for comparison. Demographic, clinical, genetic, and neuropathological data were collected. A descriptive and comparative data analysis was performed. We identified 22 patients with MND-FTD. Selective distal upper limb muscle weakness and atrophy with non-significant lower limb weakness during follow-up was the most frequent motor pattern, present in 18 patients - in 15 of them associated with severe dysphagia. Aspiration pneumonia was the most common cause of death (12/19; 63%) despite gastrostomy. One-third of the patients did not develop upper motor neuron dysfunction. When compared to classic ALS without dementia (n = 162), these features were significantly different. A neuro-pathological examination was performed on 7 patients, and it confirmed the presence of MND with TDP43 protein aggregates in all patients. The MND-FTD patients frequently displayed a distinctive motor pattern characterized by weakness and atrophy in distal upper limb muscles and dysphagia, with no or little spreading to other regions. These features may help to define specific subgroups of patients, which is important with regard to clinical management, outcome, and research. © 2018 S. Karger AG, Basel.

Sparse Feature Selection Identifies H2A.Z as a Novel, Pattern-Specific Biomarker for Asymmetrically Self-Renewing Distributed Stem Cells

PubMed Central

Huh, Yang Hoon; Noh, Minsoo; Burden, Frank R.; Chen, Jennifer C.; Winkler, David A.; Sherley, James L.

2015-01-01

There is a long-standing unmet clinical need for biomarkers with high specificity for distributed stem cells (DSCs) in tissues, or for use in diagnostic and therapeutic cell preparations (e.g., bone marrow). Although DSCs are essential for tissue maintenance and repair, accurate determination of their numbers for medical applications has been problematic. Previous searches for biomarkers expressed specifically in DSCs were hampered by difficulty obtaining pure DSCs and by the challenges in mining complex molecular expression data. To identify DSC such useful and specific biomarkers, we combined a novel sparse feature selection method with combinatorial molecular expression data focused on asymmetric self-renewal, a conspicuous property of DSCs. The analysis identified reduced expression of the histone H2A variant H2A.Z as a superior molecular discriminator for DSC asymmetric self-renewal. Subsequent molecular expression studies showed H2A.Z to be a novel “pattern-specific biomarker” for asymmetrically self-renewing cells with sufficient specificity to count asymmetrically self-renewing DSCs in vitro and potentially in situ. PMID:25636161

Conversion Discriminative Analysis on Mild Cognitive Impairment Using Multiple Cortical Features from MR Images.

PubMed

Guo, Shengwen; Lai, Chunren; Wu, Congling; Cen, Guiyin

2017-01-01

Neuroimaging measurements derived from magnetic resonance imaging provide important information required for detecting changes related to the progression of mild cognitive impairment (MCI). Cortical features and changes play a crucial role in revealing unique anatomical patterns of brain regions, and further differentiate MCI patients from normal states. Four cortical features, namely, gray matter volume, cortical thickness, surface area, and mean curvature, were explored for discriminative analysis among three groups including the stable MCI (sMCI), the converted MCI (cMCI), and the normal control (NC) groups. In this study, 158 subjects (72 NC, 46 sMCI, and 40 cMCI) were selected from the Alzheimer's Disease Neuroimaging Initiative. A sparse-constrained regression model based on the l2-1-norm was introduced to reduce the feature dimensionality and retrieve essential features for the discrimination of the three groups by using a support vector machine (SVM). An optimized strategy of feature addition based on the weight of each feature was adopted for the SVM classifier in order to achieve the best classification performance. The baseline cortical features combined with the longitudinal measurements for 2 years of follow-up data yielded prominent classification results. In particular, the cortical thickness produced a classification with 98.84% accuracy, 97.5% sensitivity, and 100% specificity for the sMCI-cMCI comparison; 92.37% accuracy, 84.78% sensitivity, and 97.22% specificity for the cMCI-NC comparison; and 93.75% accuracy, 92.5% sensitivity, and 94.44% specificity for the sMCI-NC comparison. The best performances obtained by the SVM classifier using the essential features were 5-40% more than those using all of the retained features. The feasibility of the cortical features for the recognition of anatomical patterns was certified; thus, the proposed method has the potential to improve the clinical diagnosis of sub-types of MCI and predict the risk of its conversion to Alzheimer's disease.

Breed-Specific Magnetic Resonance Imaging Characteristics of Necrotizing Encephalitis in Dogs

PubMed Central

Flegel, Thomas

2017-01-01

Diagnosing necrotizing encephalitis, with its subcategories of necrotizing leukoencephalitis and necrotizing meningoencephalitis, based on magnetic resonance imaging alone can be challenging. However, there are breed-specific imaging characteristics in both subcategories that allow establishing a clinical diagnosis with a relatively high degree of certainty. Typical breed specific imaging features, such as lesion distribution, signal intensity, contrast enhancement, and gross changes of brain structure (midline shift, ventriculomegaly, and brain herniation) are summarized here, using current literature, for the most commonly affected canine breeds: Yorkshire Terrier, French Bulldog, Pug, and Chihuahua. PMID:29255715

Is Dysfunctional Use of the Mobile Phone a Behavioural Addiction? Confronting Symptom-Based Versus Process-Based Approaches.

PubMed

Billieux, Joël; Philippot, Pierre; Schmid, Cécile; Maurage, Pierre; De Mol, Jan; Van der Linden, Martial

2015-01-01

Dysfunctional use of the mobile phone has often been conceptualized as a 'behavioural addiction' that shares most features with drug addictions. In the current article, we challenge the clinical utility of the addiction model as applied to mobile phone overuse. We describe the case of a woman who overuses her mobile phone from two distinct approaches: (1) a symptom-based categorical approach inspired from the addiction model of dysfunctional mobile phone use and (2) a process-based approach resulting from an idiosyncratic clinical case conceptualization. In the case depicted here, the addiction model was shown to lead to standardized and non-relevant treatment, whereas the clinical case conceptualization allowed identification of specific psychological processes that can be targeted with specific, empirically based psychological interventions. This finding highlights that conceptualizing excessive behaviours (e.g., gambling and sex) within the addiction model can be a simplification of an individual's psychological functioning, offering only limited clinical relevance. The addiction model, applied to excessive behaviours (e.g., gambling, sex and Internet-related activities) may lead to non-relevant standardized treatments. Clinical case conceptualization allowed identification of specific psychological processes that can be targeted with specific empirically based psychological interventions. The biomedical model might lead to the simplification of an individual's psychological functioning with limited clinical relevance. Copyright © 2014 John Wiley & Sons, Ltd.

Enabling Low-Power, Multi-Modal Neural Interfaces Through a Common, Low-Bandwidth Feature Space.

PubMed

Irwin, Zachary T; Thompson, David E; Schroeder, Karen E; Tat, Derek M; Hassani, Ali; Bullard, Autumn J; Woo, Shoshana L; Urbanchek, Melanie G; Sachs, Adam J; Cederna, Paul S; Stacey, William C; Patil, Parag G; Chestek, Cynthia A

2016-05-01

Brain-Machine Interfaces (BMIs) have shown great potential for generating prosthetic control signals. Translating BMIs into the clinic requires fully implantable, wireless systems; however, current solutions have high power requirements which limit their usability. Lowering this power consumption typically limits the system to a single neural modality, or signal type, and thus to a relatively small clinical market. Here, we address both of these issues by investigating the use of signal power in a single narrow frequency band as a decoding feature for extracting information from electrocorticographic (ECoG), electromyographic (EMG), and intracortical neural data. We have designed and tested the Multi-modal Implantable Neural Interface (MINI), a wireless recording system which extracts and transmits signal power in a single, configurable frequency band. In prerecorded datasets, we used the MINI to explore low frequency signal features and any resulting tradeoff between power savings and decoding performance losses. When processing intracortical data, the MINI achieved a power consumption 89.7% less than a more typical system designed to extract action potential waveforms. When processing ECoG and EMG data, the MINI achieved similar power reductions of 62.7% and 78.8%. At the same time, using the single signal feature extracted by the MINI, we were able to decode all three modalities with less than a 9% drop in accuracy relative to using high-bandwidth, modality-specific signal features. We believe this system architecture can be used to produce a viable, cost-effective, clinical BMI.

Contrast-enhanced MRI compared with the physical examination in the evaluation of disease activity in juvenile idiopathic arthritis.

PubMed

Hemke, Robert; Maas, Mario; van Veenendaal, Mira; Dolman, Koert M; van Rossum, Marion A J; van den Berg, J Merlijn; Kuijpers, Taco W

2014-02-01

To assess the value of magnetic resonance imaging (MRI) in discriminating between active and inactive juvenile idiopathic arthritis (JIA) patients and to compare physical examination outcomes with MRI outcomes in the assessment of disease status in JIA patients. Consecutive JIA patients with knee involvement were prospectively studied using an open-bore MRI. Imaging findings from 146 JIA patients were analysed (59.6% female; mean age, 12.9 years). Patients were classified as clinically active or inactive. MRI features were evaluated using the JAMRIS system, comprising validated scores for synovial hypertrophy, bone marrow oedema, cartilage lesions and bone erosions. Inter-reader reliability was good for all MRI features (intra-class correlation coefficient [ICC] = 0.87-0.94). No differences were found between the two groups regarding MRI scores of bone marrow oedema, cartilage lesions or bone erosions. Synovial hypertrophy scores differed significantly between groups (P = 0.016). Nonetheless, synovial hypertrophy was also present in 14 JIA patients (35.9%) with clinically inactive disease. Of JIA patients considered clinically active, 48.6% showed no signs of MRI-based synovitis. MRI can discriminate between clinically active and inactive JIA patients. However, physical examination is neither very sensitive nor specific in evaluating JIA disease activity compared with MRI. Subclinical synovitis was present in >35% of presumed clinically inactive patients. • MRI is sensitive for evaluating juvenile idiopathic arthritis (JIA) disease activity. • Contrast-enhanced MRI can distinguish clinically active and inactive JIA patients. • Subclinical synovitis is present in 35.9 % of presumed clinically inactive patients. • Physical examination is neither sensitive nor specific in evaluating JIA disease activity.

[HIV/AIDS masks in a therapist's practice].

PubMed

Roshchina, A A; Ponomareva, E Yu; Rebrov, A P

2015-01-01

To investigate clinical manifestations and diagnostic difficulties in patients with HIV/AIDS in the practice of therapeutic units of a multidisciplinary hospital. The investigation included 65 HIV/AIDS patients admitted to the therapy units of a Saratov Regional clinical hospital in 2007 to 2011. The clinical features of HIV/AIDS, immunological status, and viral load were studied. The structure of the clinical manifestation of HIV/AIDS showed a preponderance of lung injury in 45 (69%) patients. There were hematological disorders in 38 (58%) patients and nephropathy in 33 (51 %); 11 (17%) patients were diagnosed with infective endocarditis. Rheumatic symptoms and syndromes mimicking HIV/AIDS were found in 10 (15.4%) patients. The degree of immune disorders was most severe in patients with pulmonary dissemination and rheumatic masks and mutually related to the rate of cutaneous manifestations. The specific features of lung injury, infective endocarditis, pulmonary hypertension, rheumatic symptoms, and kidney injury were discussed in HIV/AIDS patients having different causes for admission to specialized therapy units. In connection with the clinical polymorphism of HIV/AIDS, physicians of all specialties should be alert for the possible clinical manifestations of this disease to timely examine patients.

Metabolomic biosignature differentiates melancholic depressive patients from healthy controls.

PubMed

Liu, Yashu; Yieh, Lynn; Yang, Tao; Drinkenburg, Wilhelmus; Peeters, Pieter; Steckler, Thomas; Narayan, Vaibhav A; Wittenberg, Gayle; Ye, Jieping

2016-08-23

Major depressive disorder (MDD) is a heterogeneous disease at the level of clinical symptoms, and this heterogeneity is likely reflected at the level of biology. Two clinical subtypes within MDD that have garnered interest are "melancholic depression" and "anxious depression". Metabolomics enables us to characterize hundreds of small molecules that comprise the metabolome, and recent work suggests the blood metabolome may be able to inform treatment decisions for MDD, however work is at an early stage. Here we examine a metabolomics data set to (1) test whether clinically homogenous MDD subtypes are also more biologically homogeneous, and hence more predictiable, (2) devise a robust machine learning framework that preserves biological meaning, and (3) describe the metabolomic biosignature for melancholic depression. With the proposed computational system we achieves around 80 % classification accuracy, sensitivity and specificity for melancholic depression, but only ~72 % for anxious depression or MDD, suggesting the blood metabolome contains more information about melancholic depression.. We develop an ensemble feature selection framework (EFSF) in which features are first clustered, and learning then takes place on the cluster centroids, retaining information about correlated features during the feature selection process rather than discarding them as most machine learning methods will do. Analysis of the most discriminative feature clusters revealed differences in metabolic classes such as amino acids and lipids as well as pathways studied extensively in MDD such as the activation of cortisol in chronic stress. We find the greater clinical homogeneity does indeed lead to better prediction based on biological measurements in the case of melancholic depression. Melancholic depression is shown to be associated with changes in amino acids, catecholamines, lipids, stress hormones, and immune-related metabolites. The proposed computational framework can be adapted to analyze data from many other biomedical applications where the data has similar characteristics.

Automated assessment of levodopa-induced dyskinesia: Evaluating the responsiveness of video-based features.

PubMed

Li, Michael H; Mestre, Tiago A; Fox, Susan H; Taati, Babak

2018-05-05

Technological solutions for quantifying Parkinson's disease (PD) symptoms may provide an objective means to track response to treatment, including side effects such as levodopa-induced dyskinesia. Vision-based systems are advantageous as they do not require physical contact with the body and have minimal instrumentation compared to wearables. We have developed a vision-based system to quantify a change in dyskinesia as reported by patients using 2D videos of clinical assessments during acute levodopa infusions. Nine participants with PD completed a total of 16 levodopa infusions, where they were asked to report important changes in dyskinesia (i.e. onset and remission). Participants were simultaneously rated using the UDysRS Part III (from video recordings analyzed post-hoc). Body joint positions and movements were tracked using a state-of-the-art deep learning pose estimation algorithm applied to the videos. 416 features (e.g. kinematics, frequency distribution) were extracted to characterize movements. The sensitivity and specificity of each feature to patient-reported changes in dyskinesia severity was computed and compared with physician-rated results. Features achieved similar or superior performance to the UDysRS for detecting the onset and remission of dyskinesia. The best AUC for detecting onset of dyskinesia was 0.822 and for remission of dyskinesia was 0.958, compared to 0.826 and 0.802 for the UDysRS. Video-based features may provide an objective means of quantifying the severity of levodopa-induced dyskinesia, and have responsiveness as good or better than the clinically-rated UDysRS. The results demonstrate encouraging evidence for future integration of video-based technology into clinical research and eventually clinical practice. Copyright © 2018 Elsevier Ltd. All rights reserved.

Clinical and psychopathological features associated with treatment-emergent mania in bipolar-II depressed outpatients exposed to antidepressants.

PubMed

Fornaro, Michele; Anastasia, Annalisa; Monaco, Francesco; Novello, Stefano; Fusco, Andrea; Iasevoli, Felice; De Berardis, Domenico; Veronese, Nicola; Solmi, Marco; de Bartolomeis, Andrea

2018-07-01

Treatment-emergent affective switch (TEAS), including treatment-emergent mania (TEM), carry significant burden in the clinical management of bipolar depression, whereas the use of antidepressants raises both efficacy, safety and tolerability concerns. The present study assesses the prevalence and clinical correlates of TEM in selected sample of Bipolar Disorder (BD) Type-II (BD-II) acute depression outpatients. Post-hoc analysis of the clinical and psychopathological features associated with TEM among 91 BD-II depressed outpatients exposed to antidepressants. Second-generation antipsychotics (SGA) (p = .005), lithium (≤ .001), cyclothymic/irritable/hyperthymic temperaments (p = ≤ .001; p = .001; p = .003, respectively), rapid-cycling (p = .005) and depressive mixed features (p = .003) differed between TEM + cases vs. TEM - controls. Upon multinomial logistic regression, the accounted psychopathological features correctly classified as much as 88.6% of TEM + cases (35/91 overall sample, or 38.46% of the sample), yet not statistically significantly [Exp(B) = .032; p = ns]. Specifically, lithium [B = - 2.385; p = .001], SGAs [B = - 2.354; p = .002] predicted lower rates of TEM + in contrast to the number of lifetime previous psychiatric hospitalizations [B = 2.380; p = .002], whereas mixed features did not [B = 1.267; p = ns]. Post-hoc analysis. Lack of systematic pharmacological history record; chance of recall bias and Berkson's biases. Permissive operational criterion for TEM. Relatively small sample size. Cyclothymic temperament and mixed depression discriminated TEM + between TEM - cases, although only lithium and the SGAs reliably predicted TEM +/- grouping. Larger-sampled/powered longitudinal replication studies are warranted to allow firm conclusions on the matter, ideally contributing to the identification of clear-cut sub-phenotypes of BD towards patient-tailored-pharmacotherapy. Copyright © 2018 Elsevier B.V. All rights reserved.

Assessing the Pathogenicity of Insertion and Deletion Variants with the Variant Effect Scoring Tool (VEST-Indel).

PubMed

Douville, Christopher; Masica, David L; Stenson, Peter D; Cooper, David N; Gygax, Derek M; Kim, Rick; Ryan, Michael; Karchin, Rachel

2016-01-01

Insertion/deletion variants (indels) alter protein sequence and length, yet are highly prevalent in healthy populations, presenting a challenge to bioinformatics classifiers. Commonly used features--DNA and protein sequence conservation, indel length, and occurrence in repeat regions--are useful for inference of protein damage. However, these features can cause false positives when predicting the impact of indels on disease. Existing methods for indel classification suffer from low specificities, severely limiting clinical utility. Here, we further develop our variant effect scoring tool (VEST) to include the classification of in-frame and frameshift indels (VEST-indel) as pathogenic or benign. We apply 24 features, including a new "PubMed" feature, to estimate a gene's importance in human disease. When compared with four existing indel classifiers, our method achieves a drastically reduced false-positive rate, improving specificity by as much as 90%. This approach of estimating gene importance might be generally applicable to missense and other bioinformatics pathogenicity predictors, which often fail to achieve high specificity. Finally, we tested all possible meta-predictors that can be obtained from combining the four different indel classifiers using Boolean conjunctions and disjunctions, and derived a meta-predictor with improved performance over any individual method. © 2015 The Authors. **Human Mutation published by Wiley Periodicals, Inc.

Managing Complex Change in Clinical Study Metadata

PubMed Central

Brandt, Cynthia A.; Gadagkar, Rohit; Rodriguez, Cesar; Nadkarni, Prakash M.

2004-01-01

In highly functional metadata-driven software, the interrelationships within the metadata become complex, and maintenance becomes challenging. We describe an approach to metadata management that uses a knowledge-base subschema to store centralized information about metadata dependencies and use cases involving specific types of metadata modification. Our system borrows ideas from production-rule systems in that some of this information is a high-level specification that is interpreted and executed dynamically by a middleware engine. Our approach is implemented in TrialDB, a generic clinical study data management system. We review approaches that have been used for metadata management in other contexts and describe the features, capabilities, and limitations of our system. PMID:15187070

The clinical and immunological significance of GAD-specific autoantibody and T-cell responses in type 1 diabetes.

PubMed

Boettler, Tobias; Pagni, Philippe P; Jaffe, Rachel; Cheng, Yang; Zerhouni, Peter; von Herrath, Matthias

2013-08-01

Antigen-specific interventions are desirable approaches in Type 1 Diabetes (T1D) as they can alter islet-specific autoimmunity without systemic side effects. Glutamic acid decarboxylase of 65 kDa (GAD65) is a major autoantigen in type 1 diabetes (T1D) and GAD-specific autoimmunity is a common feature of T1D in humans but also in mouse models of the disease. In humans, administration of the GAD65 protein in an alum formulation has been shown to reduce C-peptide decline in recently diagnosed patients, however, these observations were not confirmed in subsequent phase II/III clinical trials. As GAD-based immune interventions in different formulations have successfully been employed to prevent the establishment of T1D in mouse models of T1D, we sought to analyze the efficacy of GAD-alum treatment and the effects on the GAD-specific immune response in two different mouse models of T1D. Consistent with the latest clinical trials, mice treated with GAD-alum were not protected from diabetes, although GAD-alum induced a GAD-specific Th2-deviated immune response in transgenic rat insulin promoter-glycoprotein (RIP-GP) mice. These observations underline the importance of a thorough, preclinical evaluation of potential drugs before the initiation of clinical trials. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Clinical predictors of conversion to bipolar disorder in a prospective longitudinal familial high-risk sample: focus on depressive features.

PubMed

Frankland, Andrew; Roberts, Gloria; Holmes-Preston, Ellen; Perich, Tania; Levy, Florence; Lenroot, Rhoshel; Hadzi-Pavlovic, Dusan; Breakspear, Michael; Mitchell, Philip B

2017-11-07

Identifying clinical features that predict conversion to bipolar disorder (BD) in those at high familial risk (HR) would assist in identifying a more focused population for early intervention. In total 287 participants aged 12-30 (163 HR with a first-degree relative with BD and 124 controls (CONs)) were followed annually for a median of 5 years. We used the baseline presence of DSM-IV depressive, anxiety, behavioural and substance use disorders, as well as a constellation of specific depressive symptoms (as identified by the Probabilistic Approach to Bipolar Depression) to predict the subsequent development of hypo/manic episodes. At baseline, HR participants were significantly more likely to report ⩾4 Probabilistic features (40.4%) when depressed than CONs (6.7%; p < .05). Nineteen HR subjects later developed either threshold (n = 8; 4.9%) or subthreshold (n = 11; 6.7%) hypo/mania. The presence of ⩾4 Probabilistic features was associated with a seven-fold increase in the risk of 'conversion' to threshold BD (hazard ratio = 6.9, p < .05) above and beyond the fourteen-fold increase in risk related to major depressive episodes (MDEs) per se (hazard ratio = 13.9, p < .05). Individual depressive features predicting conversion were psychomotor retardation and ⩾5 MDEs. Behavioural disorders only predicted conversion to subthreshold BD (hazard ratio = 5.23, p < .01), while anxiety and substance disorders did not predict either threshold or subthreshold hypo/mania. This study suggests that specific depressive characteristics substantially increase the risk of young people at familial risk of BD going on to develop future hypo/manic episodes and may identify a more targeted HR population for the development of early intervention programs.

[Treatment with inhibitors of new oral direct anticoagulants in patients with severe bleedings or urgent surgical procedures. The new dabigatran antidote: the place of idarucizumab in clinical practice].

PubMed

Boda, Zoltán

2016-03-20

Only vitamin K antagonists could be applied as oral anticoagulants over the past six decades. Coumarols have narrow therapeutic range, and unpredictable anticoagulant effects are resulted by multiple drug interactions. Therefore, regular routine monitoring of the international normalized ratio is necessary. There are two groups of factor-specific anticoagulants: molecules with anti-FIIa (dabigatran) and anti-FXa (rivaroxaban, apixaban and edoxaban) effect. Author summarizes the most important clinical features of the new oral anticoagulants, their indications and the possibilities of laboratory controls. Bleedings are the most important side effects of anticoagulants. This review summarizes the current published evidences for new oral anticoagulants reversal (non-specific and specific) agents, especially in cases with severe acute bleedings or urgent surgery procedures. It reports on how to use inhibitors, the recommended doses and the most important clinical results. The review focuses on idarucizumab - already approved by the U.S. Food and Drug Administration and the European Medicines Agency - which has a key role as the first specific inhibitor of dabigatran.

Radiogenomics analysis identifies correlations of digital mammography with clinical molecular signatures in breast cancer.

PubMed

Tamez-Peña, Jose-Gerardo; Rodriguez-Rojas, Juan-Andrés; Gomez-Rueda, Hugo; Celaya-Padilla, Jose-Maria; Rivera-Prieto, Roxana-Alicia; Palacios-Corona, Rebeca; Garza-Montemayor, Margarita; Cardona-Huerta, Servando; Treviño, Victor

2018-01-01

In breast cancer, well-known gene expression subtypes have been related to a specific clinical outcome. However, their impact on the breast tissue phenotype has been poorly studied. Here, we investigate the association of imaging data of tumors to gene expression signatures from 71 patients with breast cancer that underwent pre-treatment digital mammograms and tumor biopsies. From digital mammograms, a semi-automated radiogenomics analysis generated 1,078 features describing the shape, signal distribution, and texture of tumors along their contralateral image used as control. From tumor biopsy, we estimated the OncotypeDX and PAM50 recurrence scores using gene expression microarrays. Then, we used multivariate analysis under stringent cross-validation to train models predicting recurrence scores. Few univariate features reached Spearman correlation coefficients above 0.4. Nevertheless, multivariate analysis yielded significantly correlated models for both signatures (correlation of OncotypeDX = 0.49 ± 0.07 and PAM50 = 0.32 ± 0.10 in stringent cross-validation and OncotypeDX = 0.83 and PAM50 = 0.78 for a unique model). Equivalent models trained from the unaffected contralateral breast were not correlated suggesting that the image signatures were tumor-specific and that overfitting was not a considerable issue. We also noted that models were improved by combining clinical information (triple negative status and progesterone receptor). The models used mostly wavelets and fractal features suggesting their importance to capture tumor information. Our results suggest that molecular-based recurrence risk and breast cancer subtypes have observable radiographic phenotypes. To our knowledge, this is the first study associating mammographic information to gene expression recurrence signatures.

Towards a clinically informed, data-driven definition of elderly onset epilepsy.

PubMed

Josephson, Colin B; Engbers, Jordan D T; Sajobi, Tolulope T; Jette, Nathalie; Agha-Khani, Yahya; Federico, Paolo; Murphy, William; Pillay, Neelan; Wiebe, Samuel

2016-02-01

Elderly onset epilepsy represents a distinct subpopulation that has received considerable attention due to the unique features of the disease in this age group. Research into this particular patient group has been limited by a lack of a standardized definition and understanding of the attributes associated with elderly onset epilepsy. We used a prospective cohort database to examine differences in patients stratified according to age of onset. Linear support vector machine learning incorporating all significant variables was used to predict age of onset according to prespecified thresholds. Sensitivity and specificity were calculated and plotted in receiver-operating characteristic (ROC) space. Feature coefficients achieving an absolute value of 0.25 or greater were graphed by age of onset to define how they vary with time. We identified 2,449 patients, of whom 149 (6%) had an age of seizure onset of 65 or older. Fourteen clinical variables had an absolute predictive value of at least 0.25 at some point over the age of epilepsy-onset spectrum. Area under the curve in ROC space was maximized between ages of onset of 65 and 70. Features identified through machine learning were frequently threshold specific and were similar, but not identical, to those revealed through simple univariable and multivariable comparisons. This study provides an empirical, clinically informed definition of "elderly onset epilepsy." If validated, an age threshold of 65-70 years can be used for future studies of elderly onset epilepsy and permits targeted interventions according to the patient's age of onset. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Radiogenomics analysis identifies correlations of digital mammography with clinical molecular signatures in breast cancer

PubMed Central

Tamez-Peña, Jose-Gerardo; Rodriguez-Rojas, Juan-Andrés; Gomez-Rueda, Hugo; Celaya-Padilla, Jose-Maria; Rivera-Prieto, Roxana-Alicia; Palacios-Corona, Rebeca; Garza-Montemayor, Margarita; Cardona-Huerta, Servando

2018-01-01

In breast cancer, well-known gene expression subtypes have been related to a specific clinical outcome. However, their impact on the breast tissue phenotype has been poorly studied. Here, we investigate the association of imaging data of tumors to gene expression signatures from 71 patients with breast cancer that underwent pre-treatment digital mammograms and tumor biopsies. From digital mammograms, a semi-automated radiogenomics analysis generated 1,078 features describing the shape, signal distribution, and texture of tumors along their contralateral image used as control. From tumor biopsy, we estimated the OncotypeDX and PAM50 recurrence scores using gene expression microarrays. Then, we used multivariate analysis under stringent cross-validation to train models predicting recurrence scores. Few univariate features reached Spearman correlation coefficients above 0.4. Nevertheless, multivariate analysis yielded significantly correlated models for both signatures (correlation of OncotypeDX = 0.49 ± 0.07 and PAM50 = 0.32 ± 0.10 in stringent cross-validation and OncotypeDX = 0.83 and PAM50 = 0.78 for a unique model). Equivalent models trained from the unaffected contralateral breast were not correlated suggesting that the image signatures were tumor-specific and that overfitting was not a considerable issue. We also noted that models were improved by combining clinical information (triple negative status and progesterone receptor). The models used mostly wavelets and fractal features suggesting their importance to capture tumor information. Our results suggest that molecular-based recurrence risk and breast cancer subtypes have observable radiographic phenotypes. To our knowledge, this is the first study associating mammographic information to gene expression recurrence signatures. PMID:29596496

Churg-strauss syndrome: an update.

PubMed

Abril, Andy

2011-12-01

Churg-Strauss syndrome is an uncommon disease of unknown cause described initially by Churg and Strauss in 1951. Even though it was initially thought to be a variant of polyarteritis nodosa, its pathological, clinical, and laboratory features show that it is related to the small vessel vasculitides, and it is now classified as an antineutrophil cytoplasmic antibody-associated vasculitis. The presence of asthma, usually of adult onset, along with other allergic symptoms, peripheral and tissue eosinophilia, is specific to this disease. These features usually help clinicians distinguish it from other types of small vessel vasculitis and should alert clinicians about its presence. Two different clinical subtypes defined by the presence of antineutrophil cytoplasmic antibodies recently have been recognized. Recent advances in the treatment and pathophysiology of Churg-Strauss syndrome are reviewed in this article.

Learning Optimal Individualized Treatment Rules from Electronic Health Record Data

PubMed Central

Wang, Yuanjia; Wu, Peng; Liu, Ying; Weng, Chunhua; Zeng, Donglin

2016-01-01

Medical research is experiencing a paradigm shift from “one-size-fits-all” strategy to a precision medicine approach where the right therapy, for the right patient, and at the right time, will be prescribed. We propose a statistical method to estimate the optimal individualized treatment rules (ITRs) that are tailored according to subject-specific features using electronic health records (EHR) data. Our approach merges statistical modeling and medical domain knowledge with machine learning algorithms to assist personalized medical decision making using EHR. We transform the estimation of optimal ITR into a classification problem and account for the non-experimental features of the EHR data and confounding by clinical indication. We create a broad range of feature variables that reflect both patient health status and healthcare data collection process. Using EHR data collected at Columbia University clinical data warehouse, we construct a decision tree for choosing the best second line therapy for treating type 2 diabetes patients. PMID:28503676

Spectrum of high-resolution computed tomography imaging in occupational lung disease

PubMed Central

Satija, Bhawna; Kumar, Sanyal; Ojha, Umesh Chandra; Gothi, Dipti

2013-01-01

Damage to the lungs caused by dusts or fumes or noxious substances inhaled by workers in certain specific occupation is known as occupational lung disease. Recognition of occupational lung disease is especially important not only for the primary worker, but also because of the implications with regard to primary and secondary disease prevention in the exposed co-workers. Although many of the disorders can be detected on chest radiography, high-resolution computed tomography (HRCT) is superior in delineating the lung architecture and depicting pathology. The characteristic radiological features suggest the correct diagnosis in some, whereas a combination of clinical features, occupational history, and radiological findings is essential in establishing the diagnosis in others. In the presence of a history of exposure and consistent clinical features, the diagnosis of even an uncommon occupational lung disease can be suggested by the characteristic described HRCT findings. In this article, we briefly review the HRCT appearance of a wide spectrum of occupational lung diseases. PMID:24604929

Spectrum of high-resolution computed tomography imaging in occupational lung disease.

PubMed

Satija, Bhawna; Kumar, Sanyal; Ojha, Umesh Chandra; Gothi, Dipti

2013-10-01

Damage to the lungs caused by dusts or fumes or noxious substances inhaled by workers in certain specific occupation is known as occupational lung disease. Recognition of occupational lung disease is especially important not only for the primary worker, but also because of the implications with regard to primary and secondary disease prevention in the exposed co-workers. Although many of the disorders can be detected on chest radiography, high-resolution computed tomography (HRCT) is superior in delineating the lung architecture and depicting pathology. The characteristic radiological features suggest the correct diagnosis in some, whereas a combination of clinical features, occupational history, and radiological findings is essential in establishing the diagnosis in others. In the presence of a history of exposure and consistent clinical features, the diagnosis of even an uncommon occupational lung disease can be suggested by the characteristic described HRCT findings. In this article, we briefly review the HRCT appearance of a wide spectrum of occupational lung diseases.

Chronic cough: clinical characteristics and etiologies of 510 cases.

PubMed

Jiang, Guiyuan; Huang, Xinying; Li, Tianlin; Xu, Dongping

2016-12-20

To investigate the clinical features and underlying etiologies of chronic cough (CC). Five hundred and ten CC patients were enrolled. The phases, characteristics and associated clinical manifestations of CC among the gastroesophageal reflux cough (GERC), cough-variant asthma (CVA), and upper airway cough syndrome (UACS) groups were compared, and the diagnostic values of each group were evaluated by multiple regression analysis. In the 510 patients, 404 had CC with single etiology-GERC (n = 175), CVA (n = 134), and UACS (n = 95). The characteristic features of GERC included gastric acid backflow symptoms such as sour-tasting regurgitation, heartburn, endoscopic esophagitis, poststimulation cough, frequent throat clearing, daytime mono-cough, and feelings of heaviness and pain in the chest. Patients with CVA typically exhibited sensitivity to smog and other irritants; the cough occurred mostly at night, and was associated with positive bronchodilator and provocation test results. The typical features of UACS included a history and/or symptoms of rhinitis, retropharyngeal postnasal drip, and wet cough occurring mostly during the daytime. The diagnostic specificities of above factors were >70%. The most common causes of CC include GERC, CVA, and UACS, and their diagnosis is based on the characteristics of the underlying disease.

Computed tomography in hypersensitivity pneumonitis: main findings, differential diagnosis and pitfalls.

PubMed

Dias, Olívia Meira; Baldi, Bruno Guedes; Pennati, Francesca; Aliverti, Andrea; Chate, Rodrigo Caruso; Sawamura, Márcio Valente Yamada; Carvalho, Carlos Roberto Ribeiro de; Albuquerque, André Luis Pereira de

2018-01-01

Hypersensitivity pneumonitis (HP) is a disease with variable clinical presentation in which inflammation in the lung parenchyma is caused by the inhalation of specific organic antigens or low molecular weight substances in genetically susceptible individuals. Alterations of the acute, subacute and chronic forms may eventually overlap, and the diagnosis based on temporality and presence of fibrosis (acute/inflammatory HP vs. chronic HP) seems to be more feasible and useful in clinical practice. Differential diagnosis of chronic HP with other interstitial fibrotic diseases is challenging due to the overlap of the clinical history, and the functional and imaging findings of these pathologies in the terminal stages. Areas covered: This article reviews the essential features of HP with emphasis on imaging features. Moreover, the main methodological limitations of high-resolution computed tomography (HRCT) interpretation are discussed, as well as new perspectives with volumetric quantitative CT analysis as a useful tool for retrieving detailed and accurate information from the lung parenchyma. Expert commentary: Mosaic attenuation is a prominent feature of this disease, but air trapping in chronic HP seems overestimated. Quantitative analysis has the potential to estimate the involvement of the pulmonary parenchyma more accurately and could correlate better with pulmonary function results.

Clinical, Microbial, and Biochemical Aspects of the Exfoliative Toxins Causing Staphylococcal Scalded-Skin Syndrome

PubMed Central

Ladhani, Shamez; Joannou, Christopher L.; Lochrie, Denise P.; Evans, Robert W.; Poston, Susan M.

1999-01-01

The exfoliative (epidermolytic) toxins of Staphylococcus aureus are the causative agents of the staphylococcal scalded-skin syndrome (SSSS), a blistering skin disorder that predominantly affects children. Clinical features of SSSS vary along a spectrum, ranging from a few localized blisters to generalized exfoliation covering almost the entire body. The toxins act specifically at the zona granulosa of the epidermis to produce the characteristic exfoliation, although the mechanism by which this is achieved is still poorly understood. Despite the availability of antibiotics, SSSS carries a significant mortality rate, particularly among neonates with secondary complications of epidermal loss and among adults with underlying diseases. The aim of this article is to provide a comprehensive review of the literature spanning more than a century and to cover all aspects of the disease. The epidemiology, clinical features, potential complications, risk factors, susceptibility, diagnosis, differential diagnoses, investigations currently available, treatment options, and preventive measures are all discussed in detail. Recent crystallographic data on the toxins has provided us with a clearer and more defined approach to studying the disease. Understanding their mode of action has important implications in future treatment and prevention of SSSS and other diseases, and knowledge of their specific site of action may provide a useful tool for physiologists, dermatologists, and pharmacologists. PMID:10194458

The development of a clinical outcomes survey research application: Assessment CenterSM

PubMed Central

Rothrock, Nan E.; Hanrahan, Rachel T.; Jansky, Liz J.; Harniss, Mark; Riley, William

2013-01-01

Introduction The National Institutes of Health sponsored Patient-Reported Outcome Measurement Information System (PROMIS) aimed to create item banks and computerized adaptive tests (CATs) across multiple domains for individuals with a range of chronic diseases. Purpose Web-based software was created to enable a researcher to create study-specific Websites that could administer PROMIS CATs and other instruments to research participants or clinical samples. This paper outlines the process used to develop a user-friendly, free, Web-based resource (Assessment CenterSM) for storage, retrieval, organization, sharing, and administration of patient-reported outcomes (PRO) instruments. Methods Joint Application Design (JAD) sessions were conducted with representatives from numerous institutions in order to supply a general wish list of features. Use Cases were then written to ensure that end user expectations matched programmer specifications. Program development included daily programmer “scrum” sessions, weekly Usability Acceptability Testing (UAT) and continuous Quality Assurance (QA) activities pre- and post-release. Results Assessment Center includes features that promote instrument development including item histories, data management, and storage of statistical analysis results. Conclusions This case study of software development highlights the collection and incorporation of user input throughout the development process. Potential future applications of Assessment Center in clinical research are discussed. PMID:20306332

Healthcare Reform and Preparing the Future Clinical Child and Adolescent Psychology Workforce.

PubMed

Janicke, David M; Fritz, Alyssa M; Rozensky, Ronald H

2015-01-01

The healthcare environment is undergoing important changes for both patients and providers, in part due to the Patient Protection and Affordable Care Act (ACA). Ultimately the healthcare delivery system will function very differently by the end of this decade. These changes will have important implications for the education, training, scientific inquiry, and practice of clinical child and adolescent psychologists. In this article we provide a brief description of the fundamental features of the ACA, with a specific focus on critical components of the act that have important, specific implications for clinical child and adolescents psychologists. We then provide recommendations to help position our field to thrive in the evolving healthcare environment to help facilitate further awareness and promote discussion of both challenges and opportunities that face our field in this evolving health care environment.

Pilocytic Astrocytoma of the Optic Pathway: A Tumour Deriving from Radial Glia Cells with a Specific Gene Signature

ERIC Educational Resources Information Center

Tchoghandjian, Aurelie; Fernandez, Carla; Colin, Carole; El Ayachi, Ikbale; Voutsinos-Porche, Brigitte; Fina, Frederic; Scavarda, Didier; Piercecchi-Marti, Marie-Dominique; Intagliata, Dominique; Ouafik, L'Houcine; Fraslon-Vanhulle, Caroline; Figarella-Branger, Dominique

2009-01-01

Pilocytic astrocytomas are WHO grade I gliomas that occur predominantly in childhood. They share features of both astroglial and oligodendroglial lineages. These tumours affect preferentially the cerebellum (benign clinical course) and the optic pathway, especially the hypothalamo-chiasmatic region (poor prognosis). Understanding the molecular…

Identification of men with low-risk biopsy-confirmed prostate cancer as candidates for active surveillance.

PubMed

Lin, Daniel W; Crawford, E David; Keane, Thomas; Evans, Brent; Reid, Julia; Rajamani, Saradha; Brown, Krystal; Gutin, Alexander; Tward, Jonathan; Scardino, Peter; Brawer, Michael; Stone, Steven; Cuzick, Jack

2018-06-01

A combined clinical cell-cycle risk (CCR) score that incorporates prognostic molecular and clinical information has been recently developed and validated to improve prostate cancer mortality (PCM) risk stratification over clinical features alone. As clinical features are currently used to select men for active surveillance (AS), we developed and validated a CCR score threshold to improve the identification of men with low-risk disease who are appropriate for AS. The score threshold was selected based on the 90th percentile of CCR scores among men who might typically be considered for AS based on NCCN low/favorable-intermediate risk criteria (CCR = 0.8). The threshold was validated using 10-year PCM in an unselected, conservatively managed cohort and in the subset of the same cohort after excluding men with high-risk features. The clinical effect was evaluated in a contemporary clinical cohort. In the unselected validation cohort, men with CCR scores below the threshold had a predicted mean 10-year PCM of 2.7%, and the threshold significantly dichotomized low- and high-risk disease (P = 1.2 × 10 -5 ). After excluding high-risk men from the validation cohort, men with CCR scores below the threshold had a predicted mean 10-year PCM of 2.3%, and the threshold significantly dichotomized low- and high-risk disease (P = 0.020). There were no prostate cancer-specific deaths in men with CCR scores below the threshold in either analysis. The proportion of men in the clinical testing cohort identified as candidates for AS was substantially higher using the threshold (68.8%) compared to clinicopathologic features alone (42.6%), while mean 10-year predicted PCM risks remained essentially identical (1.9% vs. 2.0%, respectively). The CCR score threshold appropriately dichotomized patients into low- and high-risk groups for 10-year PCM, and may enable more appropriate selection of patients for AS. Copyright © 2018 Elsevier Inc. All rights reserved.

Mixed Connective Tissue Disease and Epitope Spreading: An Historical Cohort Study.

PubMed

Escolà-Vergé, Laura; Pinal-Fernandez, Iago; Fernandez-Codina, Andreu; Callejas-Moraga, Eduardo L; Espinosa, Juan; Marin, Ana; Labrador-Horrillo, Moises; Selva-O'Callaghan, Albert

2017-04-01

Mixed connective tissue disease (MCTD) is characterized by the presence of anti-U1-snRNP autoantibodies and a variable set of associated clinical features. Some MCTD patients test positive over time to autoantibodies against Sm, proteins spatially related with U1-snRNP. This situation has been attributed to expanding of the autoimmune response by a phenomenon known as epitope spreading. Our aim was to study the frequency of this phenomenon in MCTD patients and the specific clinical features of those with epitope spreading. All anti-U1-RNP-positive patients (2010-2015) were retrospectively reviewed, and those meeting the MCTD criteria were included in the study. Patients showing epitope spreading were compared with the remainder of the MCTD cohort. In addition, the clinical features of patients with epitope spreading were compared before and after the phenomenon occurred. Among 72 anti-U1-RNP-positive patients, 40 (37 women) were diagnosed with MCTD. Thirteen MCTD patients (43%) presented epitope spreading, mainly during the first 2 years after the diagnosis of the disease (median, 1.4 years). Patients with epitope spreading had a significantly lower prevalence of skin sclerosis (0% vs. 44%, P = 0.004) and a greater prevalence of interstitial lung disease (46% vs. 15%, P = 0.05) than those without. Arthritis (92% vs. 25%, P = 0.02) and muscle involvement (67% vs. 17%, P = 0.02) were less frequent after epitope spreading had occurred. Epitope spreading is common in MCTD, occurring early after the diagnosis. The clinical manifestations in patients with this phenomenon differ from those without, and their clinical features change after the immunological phenomenon has occurred.

Usability Evaluation of Electronic Health Record System around Clinical Notes Usage-An Ethnographic Study.

PubMed

Rizvi, Rubina F; Marquard, Jenna L; Hultman, Gretchen M; Adam, Terrence J; Harder, Kathleen A; Melton, Genevieve B

2017-10-01

Background A substantial gap exists between current Electronic Health Record (EHR) usability and potential optimal usability. One of the fundamental reasons for this discrepancy is poor incorporation of a User-Centered Design (UCD) approach during the Graphical User Interface (GUI) development process. Objective To evaluate usability strengths and weaknesses of two widely implemented EHR GUIs for critical clinical notes usage tasks. Methods Twelve Internal Medicine resident physicians interacting with one of the two EHR systems (System-1 at Location-A and System-2 at Location-B) were observed by two usability evaluators employing an ethnographic approach. User comments and observer findings were analyzed for two critical tasks: (1) clinical notes entry and (2) related information-seeking tasks. Data were analyzed from two standpoints: (1) usability references categorized by usability evaluators as positive, negative, or equivocal and (2) usability impact of each feature measured through a 7-point severity rating scale. Findings were also validated by user responses to a post observation questionnaire. Results For clinical notes entry, System-1 surpassed System-2 with more positive (26% vs. 12%) than negative (12% vs. 34%) usability references. Greatest impact features on EHR usability (severity score pertaining to each feature) for clinical notes entry were: autopopulation (6), screen options (5.5), communication (5), copy pasting (4.5), error prevention (4.5), edit ability (4), and dictation and transcription (3.5). Both systems performed equally well on information-seeking tasks and features with greatest impacts on EHR usability were navigation for notes (7) and others (e.g., looking for ancillary data; 5.5). Ethnographic observations were supported by follow-up questionnaire responses. Conclusion This study provides usability-specific insights to inform future, improved, EHR interface that is better aligned with UCD approach.

Clinical profiles, endoscopic and laboratory features and associated factors in patients with autoimmune gastritis.

PubMed

Soykan, Irfan; Yakut, Mustafa; Keskin, Onur; Bektaş, Mehmet

2012-01-01

Autoimmune gastritis (AIG) may predispose to gastric carcinoid tumors or adenocarcinomas and may also cause unexplained iron and/or vitamin B(12) deficiency. The aims of this study were to explore clinical manifestations, endoscopic findings and laboratory features of patients with AIG. 109 patients with AIG were enrolled into the study. In addition to demographic and clinical data, gastric lesions, serum gastrin, vitamin B(12), antiparietal cell antibody (APA), current Helicobacter pylori status, and anti-H. pylori IgG were also investigated. The mean age of the patients was 53.06 ± 12.7 years (range 24-81; 72 (66.1%) women). The most common main presenting symptom was abdominal symptoms in 51 patients, consultation for iron and/or vitamin B(12) deficiency in 36, and non-specific symptoms including intermittent diarrhea in 15 patients. Endoscopic lesions were detected in 17 patients, hyperplastic polyps in 8, gastric carcinoid tumor in 4, fundic gland polyps in 3, and adenomatous polyps in 2 patients. H. pylori was negative in all patients in biopsy specimens; however, anti-H. pylori IgG was positive in 30 (27.5%) patients. 91 patients (83.4%) were positive for APA. In patients with AIG, the main symptoms prompted for clinical investigation were: abdominal symptoms, iron/B(12) deficiency and non-specific symptoms. 20% of patients with AIG had various gastric lesions including type I gastric carcinoids. None of the patients were positive for H. pylori by means of invasive tests; however, anti-H. pylori IgG was found in 27.5% of patients. Patients referring with non-specific abdominal symptoms such as bloating, diarrhea and iron/B(12) deficiency should be investigated for the presence of AIG. Copyright © 2012 S. Karger AG, Basel.

Systematic genomic identification of colorectal cancer genes delineating advanced from early clinical stage and metastasis

PubMed Central

2013-01-01

Background Colorectal cancer is the third leading cause of cancer deaths in the United States. The initial assessment of colorectal cancer involves clinical staging that takes into account the extent of primary tumor invasion, determining the number of lymph nodes with metastatic cancer and the identification of metastatic sites in other organs. Advanced clinical stage indicates metastatic cancer, either in regional lymph nodes or in distant organs. While the genomic and genetic basis of colorectal cancer has been elucidated to some degree, less is known about the identity of specific cancer genes that are associated with advanced clinical stage and metastasis. Methods We compiled multiple genomic data types (mutations, copy number alterations, gene expression and methylation status) as well as clinical meta-data from The Cancer Genome Atlas (TCGA). We used an elastic-net regularized regression method on the combined genomic data to identify genetic aberrations and their associated cancer genes that are indicators of clinical stage. We ranked candidate genes by their regression coefficient and level of support from multiple assay modalities. Results A fit of the elastic-net regularized regression to 197 samples and integrated analysis of four genomic platforms identified the set of top gene predictors of advanced clinical stage, including: WRN, SYK, DDX5 and ADRA2C. These genetic features were identified robustly in bootstrap resampling analysis. Conclusions We conducted an analysis integrating multiple genomic features including mutations, copy number alterations, gene expression and methylation. This integrated approach in which one considers all of these genomic features performs better than any individual genomic assay. We identified multiple genes that robustly delineate advanced clinical stage, suggesting their possible role in colorectal cancer metastatic progression. PMID:24308539

Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia

PubMed Central

Hodges, John R.; Knopman, David; Mendez, Mario F.; Kramer, Joel H.; Neuhaus, John; van Swieten, John C.; Seelaar, Harro; Dopper, Elise G. P.; Onyike, Chiadi U.; Hillis, Argye E.; Josephs, Keith A.; Boeve, Bradley F.; Kertesz, Andrew; Seeley, William W.; Rankin, Katherine P.; Johnson, Julene K.; Gorno-Tempini, Maria-Luisa; Rosen, Howard; Prioleau-Latham, Caroline E.; Lee, Albert; Kipps, Christopher M.; Lillo, Patricia; Piguet, Olivier; Rohrer, Jonathan D.; Rossor, Martin N.; Warren, Jason D.; Fox, Nick C.; Galasko, Douglas; Salmon, David P.; Black, Sandra E.; Mesulam, Marsel; Weintraub, Sandra; Dickerson, Brad C.; Diehl-Schmid, Janine; Pasquier, Florence; Deramecourt, Vincent; Lebert, Florence; Pijnenburg, Yolande; Chow, Tiffany W.; Manes, Facundo; Grafman, Jordan; Cappa, Stefano F.; Freedman, Morris; Grossman, Murray; Miller, Bruce L.

2011-01-01

Based on the recent literature and collective experience, an international consortium developed revised guidelines for the diagnosis of behavioural variant frontotemporal dementia. The validation process retrospectively reviewed clinical records and compared the sensitivity of proposed and earlier criteria in a multi-site sample of patients with pathologically verified frontotemporal lobar degeneration. According to the revised criteria, ‘possible’ behavioural variant frontotemporal dementia requires three of six clinically discriminating features (disinhibition, apathy/inertia, loss of sympathy/empathy, perseverative/compulsive behaviours, hyperorality and dysexecutive neuropsychological profile). ‘Probable’ behavioural variant frontotemporal dementia adds functional disability and characteristic neuroimaging, while behavioural variant frontotemporal dementia ‘with definite frontotemporal lobar degeneration’ requires histopathological confirmation or a pathogenic mutation. Sixteen brain banks contributed cases meeting histopathological criteria for frontotemporal lobar degeneration and a clinical diagnosis of behavioural variant frontotemporal dementia, Alzheimer’s disease, dementia with Lewy bodies or vascular dementia at presentation. Cases with predominant primary progressive aphasia or extra-pyramidal syndromes were excluded. In these autopsy-confirmed cases, an experienced neurologist or psychiatrist ascertained clinical features necessary for making a diagnosis according to previous and proposed criteria at presentation. Of 137 cases where features were available for both proposed and previously established criteria, 118 (86%) met ‘possible’ criteria, and 104 (76%) met criteria for ‘probable’ behavioural variant frontotemporal dementia. In contrast, 72 cases (53%) met previously established criteria for the syndrome (P < 0.001 for comparison with ‘possible’ and ‘probable’ criteria). Patients who failed to meet revised criteria were significantly older and most had atypical presentations with marked memory impairment. In conclusion, the revised criteria for behavioural variant frontotemporal dementia improve diagnostic accuracy compared with previously established criteria in a sample with known frontotemporal lobar degeneration. Greater sensitivity of the proposed criteria may reflect the optimized diagnostic features, less restrictive exclusion features and a flexible structure that accommodates different initial clinical presentations. Future studies will be needed to establish the reliability and specificity of these revised diagnostic guidelines. PMID:21810890

Standardized Computer-based Organized Reporting of EEG: SCORE

PubMed Central

Beniczky, Sándor; Aurlien, Harald; Brøgger, Jan C; Fuglsang-Frederiksen, Anders; Martins-da-Silva, António; Trinka, Eugen; Visser, Gerhard; Rubboli, Guido; Hjalgrim, Helle; Stefan, Hermann; Rosén, Ingmar; Zarubova, Jana; Dobesberger, Judith; Alving, Jørgen; Andersen, Kjeld V; Fabricius, Martin; Atkins, Mary D; Neufeld, Miri; Plouin, Perrine; Marusic, Petr; Pressler, Ronit; Mameniskiene, Ruta; Hopfengärtner, Rüdiger; Emde Boas, Walter; Wolf, Peter

2013-01-01

The electroencephalography (EEG) signal has a high complexity, and the process of extracting clinically relevant features is achieved by visual analysis of the recordings. The interobserver agreement in EEG interpretation is only moderate. This is partly due to the method of reporting the findings in free-text format. The purpose of our endeavor was to create a computer-based system for EEG assessment and reporting, where the physicians would construct the reports by choosing from predefined elements for each relevant EEG feature, as well as the clinical phenomena (for video-EEG recordings). A working group of EEG experts took part in consensus workshops in Dianalund, Denmark, in 2010 and 2011. The faculty was approved by the Commission on European Affairs of the International League Against Epilepsy (ILAE). The working group produced a consensus proposal that went through a pan-European review process, organized by the European Chapter of the International Federation of Clinical Neurophysiology. The Standardised Computer-based Organised Reporting of EEG (SCORE) software was constructed based on the terms and features of the consensus statement and it was tested in the clinical practice. The main elements of SCORE are the following: personal data of the patient, referral data, recording conditions, modulators, background activity, drowsiness and sleep, interictal findings, “episodes” (clinical or subclinical events), physiologic patterns, patterns of uncertain significance, artifacts, polygraphic channels, and diagnostic significance. The following specific aspects of the neonatal EEGs are scored: alertness, temporal organization, and spatial organization. For each EEG finding, relevant features are scored using predefined terms. Definitions are provided for all EEG terms and features. SCORE can potentially improve the quality of EEG assessment and reporting; it will help incorporate the results of computer-assisted analysis into the report, it will make possible the build-up of a multinational database, and it will help in training young neurophysiologists. PMID:23506075

Quantitative image cytometry measurements of lipids, DNA, CD45 and cytokeratin for circulating tumor cell identification in a model system

NASA Astrophysics Data System (ADS)

Futia, Gregory L.; Qamar, Lubna; Behbakht, Kian; Gibson, Emily A.

2016-04-01

Circulating tumor cell (CTC) identification has applications in both early detection and monitoring of solid cancers. The rarity of CTCs, expected at ~1-50 CTCs per million nucleated blood cells (WBCs), requires identifying methods based on biomarkers with high sensitivity and specificity for accurate identification. Discovery of biomarkers with ever higher sensitivity and specificity to CTCs is always desirable to potentially find more CTCs in cancer patients thus increasing their clinical utility. Here, we investigate quantitative image cytometry measurements of lipids with the biomarker panel of DNA, Cytokeratin (CK), and CD45 commonly used to identify CTCs. We engineered a device for labeling suspended cell samples with fluorescent antibodies and dyes. We used it to prepare samples for 4 channel confocal laser scanning microscopy. The total data acquired at high resolution from one sample is ~ 1.3 GB. We developed software to perform the automated segmentation of these images into regions of interest (ROIs) containing individual cells. We quantified image features of total signal, spatial second moment, spatial frequency second moment, and their product for each ROI. We performed measurements on pure WBCs, cancer cell line MCF7 and mixed samples. Multivariable regressions and feature selection were used to determine combination features that are more sensitive and specific than any individual feature separately. We also demonstrate that computation of spatial characteristics provides higher sensitivity and specificity than intensity alone. Statistical models allowed quantification of the required sensitivity and specificity for detecting small levels of CTCs in a human blood sample.

Sex-Specific Patterns of Aberrant Brain Function in First-Episode Treatment-Naive Patients with Schizophrenia.

PubMed

Lei, Wei; Li, Mingli; Deng, Wei; Zhou, Yi; Ma, Xiaohong; Wang, Qiang; Guo, Wanjun; Li, Yinfei; Jiang, Lijun; Han, Yuanyuan; Huang, Chaohua; Hu, Xun; Li, Tao

2015-07-16

Male and female patients with schizophrenia show significant differences in a number of important clinical features, yet the neural substrates of these differences are still poorly understood. Here we explored the sex differences in the brain functional aberrations in 124 treatment-naïve patients with first-episode schizophrenia (61 males), compared with 102 age-matched healthy controls (50 males). Maps of degree centrality (DC) and amplitude of low-frequency fluctuations (ALFF) were constructed using resting-state functional magnetic resonance imaging data and compared between groups. We found that: (1) Selective DC reduction was observed in the right putamen (Put_R) in male patients and the left middle frontal gyrus (MFG) in female patients; (2) Functional connectivity analysis (using Put_R and MFG as seeds) found that male and female patients have disturbed functional integration in two separate networks, i.e., the sensorimotor network and the default mode network; (3) Significant ALFF alterations were also observed in these two networks in both genders; (4) Sex specific brain functional alterations were associated with various symptoms in patients. These results suggested that sex-specific patterns of functional aberration existed in schizophrenia, and these patterns were associated with the clinical features both in male and female patients.

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

Lafata, K; Ren, L; Wu, Q

Purpose: To develop a data-mining methodology based on quantum clustering and machine learning to predict expected dosimetric endpoints for lung SBRT applications based on patient-specific anatomic features. Methods: Ninety-three patients who received lung SBRT at our clinic from 2011–2013 were retrospectively identified. Planning information was acquired for each patient, from which various features were extracted using in-house semi-automatic software. Anatomic features included tumor-to-OAR distances, tumor location, total-lung-volume, GTV and ITV. Dosimetric endpoints were adopted from RTOG-0195 recommendations, and consisted of various OAR-specific partial-volume doses and maximum point-doses. First, PCA analysis and unsupervised quantum-clustering was used to explore the feature-space tomore » identify potentially strong classifiers. Secondly, a multi-class logistic regression algorithm was developed and trained to predict dose-volume endpoints based on patient-specific anatomic features. Classes were defined by discretizing the dose-volume data, and the feature-space was zero-mean normalized. Fitting parameters were determined by minimizing a regularized cost function, and optimization was performed via gradient descent. As a pilot study, the model was tested on two esophageal dosimetric planning endpoints (maximum point-dose, dose-to-5cc), and its generalizability was evaluated with leave-one-out cross-validation. Results: Quantum-Clustering demonstrated a strong separation of feature-space at 15Gy across the first-and-second Principle Components of the data when the dosimetric endpoints were retrospectively identified. Maximum point dose prediction to the esophagus demonstrated a cross-validation accuracy of 87%, and the maximum dose to 5cc demonstrated a respective value of 79%. The largest optimized weighting factor was placed on GTV-to-esophagus distance (a factor of 10 greater than the second largest weighting factor), indicating an intuitively strong correlation between this feature and both endpoints. Conclusion: This pilot study shows that it is feasible to predict dose-volume endpoints based on patient-specific anatomic features. The developed methodology can potentially help to identify patients at risk for higher OAR doses, thus improving the efficiency of treatment planning. R01-184173.« less

Performance of Ultrasound in the Diagnosis of Gout in a Multicenter Study: Comparison With Monosodium Urate Monohydrate Crystal Analysis as the Gold Standard.

PubMed

Ogdie, Alexis; Taylor, William J; Neogi, Tuhina; Fransen, Jaap; Jansen, Tim L; Schumacher, H Ralph; Louthrenoo, Worawit; Vazquez-Mellado, Janitzia; Eliseev, Maxim; McCarthy, Geraldine; Stamp, Lisa K; Perez-Ruiz, Fernando; Sivera, Francisca; Ea, Hang-Korng; Gerritsen, Martijn; Cagnotto, Giovanni; Cavagna, Lorenzo; Lin, Chingtsai; Chou, Yin-Yi; Tausche, Anne-Kathrin; Lima Gomes Ochtrop, Manuella; Janssen, Matthijs; Chen, Jiunn-Horng; Slot, Ole; Lazovskis, Juris; White, Douglas; Cimmino, Marco A; Uhlig, Till; Dalbeth, Nicola

2017-02-01

To examine the performance of ultrasound (US) for the diagnosis of gout using the presence of monosodium urate monohydrate (MSU) crystals as the gold standard. We analyzed data from the Study for Updated Gout Classification Criteria (SUGAR), a large, multicenter observational cross-sectional study of consecutive subjects with at least 1 swollen joint who conceivably may have gout. All subjects underwent arthrocentesis; cases were subjects with confirmed MSU crystals. Rheumatologists or radiologists who were blinded with regard to the results of the MSU crystal analysis performed US on 1 or more clinically affected joints. US findings of interest were double contour sign, tophus, and snowstorm appearance. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Multivariable logistic regression models were used to examine factors associated with positive US results among subjects with gout. US was performed in 824 subjects (416 cases and 408 controls). The sensitivity, specificity, PPV, and NPV for the presence of any 1 of the features were 76.9%, 84.3%, 83.3%, and 78.2%, respectively. Sensitivity was higher among subjects with a disease duration of ≥2 years and among subjects with subcutaneous nodules on examination (suspected tophus). Associations with a positive US finding included suspected clinical tophus (odds ratio [OR] 4.77 [95% confidence interval (95% CI) 2.23-10.21]), any abnormality on plain radiography (OR 4.68 [95% CI 2.68-8.17]), and serum urate level (OR 1.31 [95% CI 1.06-1.62]). US features of MSU crystal deposition had high specificity and high PPV but more limited sensitivity for early gout. The specificity remained high in subjects with early disease and without clinical signs of tophi. © 2016, American College of Rheumatology.

Performance of Ultrasound in the Diagnosis of Gout in a Multi-Center Study: Comparison with Monosodium Urate Crystal Analysis as the Gold Standard

PubMed Central

Ogdie, Alexis; Taylor, William J; Neogi, Tuhina; Fransen, Jaap; Jansen, Tim L; Schumacher, H. Ralph; Louthrenoo, Worawit; Vazquez-Mellado, Janitzia; Eliseev, Maxim; McCarthy, Geraldine; Stamp, Lisa K.; Perez-Ruiz, Fernando; Sivera, Francisca; Ea, Hang-Korng; Gerritsen, Martijn; Cagnotto, Giovanni; Cavagna, Lorenzo; Lin, Chingtsai; Chou, Yin-Yi; Tausche, Anne-Kathrin; Ochtrop, Manuella Lima Gomes; Janssen, Matthijs; Chen, Jiunn-Horng; Slot, Ole; Lazovskis, Juris; White, Douglas; Cimmino, Marco A.; Uhlig, Till; Dalbeth, Nicola

2017-01-01

Objectives To examine the performance of ultrasound for the diagnosis of gout using presence of monosodium urate (MSU) crystals as the gold standard. Methods We analyzed data from the Study for Updated Gout Classification Criteria (SUGAR), a large, multi-center observational cross-sectional study of consecutive subjects with at least one swollen joint who conceivably may have gout. All subjects underwent arthrocentesis; cases were subjects with MSU crystal confirmation. Rheumatologists or radiologists, blinded to the results of the MSU crystal analysis, performed ultrasound on one or more clinically affected joints. Ultrasound findings of interest were: double contour sign (DCS), tophus, and ‘snowstorm’ appearance. Sensitivity, specificity, positive and negative predictive values (PPV and NPV) were calculated. Multivariable logistic regression models were used to examine factors associated with positive ultrasound results among subjects with gout. Results Ultrasound was performed in 824 subjects (416 cases and 408 controls). The sensitivity, specificity, PPV and NPV for the presence of any one of the features were 76.9%, 84.3%, 83.3% and 78.1% respectively. Sensitivity was higher among subjects with disease ≥2 years duration and among subjects with subcutaneous nodules on exam (suspected tophus). Associations with a positive ultrasound finding included suspected clinical tophus (odds ratio 4.77; 95% CI 2.23–10.21), any abnormal plain film radiograph (4.68; 2.68–8.17) and serum urate (1.31; 1.06–1.62). Conclusions Ultrasound features of MSU crystal deposition had high specificity and high positive predictive value but more limited sensitivity for early gout. The specificity remained high in subjects with early disease and without clinical signs of tophi. PMID:27748084

Complete stable remission and autoantibody specificity in myasthenia gravis.

PubMed

Baggi, Fulvio; Andreetta, Francesca; Maggi, Lorenzo; Confalonieri, Paolo; Morandi, Lucia; Salerno, Franco; Bernasconi, Pia; Montomoli, Cristina; Barberis, Massimo; Mantegazza, Renato; Antozzi, Carlo

2013-01-08

Patients with myasthenia gravis (MG) are subgrouped as acetylcholine receptor (AChR)-positive, muscle-specific kinase (MuSK)-positive, and AChR/MuSK-negative MG (or double negative [DN]) on the basis of autoantibody assay. We investigated the relationships between autoantibody specificity, main clinical features, and outcome of the disease, in particular the occurrence of complete stable remission (CSR), by means of a retrospective study on a cohort of 677 Italian patients with MG. A total of 517 (76%) patients with AChR-positive MG, 55 (8%) patients with MuSK-positive MG, and 105 (16%) patients with DN MG were included in the study. Kaplan-Meier and Cox proportional hazard regression analyses were used to evaluate associations between baseline characteristics, antibody specificity, and CSR. Clinical stage at onset and at maximal worsening was more severe for MuSK-positive patients: bulbar impairment at maximal worsening was found in 83.6% of MuSK-positive patients compared with 58.6% of AChR-positive patients and 43.8% of DN patients (p < 0.001). Baseline characteristics of AChR-positive and DN patients were similar. CSR was observed in 3.6% of MuSK-positive patients compared with 22.2% of AChR-positive and 21.9% of DN patients. In the whole MG cohort, onset before age 40 (hazard ratio [HR] = 1.96, 95% confidence interval [CI] 1.27-3.02, p = 0.002) and ocular and generalized clinical stages at maximal worsening were associated with CSR (ocular, HR = 8.05, 95% CI 1.88-34.53, p = 0.005; generalized, HR = 3.71, 95% CI 1.16-11.90, p = 0.023; bulbar, HR = 3.16, 95% CI 1.00-10.05, p = 0.051). MuSK antibodies identify a clinically distinguishable, more severe form of MG since the disease onset, with a lower occurrence of CSR. These features should be considered by the clinician in the management of this particular form of MG.

Exploration Clinical Decision Support System: Medical Data Architecture

NASA Technical Reports Server (NTRS)

Lindsey, Tony; Shetye, Sandeep; Shaw, Tianna (Editor)

2016-01-01

The Exploration Clinical Decision Support (ECDS) System project is intended to enhance the Exploration Medical Capability (ExMC) Element for extended duration, deep-space mission planning in HRP. A major development guideline is the Risk of "Adverse Health Outcomes & Decrements in Performance due to Limitations of In-flight Medical Conditions". ECDS attempts to mitigate that Risk by providing crew-specific health information, actionable insight, crew guidance and advice based on computational algorithmic analysis. The availability of inflight health diagnostic computational methods has been identified as an essential capability for human exploration missions. Inflight electronic health data sources are often heterogeneous, and thus may be isolated or not examined as an aggregate whole. The ECDS System objective provides both a data architecture that collects and manages disparate health data, and an active knowledge system that analyzes health evidence to deliver case-specific advice. A single, cohesive space-ready decision support capability that considers all exploration clinical measurements is not commercially available at present. Hence, this Task is a newly coordinated development effort by which ECDS and its supporting data infrastructure will demonstrate the feasibility of intelligent data mining and predictive modeling as a biomedical diagnostic support mechanism on manned exploration missions. The initial step towards ground and flight demonstrations has been the research and development of both image and clinical text-based computer-aided patient diagnosis. Human anatomical images displaying abnormal/pathological features have been annotated using controlled terminology templates, marked-up, and then stored in compliance with the AIM standard. These images have been filtered and disease characterized based on machine learning of semantic and quantitative feature vectors. The next phase will evaluate disease treatment response via quantitative linear dimension biomarkers that enable image content-based retrieval and criteria assessment. In addition, a data mining engine (DME) is applied to cross-sectional adult surveys for predicting occurrence of renal calculi, ranked by statistical significance of demographics and specific food ingestion. In addition to this precursor space flight algorithm training, the DME will utilize a feature-engineering capability for unstructured clinical text classification health discovery. The ECDS backbone is a proposed multi-tier modular architecture providing data messaging protocols, storage, management and real-time patient data access. Technology demonstrations and success metrics will be finalized in FY16.

Hybrid ANN optimized artificial fish swarm algorithm based classifier for classification of suspicious lesions in breast DCE-MRI

NASA Astrophysics Data System (ADS)

Janaki Sathya, D.; Geetha, K.

2017-12-01

Automatic mass or lesion classification systems are developed to aid in distinguishing between malignant and benign lesions present in the breast DCE-MR images, the systems need to improve both the sensitivity and specificity of DCE-MR image interpretation in order to be successful for clinical use. A new classifier (a set of features together with a classification method) based on artificial neural networks trained using artificial fish swarm optimization (AFSO) algorithm is proposed in this paper. The basic idea behind the proposed classifier is to use AFSO algorithm for searching the best combination of synaptic weights for the neural network. An optimal set of features based on the statistical textural features is presented. The investigational outcomes of the proposed suspicious lesion classifier algorithm therefore confirm that the resulting classifier performs better than other such classifiers reported in the literature. Therefore this classifier demonstrates that the improvement in both the sensitivity and specificity are possible through automated image analysis.

Pregnancy-Related Anxiety: Evidence of Distinct Clinical Significance from a Prospective Longitudinal Study

PubMed Central

Blackmore, Emma Robertson; Gustafsson, Hanna; Gilchrist, Michelle; Wyman, Claire; O’Connor, Thomas G

2016-01-01

Background Pregnancy-related anxiety (PrA) has attracted considerable research attention, but questions remain about its distinctiveness from conventional constructs and measures. In a high psychosocial risk, ethnically diverse sample, we examine the degree to which PrA is distinct from continuous and diagnostic measures of anxiety and worry in terms of longitudinal course, associations with psychosocial and perinatal risk, and prediction of postnatal mood disturbance. Methods 345 women oversampled for prenatal anxiety and depression were selected from an urban obstetrics clinic serving a predominantly low-income, ethnically diverse population. PrA was assessed at 20 and 32 weeks gestation; anxiety and depression symptoms were assessed from questionnaire and from clinical interview at 20 and 32 weeks gestation and again at 2 and 6 months postnatally. Data relevant to psychosocial and obstetric risks were ascertained from interview, medical exam, and chart review. Results Two distinct factors of PrA were identified, indexing specific concerns about the child’s health and about the birth; these two PrA factors showed distinct longitudinal patterns in the prenatal period, and modest associations with general measures of anxiety and depression from questionnaire and clinical interview. PrA was also distinguished from conventional symptom measures in its associated features and prediction of birth weight and postnatal mood. Limitations The sample was at high psychosocial risk and ethnically diverse; findings may not generalize to other samples. Conclusions PrA can be distinguished from general measures of anxiety in pregnancy in terms of longitudinal course, associated features, and prediction to postnatal mood disturbance, and may warrant specific clinical attention. PMID:26999549

Automated identification of diagnosis and co-morbidity in clinical records.

PubMed

Cano, C; Blanco, A; Peshkin, L

2009-01-01

Automated understanding of clinical records is a challenging task involving various legal and technical difficulties. Clinical free text is inherently redundant, unstructured, and full of acronyms, abbreviations and domain-specific language which make it challenging to mine automatically. There is much effort in the field focused on creating specialized ontology, lexicons and heuristics based on expert knowledge of the domain. However, ad-hoc solutions poorly generalize across diseases or diagnoses. This paper presents a successful approach for a rapid prototyping of a diagnosis classifier based on a popular computational linguistics platform. The corpus consists of several hundred of full length discharge summaries provided by Partners Healthcare. The goal is to identify a diagnosis and assign co-morbidi-ty. Our approach is based on the rapid implementation of a logistic regression classifier using an existing toolkit: LingPipe (http://alias-i.com/lingpipe). We implement and compare three different classifiers. The baseline approach uses character 5-grams as features. The second approach uses a bag-of-words representation enriched with a small additional set of features. The third approach reduces a feature set to the most informative features according to the information content. The proposed systems achieve high performance (average F-micro 0.92) for the task. We discuss the relative merit of the three classifiers. Supplementary material with detailed results is available at: http:// decsai.ugr.es/~ccano/LR/supplementary_ material/ We show that our methodology for rapid prototyping of a domain-unaware system is effective for building an accurate classifier for clinical records.

Spectrum of mucocutaneous manifestations in 277 patients with joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type.

PubMed

Castori, Marco; Dordoni, Chiara; Morlino, Silvia; Sperduti, Isabella; Ritelli, Marco; Valiante, Michele; Chiarelli, Nicola; Zanca, Arianna; Celletti, Claudia; Venturini, Marina; Camerota, Filippo; Calzavara-Pinton, Piergiacomo; Grammatico, Paola; Colombi, Marina

2015-03-01

Cutaneous manifestations are a diagnostic criterion of Ehlers-Danlos syndrome, hypermobility type (EDS-HT) and joint hypermobility syndrome (JHS). These two conditions, originally considered different disorders, are now accepted as clinically indistinguishable and often segregate as a single-familial trait. EDS-HT and JHS are still exclusion diagnoses not supported by any specific laboratory test. Accuracy of clinical diagnosis is, therefore, crucial for appropriate patients' classification and management, but it is actually hampered by the low consistency of many applied criteria including the cutaneous one. We report on mucocutaneous findings in 277 patients with JHS/EDS-HT with both sexes and various ages. Sixteen objective and five anamnestic items were selected and ascertained in two specialized outpatient clinics. Feature rates were compared by sex and age by a series of statistical tools. Data were also used for a multivariate correspondence analysis with the attempt to identify non-causal associations of features depicting recognizable phenotypic clusters. Our findings identified a few differences between sexes and thus indicated an attenuated sexual dimorphism for mucocutaneous features in JHS/EDS-HT. Ten features showed significantly distinct rates at different ages and this evidence corroborated the concept of an evolving phenotype in JHS/EDS-HT also affecting the skin. Multivariate correspondence analysis identified three relatively discrete phenotypic profiles, which may represent the cutaneous counterparts of the three disease phases previously proposed for JHS/EDS-HT. These findings could be used for revising the cutaneous criterion in a future consensus for the clinical diagnosis of JHS/EDS-HT. © 2015 Wiley Periodicals, Inc.

WE-D-BRD-01: Innovation in Radiation Therapy Delivery: Advanced Digital Linac Features

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

Xing, L; Wong, J; Li, R

2014-06-15

Last few years has witnessed significant advances in linac technology and therapeutic dose delivery method. Digital linacs equipped with high dose rate FFF beams have been clinically implemented in a number of hospitals. Gated VMAT is becoming increasingly popular in treating tumors affected by respiratory motion. This session is devoted to update the audience with these technical advances and to present our experience in clinically implementing the new linacs and dose delivery methods. Topics to be covered include, technical features of new generation of linacs from different vendors, dosimetric characteristics and clinical need for FFF-beam based IMRT and VMAT, respiration-gatedmore » VMAT, the concept and implementation of station parameter optimized radiation therapy (SPORT), beam level imaging and onboard image guidance tools. Emphasis will be on providing fundamental understanding of the new treatment delivery and image guidance strategies, control systems, and the associated dosimetric characteristics. Commissioning and acceptance experience on these new treatment delivery technologies will be reported. Clinical experience and challenges encountered during the process of implementation of the new treatment techniques and future applications of the systems will also be highlighted. Learning Objectives: Present background knowledge of emerging digital linacs and summarize their key geometric and dosimetric features. SPORT as an emerging radiation therapy modality specifically designed to take advantage of digital linacs. Discuss issues related to the acceptance and commissioning of the digital linacs and FFF beams. Describe clinical utility of the new generation of digital linacs and their future applications.« less

Undifferentiated connective tissue disease and interstitial lung disease: Trying to define patterns.

PubMed

Alberti, María Laura; Paulin, Francisco; Toledo, Heidegger Mateos; Fernández, Martín Eduardo; Caro, Fabián Matías; Rojas-Serrano, Jorge; Mejía, Mayra Edith

To identify clinical or immunological features in patients with undifferentiated connective tissue disease (UCTD) associated interstitial lung disease (ILD), in order to group them and recognize different functional and high resolution computed tomography (HRCT) behavior. Retrospective cohort study. Patients meeting Kinder criteria for UCTD were included. We defined the following predictive variables: 'highly specific' connective tissue disease (CTD) manifestations (Raynaud's phenomenon, dry eyes or arthritis), high antinuclear antibody (ANA) titer (above 1: 320), and 'specific' ANA staining patterns (centromere, cytoplasmic and nucleolar patterns). We evaluated the following outcomes: change in the percentage of the predicted forced vital capacity (FVC%) during the follow-up period, and HRCT pattern. Sixty-six patients were included. Twenty-nine (43.94%) showed at least one 'highly specific' CTD manifestation, 16 (28.57%) had a 'specific' ANA staining pattern and 29 (43.94%) high ANA titer. Patients with 'highly specific' CTD manifestations were younger (mean [SD] 52 years [14.58] vs 62.08 years [9.46], P<.001), were more likely men (10.34% vs 48.65%, P<.001) and showed a smaller decline of the FVC% (median [interquartile range] 1% [-1 to 10] vs -6% [-16 to -4], P<.006). In the multivariate analysis, the presence of highly specific manifestations was associated with improvement in the FVC% (B coefficient of 13.25 [95% confidence interval, 2.41 to 24.09]). No association was observed in relation to the HRCT pattern. The presence of 'highly specific' CTD manifestations was associated with female sex, younger age and better functional behavior. These findings highlight the impact of the clinical features in the outcome of patients with UCTD ILD. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Neuromuscular choristoma: characteristic magnetic resonance imaging findings and association with post-biopsy fibromatosis.

PubMed

Niederhauser, Blake D; Spinner, Robert J; Jentoft, Mark E; Everist, Brian M; Matsumoto, Jane M; Amrami, Kimberly K

2013-04-01

To describe imaging characteristics of neuromuscular choristomas (NMC) and to differentiate them from fibrolipomatous hamartomas (FLH). Clinical and imaging characteristics of six patients with biopsy-proven NMC and six patients with FLH were reviewed by musculoskeletal, a pediatric, and two in-training radiologists with a literature review to define typical magnetic resonance imaging features by consensus. Five radiology trainees blinded to cases and naive to the diagnosis of NMC and a musculoskeletal-trained radiologist rated each lesion as having more than or less than 50% intralesional fat, as well as an overall impression using axial T1 images. Sensitivity, specificity, accuracy, and interobserver agreement kappa were determined. Typical features of NMC include smoothly tapering, fusiform enlargement of the sciatic nerve or brachial plexus elements with T1 and T2 signal characteristics closely following those of muscle. Longitudinal bands of intervening low T1 and T2 signal were often present and likely corresponded to fibrous tissue by pathology. Four of five patients with long-term follow-up (80%) developed aggressive fibromatosis after percutaneous or surgical biopsy. Nerve fascicle thickening often resulted in a "coaxial cable" appearance similar to classic FLH, however, using a cutoff of <50% intralesional fat allowed for differentiation with 100% sensitivity by all reviewers and 100% specificity when all imaging features were utilized for impressions. Agreement was excellent with all differentiating methods (kappa 0.861-1.0). NMC can be confidently differentiated from FLH and malignancies using characteristic imaging and clinical features. When a diagnosis is made, biopsy should be avoided given frequent complication by aggressive fibromatosis.

Is an Appreciation of Isomerism the Key to Unlocking the Mysteries of the Cardiac Findings in Heterotaxy?

PubMed

Anderson, Robert H; Spicer, Diane E; Loomba, Rohit

2018-02-06

Pediatric cardiologists treating patients with severe congenital cardiac defects define "visceral heterotaxy" on the basis of isomerism of the atrial appendages. The isomeric features represent an obvious manifestation of disruption of left-right asymmetry during embryonic development. Thus, there are two subsets of individuals within the overall syndrome, with features of either right or left isomerism. Within the heart, it is only the atrial appendages that are truly isomeric. The remainder of the cardiac components shows variable morphology, as does the arrangement of the remaining body organs. Order is provided in this potentially chaotic arrangement simply by describing the specific features of each of the systems. These features as defined by clinicians, however, seem less well recognized by those investigating the developmental origins of the disruption of symmetry. Developmental biologists place much greater emphasis on ventricular looping. Although the direction of the loop can certainly be interpreted as representing an example of asymmetry, it is not comparable to the isomeric features that underscore the clinical syndromes. This is because, thus far, there is no evidence of ventricular isomerism, with the ventricles distinguished one from the other on the basis of their disparate anatomical features. In similar fashion, some consider transposition to represent abnormal lateralization, but again, clinical diagnosis depends on recognition of the lateralized features. In this review, therefore, we discuss the key questions that currently underscore the mismatch in the approaches to "lateralization" as taken by clinicians and developmental biologists.

A Combination of Molecular Markers and Clinical Features Improve the Classification of Pancreatic Cysts

PubMed Central

Springer, Simeon; Wang, Yuxuan; Molin, Marco Dal; Masica, David L.; Jiao, Yuchen; Kinde, Isaac; Blackford, Amanda; Raman, Siva P.; Wolfgang, Christopher L.; Tomita, Tyler; Niknafs, Noushin; Douville, Christopher; Ptak, Janine; Dobbyn, Lisa; Allen, Peter J.; Klimstra, David S.; Schattner, Mark A.; Schmidt, C. Max; Yip-Schneider, Michele; Cummings, Oscar W.; Brand, Randall E.; Zeh, Herbert J.; Singhi, Aatur D.; Scarpa, Aldo; Salvia, Roberto; Malleo, Giuseppe; Zamboni, Giuseppe; Falconi, Massimo; Jang, Jin-Young; Kim, Sun-Whe; Kwon, Wooil; Hong, Seung-Mo; Song, Ki-Byung; Kim, Song Cheol; Swan, Niall; Murphy, Jean; Geoghegan, Justin; Brugge, William; Fernandez-Del Castillo, Carlos; Mino-Kenudson, Mari; Schulick, Richard; Edil, Barish H.; Adsay, Volkan; Paulino, Jorge; van Hooft, Jeanin; Yachida, Shinichi; Nara, Satoshi; Hiraoka, Nobuyoshi; Yamao, Kenji; Hijioka, Susuma; van der Merwe, Schalk; Goggins, Michael; Canto, Marcia Irene; Ahuja, Nita; Hirose, Kenzo; Makary, Martin; Weiss, Matthew J.; Cameron, John; Pittman, Meredith; Eshleman, James R.; Diaz, Luis A.; Papadopoulos, Nickolas; Kinzler, Kenneth W.; Karchin, Rachel; Hruban, Ralph H.; Vogelstein, Bert; Lennon, Anne Marie

2016-01-01

Background & Aims The management of pancreatic cysts poses challenges to both patients and their physicians. We investigated whether a combination of molecular markers and clinical information could improve the classification of pancreatic cysts and management of patients. Methods We performed a multi-center, retrospective study of 130 patients with resected pancreatic cystic neoplasms (12 serous cystadenomas, 10 solid-pseudopapillary neoplasms, 12 mucinous cystic neoplasms, and 96 intraductal papillary mucinous neoplasms). Cyst fluid was analyzed to identify subtle mutations in genes known to be mutated in pancreatic cysts (BRAF, CDKN2A, CTNNB1, GNAS, KRAS, NRAS, PIK3CA, RNF43, SMAD4, TP53 and VHL); to identify loss of heterozygozity at CDKN2A, RNF43, SMAD4, TP53, and VHL tumor suppressor loci; and to identify aneuploidy. The analyses were performed using specialized technologies for implementing and interpreting massively parallel sequencing data acquisition. An algorithm was used to select markers that could classify cyst type and grade. The accuracy of the molecular markers were compared with that of clinical markers, and a combination of molecular and clinical markers. Results We identified molecular markers and clinical features that classified cyst type with 90%–100% sensitivity and 92%–98% specificity. The molecular marker panel correctly identified 67 of the 74 patients who did not require surgery, and could therefore reduce the number of unnecessary operations by 91%. Conclusions We identified a panel of molecular markers and clinical features that show promise for the accurate classification of cystic neoplasms of the pancreas and identification of cysts that require surgery. PMID:26253305

Non-specific gastrointestinal features: Could it be Fabry disease?

PubMed

Hilz, Max J; Arbustini, Eloisa; Dagna, Lorenzo; Gasbarrini, Antonio; Goizet, Cyril; Lacombe, Didier; Liguori, Rocco; Manna, Raffaele; Politei, Juan; Spada, Marco; Burlina, Alessandro

2018-05-01

Non-specific gastrointestinal symptoms, including pain, diarrhoea, nausea, and vomiting, can be the first symptoms of Fabry disease. They may suggest more common disorders, e.g. irritable bowel syndrome or inflammatory bowel disease. The confounding clinical presentation and rarity of Fabry disease often cause long diagnostic delays and multiple misdiagnoses. Therefore, specialists involved in the clinical evaluation of non-specific upper and lower gastrointestinal symptoms should recognize Fabry disease as a possible cause of the symptoms, and should consider Fabry disease as a possible differential diagnosis. When symptoms or family history suggest Fabry disease, in men, low alpha-galactosidase A enzyme levels, and in women, specific Fabry mutations confirm the diagnosis. In addition to symptomatic treatments, disease-specific enzyme replacement therapy with recombinant human alpha-galactosidase A enzyme or chaperone therapy (migalastat) in patients with amenable mutations can improve the disease, including gastrointestinal symptoms, and should be initiated as early as possible after Fabry disease has been confirmed; starting enzyme replacement therapy at as young an age as possible after diagnosis improves long-term clinical outcomes. Improved diagnostic tools, such as a modified gastrointestinal symptom rating scale, may facilitate diagnosing Fabry disease in patients with gastrointestinal symptoms of unknown cause and thus assure timely initiation of disease-specific treatment. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

The Clinical Impact of Bet v 6 in Birch Pollen-Sensitized Patients.

PubMed

Gellrich, Donata; Eder, Katharina; San Nicoló, Marion; Berghaus, Alexander; Gröger, Moritz

2017-01-01

Bet v 6, a minor birch pollen allergen, is commercially available for allergen-specific IgE antibody testing. However, there is hardly any literature on the clinical impact of Bet v 6. The aim of the present study was to analyze if testing specific IgE against Bet v 6 can add valuable benefit to the standard diagnostics of birch pollen-sensitized patients, especially in patients with unknown sensitization-eliciting allergens. Birch pollen-sensitized patients with missing IgE reactivity against Bet v 1, 2, and 4 were tested for specific IgE antibodies against Bet v 6. For comparison, an equal number of randomly selected patients with birch pollen sensitization, regardless of their individual sensitization patterns, were tested for specific anti-Bet v 6. Of 57 cases with missing reactivity against the standard birch pollen allergens, 2 patients were positive for Bet v 6. In the representative sample, 3 patients showed specific IgE against Bet v 6 - resulting in a total prevalence of 5%. None of the Bet v 6-positive patients showed allergic symptoms after exposure to birch pollen or an oral allergy syndrome. An increased prevalence of asthma and a higher degree of sensitization were the only distinctive clinical features in Bet v 6-positive patients. Among birch pollen-sensitized patients, the prevalence of specific IgE against Bet v 6 is low. Further, sensitization to Bet v 6, which shows characteristics of a panallergen, remains clinically silent. Therefore, determination of anti-Bet v 6 is not considered useful in the clinical routine. © 2017 S. Karger AG, Basel.

Validation of clinical case definition of acute intussusception in infants in Viet Nam and Australia.

PubMed

Bines, Julie E; Liem, Nguyen Thanh; Justice, Frances; Son, Tran Ngoc; Carlin, John B; de Campo, Margaret; Jamsen, Kris; Mulholland, Kim; Barnett, Peter; Barnes, Graeme L

2006-07-01

To test the sensitivity and specificity of a clinical case definition of acute intussusception in infants to assist health-care workers in settings where diagnostic facilities are not available. Prospective studies were conducted at a major paediatric hospital in Viet Nam (the National Hospital of Pediatrics, Hanoi) from November 2002 to December 2003 and in Australia (the Royal Children's Hospital, Melbourne) from March 2002 to March 2004 using a clinical case definition of intussusception. Diagnosis of intussusception was confirmed by air enema or surgery and validated in a subset of participants by an independent clinician who was blinded to the participant's status. Sensitivity of the definition was evaluated in 584 infants aged<2 years with suspected intussusception (533 infants in Hanoi; 51 in Melbourne). Specificity was evaluated in 638 infants aged<2 years presenting with clinical features consistent with intussusception but for whom another diagnosis was established (234 infants in Hanoi; 404 in Melbourne). In both locations the definition used was sensitive (96% sensitivity in Hanoi; 98% in Melbourne) and specific (95% specificity in Hanoi; 87% in Melbourne) for intussusception among infants with sufficient data to allow classification (449/533 in Hanoi; 50/51 in Melbourne). Reanalysis of patients with missing data suggests that modifying minor criteria would increase the applicability of the definition while maintaining good sensitivity (96-97%) and specificity (83-89%). The clinical case definition was sensitive and specific for the diagnosis of acute intussusception in infants in both a developing country and a developed country but minor modifications would enable it to be used more widely.

Hereditary myopathies with early respiratory insufficiency in adults.

PubMed

Naddaf, Elie; Milone, Margherita

2017-11-01

Hereditary myopathies with early respiratory insufficiency as a predominant feature of the clinical phenotype are uncommon and underestimated in adults. We reviewed the clinical and laboratory data of patients with hereditary myopathies who demonstrated early respiratory insufficiency before the need for ambulatory assistance. Only patients with disease-causing mutations or a specific histopathological diagnosis were included. Patients with cardiomyopathy were excluded. We identified 22 patients; half had isolated respiratory symptoms at onset. The diagnosis of the myopathy was often delayed, resulting in delayed ventilatory support. The most common myopathies were adult-onset Pompe disease, myofibrillar myopathy, multi-minicore disease, and myotonic dystrophy type 1. Single cases of laminopathy, MELAS (mitochondrial encephalomyopathy with lactic acidosis and strokelike events), centronuclear myopathy, and cytoplasmic body myopathy were identified. We highlighted the most common hereditary myopathies associated with early respiratory insufficiency as the predominant clinical feature, and underscored the importance of a timely diagnosis for patient care. Muscle Nerve 56: 881-886, 2017. © 2017 Wiley Periodicals, Inc.

Quality of life in anorexia nervosa, bulimia nervosa and eating disorder not-otherwise-specified

PubMed Central

2013-01-01

Background This study aimed to assess differences in Quality of Life (QoL) across eating disorder (ED) diagnoses, and to examine the relationship of QoL to specific clinical features. Results 199 patients with a diagnosed ED completed the Clinical Impairment Assessment (CIA) [Cognitive Behavior Therapy and Eating Disorders, 315–318, 2008] and the Eating Disorders Examination (EDE) [Int J Eat Disord 6:1–8]. Differences between diagnostic groups were examined, as were differences between restrictive and binge-purge subtypes. CIA scores and EDE scores were positively correlated and higher in groups with binge-purge behaviours. CIA scores were not correlated with BMI, illness duration or frequency of bingeing/purging behaviours, except in the binge-purge AN group, where CIA scores negatively correlated with BMI. Conclusions Patients with EDs have poor QoL and impairment increases with illness severity. Patients with binge/purge diagnoses are particularly impaired. It remains unclear which clinical features best predict the degree of impairment experienced by patients with EDs. PMID:24999421

Clinical applications of optical coherence tomography in the posterior pole: the 2011 José Manuel Espino Lecture – Part II

PubMed Central

Arevalo, J Fernando; Lasave, Andres F; Arias, Juan D; Serrano, Martin A; Arevalo, Fernando A

2013-01-01

Optical coherence tomography (OCT) is a high-resolution, cross-sectional imaging technique that allows detailed assessment of retinal thickness and morphologic evaluation of the retinal layers. This technology has developed quickly over the past two decades. OCT imaging has rapidly been integrated into routine ophthalmic clinical practice and trials. It has complemented fluorescein angiography in many instances, especially in the diagnosis and management of retinal disorders, including diabetic macular edema and age-related macular degeneration. With OCT, the exact localization of pathologic features can be visualized in segmentation maps of the retina, and this has allowed OCT to be used to evaluate specific features that may serve as predictive factors in the prognosis and follow up of these pathologies. Therefore, it has become an important clinical and research tool for the diagnosis, follow up, treatment, and assessment of new treatment modalities for all diseases that affect the posterior pole of the eye. PMID:24235811

Detection of Interictal Discharges With Convolutional Neural Networks Using Discrete Ordered Multichannel Intracranial EEG.

PubMed

Antoniades, Andreas; Spyrou, Loukianos; Martin-Lopez, David; Valentin, Antonio; Alarcon, Gonzalo; Sanei, Saeid; Cheong Took, Clive

2017-12-01

Detection algorithms for electroencephalography (EEG) data, especially in the field of interictal epileptiform discharge (IED) detection, have traditionally employed handcrafted features, which utilized specific characteristics of neural responses. Although these algorithms achieve high accuracy, mere detection of an IED holds little clinical significance. In this paper, we consider deep learning for epileptic subjects to accommodate automatic feature generation from intracranial EEG data, while also providing clinical insight. Convolutional neural networks are trained in a subject independent fashion to demonstrate how meaningful features are automatically learned in a hierarchical process. We illustrate how the convolved filters in the deepest layers provide insight toward the different types of IEDs within the group, as confirmed by our expert clinicians. The morphology of the IEDs found in filters can help evaluate the treatment of a patient. To improve the learning of the deep model, moderately different score classes are utilized as opposed to binary IED and non-IED labels. The resulting model achieves state-of-the-art classification performance and is also invariant to time differences between the IEDs. This paper suggests that deep learning is suitable for automatic feature generation from intracranial EEG data, while also providing insight into the data.

Precision Oncology Medicine: The Clinical Relevance of Patient-Specific Biomarkers Used to Optimize Cancer Treatment.

PubMed

Schmidt, Keith T; Chau, Cindy H; Price, Douglas K; Figg, William D

2016-12-01

Precision medicine in oncology is the result of an increasing awareness of patient-specific clinical features coupled with the development of genomic-based diagnostics and targeted therapeutics. Companion diagnostics designed for specific drug-target pairs were the first to widely utilize clinically applicable tumor biomarkers (eg, HER2, EGFR), directing treatment for patients whose tumors exhibit a mutation susceptible to an FDA-approved targeted therapy (eg, trastuzumab, erlotinib). Clinically relevant germline mutations in drug-metabolizing enzymes and transporters (eg, TPMT, DPYD) have been shown to impact drug response, providing a rationale for individualized dosing to optimize treatment. The use of multigene expression-based assays to analyze an array of prognostic biomarkers has been shown to help direct treatment decisions, especially in breast cancer (eg, Oncotype DX). More recently, the use of next-generation sequencing to detect many potential "actionable" cancer molecular alterations is further shifting the 1 gene-1 drug paradigm toward a more comprehensive, multigene approach. Currently, many clinical trials (eg, NCI-MATCH, NCI-MPACT) are assessing novel diagnostic tools with a combination of different targeted therapeutics while also examining tumor biomarkers that were previously unexplored in a variety of cancer histologies. Results from ongoing trials such as the NCI-MATCH will help determine the clinical utility and future development of the precision-medicine approach. © 2016, The American College of Clinical Pharmacology.

Trends in Diagnosis and Clinical Features of Melanoma in situ in U.S. Men and Women: a prospective, observational study

PubMed Central

Wei, Erin X.; Qureshi, Abrar A.; Han, Jiali; Li, Tricia Y.; Cho, Eunyoung; Lin, Jennifer Y.; Li, Wen-Qing

2016-01-01

Background The incidence of melanoma in situ is rising, but little is known about its characteristics. Objective To determine trends in diagnosis and clinical features of melanoma in situ. Methods Incident cases of melanoma were collected prospectively from the Nurses’ Health Study from 1976–2010 and Health Professionals Follow-up Study from 1986–2010. Results MIS incidence increased from 2 to 42 per 100,000-person-year (100KPY) among women, and from 11 to 73 per 100KPY among men, exceeding the rate of increase of invasive melanomas. Melanoma mortality initially increased during the follow-up period then plateaued. Men were more likely than women to develop in situ melanomas on upper half of the body (p<0.001). Invasive melanomas were diagnosed at a younger age than melanoma in situ (p<0.001), and were more likely to be found on the lower extremities than in situ melanomas (p<0.001). Limitations This is a strictly descriptive study without examination into mechanisms. Conclusion We found epidemiologic and clinical differences in in situ and invasive melanomas, which support further examination into the variations in etiologic pathways. The lack of improvement in mortality despite increase in detection of in situ relative to invasive lesions further highlight the need to improve invasive melanoma-specific clinical screening features. PMID:27436155

A de-novo interstitial microduplication involving 2p16.1-p15 and mirroring 2p16.1-p15 microdeletion syndrome: Clinical and molecular analysis.

PubMed

Mimouni-Bloch, Aviva; Yeshaya, Josepha; Kahana, Sarit; Maya, Idit; Basel-Vanagaite, Lina

2015-11-01

Microdeletions of various sizes in the 2p16.1-p15 chromosomal region have been grouped together under the 2p16.1-p15 microdeletion syndrome. Children with this syndrome generally share certain features including microcephaly, developmental delay, facial dysmorphism, urogenital and skeletal abnormalities. We present a child with a de-novo interstitial 1665 kb duplication of 2p16.1-p15. Clinical features of this child are distinct from those of children with the 2p16.1-p15 microdeletion syndrome, specifically the head circumference which is within the normal range and mild intellectual disability with absence of autistic behaviors. Microduplications many times bear milder clinical phenotypes in comparison with corresponding microdeletion syndromes. Indeed, as compared to the microdeletion syndrome patients, the 2p16.1-p15 microduplication seems to have a milder cognitive effect and no effect on other body systems. Limited information available in genetic databases about cases with overlapping duplications indicates that they all have abnormal developmental phenotypes. The involvement of genes in this location including BCL11A, USP34 and PEX13, affecting fundamental developmental processes both within and outside the nervous system may explain the clinical features of the individual described in this report. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Sensitivity and specificity of Addenbrooke's Cognitive Examination, Mattis Dementia Rating Scale, Frontal Assessment Battery and Mini Mental State Examination for diagnosing dementia in Parkinson's disease.

PubMed

Kaszás, B; Kovács, N; Balás, I; Kállai, J; Aschermann, Z; Kerekes, Z; Komoly, S; Nagy, F; Janszky, J; Lucza, T; Karádi, K

2012-06-01

Among the non-motor features of Parkinson's disease (PD), cognitive impairment is one of the most troublesome problems. Highly sensitive and specific screening instruments for detecting dementia in PD (PDD) are required in the clinical practice. In our study we evaluated the sensitivity and specificity of different neuropsychological tests (Addenbrooke's Cognitive Examination, ACE; Frontal Assessment Battery, FAB and Mattis Dementia Rating Scale, MDRS) in 73 Parkinson's disease patients without depression. By receiver operating characteristic curve analysis, these screening instruments were tested against the recently established clinical diagnostic criteria of PDD. Best cut-off score for ACE to identify PDD was 80 points (sensitivity = 74.0%, specificity = 78.1%). For FAB the most optimal cut-off value was 12 points (sensitivity = 66.3%, specificity = 72.2%); whereas for MDRS it was 125 points (sensitivity = 89.8%, specificity = 98.3%). Among the examined test batteries, MDRS had the best clinicometric profile for detecting PDD. Although the types of applied screening instruments might differ from movement disorder clinic to clinic within a country, determination of the most specific and sensitive test for the given population remains to be an important task. Our results demonstrated that the specificity and sensitivity of MDRS was better than those of ACE, FAB and MMSE in Hungary. However, further studies with larger sample size and more uniform criteria for participation are required to determine the most suitable screening instrument for cognitive impairment. Copyright © 2012 Elsevier Ltd. All rights reserved.

Microscopic Colitis – A Missed Diagnosis in Diarrhea-Predominant Irritable Bowel Syndrome

PubMed Central

STOICESCU, Adriana; BECHEANU, Gabriel; DUMBRAVA, Mona; GHEORGHE, Cristian; DICULESCU, Mircea

2012-01-01

ABSTRACT Background: Clinical presentation in microscopic colitis (MC) is similar in many cases to that of diarrhea-predominent irritable bowel syndrome (IBS-D). The proper differential diagnosis requires total colonoscopy with multiple biopsies from normal-appearing mucosa and a detailed histopathological exam. Specific treatment may improve symptomatology. Aim: To evaluate the prevalence of MC in patients with an initial diagnosis of IBS-D, to analyse demographic and clinical features of MC patients and to assess the efficacy of specific treatment. Material and methods: Our retrospective study analyzed patients diagnosed with microscopic colitis in clinic during a three-year period. Diagnosis was established on histological exams of the samples obtained during colonoscopy in patients previously thought to have IBS-D. We evaluated clinical manifestations, time lapsed from their onset to definitive diagnosis, the association of MC with autoimmune diseases or with prior medication and the efficacy of treatment with budesonide or mesalazine. Results: From 247 patients considered to have IBS-D, 15 patients (6.07%) had actually MC (13 lymphocytic colitis and 2 collagenous colitis). MC was associated with nonsteroidal antiinflammatory drugs (3 patients), Lansoprazole (2 patients) and autoimmune diseases (6 patients). Watery, non-bloody diarrhea was present in all patients with MC. Other frequent complaints were nocturnal diarrhea (11 patients), abdominal pain (8 patients), abdominal bloating and flatulence (8 patients) and slight weight loss (6 patients). The diagnostic samples were obtained from the right colon in 6 cases and from rectosigmoid or transverse colon in 9 patients. Treatment was initial symptomatic in all patients, but there were 5 patients that required mesalazine and/or Budesonide, with favourable outcome. Conclusions: All the patients thought to have diarrhea-irritable bowel syndrome should be evaluated for microscopic colitis. Symptomatology is almost superimposable, but a few distinct features can be noticed. The proper and early diagnosis and the specific treatment may lead to significant clinical improvement in some difficult cases of the so-called "irritable bowel syndrome". PMID:23118812

Microscopic colitis - a missed diagnosis in diarrhea-predominant irritable bowel syndrome.

PubMed

Stoicescu, Adriana; Becheanu, Gabriel; Dumbrava, Mona; Gheorghe, Cristian; Diculescu, Mircea

2012-01-01

Clinical presentation in microscopic colitis (MC) is similar in many cases to that of diarrhea-predominent irritable bowel syndrome (IBS-D). The proper differential diagnosis requires total colonoscopy with multiple biopsies from normal-appearing mucosa and a detailed histopathological exam. Specific treatment may improve symptomatology. To evaluate the prevalence of MC in patients with an initial diagnosis of IBS-D, to analyse demographic and clinical features of MC patients and to assess the efficacy of specific treatment. Our retrospective study analyzed patients diagnosed with microscopic colitis in clinic during a three-year period. Diagnosis was established on histological exams of the samples obtained during colonoscopy in patients previously thought to have IBS-D. We evaluated clinical manifestations, time lapsed from their onset to definitive diagnosis, the association of MC with autoimmune diseases or with prior medication and the efficacy of treatment with budesonide or mesalazine. From 247 patients considered to have IBS-D, 15 patients (6.07%) had actually MC (13 lymphocytic colitis and 2 collagenous colitis). MC was associated with nonsteroidal antiinflammatory drugs (3 patients), Lansoprazole (2 patients) and autoimmune diseases (6 patients). Watery, non-bloody diarrhea was present in all patients with MC. Other frequent complaints were nocturnal diarrhea (11 patients), abdominal pain (8 patients), abdominal bloating and flatulence (8 patients) and slight weight loss (6 patients). The diagnostic samples were obtained from the right colon in 6 cases and from rectosigmoid or transverse colon in 9 patients. Treatment was initial symptomatic in all patients, but there were 5 patients that required mesalazine and/or Budesonide, with favourable outcome. All the patients thought to have diarrhea-irritable bowel syndrome should be evaluated for microscopic colitis. Symptomatology is almost superimposable, but a few distinct features can be noticed. The proper and early diagnosis and the specific treatment may lead to significant clinical improvement in some difficult cases of the so-called "irritable bowel syndrome".

A genomic view of food-related and probiotic Enterococcus strains

PubMed Central

Suárez, Nadia; Hormigo, Ricardo; Fadda, Silvina; Saavedra, Lucila

2017-01-01

Abstract The study of enterococcal genomes has grown considerably in recent years. While special attention is paid to comparative genomic analysis among clinical relevant isolates, in this study we performed an exhaustive comparative analysis of enterococcal genomes of food origin and/or with potential to be used as probiotics. Beyond common genetic features, we especially aimed to identify those that are specific to enterococcal strains isolated from a certain food-related source as well as features present in a species-specific manner. Thus, the genome sequences of 25 Enterococcus strains, from 7 different species, were examined and compared. Their phylogenetic relationship was reconstructed based on orthologous proteins and whole genomes. Likewise, markers associated with a successful colonization (bacteriocin genes and genomic islands) and genome plasticity (phages and clustered regularly interspaced short palindromic repeats) were investigated for lifestyle specific genetic features. At the same time, a search for antibiotic resistance genes was carried out, since they are of big concern in the food industry. Finally, it was possible to locate 1617 FIGfam families as a core proteome universally present among the genera and to determine that most of the accessory genes code for hypothetical proteins, providing reasonable hints to support their functional characterization. PMID:27773878

Psychiatric Symptoms in Adults with Down Syndrome and Alzheimer's Disease

ERIC Educational Resources Information Center

Urv, Tiina K.; Zigman, Warren B.; Silverman, Wayne

2010-01-01

Changes in psychiatric symptoms related to specific stages of dementia were investigated in 224 adults 45 years of age or older with Down syndrome. Findings indicate that psychiatric symptoms are a prevalent feature of dementia in the population with Down syndrome and that clinical presentation is qualitatively similar to that seen in Alzheimer's…

Reticulate Dermatoses

PubMed Central

Adya, Keshavmurthy A; Inamadar, Arun C; Palit, Aparna

2014-01-01

The term “reticulate” is used for clinical description of skin lesions that are configured in a net-like pattern. Many primary and secondary dermatoses present in such patterns involving specific body sites. Certain cutaneous manifestations of systemic diseases or genodermatoses also present in such manner. This review classifies and describes such conditions with reticulate lesions and briefly, their associated features. PMID:24470653

Linking Anxiety and Insistence on Sameness in Autistic Children: The Role of Sensory Hypersensitivity

ERIC Educational Resources Information Center

Black, Karen R.; Stevenson, Ryan A.; Segers, Magali; Ncube, Busiswe L.; Sun, Sol Z.; Philipp-Muller, Aviva; Bebko, James M.; Barense, Morgan D.; Ferber, Susanne

2017-01-01

Sensory hypersensitivity and insistence on sameness (I/S) are common, co-occurring features of autism, yet the relationship between them is poorly understood. This study assessed the impact of sensory hypersensitivity on the clinical symptoms of specific phobia, separation anxiety, social anxiety and I/S for autistic and typically developing (TD)…

Utility of MLH1 Methylation Analysis in the Clinical Evaluation of Lynch Syndrome in Women with Endometrial Cancer

PubMed Central

Bruegl, Amanda S.; Djordjevic, Bojana; Urbauer, Diana L.; Westin, Shannon N.; Soliman, Pamela T.; Lu, Karen H.; Luthra, Rajyalakshmi; Broaddus, Russell R.

2013-01-01

Clinical screening criteria, such as young age of endometrial cancer diagnosis and family history of signature cancers, have traditionally been used to identify women with Lynch Syndrome, which is caused by mutation of a DNA mismatch repair gene. Immunohistochemistry and microsatellite instability analysis have evolved as important screening tools to evaluate endometrial cancer patients for Lynch Syndrome. A complicating factor is that 15-20% of sporadic endometrial cancers have immunohistochemical loss of the DNA mismatch repair protein MLH1 and high levels of microsatellite instability due to methylation of MLH1. The PCR-based MLH1 methylation assay potentially resolves this issue, yet many clinical laboratories do not perform this assay. The objective of this study was to determine if clinical and pathologic features help to distinguish sporadic endometrial carcinomas with MLH1 loss secondary to MLH1 methylation from Lynch Syndrome-associated endometrial carcinomas with MLH1 loss and absence of MLH1 methylation. Of 337 endometrial carcinomas examined, 54 had immunohistochemical loss of MLH1. 40/54 had MLH1 methylation and were designated as sporadic, while 14/54 lacked MLH1 methylation and were designated as Lynch Syndrome. Diabetes and deep myometrial invasion were associated with Lynch Syndrome; no other clinical or pathological variable distinguished the 2 groups. Combining Society of Gynecologic Oncology screening criteria with these 2 features accurately captured all Lynch Syndrome cases, but with low specificity. In summary, no single clinical/pathologic feature or screening criteria tool accurately identified all Lynch Syndrome-associated endometrial carcinomas, highlighting the importance of the MLH1 methylation assay in the clinical evaluation of these patients. PMID:23888949

Utility of MLH1 methylation analysis in the clinical evaluation of Lynch Syndrome in women with endometrial cancer.

PubMed

Bruegl, Amanda S; Djordjevic, Bojana; Urbauer, Diana L; Westin, Shannon N; Soliman, Pamela T; Lu, Karen H; Luthra, Rajyalakshmi; Broaddus, Russell R

2014-01-01

Clinical screening criteria, such as young age of endometrial cancer diagnosis and family history of signature cancers, have traditionally been used to identify women with Lynch Syndrome, which is caused by mutation of a DNA mismatch repair gene. Immunohistochemistry and microsatellite instability analysis have evolved as important screening tools to evaluate endometrial cancer patients for Lynch Syndrome. A complicating factor is that 15-20% of sporadic endometrial cancers have immunohistochemical loss of the DNA mismatch repair protein MLH1 and high levels of microsatellite instability due to methylation of MLH1. The PCR-based MLH1 methylation assay potentially resolves this issue, yet many clinical laboratories do not perform this assay. The objective of this study was to determine if clinical and pathologic features help to distinguish sporadic endometrial carcinomas with MLH1 loss secondary to MLH1 methylation from Lynch Syndrome-associated endometrial carcinomas with MLH1 loss and absence of MLH1 methylation. Of 337 endometrial carcinomas examined, 54 had immunohistochemical loss of MLH1. 40/54 had MLH1 methylation and were designated as sporadic, while 14/54 lacked MLH1 methylation and were designated as Lynch Syndrome. Diabetes and deep myometrial invasion were associated with Lynch Syndrome; no other clinical or pathological variable distinguished the 2 groups. Combining Society of Gynecologic Oncology screening criteria with these 2 features accurately captured all Lynch Syndrome cases, but with low specificity. In summary, no single clinical/pathologic feature or screening criteria tool accurately identified all Lynch Syndrome-associated endometrial carcinomas, highlighting the importance of the MLH1 methylation assay in the clinical evaluation of these patients.

Specific IgE in tear fluid and features of allergic conjunctivitis.

PubMed

Mimura, Tatsuya; Yamagami, Satoru; Kamei, Yuko; Goto, Mari; Matsubara, Masao

2013-09-01

The level of specific class E immunoglobulins (IgE) in tear fluid is a useful diagnostic indicator for allergic conjunctivitis, but it is still unclear whether the measurement of tear fluid IgE is helpful for assessing the severity of allergic conjunctivitis. In this study, we evaluated the relation between tear fluid levels of specific IgE and features of allergic conjunctivitis. A prospective, nonrandomized, cross-sectional study was conducted in patients with allergic conjunctivitis (n = 55, allergic group) and age- and sex-matched healthy control subjects (n = 50, control group). Levels of specific IgE for cedar pollen, cat epithelium/dander and Dermatophagoides pteronyssinus were measured in tear fluid with the Immfast Check J1®. A severity score (0, 1, 2 or 3) was assigned for various changes of the palpebral and bulbar conjunctiva, as well as for limbal and corneal lesions. The levels of specific IgE for both cedar pollen, and D. pteronyssinus were significantly higher in the allergic group compared with the control group (p < 0.0001), while the level of specific IgE for cat epithelium/dander showed no significant difference between the two groups (p = 0.0777). When IgE levels were divided into four classes, the classes for both D. Pteronyssinus and cat epithelium/dander IgE were correlated with four features of allergic conjunctivitis. On the other hand, no correlation was found between the class of cedar pollen IgE and any of the features of allergic conjunctivitis. This study demonstrated that measurement of specific IgE in tear fluid may be useful for determining the severity of allergic conjunctivitis induced by indoor allergens. Although measurement of IgE in tear fluid is only a supplemental tool for evaluating the clinical activity of allergic conjunctivitis, the test can be useful for detecting specific IgE antibodies responsible for this condition.

Lymph nodes fine needle cytology in the diagnosis of infectious diseases: clinical settings.

PubMed

Natella, Valentina; Cozzolino, Immacolata; Sosa Fernandez, Laura Virginia; Vigliar, Elena

2012-01-01

Lymph node reactive hyperplasia, caused by specific infectious etiologic factors, represents the most frequent cause of enlarged peripheral lymph nodes. The main infectious agents are viruses, pyogenic bacteria, mycobacteria, fungi and protozoa that may determine unspecific or specific pathological entities, such as cat-scratch disease, toxoplasmosis or infectious mononucleosis. Lymph node fine needle cytology (FNC) is a safe, simple, cost-effective and efficient technique that quickly provides information about the cell population and the nature of the process. FNC can also provide suitable material for ancillary techniques, such as flow cytometry, immunocytochemistry, molecular biology and microbiological examinations. This study focuses on the cytological features of benign lymphadenopathy of infectious origin and their possible contribution to the clinical setting definition of corresponding patients.

Progress in atherosclerotic plaque imaging

PubMed Central

Soloperto, Giulia; Casciaro, Sergio

2012-01-01

Cardiovascular diseases are the primary cause of mortality in the industrialized world, and arterial obstruction, triggered by rupture-prone atherosclerotic plaques, lead to myocardial infarction and cerebral stroke. Vulnerable plaques do not necessarily occur with flow-limiting stenosis, thus conventional luminographic assessment of the pathology fails to identify unstable lesions. In this review we discuss the currently available imaging modalities used to investigate morphological features and biological characteristics of the atherosclerotic plaque. The different imaging modalities such as ultrasound, magnetic resonance imaging, computed tomography, nuclear imaging and their intravascular applications are illustrated, highlighting their specific diagnostic potential. Clinically available and upcoming methodologies are also reviewed along with the related challenges in their clinical translation, concerning the specific invasiveness, accuracy and cost-effectiveness of these methods. PMID:22937215

Redefining dermatomyositis: a description of new diagnostic criteria that differentiate pure dermatomyositis from overlap myositis with dermatomyositis features.

PubMed

Troyanov, Yves; Targoff, Ira N; Payette, Marie-Pier; Raynauld, Jean-Pierre; Chartier, Suzanne; Goulet, Jean-Richard; Bourré-Tessier, Josiane; Rich, Eric; Grodzicky, Tamara; Fritzler, Marvin J; Joyal, France; Koenig, Martial; Senécal, Jean-Luc

2014-11-01

Dermatomyositis (DM) is a major clinical subset of autoimmune myositis (AIM). The characteristic DM rash (Gottron papules, heliotrope rash) and perifascicular atrophy at skeletal muscle biopsy are regarded as specific features for this diagnosis. However, new concepts are challenging the current definition of DM. A modified Bohan and Peter classification of AIM was proposed in which the core concept was the inclusion of the diagnostic significance of overlap connective tissue disease features. In this clinical classification, a DM rash in association with myositis in the absence of overlap features indicates a diagnosis of pure DM. However, overlap features in association with myositis allow a diagnosis of overlap myositis (OM), irrespective of the presence or absence of the DM rash. Perifascicular atrophy may be present in both pure DM and OM. Recently, the presence of perifascicular atrophy in myositis without a DM rash was proposed as diagnostic of a novel entity, adermatopathic DM. We conducted the present study to evaluate these new concepts to further differentiate pure DM from OM.Using the modified Bohan and Peter classification, we performed a follow-up study of a longitudinal cohort of 100 consecutive adult French Canadian patients with AIM, including 44 patients with a DM phenotype, defined as a DM rash, and/or DM-type calcinosis, and/or the presence of perifascicular atrophy on muscle biopsy. A detailed evaluation was performed for overlap features, the extent and natural history of the DM rash, adermatopathic DM, DM-specific and overlap autoantibodies by protein A immunoprecipitation on coded serum samples, and associations with cancer and survival.Two distinct subsets were identified in patients with a DM phenotype: pure DM (n = 24) and OM with DM features, or OMDM (n = 20). In pure DM, the DM rash was a dominant finding. It was the first disease manifestation, was always present at the time of myositis diagnosis, and was associated with a high cutaneous score and chronicity. Concurrent heliotrope rash and Gottron papules (positive predictive value [PPV] 91%), as well as the V-sign and/or shawl sign (PPV 100%), were diagnostic of pure DM. Anti-Mi-2, anti-MJ, and anti-p155 autoantibodies were present in 50% of pure DM patients and were restricted to this subset (PPV 100%). Cancer was present in 21% of pure DM patients. The 15-year survival was excellent (92%).In contrast, in patients with OMDM, the first manifestation was proximal muscle weakness or other skeletal muscle-related complaints. The DM rash appeared at diagnosis or at follow-up, was associated with a low cutaneous extent score and was transient. Adermatopathic DM, which was absent in pure DM, was highly predictive (PPV 100%) of OMDM. Overlap autoantibodies (including anti-Jo-1, anti-PL-7, anti-PM-Scl, anti-U1RNP, and/or anti-U5-RNP) were found in 70% of OMDM patients. OMDM was not associated with cancer, but the 15-year survival was significantly decreased (65%).Perifascicular atrophy occurred as commonly in OMDM (n = 6/20, 30%) as in pure DM (n = 4/24, 17%) patients. These 6 OMDM patients had adermatopathic DM at myositis diagnosis, and only 1 of them developed a DM rash at follow-up, emphasizing the lack of specificity of perifascicular atrophy for pure DM.In conclusion, using the modified Bohan and Peter classification of AIM allowed identification of OMDM, a new clinical subset of OM. Furthermore, identification of OMDM allowed recognition of pure DM as a new entity that was distinct from OMDM or from OM without DM features. However, the absolute specificity of a DM rash and perifascicular muscle atrophy for the diagnosis of pure DM was lost. The distinctive clinical manifestations and autoantibody profiles presented are proposed as diagnostic criteria to differentiate pure DM from OMDM.

Clinical aspects of autoimmune rheumatic diseases.

PubMed

Goldblatt, Fiona; O'Neill, Sean G

2013-08-31

Multisystem autoimmune rheumatic diseases are heterogeneous rare disorders associated with substantial morbidity and mortality. Efforts to create international consensus within the past decade have resulted in the publication of new classification or nomenclature criteria for several autoimmune rheumatic diseases, specifically for systemic lupus erythematosus, Sjögren's syndrome, and the systemic vasculitides. Substantial progress has been made in the formulation of new criteria in systemic sclerosis and idiopathic inflammatory myositis. Although the autoimmune rheumatic diseases share many common features and clinical presentations, differentiation between the diseases is crucial because of important distinctions in clinical course, appropriate drugs, and prognoses. We review some of the dilemmas in the diagnosis of these autoimmune rheumatic diseases, and focus on the importance of new classification criteria, clinical assessment, and interpretation of autoimmune serology. In this era of improvement of mortality rates for patients with autoimmune rheumatic diseases, we pay particular attention to the effect of leading complications, specifically cardiovascular manifestations and cancer, and we update epidemiology and prognosis. Copyright © 2013 Elsevier Ltd. All rights reserved.

Advances in the in Vivo Raman Spectroscopy of Malignant Skin Tumors Using Portable Instrumentation

PubMed Central

Kourkoumelis, Nikolaos; Balatsoukas, Ioannis; Moulia, Violetta; Elka, Aspasia; Gaitanis, Georgios; Bassukas, Ioannis D.

2015-01-01

Raman spectroscopy has emerged as a promising tool for real-time clinical diagnosis of malignant skin tumors offering a number of potential advantages: it is non-intrusive, it requires no sample preparation, and it features high chemical specificity with minimal water interference. However, in vivo tissue evaluation and accurate histopathological classification remain a challenging task for the successful transition from laboratory prototypes to clinical devices. In the literature, there are numerous reports on the applications of Raman spectroscopy to biomedical research and cancer diagnostics. Nevertheless, cases where real-time, portable instrumentations have been employed for the in vivo evaluation of skin lesions are scarce, despite their advantages in use as medical devices in the clinical setting. This paper reviews the advances in real-time Raman spectroscopy for the in vivo characterization of common skin lesions. The translational momentum of Raman spectroscopy towards the clinical practice is revealed by (i) assembling the technical specifications of portable systems and (ii) analyzing the spectral characteristics of in vivo measurements. PMID:26132563

[Attention deficit hyperactivity disorder: from a neurodevelopmental perspective].

PubMed

Fernandez-Jaen, A; Lopez-Martin, S; Albert, J; Martin Fernandez-Mayoralas, D; Fernandez-Perrone, A L; Calleja-Perez, B; Lopez-Arribas, S

2017-02-24

Neurodevelopmental disorders cover a heterogeneous group of disorders such as intellectual disability, autism spectrum disorders or specific learning difficulties, among others. The neurobiological and clinical variables seem to clearly justify the recent inclusion of attention deficit hyperactivity disorder (ADHD) as a neurodevelopmental disorder in the international classifications. Neurodevelopmental disorders are characterised by their dimensional nature and the distribution of the different symptoms in the population. These aspects are reviewed, specifically from the perspective of the clinical features and the neuropsychology of ADHD. The dimensional symptomatic nature of ADHD contrasts with the diagnostic criteria of this disorder according to different classifications or clinical guidelines. It also contrasts with the data collected by means of different complementary examinations (scales, tests, etc.). It is essential to understand the clinical continuum within each neurodevelopmental disorder (including ADHD), among the different neurodevelopmental disorders, and among the neurodevelopmental disorders and normality for their research, diagnosis and management. The development of instruments that provide support for this dimensional component is equally significant.

Bilateral sudden sensorineural hearing loss as a presenting feature of systemic lupus erythematosus

PubMed Central

Chawki, Sylvain; Aouizerate, Jessie; Trad, Selim; Prinseau, Jacques; Hanslik, Thomas

2016-01-01

Abstract Introduction: Sudden sensorineural hearing loss is an unusual presenting clinical feature of systemic lupus erythematosus. Case report: We report the case of a young woman who was admitted to hospital for sudden sensorineural hearing loss and hemophagocytic syndrome which was attributed to systemic lupus erythematosus on the basis of specific renal involvement, thrombocytopenia, and consistent autoantibodies. Favorable outcome was obtained on high-dose corticosteroids, and the hearing fully recovered. Discussion: Sudden sensorineural hearing loss in systemic lupus erythematosus is seemingly more frequently associated with severe systemic involvement and antiphospholipid antibodies may be present. Although management remains empirical, the high risk of permanent hearing impairment seems to justify emergency treatment with high-dose corticosteroids. When the clinical and laboratory criteria of antiphospholipid syndrome are met, antiplatelets agents or anticoagulation therapy shall be considered. PMID:27603334

Joint Facial Action Unit Detection and Feature Fusion: A Multi-conditional Learning Approach.

PubMed

Eleftheriadis, Stefanos; Rudovic, Ognjen; Pantic, Maja

2016-10-05

Automated analysis of facial expressions can benefit many domains, from marketing to clinical diagnosis of neurodevelopmental disorders. Facial expressions are typically encoded as a combination of facial muscle activations, i.e., action units. Depending on context, these action units co-occur in specific patterns, and rarely in isolation. Yet, most existing methods for automatic action unit detection fail to exploit dependencies among them, and the corresponding facial features. To address this, we propose a novel multi-conditional latent variable model for simultaneous fusion of facial features and joint action unit detection. Specifically, the proposed model performs feature fusion in a generative fashion via a low-dimensional shared subspace, while simultaneously performing action unit detection using a discriminative classification approach. We show that by combining the merits of both approaches, the proposed methodology outperforms existing purely discriminative/generative methods for the target task. To reduce the number of parameters, and avoid overfitting, a novel Bayesian learning approach based on Monte Carlo sampling is proposed, to integrate out the shared subspace. We validate the proposed method on posed and spontaneous data from three publicly available datasets (CK+, DISFA and Shoulder-pain), and show that both feature fusion and joint learning of action units leads to improved performance compared to the state-of-the-art methods for the task.

[Clinical and genetic analysis of a patient with Treacher Collins syndrome in TCOF1 gene].

PubMed

Li, Hongbo; Zhang, Xu; Li, Zhenyue; Chen, Jing; Lu, Yu; Jia, Jingjie; Yuan, Huijun; Han, Dongyi

2012-05-01

To analyze the clinical and genetic features of a patient with Treacher Collins syndrome (TCS), and identify the mutation in TCOF1 gene. The medical history was taken, and general physical examinations and otological examinations were conducted in this patient. Genomic DNA was extracted from this patient and his parents and complete TCOF1 gene coding exons were amplified by specific PCR primers. Direct sequencing was carried out to identify the mutations. The raw data was analyzed with GeneTool software and molecular biological website. We detected a heterozygous c. 1639 delAG mutation in exon 11 of TCOF1, which resulted in a truncated protein lacking normal function. This mutation is a novel mutation and the second case identified in exon 11 of in TCS. TCS patient reported in this study has unique clinical phenotype. TCOF1 gene mutation is the specific risk factor.

Medulloblastoma: experimental models and reality.

PubMed

Neumann, Julia E; Swartling, Fredrik J; Schüller, Ulrich

2017-11-01

Medulloblastoma is the most frequent malignant brain tumor in childhood, but it may also affect infants, adolescents, and young adults. Recent advances in the understanding of the disease have shed light on molecular and clinical heterogeneity, which is now reflected in the updated WHO classification of brain tumors. At the same time, it is well accepted that preclinical research and clinical trials have to be subgroup-specific. Hence, valid models have to be generated specifically for every medulloblastoma subgroup to properly mimic molecular fingerprints, clinical features, and responsiveness to targeted therapies. This review summarizes the availability of experimental medulloblastoma models with a particular focus on how well these models reflect the actual disease subgroup. We further describe technical advantages and disadvantages of the models and finally point out how some models have successfully been used to introduce new drugs and why some medulloblastoma subgroups are extraordinary difficult to model.

Shoulder pain in primary care: diagnostic accuracy of clinical examination tests for non-traumatic acromioclavicular joint pain

PubMed Central

2013-01-01

Background Despite numerous methodological flaws in previous study designs and the lack of validation in primary care populations, clinical tests for identifying acromioclavicular joint (ACJ) pain are widely utilised without concern for such issues. The aim of this study was to estimate the diagnostic accuracy of traditional ACJ tests and to compare their accuracy with other clinical examination features for identifying a predominant ACJ pain source in a primary care cohort. Methods Consecutive patients with shoulder pain were recruited prospectively from primary health care clinics. Following a standardised clinical examination and diagnostic injection into the subacromial bursa, all participants received a fluoroscopically guided diagnostic block of 1% lidocaine hydrochloride (XylocaineTM) into the ACJ. Diagnostic accuracy statistics including sensitivity, specificity, predictive values, positive and negative likelihood ratios (LR+ and LR-) were calculated for traditional ACJ tests (Active Compression/O’Brien’s test, cross-body adduction, localised ACJ tenderness and Hawkins-Kennedy test), and for individual and combinations of clinical examination variables that were associated with a positive anaesthetic response (PAR) (P≤0.05) defined as 80% or more reduction in post-injection pain intensity during provocative clinical tests. Results Twenty two of 153 participants (14%) reported an 80% PAR. None of the traditional ACJ tests were associated with an 80% PAR (P<0.05) and combinations of traditional tests were not able to discriminate between a PAR and a negative anaesthetic response (AUC 0.507; 95% CI: 0.366, 0.647; P>0.05). Five clinical examination variables (repetitive mechanism of pain onset, no referred pain below the elbow, thickened or swollen ACJ, no symptom provocation during passive glenohumeral abduction and external rotation) were associated with an 80% PAR (P<0.05) and demonstrated an ability to accurately discriminate between an PAR and NAR (AUC 0.791; 95% CI 0.702, 0.880; P<0.001). Less than two positive clinical features resulted in 96% sensitivity (95% CI 0.78, 0.99) and a LR- 0.09 (95% CI 0.02, 0.41) and four positive clinical features resulted in 95% specificity (95% CI 0.90, 0.98) and a LR+ of 4.98 (95% CI 1.69, 13.84). Conclusions In this cohort of primary care patients with predominantly subacute or chronic ACJ pain of non-traumatic onset, traditional ACJ tests were of limited diagnostic value. Combinations of other history and physical examination findings were able to more accurately identify injection-confirmed ACJ pain in this cohort. PMID:23634871

Building an automated SOAP classifier for emergency department reports.

PubMed

Mowery, Danielle; Wiebe, Janyce; Visweswaran, Shyam; Harkema, Henk; Chapman, Wendy W

2012-02-01

Information extraction applications that extract structured event and entity information from unstructured text can leverage knowledge of clinical report structure to improve performance. The Subjective, Objective, Assessment, Plan (SOAP) framework, used to structure progress notes to facilitate problem-specific, clinical decision making by physicians, is one example of a well-known, canonical structure in the medical domain. Although its applicability to structuring data is understood, its contribution to information extraction tasks has not yet been determined. The first step to evaluating the SOAP framework's usefulness for clinical information extraction is to apply the model to clinical narratives and develop an automated SOAP classifier that classifies sentences from clinical reports. In this quantitative study, we applied the SOAP framework to sentences from emergency department reports, and trained and evaluated SOAP classifiers built with various linguistic features. We found the SOAP framework can be applied manually to emergency department reports with high agreement (Cohen's kappa coefficients over 0.70). Using a variety of features, we found classifiers for each SOAP class can be created with moderate to outstanding performance with F(1) scores of 93.9 (subjective), 94.5 (objective), 75.7 (assessment), and 77.0 (plan). We look forward to expanding the framework and applying the SOAP classification to clinical information extraction tasks. Copyright © 2011. Published by Elsevier Inc.

Speculation detection for Chinese clinical notes: Impacts of word segmentation and embedding models.

PubMed

Zhang, Shaodian; Kang, Tian; Zhang, Xingting; Wen, Dong; Elhadad, Noémie; Lei, Jianbo

2016-04-01

Speculations represent uncertainty toward certain facts. In clinical texts, identifying speculations is a critical step of natural language processing (NLP). While it is a nontrivial task in many languages, detecting speculations in Chinese clinical notes can be particularly challenging because word segmentation may be necessary as an upstream operation. The objective of this paper is to construct a state-of-the-art speculation detection system for Chinese clinical notes and to investigate whether embedding features and word segmentations are worth exploiting toward this overall task. We propose a sequence labeling based system for speculation detection, which relies on features from bag of characters, bag of words, character embedding, and word embedding. We experiment on a novel dataset of 36,828 clinical notes with 5103 gold-standard speculation annotations on 2000 notes, and compare the systems in which word embeddings are calculated based on word segmentations given by general and by domain specific segmenters respectively. Our systems are able to reach performance as high as 92.2% measured by F score. We demonstrate that word segmentation is critical to produce high quality word embedding to facilitate downstream information extraction applications, and suggest that a domain dependent word segmenter can be vital to such a clinical NLP task in Chinese language. Copyright © 2016 Elsevier Inc. All rights reserved.

[Rapidly progressive pulmonary malignant perivascular epithelioid cell tumor: a case report and literature review].

PubMed

Shi, X Y; Long, F; Liang, B; Su, L L; Li, H C; Jiang, S J

2016-10-12

Objective: To analyze the pathogenesis, clinical features, diagnosis and differential diagnosis of primary perivascular epithelioid cell tumor(PEComa). Methods: The clinical features, auxiliary examinations and diagnosis of a case with rapidly progressive pulmonary malignant PEComa were reported and the related literatures were reviewed.The literature review was carried out respectively in Wanfang Data, CNKI and PubMed from Jan. 1975 to Jul. 2015 with "pulmonary malignant perivascular epithelioid cell tumor" and "PEComa" being the search terms. Results: A 50 year-old female patient was admitted to the hospital on September 4, 2014 because of cough and dyspnea for 60 days, hemoptysis for 40 days and fever for 7 days.Chest CT scan showed diffuse small nodules with infiltrative border and multiple pure and mixed ground-glass opacity. Transbronchial lung biopsy (TBLB) was performed and the pathological study confirmed the diagnosis of primary pulmonary malignant PEComa. The patient declined further specific therapy, but followed by rapidly progressive respiratory failure, and died two weeks after the diagnosis. A total of 8 literatures were retrieved from Wanfang Data, CNKI and PubMed and all of them were case reports.There were 3 male and 5 female patients, aging from 50 to 79 years.Radiographically, the previously reported cases presented as round and well-circumscribed masses with or without multiple nodules in both lungs. The symptoms had no specificity. Conclusions: Pulmonary malignant PEComa is a rare disease.It is easily misdiagnosed because of non-specific clinical and imaging manifestations.The final diagnosis depends on pathological biopsy.TBLB is an effective diagnostic method.

Towards noncontact skin melanoma selection by multispectral imaging analysis.

PubMed

Kuzmina, Ilona; Diebele, Ilze; Jakovels, Dainis; Spigulis, Janis; Valeine, Lauma; Kapostinsh, Janis; Berzina, Anna

2011-06-01

A clinical trial comprising 334 pigmented and vascular lesions has been performed in three Riga clinics by means of multispectral imaging analysis. The imaging system Nuance 2.4 (CRi) and self-developed software for mapping of the main skin chromophores were used. Specific features were observed and analyzed for malignant skin melanomas: notably higher absorbance (especially as the difference of optical density relative to the healthy skin), uneven chromophore distribution over the lesion area, and the possibility to select the "melanoma areas" in the correlation graphs of chromophores. The obtained results indicate clinical potential of this technology for noncontact selection of melanoma from other pigmented and vascular skin lesions.

Loss of integrity and atrophy in cingulate structural covariance networks in Parkinson's disease.

PubMed

de Schipper, Laura J; van der Grond, Jeroen; Marinus, Johan; Henselmans, Johanna M L; van Hilten, Jacobus J

2017-01-01

In Parkinson's disease (PD), the relation between cortical brain atrophy on MRI and clinical progression is not straightforward. Determination of changes in structural covariance networks - patterns of covariance in grey matter density - has shown to be a valuable technique to detect subtle grey matter variations. We evaluated how structural network integrity in PD is related to clinical data. 3 Tesla MRI was performed in 159 PD patients. We used nine standardized structural covariance networks identified in 370 healthy subjects as a template in the analysis of the PD data. Clinical assessment comprised motor features (Movement Disorder Society-Unified Parkinson's Disease Rating Scale; MDS-UPDRS motor scale) and predominantly non-dopaminergic features (SEverity of Non-dopaminergic Symptoms in Parkinson's Disease; SENS-PD scale: postural instability and gait difficulty, psychotic symptoms, excessive daytime sleepiness, autonomic dysfunction, cognitive impairment and depressive symptoms). Voxel-based analyses were performed within networks significantly associated with PD. The anterior and posterior cingulate network showed decreased integrity, associated with the SENS-PD score, p = 0.001 (β = - 0.265, η p 2  = 0.070) and p = 0.001 (β = - 0.264, η p 2  = 0.074), respectively. Of the components of the SENS-PD score, cognitive impairment and excessive daytime sleepiness were associated with atrophy within both networks. We identified loss of integrity and atrophy in the anterior and posterior cingulate networks in PD patients. Abnormalities of both networks were associated with predominantly non-dopaminergic features, specifically cognition and excessive daytime sleepiness. Our findings suggest that (components of) the cingulate networks display a specific vulnerability to the pathobiology of PD and may operate as interfaces between networks involved in cognition and alertness.

High-Performance Computational Analysis of Glioblastoma Pathology Images with Database Support Identifies Molecular and Survival Correlates.

PubMed

Kong, Jun; Wang, Fusheng; Teodoro, George; Cooper, Lee; Moreno, Carlos S; Kurc, Tahsin; Pan, Tony; Saltz, Joel; Brat, Daniel

2013-12-01

In this paper, we present a novel framework for microscopic image analysis of nuclei, data management, and high performance computation to support translational research involving nuclear morphometry features, molecular data, and clinical outcomes. Our image analysis pipeline consists of nuclei segmentation and feature computation facilitated by high performance computing with coordinated execution in multi-core CPUs and Graphical Processor Units (GPUs). All data derived from image analysis are managed in a spatial relational database supporting highly efficient scientific queries. We applied our image analysis workflow to 159 glioblastomas (GBM) from The Cancer Genome Atlas dataset. With integrative studies, we found statistics of four specific nuclear features were significantly associated with patient survival. Additionally, we correlated nuclear features with molecular data and found interesting results that support pathologic domain knowledge. We found that Proneural subtype GBMs had the smallest mean of nuclear Eccentricity and the largest mean of nuclear Extent, and MinorAxisLength. We also found gene expressions of stem cell marker MYC and cell proliferation maker MKI67 were correlated with nuclear features. To complement and inform pathologists of relevant diagnostic features, we queried the most representative nuclear instances from each patient population based on genetic and transcriptional classes. Our results demonstrate that specific nuclear features carry prognostic significance and associations with transcriptional and genetic classes, highlighting the potential of high throughput pathology image analysis as a complementary approach to human-based review and translational research.

Computer-assisted diagnosis of melanoma.

PubMed

Fuller, Collin; Cellura, A Paul; Hibler, Brian P; Burris, Katy

2016-03-01

The computer-assisted diagnosis of melanoma is an exciting area of research where imaging techniques are combined with diagnostic algorithms in an attempt to improve detection and outcomes for patients with skin lesions suspicious for malignancy. Once an image has been acquired, it undergoes a processing pathway which includes preprocessing, enhancement, segmentation, feature extraction, feature selection, change detection, and ultimately classification. Practicality for everyday clinical use remains a vital question. A successful model must obtain results that are on par or outperform experienced dermatologists, keep costs at a minimum, be user-friendly, and be time efficient with high sensitivity and specificity. ©2015 Frontline Medical Communications.

Evaluating depressive symptoms in hypomanic and manic episodes using a structured diagnostic tool: validation of a new Mini International Neuropsychiatric Interview (M.I.N.I.) module for the DSM-5 'With Mixed Features' specifier.

PubMed

Hergueta, Thierry; Weiller, Emmanuelle

2013-01-01

The Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5), includes a new 'With Mixed Features' specifier for mood episodes. In (hypo-)manic episodes, the specifier is given if three or more depressive symptoms are present nearly every day during the episode. A new module of the Mini International Neuropsychiatric Interview (M.I.N.I.) has been developed as a patient-completed questionnaire to evaluate the DSM-5 specifier for (hypo-)manic episodes. The objective of this study was to validate this new module. In Phase I, patients with a manic episode in the past 6 months completed the module and were asked whether the wording was clear, understandable, relevant and specific. Based on their feedback, the module was refined and finalised. In Phase II, psychiatrists each invited five patients to complete the module. The psychiatrists completed record forms for these five patients, which included their diagnoses, made according to DSM-5 criteria during clinical interviewing. The module was validated by comparing depressive symptoms reported by the patients themselves using the M.I.N.I. module with those evaluated by their psychiatrist using DSM-5 criteria during clinical interviewing. In Phase I, a few changes were made to the M.I.N.I. module based on feedback from 20 patients (60% of whom had mixed features). In Phase II, 23 psychiatrists completed record forms for 115 patients, 99 (86.1%) of whom completed the M.I.N.I. module. Agreement between psychiatrists' DSM-5 diagnoses and patients' M.I.N.I. responses was substantial (Cohen's kappa coefficient, 0.60). The overall sensitivity of the M.I.N.I. was 0.91 and its specificity was 0.70. Sensitivity ranged from 0.63 for psychomotor retardation to 0.90 for suicidal thoughts. Specificity ranged from 0.63 for diminished interest/pleasure to 0.90 for suicidal thoughts. The module's positive and negative predictive values were 0.72 and 0.90, respectively. In summary, the M.I.N.I. module demonstrated good concurrent validity with psychiatrists' evaluation of DSM-5 mixed features in manic patients, accurately detecting mixed features with limited risk of over-diagnosis. Due to its simplicity, the M.I.N.I. module could be incorporated into routine psychiatric evaluation of patients with manic episodes. It could also provide a valuable standardised tool for clinical and epidemiological research.

Frontiers of monoclonal antibodies: Applications in medical practices.

PubMed

Ghagane, Shridhar C; Puranik, Sridevi I; Gan, Siew Hua; Hiremath, Murigendra B; Nerli, R B; Ravishankar, M V

2017-01-01

With the flourishing of innovation in drug discovery into a new era of personalized therapy, the use of monoclonal antibodies (mAbs) in the treatment of various ailments lies at the forefront. Major improvements in genetic sequencing and biomedical techniques as well as research into mAbs emphasize on determining new targets for advanced therapy while maximizing efficacy for clinical application. However, a balance has to be achieved concerning developing a target with low toxicity combined with high specificity and versatility, to allow a specific antibody to facilitate several biotic effects, ranging from neutralization of virus mechanisms to modulation of immune response and maintaining low global economic cost. Presently, there are approximately 30 mAbs' permitted for therapeutic use with many more being tested in clinical trials. Nevertheless, the heavy cost of mAbs' production, stowage and management as well as the subsequent hindrances to their development are outweighed by mAbs' clinical advantages. Compared to conventional drugs, since mAbs use as pharmacologic iotas have specific physical features and modes of action, they should be considered as a discrete therapeutic category. In this review, the history of mAb generation and the innovative technological applications of mAbs that has advanced in clinical practices is reviewed.

DISSECT: a new mnemonic-based approach to the categorization of aortic dissection.

PubMed

Dake, M D; Thompson, M; van Sambeek, M; Vermassen, F; Morales, J P

2013-08-01

Classification systems for aortic dissection provide important guides to clinical decision-making, but the relevance of traditional categorization schemes is being questioned in an era when endovascular techniques are assuming a growing role in the management of this frequently complex and catastrophic entity. In recognition of the expanding range of interventional therapies now used as alternatives to conventional treatment approaches, the Working Group on Aortic Diseases of the DEFINE Project developed a categorization system that features the specific anatomic and clinical manifestations of the disease process that are most relevant to contemporary decision-making. The DISSECT classification system is a mnemonic-based approach to the evaluation of aortic dissection. It guides clinicians through an assessment of six critical characteristics that facilitate optimal communication of the most salient details that currently influence the selection of a therapeutic option, including those findings that are key when considering an endovascular procedure, but are not taken into account by the DeBakey or Stanford categorization schemes. The six features of aortic dissection include: duration of disease; intimal tear location; size of the dissected aorta; segmental extent of aortic involvement; clinical complications of the dissection, and thrombus within the aortic false lumen. In current clinical practice, endovascular therapy is increasingly considered as an alternative to medical management or open surgical repair in select cases of type B aortic dissection. Currently, endovascular aortic repair is not used for patients with type A aortic dissection, but catheter-based techniques directed at peripheral branch vessel ischemia that may complicate type A dissection are considered valuable adjunctive interventions, when indicated. The use of a new system for categorization of aortic dissection, DISSECT, addresses the shortcomings of well-known established schemes devised more than 40 years ago, before the introduction of endovascular techniques. It will serve as a guide to support a critical analysis of contemporary therapeutic options and inform management decisions based on specific features of the disease process. Copyright © 2013 European Society for Vascular Surgery. All rights reserved.

Case-Case Analysis Using 7 Years of Travelers' Diarrhea Surveillance Data: Preventive and Travel Medicine Applications in Cusco, Peru.

PubMed

Jennings, Mary Carol; Tilley, Drake H; Ballard, Sarah-Blythe; Villanueva, Miguel; Costa, Fernando Maldonado; Lopez, Martha; Steinberg, Hannah E; Luna, C Giannina; Meza, Rina; Silva, Maria E; Gilman, Robert H; Simons, Mark P; Maves, Ryan C; Cabada, Miguel M

2017-05-01

AbstractIn Cusco, Peru, and South America in general, there is a dearth of travelers' diarrhea (TD) data concerning the clinical features associated with enteropathogen-specific infections and destination-specific risk behaviors. Understanding these factors would allow travel medicine providers to tailor interventions to patients' risk profiles and travel destination. To characterize TD etiology, evaluate region-specific TD risk factors, and examine relationships between preventive recommendations and risk-taking behaviors among medium- to long-term travelers' from high-income countries, we conducted this case-case analysis using 7 years of prospective surveillance data from adult travelers' presenting with TD to a physician in Cusco. At the time of enrollment, participants provided a stool sample and answered survey questions about demographics, risk behaviors, and the clinical features of illness. Stool samples were tested for norovirus (NV), bacteria, and parasites using conventional methods. Data obtained were then analyzed using case-case methods. NV (14%), enterotoxigenic Escherichia coli (11%), and Campylobacter (9%), notably ciprofloxacin-resistant Campylobacter , were the most frequently identified pathogens among adults with TD. Coinfection with multiple enteropathogens occurred in 5% of cases. NV caused severe disease relative to other TD-associated pathogens identified, confining over 90% of infected individuals to bed. Destination-specific risk factors include consumption of the local beverage "chicha," which was associated with Cryptosporidium infection. Preventive interventions, such as vaccines, directed against these pathogens could significantly reduce the burden of TD.

Case–Case Analysis Using 7 Years of Travelers' Diarrhea Surveillance Data: Preventive and Travel Medicine Applications in Cusco, Peru

PubMed Central

Jennings, Mary Carol; Tilley, Drake H.; Ballard, Sarah-Blythe; Villanueva, Miguel; Costa, Fernando Maldonado; Lopez, Martha; Steinberg, Hannah E.; Luna, C. Giannina; Meza, Rina; Silva, Maria E.; Gilman, Robert H.; Simons, Mark P.; Maves, Ryan C.; Cabada, Miguel M.

2017-01-01

In Cusco, Peru, and South America in general, there is a dearth of travelers' diarrhea (TD) data concerning the clinical features associated with enteropathogen-specific infections and destination-specific risk behaviors. Understanding these factors would allow travel medicine providers to tailor interventions to patients' risk profiles and travel destination. To characterize TD etiology, evaluate region-specific TD risk factors, and examine relationships between preventive recommendations and risk-taking behaviors among medium- to long-term travelers' from high-income countries, we conducted this case–case analysis using 7 years of prospective surveillance data from adult travelers' presenting with TD to a physician in Cusco. At the time of enrollment, participants provided a stool sample and answered survey questions about demographics, risk behaviors, and the clinical features of illness. Stool samples were tested for norovirus (NV), bacteria, and parasites using conventional methods. Data obtained were then analyzed using case–case methods. NV (14%), enterotoxigenic Escherichia coli (11%), and Campylobacter (9%), notably ciprofloxacin-resistant Campylobacter, were the most frequently identified pathogens among adults with TD. Coinfection with multiple enteropathogens occurred in 5% of cases. NV caused severe disease relative to other TD-associated pathogens identified, confining over 90% of infected individuals to bed. Destination-specific risk factors include consumption of the local beverage “chicha,” which was associated with Cryptosporidium infection. Preventive interventions, such as vaccines, directed against these pathogens could significantly reduce the burden of TD. PMID:28167602

Supraorbital Postmortem Brain Sampling for Definitive Quantitative Confirmation of Cerebral Sequestration of Plasmodium falciparum Parasites

PubMed Central

Milner, Danny A.; Valim, Clarissa; Luo, Robert; Playforth, Krupa B.; Kamiza, Steve; Molyneux, Malcolm E.; Seydel, Karl B.; Taylor, Terrie E.

2012-01-01

Background The conventional clinical case definition of cerebral malaria (CM) is imprecise but specificity is improved by a definitive clinical feature such as retinopathy or confirming sequestration of parasites in a post-mortem examination of the brain. A full autopsy is often not possible, since it is costly and may encounter resistance of the deceased's family. Methods We have assessed the use of a cytological smear of brain tissue, obtained post-mortem by supraorbital sampling, for the purpose of quantifying cerebral sequestration in children with fatal malaria in Blantyre, Malawi. We have compared this method to histological quantification of parasites at autopsy. Results The number of parasites present on cytological smears correlated with the proportion of vessels parasitized as assessed by histology of fixed and stained brain tissue. Use of cytological results in addition to the standard clinical case definition increases the specificity of the clinical case definition alone from 48.3% to 100% with a minimal change in sensitivity. Conclusions Post-mortem supraorbital sampling of brain tissue improves the specificity of the diagnosis of fatal cerebral malaria and provides accurate quantitative estimates of cerebral sequestration. This tool can be of great value in clinical, pathogenetic, and epidemiological research studies on cerebral malaria. PMID:22291197

Anaphylaxis to dyes during the perioperative period: reports of 14 clinical cases.

PubMed

Mertes, Paul Michel; Malinovsky, Jean Marc; Mouton-Faivre, Claudie; Bonnet-Boyer, Marie Caroline; Benhaijoub, Abdelhaouad; Lavaud, François; Valfrey, Jocelyne; O'Brien, James; Pirat, Philippe; Lalourcey, Laurent; Demoly, Pascal

2008-08-01

Vital dyes are widely used for lymphatic mapping and sentinel lymph node biopsy in patients with malignant tumors, and reports of anaphylactic reactions are becoming more frequent. Our aims were to describe specific clinical features of hypersensitivity reactions to Patent Blue (Guerbet, Roissy, France), results of the allergy workup, and their consequences for patient management. We report a series of 14 clinical cases of dye-induced anaphylaxis recorded between 2004 and 2006 in 4 member centers of a network of French allergoanesthesia outpatient clinics. Reactions appeared to be relatively severe (6/14 grade III reactions). An average 30 +/- 6-minute delay was observed between dye injection and symptom onset. In 9 (65%) patients reactions were sustained for several hours, requiring prolonged continuous epinephrine infusion and transfer to an intensive care unit. Prick test results were positive in 8 patients. In 5 patients prick test results were negative, whereas intradermal test results were positive. Anesthesiologists and allergologists must be aware of this specific risk and of the clinical characteristics of these reactions, which are usually delayed and long lasting.

Cascade detection for the extraction of localized sequence features; specificity results for HIV-1 protease and structure-function results for the Schellman loop.

PubMed

Newell, Nicholas E

2011-12-15

The extraction of the set of features most relevant to function from classified biological sequence sets is still a challenging problem. A central issue is the determination of expected counts for higher order features so that artifact features may be screened. Cascade detection (CD), a new algorithm for the extraction of localized features from sequence sets, is introduced. CD is a natural extension of the proportional modeling techniques used in contingency table analysis into the domain of feature detection. The algorithm is successfully tested on synthetic data and then applied to feature detection problems from two different domains to demonstrate its broad utility. An analysis of HIV-1 protease specificity reveals patterns of strong first-order features that group hydrophobic residues by side chain geometry and exhibit substantial symmetry about the cleavage site. Higher order results suggest that favorable cooperativity is weak by comparison and broadly distributed, but indicate possible synergies between negative charge and hydrophobicity in the substrate. Structure-function results for the Schellman loop, a helix-capping motif in proteins, contain strong first-order features and also show statistically significant cooperativities that provide new insights into the design of the motif. These include a new 'hydrophobic staple' and multiple amphipathic and electrostatic pair features. CD should prove useful not only for sequence analysis, but also for the detection of multifactor synergies in cross-classified data from clinical studies or other sources. Windows XP/7 application and data files available at: https://sites.google.com/site/cascadedetect/home. nacnewell@comcast.net Supplementary information is available at Bioinformatics online.

Gastrointestinal tuberculosis.

PubMed

Galloway, D J; Scott, R N

1986-10-01

In the developed countries gastrointestinal tuberculosis is no longer common in clinical practice. In this setting the importance of the condition lies in the vagaries of its presentation and the fact that it is eminently treatable, usually by a combination of chemotherapy and surgery. The clinical features and complications of gastrointestinal tuberculosis are highlighted by the seven cases which we report. Diagnosis and treatment of this condition is discussed and attention is drawn to the importance of case notification. Clinicians should bear in mind the diagnosis of gastrointestinal tuberculosis when dealing with any patient with non-specific abdominal symptoms.

Temporo-mandibular joint disease in ankylosing spondylitis.

PubMed Central

Davidson, C; Wojtulewski, J A; Bacon, P A; Winstock, D

1975-01-01

The occurrence of temporo-mandibular joint (TMJ) disease in ankylosing spondylitis is not widely recognized and its incidence is disputed. Seventy-nine patients attending two routine rheumatology clinics were therefore examined by dental surgeon and nine (11-5 per cent) were considered to have specific TMJ involvement. These patients were older than the remainder, and had more extensive spinal and peripheral joint disease. Symptoms were mild and the predominant clinical feature was restricted mouth opening, which could present considerable difficulties during emergency anaesthesia. Bilateral condylectomy was undertaken in one patient with some benefit. Images PMID:1124959

[New Radiopharmaceuticals Based on Prostate-Specific Inhibitors of Membrane Antigen for Diagnostics and Therapy of Metastatic Prostate Cancer].

PubMed

Vlasova, O P; German, K E; Krilov, V V; Petriev, V M; Epstein, N B

2015-01-01

About 10.7% cases of prostate cancer were registered in Russia in 2011 (40,000 patients). More than half of cancer cases were revealed in advanced (III-IV) stages when metastases inevitably developed quickly. Clinical problem of early diagnostics and treatment of metastatic prostate cancer is still not solved. Anatomical imaging techniques have low sensitivity and specificity for the detection of this disease. Metabolic visualization methods which use prostate specific antigen (PSA) as a marker are also ineffective. This article describes prostate-specific membrane antigens (PSMA) that are proposed as a marker for diagnostics and therapy of prostate cancer. The most promising PSMA-based radiopharmaceutical agent for diagnostics has been developed and clinically tested in the European countries. These pharmaceuticals are based on small peptide molecules modified with urea, and have the highest affinity to PSMA. Favorable phannacokinetics, rapid accumulation in the tumor and rapid excretion from the body are beneficial features of these pharmaceuticals.

Reduced hemispheric asymmetry of brain anatomical networks in attention deficit hyperactivity disorder.

PubMed

Li, Dandan; Li, Ting; Niu, Yan; Xiang, Jie; Cao, Rui; Liu, Bo; Zhang, Hui; Wang, Bin

2018-05-11

Despite many studies reporting a variety of alterations in brain networks in patients with attention deficit hyperactivity disorder (ADHD), alterations in hemispheric anatomical networks are still unclear. In this study, we investigated topology alterations in hemispheric white matter in patients with ADHD and the relationship between these alterations and clinical features of the illness. Weighted hemispheric brain anatomical networks were first constructed for each of 40 right-handed patients with ADHD and 53 matched normal controls. Then, graph theoretical approaches were utilized to compute hemispheric topological properties. The small-world property was preserved in the hemispheric network. Furthermore, a significant group-by-hemisphere interaction was revealed in global efficiency, local efficiency and characteristic path length, attributed to the significantly reduced hemispheric asymmetry of global and local integration in patients with ADHD compared with normal controls. Specifically, reduced asymmetric regional efficiency was found in three regions. Finally, we found that the abnormal asymmetry of hemispheric brain anatomical network topology and regional efficiency were both associated with clinical features (the Adult ADHD Self-Report Scale and Wechsler Adult Intelligence Scale) in patients. Our findings provide new insights into the lateralized nature of hemispheric dysconnectivity and highlight the potential for using brain network measures of hemispheric asymmetry as neural biomarkers for ADHD and its clinical features.

Evaluation of a patient with suspected chronic demyelinating polyneuropathy.

PubMed

Jani-Acsadi, Agnes; Lewis, Richard A

2013-01-01

Demyelinating neuropathies are typically characterized by physiological slowing of conduction velocity and pathologically by segmental loss of myelin and in some instances, evidence of remyelination. Clinically, patients with demyelinating neuropathy can be seen with inherited disorders (Charcot-Marie-Tooth disease) or acquired disorders, typically immune-mediated or inflammatory. The acquired disorders can be either acute or subacute as seen in the acute inflammatory demyelinating polyneuropathy (AIDP) form of Guillain-Barré syndrome or chronic progressive or relapsing disorders such as chronic inflammatory demyelinating polyneuropathy. It is important to develop a logical approach to diagnosing these disorders. This requires an understanding of the clinical, genetic, physiological, and pathological features of these neuropathies. Clinically, important features to consider are the temporal progression, degree of symmetry, and involvement of proximal as well as distal muscles. Genetically, recognizing the different inheritance patterns and age of onset allow for a coordinated approach to determining a specific genotype. Physiologically, besides nerve conduction slowing, other physiological hallmarks of demyelination include temporal dispersion of compound motor action potentials (CMAP) on proximal stimulation, conduction block, and distal CMAP duration prolongation with certain patterns of involvement pointing to specific disorders. This chapter focuses on these various aspects of the evaluation of patients with chronic acquired demyelinating neuropathies to develop a comprehensive and thoughtful diagnostic concept. Copyright © 2013 Elsevier B.V. All rights reserved.

Perineural Infiltration of Cutaneous Squamous Cell Carcinoma and Basal Cell Carcinoma Without Clinical Features

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

Lin, Charles, E-mail: Charles_Lin@health.qld.gov.au; Tripcony, Lee; Keller, Jacqui

2012-01-01

Purpose: To review the factors that influence outcome and patterns of relapse in patients with cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) with perineural infiltration (PNI) without clinical or radiologic features, treated with surgery and radiotherapy. Methods and Materials: Between 1991 and 2004, 222 patients with SCC or BCC with PNI on pathologic examination but without clinical or radiologic PNI features were identified. Charts were reviewed retrospectively and relevant data collected. All patients were treated with curative intent; all had radiotherapy, and most had surgery. The primary endpoint was 5-year relapse-free survival from the time of diagnosis.more » Results: Patients with SCC did significantly worse than those with BCC (5-year relapse-free survival, 78% vs. 91%; p < 0.01). Squamous cell carcinoma with PNI at recurrence did significantly worse than de novo in terms of 5-year local failure (40% vs. 19%; p < 0.01) and regional relapse (29% vs. 5%; p < 0.01). Depth of invasion was also a significant factor. Of the PNI-specific factors for SCC, focal PNI did significantly better than more-extensive PNI, but involved nerve diameter or presence of PNI at the periphery of the tumor were not significant factors. Conclusions: Radiotherapy in conjunction with surgery offers an acceptable outcome for cutaneous SCC and BCC with PNI. This study suggests that focal PNI is not an adverse feature.« less

Rapid screening for inflammatory neuropathies by standardized clinical criteria

PubMed Central

Tramontozzi, Louis A.

2016-01-01

Abstract Background: Delay in recognition and treatment of inflammatory neuropathies increases morbidity and mortality. We have developed and standardized 3 clinical screening criteria that rapidly detect inflammatory neuropathies. Methods: We reviewed all patients with definite large fiber neuropathy in 2 different patient populations: 1 from a private neurology clinic and the other from a tertiary care center. Patients were divided into 2 groups: those with an inflammatory neuropathy and those with a noninflammatory neuropathy. We specifically noted the 3 key neuropathy characteristics: onset, distribution, and associated systemic features (ODS). We studied the sensitivity and specificity of ODS in differentiating between inflammatory and noninflammatory neuropathies. Results: A total of 206 patients were included: 51 from the private clinic and 155 from the tertiary care center. The sensitivity of using ODS in detecting an inflammatory neuropathy was 96% and the specificity was 85%. The positive predictive value of ODS was 0.8 and negative predictive value was 0.97. Conclusions: Rapid screening for inflammatory neuropathies by ODS clinical criteria is highly sensitive and has a high negative predictive value for noninflammatory neuropathies. ODS uses simple clinical criteria to rapidly screen for patients with a potentially treatable form of neuropathy and accelerate their diagnostic evaluation. Classification of evidence: This study provides Class IV evidence that 3 neuropathy characteristics—onset, distribution, and associated systemic features—accurately identify patients with inflammatory neuropathies. PMID:29443273

Dengvaxia sensitizes seronegatives to vaccine enhanced disease regardless of age.

PubMed

Halstead, Scott B

2017-11-07

During a large scale clinical efficacy trial of the Sanofipasteur live-attenuated tetravalent dengue vaccine (Dengvaxia), features of hospitalized disease accompanying dengue infections in placebo recipients were closely similar to those in vaccinated children. However, the age specific hospitalization curves for these two populations differed. The curve for children vaccinated at ages 2-16 years closely resembled the 1981 age specific hospitalization rate curve for Cuban children infected with DENV 2 who were sensitized by a prior DENV 1 infection. The corresponding age specific hospitalization curve for placebos experiencing heterotypic secondary dengue infections peaked at age, 9-11 years. These differing epidemiological features support the conclusion that antibody dependent enhanced (ADE) dengue disease occurred in seronegatives who were sensitized by vaccine. As hospitalizations continue to occur in all age groups Dengvaxia consumers should be warned that sensitized vaccinated seronegatives will experience enhanced dengue disease into the forseeable future. Copyright © 2017 Elsevier Ltd. All rights reserved.

Lysosomal Storage Disorders in the Newborn

PubMed Central

Staretz-Chacham, Orna; Lang, Tess C.; LaMarca, Mary E.; Krasnewich, Donna; Sidransky, Ellen

2009-01-01

Lysosomal storage disorders are rare inborn errors of metabolism, with a combined incidence of 1 in 1500 to 7000 live births. These relatively rare disorders are seldom considered when evaluating a sick newborn. A significant number of the >50 different lysosomal storage disorders, however, do manifest in the neonatal period and should be part of the differential diagnosis of several perinatal phenotypes. We review the earliest clinical features, diagnostic tests, and treatment options for lysosomal storage disorders that can present in the newborn. Although many of the lysosomal storage disorders are characterized by a range in phenotypes, the focus of this review is on the specific symptoms and clinical findings that present in the perinatal period, including neurologic, respiratory, endocrine, and cardiovascular manifestations, dysmorphic features, hepatosplenomegaly, skin or ocular involvement, and hydrops fetalis/congenital ascites. A greater awareness of these features may help to reduce misdiagnosis and promote the early detection of lysosomal storage disorders. Implementing therapy at the earliest stage possible is crucial for several of the lysosomal storage disorders; hence, an early appreciation of these disorders by physicians who treat newborns is essential. PMID:19336380

The relationship between increased levels of Anti-dsDNA with clinical manifestation in patients with SLE in Haji Adam Malik General Hospital Medan

NASA Astrophysics Data System (ADS)

Marpaung, B.; Patrick, J.

2018-03-01

Systemic Lupus Erythematosus (SLE) is an autoimmune rheumatic disease characterized by widespread inflammation and affects any organism the body. Many autoimmune diseases result in autoantibody production, but Anti-dsDNA antibodies are highly specific to SLE. Previous study found that Anti-dsDNA antibodies are associated with severe clinical manifestations of lupus. The aim of this study was to examine the relationship between anti-dsDNA level with clinical features and laboratory findings in SLE patients. This cross-sectional study was conducted in Hospital Haji Adam Malik Medan in May-October 2016.We examine anti-dsDNA, clinical features and kidney laboratory profile in all patient. Data were statistically analyzed.81 SLE patients with median level of anti-dsDNA 294 (6.1-1317). There was no significant relationship between increased level of Anti-dsDNA with clinical manifestations (p>0.05). There were significant relationships between increased level of Anti-dsDNA with renal impairment (p=0.049), urea level (p=0.016), urine protein (p=0.042) and hematology disorder (p=0.005). Arthritis is the most frequent clinical manifestation (96.3%) followed by malar rash (77.8%). Elevated anti-dsDNA level was not related with clinical manifestations but there was significant relationship with hematology disorder, urea, creatinine, and proteinuria in SLE patents.

Splenic marginal zone lymphoma.

PubMed

Piris, Miguel A; Onaindía, Arantza; Mollejo, Manuela

Splenic marginal zone lymphoma (SMZL) is an indolent small B-cell lymphoma involving the spleen and bone marrow characterized by a micronodular tumoral infiltration that replaces the preexisting lymphoid follicles and shows marginal zone differentiation as a distinctive finding. SMZL cases are characterized by prominent splenomegaly and bone marrow and peripheral blood infiltration. Cells in peripheral blood show a villous cytology. Bone marrow and peripheral blood characteristic features usually allow a diagnosis of SMZL to be performed. Mutational spectrum of SMZL identifies specific findings, such as 7q loss and NOTCH2 and KLF2 mutations, both genes related with marginal zone differentiation. There is a striking clinical variability in SMZL cases, dependent of the tumoral load and performance status. Specific molecular markers such as 7q loss, p53 loss/mutation, NOTCH2 and KLF2 mutations have been found to be associated with the clinical variability. Distinction from Monoclonal B-cell lymphocytosis with marginal zone phenotype is still an open issue that requires identification of precise and specific thresholds with clinical meaning. Copyright © 2016 Elsevier Ltd. All rights reserved.

Detection of Pseudomonas aeruginosa biomarkers from thermally injured mice in situ using imaging mass spectrometry.

PubMed

Hamerly, Timothy; Everett, Jake A; Paris, Nina; Fisher, Steve T; Karunamurthy, Arivarasan; James, Garth A; Rumbaugh, Kendra P; Rhoads, Daniel D; Bothner, Brian

2017-12-15

Monitoring patients with burn wounds for infection is standard practice because failure to rapidly and specifically identify a pathogen can result in poor clinical outcomes, including death. Therefore, a method that facilitates detection and identification of pathogens in situ within minutes of biopsy would be a significant benefit to clinicians. Mass spectrometry is rapidly becoming a standard tool in clinical settings, capable of identifying specific pathogens from complex samples. Imaging mass spectrometry (IMS) expands the information content by enabling spatial resolution of biomarkers in tissue samples as in histology, without the need for specific stains/antibodies. Herein, a murine model of thermal injury was used to study infection of burn tissue by Pseudomonas aeruginosa. This is the first use of IMS to detect P. aeruginosa infection in situ from thermally injured tissue. Multiple molecular features could be spatially resolved to infected or uninfected tissue. This demonstrates the potential use of IMS in a clinical setting to aid doctors in identifying both presence and species of pathogens in tissue. Copyright © 2017. Published by Elsevier Inc.

Planning: supporting and optimizing clinical guidelines execution.

PubMed

Anselma, Luca; Montani, Stefania

2008-01-01

A crucial feature of computerized clinical guidelines (CGs) lies in the fact that they may be used not only as conventional documents (as if they were just free text) describing general procedures that users have to follow. In fact, thanks to a description of their actions and control flow in some semiformal representation language, CGs can also take advantage of Computer Science methods and Information Technology infrastructures and techniques, to become executable documents, in the sense that they may support clinical decision making and clinical procedures execution. In order to reach this goal, some advanced planning techniques, originally developed within the Artificial Intelligence (AI) community, may be (at least partially) resorted too, after a proper adaptation to the specific CG needs has been carried out.

The Genome sequences of four non-human/non-clinical Salmonella enterica serovar Kentucky ST198 isolates recovered between 1972 and 1973

USDA-ARS?s Scientific Manuscript database

Salmonella Kentucky is a polyphyletic member of S. enterica subclade A1 with multiple sequence types that often colonize the same hosts but in different frequencies on different continents. To evaluate the genomic features involved in S. Kentucky host specificity we sequenced the genomes of four iso...

Exploring Temporal Frameworks for Constructing Longitudinal Instance-Specific Models from Clinical Data

ERIC Educational Resources Information Center

Watt, Emily

2012-01-01

The prevalence of the EMR in biomedical research is growing, the EMR being regarded as a source of contextually rich, longitudinal data for computation and statistical/trend analysis. However, models trained with data abstracted from the EMR often (1) do not capture all features needed to accurately predict the patient's future state and to…

Nutrition in clinical practice-the refeeding syndrome: illustrative cases and guidelines for prevention and treatment.

PubMed

Stanga, Z; Brunner, A; Leuenberger, M; Grimble, R F; Shenkin, A; Allison, S P; Lobo, D N

2008-06-01

The refeeding syndrome is a potentially lethal complication of refeeding in patients who are severely malnourished from whatever cause. Too rapid refeeding, particularly with carbohydrate may precipitate a number of metabolic and pathophysiological complications, which may adversely affect the cardiac, respiratory, haematological, hepatic and neuromuscular systems leading to clinical complications and even death. We aimed to review the development of the refeeding syndrome in a variety of situations and, from this and the literature, devise guidelines to prevent and treat the condition. We report seven cases illustrating different aspects of the refeeding syndrome and the measures used to treat it. The specific complications encountered, their physiological mechanisms, identification of patients at risk, and prevention and treatment are discussed. Each case developed one or more of the features of the refeeding syndrome including deficiencies and low plasma levels of potassium, phosphate, magnesium and thiamine combined with salt and water retention. These responded to specific interventions. In most cases, these abnormalities could have been anticipated and prevented. The main features of the refeeding syndrome are described with a protocol to anticipate, prevent and treat the condition in adults.

Post-SELEX optimization of aptamers.

PubMed

Gao, Shunxiang; Zheng, Xin; Jiao, Binghua; Wang, Lianghua

2016-07-01

Aptamers are functional single-stranded DNA or RNA oligonucleotides, selected in vitro by SELEX (Systematic Evolution of Ligands by Exponential Enrichment), which can fold into stable unique three-dimensional structures that bind their target ligands with high affinity and specificity. Although aptamers show a number of favorable advantages such as better stability and easier modification when compared with the properties of antibodies, only a handful of aptamers have entered clinical trials and only one, pegaptanib, has received US Food and Drug Administration approval for clinical use. The main reasons that limit the practical application of aptamers are insufficient nuclease stability, bioavailability, thermal stability, or even affinity. Some aptamers obtained from modified libraries show better properties; however, polymerase amplification of nucleic acids containing non-natural bases is currently a primary drawback of the SELEX process. This review focuses on several post-SELEX optimization strategies of aptamers identified in recent years. We describe four common methods in detail: truncation, chemical modification, bivalent or multivalent aptamer construction, and mutagenesis. We believe that these optimization strategies should improve one or more specific properties of aptamers, and the type of feature(s) selected for improvement will be dependent on the application purpose.

Characterizing psychological dimensions in non-pathological subjects through autonomic nervous system dynamics

PubMed Central

Nardelli, Mimma; Valenza, Gaetano; Cristea, Ioana A.; Gentili, Claudio; Cotet, Carmen; David, Daniel; Lanata, Antonio; Scilingo, Enzo P.

2015-01-01

The objective assessment of psychological traits of healthy subjects and psychiatric patients has been growing interest in clinical and bioengineering research fields during the last decade. Several experimental evidences strongly suggest that a link between Autonomic Nervous System (ANS) dynamics and specific dimensions such as anxiety, social phobia, stress, and emotional regulation might exist. Nevertheless, an extensive investigation on a wide range of psycho-cognitive scales and ANS non-invasive markers gathered from standard and non-linear analysis still needs to be addressed. In this study, we analyzed the discerning and correlation capabilities of a comprehensive set of ANS features and psycho-cognitive scales in 29 non-pathological subjects monitored during resting conditions. In particular, the state of the art of standard and non-linear analysis was performed on Heart Rate Variability, InterBreath Interval series, and InterBeat Respiration series, which were considered as monovariate and multivariate measurements. Experimental results show that each ANS feature is linked to specific psychological traits. Moreover, non-linear analysis outperforms the psychological assessment with respect to standard analysis. Considering that the current clinical practice relies only on subjective scores from interviews and questionnaires, this study provides objective tools for the assessment of psychological dimensions. PMID:25859212

On subclasses of opioid analgesics.

PubMed

Raffa, Robert B

2014-12-01

The history of discovery of analgesic drugs has followed a trajectory from original serendipitous discovery of plant-derived substances to laboratory creation of customized molecules that are intentionally designed to interact with specific receptors of neurotransmitters involved in either the transmission of the pain signal or the attenuation of such a signal. The drugs most recently developed have been designed to provide incremental greater separation between pain relief and adverse effects. The result has been drugs that have individualized pharmacodynamic and pharmacokinetic characteristics that represent specific advances in basic science and translate into unique clinical profiles. Several of the drugs include non-opioid components. They retain some of the features of opioids, but have distinct clinical characteristics that differentiate them from traditional opioids. Thus they defy simple classification as opioids. A summary is provided of the development of the modern view of multi-mechanistic pain and its treatment using analgesics that have multi-mechanisms of action (consisting of both opioid and non-opioid components). Descriptions of examples of such current analgesics and of those that have pharmacokinetic characteristics that result in atypical opioid clinical profiles are given. By serendipity or design, several current strong analgesics have opioid components of action, but have an additional non-opioid mechanism of action or some pharmacokinetic feature that gives them an atypical opioid clinical profile and renders them not easily classified as classical opioids. An appreciation that there are now opioid analgesics that differentiate from classical opioids in ways that defy their simplistic classification as opioids suggests that recognition of subclasses of opioid analgesics would be more accurate scientifically and would be more informative for healthcare providers and regulators. This would likely lead to positive outcomes for the clinical use and regulatory control of the current drugs, and provide direction/strategy for the discovery of new drugs.

Clinical and serologic parallels to APS-I in patients with thymomas, and autoantigen transcripts in their tumors1

PubMed Central

Wolff, Anette S. B.; Kärner, Jaanika; Owe, Jone F.; Oftedal, Bergithe E.V.; Gilhus, Nils Erik; Erichsen, Martina M.; Kämpe, Olle; Meager, Anthony; Peterson, Pärt; Kisand, Kai; Willcox, Nick; Husebye, Eystein S.

2014-01-01

Patients with the autoimmune polyendocrine syndrome type I (APS-I), caused by mutations in the autoimmune regulator (AIRE) gene, and myasthenia gravis (MG) with thymoma, show intriguing but unexplained parallels. They include uncommon manifestations like autoimmune adrenal insufficiency (AI), hypoparathyroidism (HP), and chronic mucocutaneous candidiasis (CMC) plus autoantibodies neutralizing IL-17, IL-22 and type I interferons. Thymopoiesis in the absence of AIRE is implicated in both syndromes. To test whether these parallels extend further, we screened 247 patients with MG and/or thymoma for clinical features and organ-specific autoantibodies characteristic of APS-I patients, and assayed 26 thymoma samples for transcripts for AIRE and 16 peripheral tissue-specific autoantigens (TSAgs) by quantitative PCR. We found APS-I-typical autoantibodies and clinical manifestations, including CMC, AI and asplenia, respectively in 49/121 (40%) and 10/121 (8%) thymoma patients, but clinical features seldom co-occurred with the corresponding autoantibodies. Both were rare in other MG subgroups (N=126). In 38 APS-I patients, by contrast, we observed neither autoantibodies against muscle antigens nor any neuromuscular disorders. Whereas relative transcript levels for AIRE and 7 of 16 TSAgs showed the expected under-expression in thymomas, levels were increased for 4 of the 5 TSAgs most frequently targeted by these patients’ autoAbs. Hence the clinical and serologic parallels to APS-I in patients with thymomas are not explained purely by deficient TSAg transcription in these aberrant AIRE-deficient tumors. We therefore propose additional explanations for the unusual autoimmune biases they provoke. Thymoma patients should be monitored for potentially life-threatening APS-I manifestations such as AI and HP. PMID:25230752

Fat embolism syndrome in long bone trauma following vehicular accidents: Experience from a tertiary care hospital in north India.

PubMed

Koul, Parvaiz A; Ahmad, Feroze; Gurcoo, Showkat A; Khan, Umar H; Naqash, Imtiyaz A; Sidiq, Suhail; Jan, Rafi Ahmad; Koul, Ajaz N; Ashraf, Mohammad; Bhat, Mubasher Ahmad

2013-04-01

Fat embolism syndrome (FES) is a clinical problem arising mainly due to fractures particularly of long bones and pelvis. Not much literature is available about FES from the Indian subcontinent. Thirty-five patients referred/admitted prospectively over a 3-year period for suspected FES to a north Indian tertiary care center and satisfying the clinical criteria proposed by Gurd and Wilson, and Schonfeld were included in the study. Clinical features, risk factors, complications, response to treatment and any sequelae were recorded. The patients (all male) presented with acute onset breathlessness, 36-120 hours following major bone trauma due to vehicular accidents. Associated features included features of cerebral dysfunction (n = 24, 69%), petechial rash (14%), tachycardia (94%) and fever (46%). Hypoxemia was demonstrable in 80% cases, thrombocytopenia in 91%, anemia in 94% and hypoalbuminemia in 59%. Bilateral alveolar infiltrates were seen on chest radiography in 28 patients and there was evidence of bilateral ground glass appearance in 5 patients on CT. Eleven patients required ventilatory assistance whereas others were treated with supportive management. Three patients expired due to associated sepsis and respiratory failure, whereas others recovered with a mean hospital stay of 9 days. No long term sequelae were observed. FES remains a clinical challenge and is a diagnosis of exclusion based only on clinical grounds because of the absence of any specific laboratory test. A high index of suspicion is required for diagnosis and initiating supportive management in patients with traumatic fractures, especially in those having undergone an invasive orthopedic procedure.

Fat embolism syndrome in long bone trauma following vehicular accidents: Experience from a tertiary care hospital in north India

PubMed Central

Koul, Parvaiz A.; Ahmad, Feroze; Gurcoo, Showkat A.; Khan, Umar H.; Naqash, Imtiyaz A.; Sidiq, Suhail; Jan, Rafi Ahmad; Koul, Ajaz N.; Ashraf, Mohammad; Bhat, Mubasher Ahmad

2013-01-01

Background: Fat embolism syndrome (FES) is a clinical problem arising mainly due to fractures particularly of long bones and pelvis. Not much literature is available about FES from the Indian subcontinent. Materials and Methods: Thirty-five patients referred/admitted prospectively over a 3-year period for suspected FES to a north Indian tertiary care center and satisfying the clinical criteria proposed by Gurd and Wilson, and Schonfeld were included in the study. Clinical features, risk factors, complications, response to treatment and any sequelae were recorded. Results: The patients (all male) presented with acute onset breathlessness, 36-120 hours following major bone trauma due to vehicular accidents. Associated features included features of cerebral dysfunction (n = 24, 69%), petechial rash (14%), tachycardia (94%) and fever (46%). Hypoxemia was demonstrable in 80% cases, thrombocytopenia in 91%, anemia in 94% and hypoalbuminemia in 59%. Bilateral alveolar infiltrates were seen on chest radiography in 28 patients and there was evidence of bilateral ground glass appearance in 5 patients on CT. Eleven patients required ventilatory assistance whereas others were treated with supportive management. Three patients expired due to associated sepsis and respiratory failure, whereas others recovered with a mean hospital stay of 9 days. No long term sequelae were observed. Conclusion: FES remains a clinical challenge and is a diagnosis of exclusion based only on clinical grounds because of the absence of any specific laboratory test. A high index of suspicion is required for diagnosis and initiating supportive management in patients with traumatic fractures, especially in those having undergone an invasive orthopedic procedure. PMID:23741088

Identifying Group-Specific Sequences for Microbial Communities Using Long k-mer Sequence Signatures

PubMed Central

Wang, Ying; Fu, Lei; Ren, Jie; Yu, Zhaoxia; Chen, Ting; Sun, Fengzhu

2018-01-01

Comparing metagenomic samples is crucial for understanding microbial communities. For different groups of microbial communities, such as human gut metagenomic samples from patients with a certain disease and healthy controls, identifying group-specific sequences offers essential information for potential biomarker discovery. A sequence that is present, or rich, in one group, but absent, or scarce, in another group is considered “group-specific” in our study. Our main purpose is to discover group-specific sequence regions between control and case groups as disease-associated markers. We developed a long k-mer (k ≥ 30 bps)-based computational pipeline to detect group-specific sequences at strain resolution free from reference sequences, sequence alignments, and metagenome-wide de novo assembly. We called our method MetaGO: Group-specific oligonucleotide analysis for metagenomic samples. An open-source pipeline on Apache Spark was developed with parallel computing. We applied MetaGO to one simulated and three real metagenomic datasets to evaluate the discriminative capability of identified group-specific markers. In the simulated dataset, 99.11% of group-specific logical 40-mers covered 98.89% disease-specific regions from the disease-associated strain. In addition, 97.90% of group-specific numerical 40-mers covered 99.61 and 96.39% of differentially abundant genome and regions between two groups, respectively. For a large-scale metagenomic liver cirrhosis (LC)-associated dataset, we identified 37,647 group-specific 40-mer features. Any one of the features can predict disease status of the training samples with the average of sensitivity and specificity higher than 0.8. The random forests classification using the top 10 group-specific features yielded a higher AUC (from ∼0.8 to ∼0.9) than that of previous studies. All group-specific 40-mers were present in LC patients, but not healthy controls. All the assembled 11 LC-specific sequences can be mapped to two strains of Veillonella parvula: UTDB1-3 and DSM2008. The experiments on the other two real datasets related to Inflammatory Bowel Disease and Type 2 Diabetes in Women consistently demonstrated that MetaGO achieved better prediction accuracy with fewer features compared to previous studies. The experiments showed that MetaGO is a powerful tool for identifying group-specific k-mers, which would be clinically applicable for disease prediction. MetaGO is available at https://github.com/VVsmileyx/MetaGO. PMID:29774017

Oropharyngeal Dysphagia in Dermatomyositis: Associations with Clinical and Laboratory Features Including Autoantibodies

PubMed Central

Mugii, Naoki; Hasegawa, Minoru; Matsushita, Takashi; Hamaguchi, Yasuhito; Oohata, Sacihe; Okita, Hirokazu; Yahata, Tetsutarou; Someya, Fujiko; Inoue, Katsumi; Murono, Shigeyuki; Fujimoto, Manabu; Takehara, Kazuhiko

2016-01-01

Objective Dysphagia develops with low frequency in patients with dermatomyositis. Our objective was to determine the clinical and laboratory features that can estimate the development of dysphagia in dermatomyositis. Methods This study included 92 Japanese patients with adult-onset dermatomyositis. The associations between dysphagia and clinical and laboratory features including disease-specific autoantibodies determined by immunoprecipitation assays were analyzed. Results Videofluoroscopy swallow study (VFSS) was performed for all patients with clinical dysphagia (n = 13, 14.1%) but not for patients without clinical dysphagia. Typical findings of dysphagia (pharyngeal pooling, n = 11 and/or nasal regurgitation, n = 4) was detected by VFSS in all patients with clinical dysphagia. Eleven patients with dysphagia (84.6%) had anti-transcription intermediary factor 1γ (TIF-1γ) antibody. By univariate analysis, the average age and the male to female ratio, internal malignancy, and anti-TIF-1γ antibody were significantly higher and the frequency of interstitial lung diseases and manual muscle testing (MMT) scores of sternomastoid and dertoid muscles were significantly lower in patients with dysphagia than in patients without dysphagia. Among patients with anti-TIF-1γ antibody, the mean age, the ratios of male to female and internal malignancy were significantly higher and mean MMT scores of sternomastoid muscle were significantly lower in patients with dysphagia compared with patients without dysphagia. By multivariable analysis, the risk of dysphagia was strongly associated with the existence of internal malignancy and ant-TIF-1γ antibody and was also associated with reduced scores of manual muscle test of sternomastoid muscle. Dysphagia was markedly improved after the treatment against myositis in all 13 patients. Conclusion These findings indicate that dysphagia can develop frequently in patients with internal malignancy, anti-TIF-1γ antibody, or severe muscle weakness of sternomastoid muscle. PMID:27167831

A combination of molecular markers and clinical features improve the classification of pancreatic cysts.

PubMed

Springer, Simeon; Wang, Yuxuan; Dal Molin, Marco; Masica, David L; Jiao, Yuchen; Kinde, Isaac; Blackford, Amanda; Raman, Siva P; Wolfgang, Christopher L; Tomita, Tyler; Niknafs, Noushin; Douville, Christopher; Ptak, Janine; Dobbyn, Lisa; Allen, Peter J; Klimstra, David S; Schattner, Mark A; Schmidt, C Max; Yip-Schneider, Michele; Cummings, Oscar W; Brand, Randall E; Zeh, Herbert J; Singhi, Aatur D; Scarpa, Aldo; Salvia, Roberto; Malleo, Giuseppe; Zamboni, Giuseppe; Falconi, Massimo; Jang, Jin-Young; Kim, Sun-Whe; Kwon, Wooil; Hong, Seung-Mo; Song, Ki-Byung; Kim, Song Cheol; Swan, Niall; Murphy, Jean; Geoghegan, Justin; Brugge, William; Fernandez-Del Castillo, Carlos; Mino-Kenudson, Mari; Schulick, Richard; Edil, Barish H; Adsay, Volkan; Paulino, Jorge; van Hooft, Jeanin; Yachida, Shinichi; Nara, Satoshi; Hiraoka, Nobuyoshi; Yamao, Kenji; Hijioka, Susuma; van der Merwe, Schalk; Goggins, Michael; Canto, Marcia Irene; Ahuja, Nita; Hirose, Kenzo; Makary, Martin; Weiss, Matthew J; Cameron, John; Pittman, Meredith; Eshleman, James R; Diaz, Luis A; Papadopoulos, Nickolas; Kinzler, Kenneth W; Karchin, Rachel; Hruban, Ralph H; Vogelstein, Bert; Lennon, Anne Marie

2015-11-01

The management of pancreatic cysts poses challenges to both patients and their physicians. We investigated whether a combination of molecular markers and clinical information could improve the classification of pancreatic cysts and management of patients. We performed a multi-center, retrospective study of 130 patients with resected pancreatic cystic neoplasms (12 serous cystadenomas, 10 solid pseudopapillary neoplasms, 12 mucinous cystic neoplasms, and 96 intraductal papillary mucinous neoplasms). Cyst fluid was analyzed to identify subtle mutations in genes known to be mutated in pancreatic cysts (BRAF, CDKN2A, CTNNB1, GNAS, KRAS, NRAS, PIK3CA, RNF43, SMAD4, TP53, and VHL); to identify loss of heterozygozity at CDKN2A, RNF43, SMAD4, TP53, and VHL tumor suppressor loci; and to identify aneuploidy. The analyses were performed using specialized technologies for implementing and interpreting massively parallel sequencing data acquisition. An algorithm was used to select markers that could classify cyst type and grade. The accuracy of the molecular markers was compared with that of clinical markers and a combination of molecular and clinical markers. We identified molecular markers and clinical features that classified cyst type with 90%-100% sensitivity and 92%-98% specificity. The molecular marker panel correctly identified 67 of the 74 patients who did not require surgery and could, therefore, reduce the number of unnecessary operations by 91%. We identified a panel of molecular markers and clinical features that show promise for the accurate classification of cystic neoplasms of the pancreas and identification of cysts that require surgery. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Oropharyngeal Dysphagia in Dermatomyositis: Associations with Clinical and Laboratory Features Including Autoantibodies.

PubMed

Mugii, Naoki; Hasegawa, Minoru; Matsushita, Takashi; Hamaguchi, Yasuhito; Oohata, Sacihe; Okita, Hirokazu; Yahata, Tetsutarou; Someya, Fujiko; Inoue, Katsumi; Murono, Shigeyuki; Fujimoto, Manabu; Takehara, Kazuhiko

2016-01-01

Dysphagia develops with low frequency in patients with dermatomyositis. Our objective was to determine the clinical and laboratory features that can estimate the development of dysphagia in dermatomyositis. This study included 92 Japanese patients with adult-onset dermatomyositis. The associations between dysphagia and clinical and laboratory features including disease-specific autoantibodies determined by immunoprecipitation assays were analyzed. Videofluoroscopy swallow study (VFSS) was performed for all patients with clinical dysphagia (n = 13, 14.1%) but not for patients without clinical dysphagia. Typical findings of dysphagia (pharyngeal pooling, n = 11 and/or nasal regurgitation, n = 4) was detected by VFSS in all patients with clinical dysphagia. Eleven patients with dysphagia (84.6%) had anti-transcription intermediary factor 1γ (TIF-1γ) antibody. By univariate analysis, the average age and the male to female ratio, internal malignancy, and anti-TIF-1γ antibody were significantly higher and the frequency of interstitial lung diseases and manual muscle testing (MMT) scores of sternomastoid and dertoid muscles were significantly lower in patients with dysphagia than in patients without dysphagia. Among patients with anti-TIF-1γ antibody, the mean age, the ratios of male to female and internal malignancy were significantly higher and mean MMT scores of sternomastoid muscle were significantly lower in patients with dysphagia compared with patients without dysphagia. By multivariable analysis, the risk of dysphagia was strongly associated with the existence of internal malignancy and ant-TIF-1γ antibody and was also associated with reduced scores of manual muscle test of sternomastoid muscle. Dysphagia was markedly improved after the treatment against myositis in all 13 patients. These findings indicate that dysphagia can develop frequently in patients with internal malignancy, anti-TIF-1γ antibody, or severe muscle weakness of sternomastoid muscle.

Syringotropic mycosis fungoides: clinical and histologic features, response to treatment, and outcome in 19 patients.

PubMed

de Masson, Adèle; Battistella, Maxime; Vignon-Pennamen, Marie-Dominique; Cavelier-Balloy, Bénédicte; Mouly, Frédéric; Rybojad, Michel; Bouaziz, Jean-David; Petit, Antoine; Saussine, Anne; Ronceray, Sophie; Le Gall, François; Ram-Wolff, Caroline; Assouly, Philippe; Dereure, Olivier; Joly, Pascal; Dallot, Alexiane; Dupuy, Alain; Lebbé, Céleste; Moulonguet, Isabelle; Rivet, Jacqueline; Janin, Anne; Bagot, Martine

2014-11-01

A rare variant of mycosis fungoides (MF), syringotropic MF (STMF) is characterized by a particular tropism of the lymphocytic infiltrate for the eccrine structures, and included in the follicular subtype of MF in the World Health Organization-European Organization for Research and Treatment of Cancer classification of cutaneous lymphomas. We sought to determine the clinicopathologic features and disease course of patients with STMF. A retrospective study was conducted to identify patients with STMF from 1998 to 2013. Nineteen patients were included: 15 men and 4 women, mean age 55 years (range, 24-86). Most had multiple lesions (n=16, 84%) with associated alopecia (n=12, 63%) and/or punctuated aspect (n=12, 63%). Palms or soles were involved in 10 cases (53%). Folliculotropism was found in 13 cases (68%). After a median follow-up of 70 months (range, 2-140), 3 patients died, 1 from disease-related death. The 5-year overall and disease-specific survival were 100%. The disease-specific survival was significantly higher than in 54 patients with folliculotropic MF without syringotropism (5-year disease-specific survival, 74%; 95% confidence interval, 58%-94%, P=.02). Retrospective setting is a limitation. In the spectrum of adnexotropic MF, STMF appears as a distinct entity from follicular MF, with peculiar clinical characteristics and natural history. Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Clinical and radiological features of invasive Klebsiella pneumoniae liver abscess syndrome.

PubMed

Shin, Sung Ui; Park, Chang Min; Lee, Youkyung; Kim, Eui-Chong; Kim, Soo Jin; Goo, Jin Mo

2013-06-01

Recently, a striking new clinical manifestation of Klebsiella pneumoniae (KP) infection referred to as invasive KP liver abscess syndrome (IKPLAS), defined by liver abscess with contemporaneous metastatic KP infections at other body sites has been documented. Until now, however, there have been relatively few reports regarding its radiologic features. To describe the clinical and radiological features of IKPLAS patients, and to compare them with those with KP liver abscess without metastatic infections to ascertain possible predictors of IKPLAS. From January 2008 to May 2010, 35 patients (26 men and 9 women; mean age, 59.4 years) with both liver abscess and metastatic KP infections were diagnosed with IKPLAS. Their clinical and radiological features were retrospectively evaluated and compared with those of 25 contemporaneous non-metastatic patients to investigate predictive factors for metastatic infections. The rate of intensive care unit admissions and overall mortality was 34.3% and 17.1% in IKPLAS patients, and was significantly higher than those of the non-metastatic group (8% and 0%, respectively). As for metastatic infections, the lung was the most common site and multiple nodules or masses (n = 9) were the most common manifestations. Univariate analysis revealed that liver abscess ≤5.8 cm, bilobar involvement of abscess and altered mentality were significantly related with IKPLAS. At multivariate analysis, liver abscess ≤5.8 cm was proven to be a significant independent predictor of IKPLAS (OR, 3.6; P = 0.038). In addition, altered mentality was present solely in IKPLAS (25.7% vs. 0%) although its P value (P = 0.052) did not reach a statistical significance at multivariate analysis. IKPLAS has significantly worse prognosis than non-metastatic KP abscess patients. In patients with KP liver abscess, liver abscess ≤5.8 cm can be used as an independent predictor of IKPLAS and altered mentality as a very specific feature in diagnosing IKPLAS. © 2013 The Foundation Acta Radiologica.

Measuring how typical and atypical minds read other's intentions. Comment on "Seeing mental states: An experimental strategy for measuring the observability of other minds" by Cristina Becchio et al.

NASA Astrophysics Data System (ADS)

Parma, Valentina; Sartori, Luisa; Castiello, Umberto

2018-03-01

Becchio et al. [1] propose a model to render other's minds observable against the Unobservability Principle. Such model develops over four, distinct steps. First, it provides experimental evidence indicating that mental states (i.e., intentions) can be encoded in behavioral patterns (e.g., movement kinematics). Second, it provides strategies to test the efficiency of the quantification of such intention-related behavioral manifestations (i.e., resolution of the uncertainty between two intentions based on different patterns of accumulation of kinematic parameters). Third, it indicates specific features of the observed behavior that viewers use to detect different intentions (i.e., a series of decision rules based on kinematic features through which intention categorization occurs). Fourth, it proposes a manner to manipulate such specific behavioral features so that an observer can detect different intentions, based on how informative such behavioral features are. We see in this operational/experimental approach a significant contribution to the theoretical debate on the possibility to observe mental states, allowing the direct testing of the unobservability principle and therefore providing falsifiable hypotheses. Besides this already central aspect, we believe this approach holds promise to the elucidation of clinical open questions, such as those posed by autism spectrum disorders (ASD). Indeed, experimentally evaluating the ability to observe and manipulate other's intentions allow us to quantify with high accuracy the deficits in the representation of other people's minds that so chiefly characterize ASD as well as the outcomes of treatment options focusing on this aspect. Here we suggest a few clarifications and extensions of the proposed model which will make it possibly tailored for clinical applications.

Th1-like Plasmodium-Specific Memory CD4+ T Cells Support Humoral Immunity.

PubMed

Zander, Ryan A; Vijay, Rahul; Pack, Angela D; Guthmiller, Jenna J; Graham, Amy C; Lindner, Scott E; Vaughan, Ashley M; Kappe, Stefan H I; Butler, Noah S

2017-11-14

Effector T cells exhibiting features of either T helper 1 (Th1) or T follicular helper (Tfh) populations are essential to control experimental Plasmodium infection and are believed to be critical for resistance to clinical malaria. To determine whether Plasmodium-specific Th1- and Tfh-like effector cells generate memory populations that contribute to protection, we developed transgenic parasites that enable high-resolution study of anti-malarial memory CD4 T cells in experimental models. We found that populations of both Th1- and Tfh-like Plasmodium-specific memory CD4 T cells persist. Unexpectedly, Th1-like memory cells exhibit phenotypic and functional features of Tfh cells during recall and provide potent B cell help and protection following transfer, characteristics that are enhanced following ligation of the T cell co-stimulatory receptor OX40. Our findings delineate critical functional attributes of Plasmodium-specific memory CD4 T cells and identify a host-specific factor that can be targeted to improve resolution of acute malaria and provide durable, long-term protection against Plasmodium parasite re-exposure. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Towards in vivo focal cortical dysplasia phenotyping using quantitative MRI.

PubMed

Adler, Sophie; Lorio, Sara; Jacques, Thomas S; Benova, Barbora; Gunny, Roxana; Cross, J Helen; Baldeweg, Torsten; Carmichael, David W

2017-01-01

Focal cortical dysplasias (FCDs) are a range of malformations of cortical development each with specific histopathological features. Conventional radiological assessment of standard structural MRI is useful for the localization of lesions but is unable to accurately predict the histopathological features. Quantitative MRI offers the possibility to probe tissue biophysical properties in vivo and may bridge the gap between radiological assessment and ex-vivo histology. This review will cover histological, genetic and radiological features of FCD following the ILAE classification and will explain how quantitative voxel- and surface-based techniques can characterise these features. We will provide an overview of the quantitative MRI measures available, their link with biophysical properties and finally the potential application of quantitative MRI to the problem of FCD subtyping. Future research linking quantitative MRI to FCD histological properties should improve clinical protocols, allow better characterisation of lesions in vivo and tailored surgical planning to the individual.

Body dysmorphic symptoms: phenomenology and ethnicity.

PubMed

Marques, Luana; LeBlanc, Nicole; Weingarden, Hilary; Greenberg, Jennifer L; Traeger, Lara N; Keshaviah, Aparna; Wilhelm, Sabine

2011-03-01

Differences in the presentation of clinical features of body dysmorphic disorder (BDD) across ethnic groups have received little investigation. The current study assessed BDD symptoms in an ethnically diverse sample of adults (n=401) using an online survey. Participants completed self-report measures assessing BDD symptoms, body parts of concern and BDD behaviors. Compared to Caucasian participants, no significant differences were found in body parts or behaviors reported by Latino or African American participants. Significant group differences did emerge between Asian and Caucasian participants. Specifically, Asians reported more concern with straight hair and dark skin and fewer body shape concerns than Caucasians. Asians also endorsed lower rates of grooming, touching body parts, and camouflaging and higher rates of exercise compared to Caucasians. Although most clinical features of BDD appear similar across ethnic groups, results showed some differences in body parts and behaviors between Caucasians and Asian Americans with BDD symptoms. Copyright © 2011 Elsevier Ltd. All rights reserved.

Effects of a kinesthetic cursive handwriting intervention for grade 4-6 students.

PubMed

Roberts, Gwenyth I; Siever, Jodi E; Mair, Judith A

2010-01-01

We studied whether Grade 4-6 students who participated in a kinesthetic writing intervention improved in legibility, speed, and personal satisfaction with cursive handwriting. Small groups of students with handwriting difficulties were seen weekly for 7 wk using a kinesthetic writing system. A repeated measures design was used to evaluate change in global legibility, individual letter formation, specific features of handwriting, and personal satisfaction. Analysis revealed (1) a significant increase in ratings of global legibility (p <.01; clinically significant improvements in 39% of students); (2) significant improvements in letter formation and legibility features of baseline, closure, and line quality (all p < .05); (3) increased handwriting speed (p < .05; not clinically significant); and (4) significant increase in measures with personal satisfaction of handwriting (p < .01). CONCLUSION. A kinesthetic handwriting intervention may be effective in improving the skills of students with handwriting challenges.

Maternal stress and perinatal features in autism and attention deficit/hyperactivity disorder.

PubMed

Say, Gökçe Nur; Karabekiroğlu, Koray; Babadağı, Zehra; Yüce, Murat

2016-04-01

We investigated the shared and non-shared perinatal risk factors for autism spectrum disorders (ASD) and attention deficit/hyperactivity disorder (ADHD) in a clinical sample. Additionally, we compared these groups regarding pre/postpartum maternal stress and the duration of breastfeeding. Children aged 3-18 years old with ASD (n = 100) were compared with age- and gender-matched children with ADHD (n = 100) and with age- and gender-matched healthy controls (n = 80). Prematurity of the neonate and maternal stress/depressive mood in pregnancy were common risk factors shared by ASD and ADHD. Postpartum maternal depressive mood may be more specific to ASD, while shorter duration of breastfeeding may be related to ADHD. ASD and ADHD may have some perinatal features in common. Identification of perinatal factors for ASD and ADHD carries clinical implications in terms of primary prevention. © 2015 Japan Pediatric Society.

Chronic neuropathologies of single and repetitive TBI: substrates of dementia?

PubMed Central

Smith, Douglas H.; Johnson, Victoria E.; Stewart, William

2014-01-01

Traumatic brain injury (TBI) has long been recognized to be a risk factor for dementia. This association has, however, only recently gained widespread attention through the increased awareness of ‘chronic traumatic encephalopathy’ (CTE) in athletes exposed to repetitive head injury. Originally termed ‘dementia pugilistica’ and linked to a career in boxing, descriptions of the neuropathological features of CTE include brain atrophy, cavum septum pellucidum, and amyloid-β, tau and TDP-43 pathologies, many of which might contribute to clinical syndromes of cognitive impairment. Similar chronic pathologies are also commonly found years after just a single moderate to severe TBI. However, little consensus currently exists on specific features of these post-TBI syndromes that might permit their confident clinical and/or pathological diagnosis. Moreover, the mechanisms contributing to neurodegeneration following TBI largely remain unknown. Here, we review the current literature and controversies in the study of chronic neuropathological changes after TBI. PMID:23458973

A Simplified Approach to Encephalitis and Its Mimics: Key Clinical Decision Points in the Setting of Specific Imaging Abnormalities.

PubMed

McKnight, Colin D; Kelly, Aine M; Petrou, Myria; Nidecker, Anna E; Lorincz, Matthew T; Altaee, Duaa K; Gebarski, Stephen S; Foerster, Bradley

2017-06-01

Infectious encephalitis is a relatively common cause of morbidity and mortality. Treatment of infectious encephalitis with antiviral medication can be highly effective when administered promptly. Clinical mimics of encephalitis arise from a broad range of pathologic processes, including toxic, metabolic, neoplastic, autoimmune, and cardiovascular etiologies. These mimics need to be rapidly differentiated from infectious encephalitis to appropriately manage the correct etiology; however, the many overlapping signs of these various entities present a challenge to accurate diagnosis. A systematic approach that considers both the clinical manifestations and the imaging findings of infectious encephalitis and its mimics can contribute to more accurate and timely diagnosis. Following an institutional review board approval, a health insurance portability and accountability act (HIPAA)-compliant search of our institutional imaging database (teaching files) was conducted to generate a list of adult and pediatric patients who presented between January 1, 1995 and October 10, 2013 for imaging to evaluate possible cases of encephalitis. Pertinent medical records, including clinical notes as well as surgical and pathology reports, were reviewed and correlated with imaging findings. Clinical and imaging findings were combined to generate useful flowcharts designed to assist in distinguishing infectious encephalitis from its mimics. Key imaging features were reviewed and were placed in the context of the provided flowcharts. Four flowcharts were presented based on the primary anatomic site of imaging abnormality: group 1: temporal lobe; group 2: cerebral cortex; group 3: deep gray matter; and group 4: white matter. An approach that combines features on clinical presentation was then detailed. Imaging examples were used to demonstrate similarities and key differences. Early recognition of infectious encephalitis is critical, but can be quite complex due to diverse pathologies and overlapping features. Synthesis of both the clinical and imaging features of infectious encephalitis and its mimics is critical to a timely and accurate diagnosis. The use of the flowcharts presented in this article can further enable both clinicians and radiologists to more confidently differentiate encephalitis from its mimics and improve patient care. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Hardware Development and Locomotion Control Strategy for an Over-Ground Gait Trainer: NaTUre-Gaits.

PubMed

Luu, Trieu Phat; Low, Kin Huat; Qu, Xingda; Lim, Hup Boon; Hoon, Kay Hiang

2014-01-01

Therapist-assisted body weight supported (TABWS) gait rehabilitation was introduced two decades ago. The benefit of TABWS in functional recovery of walking in spinal cord injury and stroke patients has been demonstrated and reported. However, shortage of therapists, labor-intensiveness, and short duration of training are some limitations of this approach. To overcome these deficiencies, robotic-assisted gait rehabilitation systems have been suggested. These systems have gained attentions from researchers and clinical practitioner in recent years. To achieve the same objective, an over-ground gait rehabilitation system, NaTUre-gaits, was developed at the Nanyang Technological University. The design was based on a clinical approach to provide four main features, which are pelvic motion, body weight support, over-ground walking experience, and lower limb assistance. These features can be achieved by three main modules of NaTUre-gaits: 1) pelvic assistance mechanism, mobile platform, and robotic orthosis. Predefined gait patterns are required for a robotic assisted system to follow. In this paper, the gait pattern planning for NaTUre-gaits was accomplished by an individual-specific gait pattern prediction model. The model generates gait patterns that resemble natural gait patterns of the targeted subjects. The features of NaTUre-gaits have been demonstrated by walking trials with several subjects. The trials have been evaluated by therapists and doctors. The results show that 10-m walking trial with a reduction in manpower. The task-specific repetitive training approach and natural walking gait patterns were also successfully achieved.

The effect of defect cluster size and interpolation on radiographic image quality

NASA Astrophysics Data System (ADS)

Töpfer, Karin; Yip, Kwok L.

2011-03-01

For digital X-ray detectors, the need to control factory yield and cost invariably leads to the presence of some defective pixels. Recently, a standard procedure was developed to identify such pixels for industrial applications. However, no quality standards exist in medical or industrial imaging regarding the maximum allowable number and size of detector defects. While the answer may be application specific, the minimum requirement for any defect specification is that the diagnostic quality of the images be maintained. A more stringent criterion is to keep any changes in the images due to defects below the visual threshold. Two highly sensitive image simulation and evaluation methods were employed to specify the fraction of allowable defects as a function of defect cluster size in general radiography. First, the most critical situation of the defect being located in the center of the disease feature was explored using image simulation tools and a previously verified human observer model, incorporating a channelized Hotelling observer. Detectability index d' was obtained as a function of defect cluster size for three different disease features on clinical lung and extremity backgrounds. Second, four concentrations of defects of four different sizes were added to clinical images with subtle disease features and then interpolated. Twenty observers evaluated the images against the original on a single display using a 2-AFC method, which was highly sensitive to small changes in image detail. Based on a 50% just-noticeable difference, the fraction of allowed defects was specified vs. cluster size.

Hardware Development and Locomotion Control Strategy for an Over-Ground Gait Trainer: NaTUre-Gaits

PubMed Central

Low, Kin Huat; Qu, Xingda; Lim, Hup Boon; Hoon, Kay Hiang

2014-01-01

Therapist-assisted body weight supported (TABWS) gait rehabilitation was introduced two decades ago. The benefit of TABWS in functional recovery of walking in spinal cord injury and stroke patients has been demonstrated and reported. However, shortage of therapists, labor-intensiveness, and short duration of training are some limitations of this approach. To overcome these deficiencies, robotic-assisted gait rehabilitation systems have been suggested. These systems have gained attentions from researchers and clinical practitioner in recent years. To achieve the same objective, an over-ground gait rehabilitation system, NaTUre-gaits, was developed at the Nanyang Technological University. The design was based on a clinical approach to provide four main features, which are pelvic motion, body weight support, over-ground walking experience, and lower limb assistance. These features can be achieved by three main modules of NaTUre-gaits: 1) pelvic assistance mechanism, mobile platform, and robotic orthosis. Predefined gait patterns are required for a robotic assisted system to follow. In this paper, the gait pattern planning for NaTUre-gaits was accomplished by an individual-specific gait pattern prediction model. The model generates gait patterns that resemble natural gait patterns of the targeted subjects. The features of NaTUre-gaits have been demonstrated by walking trials with several subjects. The trials have been evaluated by therapists and doctors. The results show that 10-m walking trial with a reduction in manpower. The task-specific repetitive training approach and natural walking gait patterns were also successfully achieved. PMID:27170876

Developing care pathways--lessons from the Steele Review implementation in England.

PubMed

Rooney, Eric

2014-02-01

This paper sets out to discuss the concept of care pathways, review their definition, features and implementation and using an example from the NHS dental system in England guide the development of an elder care pathway. Care pathways have developed from quality management approaches in industry and focus on a number of steps which are intended to lead to expected outcomes. The existing definition and descriptors of care pathways serve well, but miss the complex process underlying the development of pathways, their structure, implementation and evaluation. The literature identifies key features of clinical pathways and from the developing field of implementation science, the factors likely to support pathway implementation. Pathways must be generic enough to enable them to be applicable broadly, but specific enough for them to be locally relevant and population specific. The development of care pathways in the National Health Service (NHS) Dental Service in England is described and when compared with the implementation science literature exhibits features identified as positive factors for implementation. As a result a contribution to the pathway definition literature is offered. Learning from the literature and the practical experience described from England, the process for developing dental care pathways for dependent elders should begin with the creation of a high level pathway, which is cognisant of the clinical and implementation science evidence base. © 2014 John Wiley & Sons A/S and The Gerodontology Society. Published by John Wiley & Sons Ltd.

GNAO1 encephalopathy: Broadening the phenotype and evaluating treatment and outcome.

PubMed

Danti, Federica Rachele; Galosi, Serena; Romani, Marta; Montomoli, Martino; Carss, Keren J; Raymond, F Lucy; Parrini, Elena; Bianchini, Claudia; McShane, Tony; Dale, Russell C; Mohammad, Shekeeb S; Shah, Ubaid; Mahant, Neil; Ng, Joanne; McTague, Amy; Samanta, Rajib; Vadlamani, Gayatri; Valente, Enza Maria; Leuzzi, Vincenzo; Kurian, Manju A; Guerrini, Renzo

2017-04-01

To describe better the motor phenotype, molecular genetic features, and clinical course of GNAO1 -related disease. We reviewed clinical information, video recordings, and neuroimaging of a newly identified cohort of 7 patients with de novo missense and splice site GNAO1 mutations, detected by next-generation sequencing techniques. Patients first presented in early childhood (median age of presentation 10 months, range 0-48 months), with a wide range of clinical symptoms ranging from severe motor and cognitive impairment with marked choreoathetosis, self-injurious behavior, and epileptic encephalopathy to a milder phenotype, featuring moderate developmental delay associated with complex stereotypies, mainly facial dyskinesia and mild epilepsy. Hyperkinetic movements were often exacerbated by specific triggers, such as voluntary movement, intercurrent illnesses, emotion, and high ambient temperature, leading to hospital admissions. Most patients were resistant to drug intervention, although tetrabenazine was effective in partially controlling dyskinesia for 2/7 patients. Emergency deep brain stimulation (DBS) was life saving in 1 patient, resulting in immediate clinical benefit with complete cessation of violent hyperkinetic movements. Five patients had well-controlled epilepsy and 1 had drug-resistant seizures. Structural brain abnormalities, including mild cerebral atrophy and corpus callosum dysgenesis, were evident in 5 patients. One patient had a diffuse astrocytoma (WHO grade II), surgically removed at age 16. Our findings support the causative role of GNAO1 mutations in an expanded spectrum of early-onset epilepsy and movement disorders, frequently exacerbated by specific triggers and at times associated with self-injurious behavior. Tetrabenazine and DBS were the most useful treatments for dyskinesia.

Molecular subgroups of adult medulloblastoma: a long-term single-institution study.

PubMed

Zhao, Fu; Ohgaki, Hiroko; Xu, Lei; Giangaspero, Felice; Li, Chunde; Li, Peng; Yang, Zhijun; Wang, Bo; Wang, Xingchao; Wang, Zhenmin; Ai, Lin; Zhang, Jing; Luo, Lin; Liu, Pinan

2016-07-01

Recent transcriptomic approaches have demonstrated that there are at least 4 distinct subgroups in medulloblastoma (MB); however, survival studies of molecular subgroups in adult MB have been inconclusive because of small sample sizes. The aim of this study is to investigate the molecular subgroups in adult MB and identify their clinical and prognostic implications in a large, single-institution cohort. We determined gene expression profiles for 13 primary adult MBs. Bioinformatics tools were used to establish distinct molecular subgroups based on the most informative genes in the dataset. Immunohistochemistry with subgroup-specific antibodies was then used for validation within an independent cohort of 201 formalin-fixed MB tumors, in conjunction with a systematic analysis of clinical and histological characteristics. Three distinct molecular variants of adult MB were identified: the SHH, WNT, and group 4 subgroups. Validation of these subgroups in the 201-tumor cohort by immunohistochemistry identified significant differences in subgroup-specific demographics, histology, and metastatic status. The SHH subgroup accounted for the majority of the tumors (62%), followed by the group 4 subgroup (28%) and the WNT subgroup (10%). Group 4 tumors had significantly worse progression-free and overall survival compared with tumors of the other molecular subtypes. We have identified 3 subgroups of adult MB, characterized by distinct expression profiles, clinical features, pathological features, and prognosis. Clinical variables incorporated with molecular subgroup are more significantly informative for predicting adult patient outcome. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Congenital malformations and genetic diseases in comic books.

PubMed

Mégarbané, A; Adib, S M

2003-01-01

Medical syndromes have often been represented in fine arts, but rarely have clinical diagnoses been discussed in comic book characters. Since their first appearance in Europe in the middle of the 19th century and in America in 1895, comic books have been considered as "the 9th art". In many comic books, the appearance and/or the behavior of central or support characters are suggestive of already well-defined medical disorders. The representation of five particular groups or clinical features: mental retardation, abnormal stature, abnormal hair, obesity, and cranial malformations is discussed from mostly European comic series. Whether comic authors intended to describe specific clinical entities while drawing their characters or whether such situations appeared by mere luck, is open to debate. In many series from the first half of the 20th century characters with remarkable clinical features were also painted as psycho-social deviants. Such stereotypes are found much less frequently nowadays. Writers of comic books, realizing the major impact of their work especially in adolescent age groups, have increasingly been using their series to actually promote issues of equity and well being for physically or mentally impaired people.

The anatomy of decision support during inpatient care provider order entry (CPOE): Empirical observations from a decade of CPOE experience at Vanderbilt

PubMed Central

Miller, Randolph A.; Waitman, Lemuel R.; Chen, Sutin; Rosenbloom, S. Trent

2006-01-01

The authors describe a pragmatic approach to the introduction of clinical decision support at the point of care, based on a decade of experience in developing and evolving Vanderbilt’s inpatient “WizOrder” care provider order entry (CPOE) system. The inpatient care setting provides a unique opportunity to interject CPOE-based decision support features that restructure clinical workflows, deliver focused relevant educational materials, and influence how care is delivered to patients. From their empirical observations, the authors have developed a generic model for decision support within inpatient CPOE systems. They believe that the model’s utility extends beyond Vanderbilt, because it is based on characteristics of end-user workflows and on decision support considerations that are common to a variety of inpatient settings and CPOE systems. The specific approach to implementing a given clinical decision support feature within a CPOE system should involve evaluation along three axes: what type of intervention to create (for which the authors describe 4 general categories); when to introduce the intervention into the user’s workflow (for which the authors present 7 categories), and how disruptive, during use of the system, the intervention might be to end-users’ workflows (for which the authors describe 6 categories). Framing decision support in this manner may help both developers and clinical end-users plan future alterations to their systems when needs for new decision support features arise. PMID:16290243

Detection of EML4-ALK fusion gene and features associated with EGFR mutations in Chinese patients with non-small-cell lung cancer.

PubMed

Wen, Miaomiao; Wang, Xuejiao; Sun, Ying; Xia, Jinghua; Fan, Liangbo; Xing, Hao; Zhang, Zhipei; Li, Xiaofei

2016-01-01

Echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) and epidermal growth factor receptor (EGFR) define specific molecular subsets of lung cancer with distinct clinical features. We aimed at revealing the clinical features of EML4-ALK fusion gene and EGFR mutation in non-small-cell lung cancer (NSCLC). We enrolled 694 Chinese patients with NSCLC for analysis. EML4-ALK fusion gene was analyzed by real-time polymerase chain reaction, and EGFR mutations were analyzed by amplified refractory mutation system. Among the 694 patients, 60 (8.65%) patients had EML4-ALK fusions. In continuity correction χ (2) test analysis, EML4-ALK fusion gene was correlated with sex, age, smoking status, and histology, but no significant association was observed between EML4-ALK fusion gene and clinical stage. A total of 147 (21.18%) patients had EGFR mutations. In concordance with previous reports, EGFR mutation was correlated with age, smoking status, histology, and clinical stage, whereas patient age was not significantly associated with EGFR mutation. Meanwhile, to our surprise, six (0.86%) patients had coexisting EML4-ALK fusions and EGFR mutations. EML4-ALK fusion gene defines a new molecular subset in patients with NSCLC. Six patients who harbored both EML4-ALK fusion genes and EGFR mutations were identified in our study. The EGFR mutations and the EML4-ALK fusion genes are coexistent.

Detection of EML4-ALK fusion gene and features associated with EGFR mutations in Chinese patients with non-small-cell lung cancer

PubMed Central

Wen, Miaomiao; Wang, Xuejiao; Sun, Ying; Xia, Jinghua; Fan, Liangbo; Xing, Hao; Zhang, Zhipei; Li, Xiaofei

2016-01-01

Purpose Echinoderm microtubule-associated protein-like 4–anaplastic lymphoma kinase (EML4-ALK) and epidermal growth factor receptor (EGFR) define specific molecular subsets of lung cancer with distinct clinical features. We aimed at revealing the clinical features of EML4-ALK fusion gene and EGFR mutation in non-small-cell lung cancer (NSCLC). Methods We enrolled 694 Chinese patients with NSCLC for analysis. EML4-ALK fusion gene was analyzed by real-time polymerase chain reaction, and EGFR mutations were analyzed by amplified refractory mutation system. Results Among the 694 patients, 60 (8.65%) patients had EML4-ALK fusions. In continuity correction χ2 test analysis, EML4-ALK fusion gene was correlated with sex, age, smoking status, and histology, but no significant association was observed between EML4-ALK fusion gene and clinical stage. A total of 147 (21.18%) patients had EGFR mutations. In concordance with previous reports, EGFR mutation was correlated with age, smoking status, histology, and clinical stage, whereas patient age was not significantly associated with EGFR mutation. Meanwhile, to our surprise, six (0.86%) patients had coexisting EML4-ALK fusions and EGFR mutations. Conclusion EML4-ALK fusion gene defines a new molecular subset in patients with NSCLC. Six patients who harbored both EML4-ALK fusion genes and EGFR mutations were identified in our study. The EGFR mutations and the EML4-ALK fusion genes are coexistent. PMID:27103824

Mutations in chromatin regulators functionally link Cornelia de Lange syndrome and clinically overlapping phenotypes.

PubMed

Parenti, Ilaria; Teresa-Rodrigo, María E; Pozojevic, Jelena; Ruiz Gil, Sara; Bader, Ingrid; Braunholz, Diana; Bramswig, Nuria C; Gervasini, Cristina; Larizza, Lidia; Pfeiffer, Lutz; Ozkinay, Ferda; Ramos, Feliciano; Reiz, Benedikt; Rittinger, Olaf; Strom, Tim M; Watrin, Erwan; Wendt, Kerstin; Wieczorek, Dagmar; Wollnik, Bernd; Baquero-Montoya, Carolina; Pié, Juan; Deardorff, Matthew A; Gillessen-Kaesbach, Gabriele; Kaiser, Frank J

2017-03-01

The coordinated tissue-specific regulation of gene expression is essential for the proper development of all organisms. Mutations in multiple transcriptional regulators cause a group of neurodevelopmental disorders termed "transcriptomopathies" that share core phenotypical features including growth retardation, developmental delay, intellectual disability and facial dysmorphism. Cornelia de Lange syndrome (CdLS) belongs to this class of disorders and is caused by mutations in different subunits or regulators of the cohesin complex. Herein, we report on the clinical and molecular characterization of seven patients with features overlapping with CdLS who were found to carry mutations in chromatin regulators previously associated to other neurodevelopmental disorders that are frequently considered in the differential diagnosis of CdLS. The identified mutations affect the methyltransferase-encoding genes KMT2A and SETD5 and different subunits of the SWI/SNF chromatin-remodeling complex. Complementary to this, a patient with Coffin-Siris syndrome was found to carry a missense substitution in NIPBL. Our findings indicate that mutations in a variety of chromatin-associated factors result in overlapping clinical phenotypes, underscoring the genetic heterogeneity that should be considered when assessing the clinical and molecular diagnosis of neurodevelopmental syndromes. It is clear that emerging molecular mechanisms of chromatin dysregulation are central to understanding the pathogenesis of these clinically overlapping genetic disorders.

Kinematic and Pressure Features of Handwriting and Drawing: Preliminary Results Between Patients with Mild Cognitive Impairment, Alzheimer Disease and Healthy Controls

PubMed Central

Garre-Olmo, Josep; Faúndez-Zanuy, Marcos; López-de-Ipiña, Karmele; Calvó-Perxas, Laia; Turró-Garriga, Oriol

2017-01-01

Background: Alzheimer’s disease (AD) is the most common neurodegenerative dementia of old age, and the leading chronic disease contributor to disability and dependence among older people worldwide. Clinically, AD is characterized by a progressive cognitive decline that interferes with the abil-ity to perform the activities of daily living. Handwriting and drawing are complex human activities that entail an intricate blend of cognitive, kinesthetic, and perceptual-motor features. Objective: To compare the kinematic characteristics of handwriting and drawing between patients with AD, patients with mild cognitive impairment (MCI) and healthy controls. Methods: We used a cross-sectional and observational design to assess the kinematic and pressure fea-tures of handwriting and drawing using a computerized system. Participants were asked to copy one sen-tence, write a dictated sentence and an own sentence, copy two and-three dimensions drawings, and to execute the clock drawing test. By means of discriminant analyses, we explored the value of several kin-ematic features in order to classify participants depending on their degree of cognitive functioning. Results: The sample consisted of 52 participants (23 AD, 12 MCI, and 17 healthy controls) with a mean age of 69.7 years (SD=8.11). The degree of correct classification was largely dependent on the nature of the groups to be classified and the specific task, and ranged between 63.5% and 100%. Diagnostic accu-racy based on kinematic measures showed higher specificity values for distinguishing between normal and impaired cognition (MCI and AD), and higher sensitivity was obtained when distinguishing between impaired cognition levels (MCI vs. AD). Conclusion: The kinematic features of writing and drawing procedures, rather than the final product, may be a useful and objective complement to the clinical assessment of patients with cognitive impairment. PMID:28290244

Kinematic and Pressure Features of Handwriting and Drawing: Preliminary Results Between Patients with Mild Cognitive Impairment, Alzheimer Disease and Healthy Controls.

PubMed

Garre-Olmo, Josep; Faúndez-Zanuy, Marcos; López-de-Ipiña, Karmele; Calvó-Perxas, Laia; Turró-Garriga, Oriol

2017-01-01

Alzheimer's disease (AD) is the most common neurodegenerative dementia of old age, and the leading chronic disease contributor to disability and dependence among older people worldwide. Clinically, AD is characterized by a progressive cognitive decline that interferes with the ability to perform the activities of daily living. Handwriting and drawing are complex human activities that entail an intricate blend of cognitive, kinesthetic, and perceptual-motor features. To compare the kinematic characteristics of handwriting and drawing between patients with AD, patients with mild cognitive impairment (MCI) and healthy controls. We used a cross-sectional and observational design to assess the kinematic and pressure features of handwriting and drawing using a computerized system. Participants were asked to copy one sentence, write a dictated sentence and an own sentence, copy two and-three dimensions drawings, and to execute the clock drawing test. By means of discriminant analyses, we explored the value of several kinematic features in order to classify participants depending on their degree of cognitive functioning. The sample consisted of 52 participants (23 AD, 12 MCI, and 17 healthy controls) with a mean age of 69.7 years (SD=8.11). The degree of correct classification was largely dependent on the nature of the groups to be classified and the specific task, and ranged between 63.5% and 100%. Diagnostic accuracy based on kinematic measures showed higher specificity values for distinguishing between normal and impaired cognition (MCI and AD), and higher sensitivity was obtained when distinguishing between impaired cognition levels (MCI vs. AD). The kinematic features of writing and drawing procedures, rather than the final product, may be a useful and objective complement to the clinical assessment of patients with cognitive impairment. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Redefining Dermatomyositis

PubMed Central

Troyanov, Yves; Targoff, Ira N; Payette, Marie-Pier; Raynauld, Jean-Pierre; Chartier, Suzanne; Goulet, Jean-Richard; Bourré-Tessier, Josiane; Rich, Eric; Grodzicky, Tamara; Fritzler, Marvin J.; Joyal, France; Koenig, Martial; Senécal, Jean-Luc

2014-01-01

Abstract Dermatomyositis (DM) is a major clinical subset of autoimmune myositis (AIM). The characteristic DM rash (Gottron papules, heliotrope rash) and perifascicular atrophy at skeletal muscle biopsy are regarded as specific features for this diagnosis. However, new concepts are challenging the current definition of DM. A modified Bohan and Peter classification of AIM was proposed in which the core concept was the inclusion of the diagnostic significance of overlap connective tissue disease features. In this clinical classification, a DM rash in association with myositis in the absence of overlap features indicates a diagnosis of pure DM. However, overlap features in association with myositis allow a diagnosis of overlap myositis (OM), irrespective of the presence or absence of the DM rash. Perifascicular atrophy may be present in both pure DM and OM. Recently, the presence of perifascicular atrophy in myositis without a DM rash was proposed as diagnostic of a novel entity, adermatopathic DM. We conducted the present study to evaluate these new concepts to further differentiate pure DM from OM. Using the modified Bohan and Peter classification, we performed a follow-up study of a longitudinal cohort of 100 consecutive adult French Canadian patients with AIM, including 44 patients with a DM phenotype, defined as a DM rash, and/or DM-type calcinosis, and/or the presence of perifascicular atrophy on muscle biopsy. A detailed evaluation was performed for overlap features, the extent and natural history of the DM rash, adermatopathic DM, DM-specific and overlap autoantibodies by protein A immunoprecipitation on coded serum samples, and associations with cancer and survival. Two distinct subsets were identified in patients with a DM phenotype: pure DM (n = 24) and OM with DM features, or OMDM (n = 20). In pure DM, the DM rash was a dominant finding. It was the first disease manifestation, was always present at the time of myositis diagnosis, and was associated with a high cutaneous score and chronicity. Concurrent heliotrope rash and Gottron papules (positive predictive value [PPV] 91%), as well as the V-sign and/or shawl sign (PPV 100%), were diagnostic of pure DM. Anti-Mi-2, anti-MJ, and anti-p155 autoantibodies were present in 50% of pure DM patients and were restricted to this subset (PPV 100%). Cancer was present in 21% of pure DM patients. The 15-year survival was excellent (92%). In contrast, in patients with OMDM, the first manifestation was proximal muscle weakness or other skeletal muscle-related complaints. The DM rash appeared at diagnosis or at follow-up, was associated with a low cutaneous extent score and was transient. Adermatopathic DM, which was absent in pure DM, was highly predictive (PPV 100%) of OMDM. Overlap autoantibodies (including anti-Jo-1, anti-PL-7, anti-PM-Scl, anti-U1RNP, and/or anti-U5-RNP) were found in 70% of OMDM patients. OMDM was not associated with cancer, but the 15-year survival was significantly decreased (65%). Perifascicular atrophy occurred as commonly in OMDM (n = 6/20, 30%) as in pure DM (n = 4/24, 17%) patients. These 6 OMDM patients had adermatopathic DM at myositis diagnosis, and only 1 of them developed a DM rash at follow-up, emphasizing the lack of specificity of perifascicular atrophy for pure DM. In conclusion, using the modified Bohan and Peter classification of AIM allowed identification of OMDM, a new clinical subset of OM. Furthermore, identification of OMDM allowed recognition of pure DM as a new entity that was distinct from OMDM or from OM without DM features. However, the absolute specificity of a DM rash and perifascicular muscle atrophy for the diagnosis of pure DM was lost. The distinctive clinical manifestations and autoantibody profiles presented are proposed as diagnostic criteria to differentiate pure DM from OMDM. PMID:25500701

Congenital renal rhabdoid tumor with placental metastases: immunohistochemistry, cytogenetic, and ultrastructural findings.

PubMed

de Tar, Michael; Sanford Biggerstaff, Julie

2006-01-01

Malignant congenital tumors of fetal origin are rare lesions, the most common type being congenital neuroblastoma. Although prenatal diagnosis is possible in large tumors, occasionally the tumor will be diagnosed first by its metastatic involvement of the placenta. Placental metastases can reflect either maternal or fetal primary sites, and each has relatively specific patterns of placental involvement. We describe the clinical and pathologic features of a widely metastatic congenital renal rhabdoid tumor with its placental and autopsy findings, and include the immunohistochemical, cytogenetic, and ultrastructural features. The pathologic features of the placenta in congenital renal rhabdoid tumor with placental metastasis have not been previously described. The examination of the placenta in this case led to the initial diagnosis and obviated the need for additional diagnostic procedures.

PCOS remains a diagnosis of exclusion: a concise review of key endocrinopathies to exclude.

PubMed

Kyritsi, Eleni Magdalini; Dimitriadis, George K; Kyrou, Ioannis; Kaltsas, Gregory; Randeva, Harpal S

2017-01-01

Polycystic ovarian syndrome (PCOS) is a heterogenous disorder associated with clinical, endocrine and ultrasonographic features that can also be encountered in a number of other diseases. It has traditionally been suggested that prolactin excess, enzymatic steroidogenic abnormalities and thyroid disorders need to be excluded before a diagnosis of PCOS is made. However, there is paucity of data regarding the prevalence of PCOS phenotype in some of these disorders, whereas other endocrine diseases that exhibit PCOS-like features may elude diagnosis and proper management if not considered. This article reviews the data of currently included entities that exhibit a PCOS phenotype and those that potentially need to be looked for, and attempts to identify specific features that distinguish them from idiopathic PCOS. © 2016 John Wiley & Sons Ltd.

[Abnormal vaginal secretion: sensitivity, specificity and concordance between clinical and cytological diagnosis].

PubMed

de Camargo, Kélvia Cristina; Alves, Rosane Ribeiro Figueiredo; Baylão, Luciano Augusto; Ribeiro, Andrea Alves; Araujo, Nadja Lindany Alves de Souza; Tavares, Suelene Brito do Nascimento; dos Santos, Sílvia Helena Rabelo

2015-05-01

To estimate the prevalence of bacterial vaginosis (BV), candidiasis and trichomoniasis and compare the findings of physical examination of the vaginal secretion with the microbiological diagnosis obtained by cytology study of a vaginal smear using the Papanicolaou method. A cross-sectional study of 302 women aged 20 to 87 years, interviewed and submitted to a gynecology test for the evaluation of vaginal secretion and collection of a cytology smear, from June 2012 to May 2013. Sensitivity analyses were carried out and specificity, positive predictive value (PPV) and negative predictive value (NPV) with their respective 95%CI were determined to assess the accuracy of the characteristics of vaginal secretion in relation to the microbiological diagnosis of the cytology smear . The kappa index (k) was used to assess the degree of agreement between the clinical features of vaginal secretion and the microbiological findings obtained by cytology. RESULTS The prevalence of BV, candidiasis and trichomoniasis was 25.5, 9.3 and 2.0%, respectively. The sensitivity, specificity, PPV and NPV of the clinical characteristics of vaginal secretion for the cytological diagnosis of BV were 74, 78.6, 54.3 and 89.9%, respectively. The sensitivity, specificity, PPV and the NPV of the clinical characteristics of vaginal secretion for the cytological diagnosis of candidiasis were 46.4, 86.2, 25.5 and 94%, respectively. The correlation between the clinical evaluation of vaginal secretion and the microbiological diagnosis of BV, candidiasis and trichomoniasis, assessed by the kappa index, was 0.47, 0.23 and 0.28, respectively. CONCLUSION The most common cause of abnormal vaginal secretion was BV. The clinical evaluation of vaginal secretion presented amoderate to weak agreement with the microbiological diagnosis, indicating the need for complementary investigation of the clinical findings of abnormal vaginal secretion.

Diagnostic standards for dopaminergic augmentation of restless legs syndrome: report from a World Association of Sleep Medicine-International Restless Legs Syndrome Study Group consensus conference at the Max Planck Institute.

PubMed

García-Borreguero, Diego; Allen, Richard P; Kohnen, Ralf; Högl, Birgit; Trenkwalder, Claudia; Oertel, Wolfgang; Hening, Wayne A; Paulus, Walter; Rye, David; Walters, Arthur; Winkelmann, Juliane; Earley, Christopher J

2007-08-01

Augmentation of symptom severity is the main complication of dopaminergic treatment of restless legs syndrome (RLS). The current article reports on the considerations of augmentation that were made during a European Restless Legs Syndrome Study Group (EURLSSG)-sponsored Consensus Conference in April 2006 at the Max Planck Institute (MPI) in Munich, Germany, the conclusions of which were endorsed by the International RLS Study Group (IRLSSG) and the World Association of Sleep Medicine (WASM). The Consensus Conference sought to develop a better understanding of augmentation and generate a better operational definition for its clinical identification. Current concepts of the pathophysiology, clinical features, and therapy of RLS augmentation were evaluated by subgroups who presented a summary of their findings for general consideration and discussion. Recent data indicating sensitivity and specificity of augmentation features for identification of augmentation were also evaluated. The diagnostic criteria of augmentation developed at the National Institutes of Health (NIH) conference in 2002 were reviewed in light of current data and theoretical understanding of augmentation. The diagnostic value and criteria for each of the accepted features of augmentation were considered by the group. A consensus was then developed for a revised statement of the diagnostic criteria for augmentation. Five major diagnostic features of augmentation were identified: usual time of RLS symptom onset each day, number of body parts with RLS symptoms, latency to symptoms at rest, severity of the symptoms when they occur, and effects of dopaminergic medication on symptoms. The quantitative data available relating the time of RLS onset and the presence of other features indicated optimal augmentation criteria of either a 4-h advance in usual starting time for RLS symptoms or a combination of the occurrence of other features. A paradoxical response to changes in medication dose also indicates augmentation. Clinical significance of augmentation is defined. The Consensus Conference agreed upon new operational criteria for the clinical diagnosis of RLS augmentation: the MPI diagnostic criteria for augmentation. Areas needing further consideration for validating these criteria and for understanding the underlying biology of RLS augmentation are indicated.

Mapping Gene Associations in Human Mitochondria using Clinical Disease Phenotypes

PubMed Central

Scharfe, Curt; Lu, Henry Horng-Shing; Neuenburg, Jutta K.; Allen, Edward A.; Li, Guan-Cheng; Klopstock, Thomas; Cowan, Tina M.; Enns, Gregory M.; Davis, Ronald W.

2009-01-01

Nuclear genes encode most mitochondrial proteins, and their mutations cause diverse and debilitating clinical disorders. To date, 1,200 of these mitochondrial genes have been recorded, while no standardized catalog exists of the associated clinical phenotypes. Such a catalog would be useful to develop methods to analyze human phenotypic data, to determine genotype-phenotype relations among many genes and diseases, and to support the clinical diagnosis of mitochondrial disorders. Here we establish a clinical phenotype catalog of 174 mitochondrial disease genes and study associations of diseases and genes. Phenotypic features such as clinical signs and symptoms were manually annotated from full-text medical articles and classified based on the hierarchical MeSH ontology. This classification of phenotypic features of each gene allowed for the comparison of diseases between different genes. In turn, we were then able to measure the phenotypic associations of disease genes for which we calculated a quantitative value that is based on their shared phenotypic features. The results showed that genes sharing more similar phenotypes have a stronger tendency for functional interactions, proving the usefulness of phenotype similarity values in disease gene network analysis. We then constructed a functional network of mitochondrial genes and discovered a higher connectivity for non-disease than for disease genes, and a tendency of disease genes to interact with each other. Utilizing these differences, we propose 168 candidate genes that resemble the characteristic interaction patterns of mitochondrial disease genes. Through their network associations, the candidates are further prioritized for the study of specific disorders such as optic neuropathies and Parkinson disease. Most mitochondrial disease phenotypes involve several clinical categories including neurologic, metabolic, and gastrointestinal disorders, which might indicate the effects of gene defects within the mitochondrial system. The accompanying knowledgebase (http://www.mitophenome.org/) supports the study of clinical diseases and associated genes. PMID:19390613

Bronchoalveolar carcinoma: current treatment and future trends.

PubMed

Laskin, Janessa J

2004-12-01

Bronchoalveolar carcinoma (BAC) is a subtype of non-small-cell lung cancer (NSCLC) with unique clinical and pathologic characteristics. The most recent classification system defines BAC as a primary lung cancer that tends to be peripheral and grow in a lepedic fashion along the alveolar septae without parenchymal invasion. Most of the clinical information on BAC comes from retrospective institutional reviews; however, recent studies have focused more specifically on BAC. In particular, clinical trials of molecular-targeted anticancer therapies against the epidermal growth factor receptor have led to a deeper understanding of the distinct features of this cancer and suggest that BAC may require a therapeutic paradigm different from that of other NSCLCs.

Partial epilepsy and 47,XXX karyotype: report of four cases.

PubMed

Roubertie, Agathe; Humbertclaude, Véronique; Leydet, Julie; Lefort, Geneviève; Echenne, Bernard

2006-07-01

Epilepsy is a common finding in chromosomal imbalances, but only a few chromosome abnormalities have a characteristic electro-clinical pattern. Trisomy X is one of the most common sex chromosome abnormalities in females, and is associated with considerable phenotypic variability. This report describes four 47,XXX females with mental deficiency and epilepsy. Although a specific electro-clinical pattern could not be defined, the epileptic phenotypes of these patients share many features; we suggest that the association 47,XXX/epilepsy/mental retardation may not be coincidental. This report also enlarges the clinical spectrum of the 47,XXX phenotype. Moreover, these observations highlight the critical role of chromosome X in epilepsy and mental retardation.

A genomic view of food-related and probiotic Enterococcus strains.

PubMed

Bonacina, Julieta; Suárez, Nadia; Hormigo, Ricardo; Fadda, Silvina; Lechner, Marcus; Saavedra, Lucila

2017-02-01

The study of enterococcal genomes has grown considerably in recent years. While special attention is paid to comparative genomic analysis among clinical relevant isolates, in this study we performed an exhaustive comparative analysis of enterococcal genomes of food origin and/or with potential to be used as probiotics. Beyond common genetic features, we especially aimed to identify those that are specific to enterococcal strains isolated from a certain food-related source as well as features present in a species-specific manner. Thus, the genome sequences of 25 Enterococcus strains, from 7 different species, were examined and compared. Their phylogenetic relationship was reconstructed based on orthologous proteins and whole genomes. Likewise, markers associated with a successful colonization (bacteriocin genes and genomic islands) and genome plasticity (phages and clustered regularly interspaced short palindromic repeats) were investigated for lifestyle specific genetic features. At the same time, a search for antibiotic resistance genes was carried out, since they are of big concern in the food industry. Finally, it was possible to locate 1617 FIGfam families as a core proteome universally present among the genera and to determine that most of the accessory genes code for hypothetical proteins, providing reasonable hints to support their functional characterization. © The Author 2016. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.

Assessing the Pathogenicity of Insertion and Deletion Variants with the Variant Effect Scoring Tool (VEST‐Indel)

PubMed Central

Douville, Christopher; Masica, David L.; Stenson, Peter D.; Cooper, David N.; Gygax, Derek M.; Kim, Rick; Ryan, Michael

2015-01-01

ABSTRACT Insertion/deletion variants (indels) alter protein sequence and length, yet are highly prevalent in healthy populations, presenting a challenge to bioinformatics classifiers. Commonly used features—DNA and protein sequence conservation, indel length, and occurrence in repeat regions—are useful for inference of protein damage. However, these features can cause false positives when predicting the impact of indels on disease. Existing methods for indel classification suffer from low specificities, severely limiting clinical utility. Here, we further develop our variant effect scoring tool (VEST) to include the classification of in‐frame and frameshift indels (VEST‐indel) as pathogenic or benign. We apply 24 features, including a new “PubMed” feature, to estimate a gene's importance in human disease. When compared with four existing indel classifiers, our method achieves a drastically reduced false‐positive rate, improving specificity by as much as 90%. This approach of estimating gene importance might be generally applicable to missense and other bioinformatics pathogenicity predictors, which often fail to achieve high specificity. Finally, we tested all possible meta‐predictors that can be obtained from combining the four different indel classifiers using Boolean conjunctions and disjunctions, and derived a meta‐predictor with improved performance over any individual method. PMID:26442818

Arima syndrome caused by CEP290 specific variant and accompanied with pathological cilium; clinical comparison with Joubert syndrome and its related diseases.

PubMed

Itoh, Masayuki; Ide, Shuhei; Iwasaki, Yuji; Saito, Takashi; Narita, Keishi; Dai, Hongmei; Yamakura, Shinji; Furue, Takeki; Kitayama, Hirotsugu; Maeda, Keiko; Takahashi, Eihiko; Matsui, Kiyoshi; Goto, Yu-Ichi; Takeda, Sen; Arima, Masataka

2018-04-01

Arima syndrome (AS) is a rare disease and its clinical features mimic those of Joubert syndrome or Joubert syndrome-related diseases (JSRD). Recently, we clarified the AS diagnostic criteria and its severe phenotype. However, genetic evidence of AS remains unknown. We explored causative genes of AS and compared the clinical and genetic features of AS with the other JSRD. We performed genetic analyses of 4 AS patients of 3 families with combination of whole-exome sequencing and Sanger sequencing. Furthermore, we studied cell biology with the cultured fibroblasts of 3 AS patients. All patients had a specific homozygous variant (c.6012-12T>A, p.Arg2004Serfs*7) or compound heterozygous variants (c.1711+1G>A; c.6012-12T>A, p.Gly570Aspfs*19;Arg2004Serfs*7) in centrosomal protein 290 kDa (CEP290) gene. These unique variants lead to abnormal splicing and premature termination. Morphological analysis of cultured fibroblasts from AS patients revealed a marked decrease of the CEP290-positive cell number with significantly longer cilium and naked and protruded ciliary axoneme without ciliary membrane into the cytoplasm. AS resulted in cilia dysfunction from centrosome disruption. The unique variant of CEP290 could be strongly linked to AS pathology. Here, we provided AS specific genetic evidence, which steers the structure and functions of centrosome that is responsible for normal ciliogenesis. This is the first report that has demonstrated the molecular basis of Arima syndrome. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

The characteristic ultrasound features of specific types of ovarian pathology (Review)

PubMed Central

SAYASNEH, AHMAD; EKECHI, CHRISTINE; FERRARA, LAURA; KAIJSER, JEROEN; STALDER, CATRIONA; SUR, SHYAMALY; TIMMERMAN, DIRK; BOURNE, TOM

2015-01-01

Characterizing ovarian masses enables patients with malignancy to be appropriately triaged for treatment by subspecialist gynecological oncologists, which has been shown to optimize care and improve survival. Furthermore, correctly classifying benign masses facilitates the selection of patients with ovarian pathology that may either not require intervention, or be suitable for minimal access surgery if intervention is required. However, predicting whether a mass is benign or malignant is not the only clinically relevant information that we need to know before deciding on appropriate treatment. Knowing the specific histology of a mass is becoming of increasing importance as management options become more tailored to the individual patient. For example predicting a mucinous borderline tumor gives the opportunity for fertility sparing surgery, and will highlight the need for further gastrointestinal assessment. For benign disease, predicting the presence of an endometrioma and possible deeply infiltrating endometriosis is important when considering both who should perform and the extent of surgery. An examiner’s subjective assessment of the morphological and vascular features of a mass using ultrasonography has been shown to be highly effective for predicting whether a mass is benign or malignant. Many masses also have features that enable a reliable diagnosis of the specific pathology of a particular mass to be made. In this narrative review we aim to describe the typical morphological features seen on ultrasound of different adnexal masses and illustrate these by showing representative ultrasound images. PMID:25406094

Evaluation of a web based informatics system with data mining tools for predicting outcomes with quantitative imaging features in stroke rehabilitation clinical trials

NASA Astrophysics Data System (ADS)

Wang, Ximing; Kim, Bokkyu; Park, Ji Hoon; Wang, Erik; Forsyth, Sydney; Lim, Cody; Ravi, Ragini; Karibyan, Sarkis; Sanchez, Alexander; Liu, Brent

2017-03-01

Quantitative imaging biomarkers are used widely in clinical trials for tracking and evaluation of medical interventions. Previously, we have presented a web based informatics system utilizing quantitative imaging features for predicting outcomes in stroke rehabilitation clinical trials. The system integrates imaging features extraction tools and a web-based statistical analysis tool. The tools include a generalized linear mixed model(GLMM) that can investigate potential significance and correlation based on features extracted from clinical data and quantitative biomarkers. The imaging features extraction tools allow the user to collect imaging features and the GLMM module allows the user to select clinical data and imaging features such as stroke lesion characteristics from the database as regressors and regressands. This paper discusses the application scenario and evaluation results of the system in a stroke rehabilitation clinical trial. The system was utilized to manage clinical data and extract imaging biomarkers including stroke lesion volume, location and ventricle/brain ratio. The GLMM module was validated and the efficiency of data analysis was also evaluated.

Phenomenology and classification of dystonia: a consensus update

PubMed Central

Albanese, Alberto; Bhatia, Kailash; Bressman, Susan B.; DeLong, Mahlon R.; Fahn, Stanley; Fung, Victor S.C.; Hallett, Mark; Jankovic, Joseph; Jinnah, H.A.; Klein, Christine; Lang, Anthony E.; Mink, Jonathan W.; Teller, Jan K.

2013-01-01

This report describes the consensus outcome of an international panel consisting of investigators with years of experience in this field that reviewed the definition and classification of dystonia. Agreement was obtained based on a consensus development methodology during three in-person meetings and manuscript review by mail. Dystonia is defined as a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both. Dystonic movements are typically patterned and twisting, and may be tremulous. Dystonia is often initiated or worsened by voluntary action and associated with overflow muscle activation. Dystonia is classified along two axes: clinical characteristics, including age at onset, body distribution, temporal pattern and associated features (additional movement disorders or neurological features), and etiology, which includes nervous system pathology and inheritance. The clinical characteristics fall into several specific dystonia syndromes that help to guide diagnosis and treatment. We provide here a new general definition of dystonia and propose a new classification. We encourage clinicians and researchers to use these innovative definition and classification and test them in the clinical setting on a variety of patients with dystonia. PMID:23649720

PubMed searches: overview and strategies for clinicians.

PubMed

Lindsey, Wesley T; Olin, Bernie R

2013-04-01

PubMed is a biomedical and life sciences database maintained by a division of the National Library of Medicine known as the National Center for Biotechnology Information (NCBI). It is a large resource with more than 5600 journals indexed and greater than 22 million total citations. Searches conducted in PubMed provide references that are more specific for the intended topic compared with other popular search engines. Effective PubMed searches allow the clinician to remain current on the latest clinical trials, systematic reviews, and practice guidelines. PubMed continues to evolve by allowing users to create a customized experience through the My NCBI portal, new arrangements and options in search filters, and supporting scholarly projects through exportation of citations to reference managing software. Prepackaged search options available in the Clinical Queries feature also allow users to efficiently search for clinical literature. PubMed also provides information regarding the source journals themselves through the Journals in NCBI Databases link. This article provides an overview of the PubMed database's structure and features as well as strategies for conducting an effective search.

Diagnostic features of Alzheimer's disease extracted from PET sinograms

NASA Astrophysics Data System (ADS)

Sayeed, A.; Petrou, M.; Spyrou, N.; Kadyrov, A.; Spinks, T.

2002-01-01

Texture analysis of positron emission tomography (PET) images of the brain is a very difficult task, due to the poor signal to noise ratio. As a consequence, very few techniques can be implemented successfully. We use a new global analysis technique known as the Trace transform triple features. This technique can be applied directly to the raw sinograms to distinguish patients with Alzheimer's disease (AD) from normal volunteers. FDG-PET images of 18 AD and 10 normal controls obtained from the same CTI ECAT-953 scanner were used in this study. The Trace transform triple feature technique was used to extract features that were invariant to scaling, translation and rotation, referred to as invariant features, as well as features that were sensitive to rotation but invariant to scaling and translation, referred to as sensitive features in this study. The features were used to classify the groups using discriminant function analysis. Cross-validation tests using stepwise discriminant function analysis showed that combining both sensitive and invariant features produced the best results, when compared with the clinical diagnosis. Selecting the five best features produces an overall accuracy of 93% with sensitivity of 94% and specificity of 90%. This is comparable with the classification accuracy achieved by Kippenhan et al (1992), using regional metabolic activity.

[Alienation: Differential Psychopathology of Ego-Disturbances].

PubMed

Bodatsch, M; Kuhn, J

2016-11-01

Alienation, i. e. disorders of the inner experience of integrity, continuity, and agency, represents a feature of both psychotic and non-psychotic disorders. Thereby, ego disturbances are thought to be specific for schizophrenia. Depersonalisation, in contrast, has been reported in schizophrenia as well as a neurotic, probably distinct syndrome. The differentiation of psychotic vs. non-psychotic alienation is often all but trivial. The present paper provides an overview of the historical roots and the psychopathological conceptualizations of alienation. Clinically relevant features of psychotic alienation are highlighted. Experience of passivity, loss of authenticity and disturbances of striving and volition appear as psychotic characteristics. © Georg Thieme Verlag KG Stuttgart · New York.

Hemodialysis-related headache.

PubMed

Sav, Murat Yusuf; Sav, Tansu; Senocak, Elif; Sav, Nadide Melike

2014-10-01

Headache is one of the most frequently encountered neurological symptoms during hemodialysis. According to International Classification of Headache criteria dialysis-related headache was defined as the headache occurring during hemodialysis with no specific characteristic. It resolves spontaneously within 72 hours after the hemodialysis session ends. There are few studies in the literature investigating the clinical features of dialysis headache. The pathophysiology of hemodialysis-related headache is not known, but various triggering factors have been identified, including changes in blood pressure, serum sodium and magnesium levels during hemodialysis sessions, caffeine deprivation and stress. The aim of this article is to evaluate and analyze features of headache in patients undergoing hemodialysis. © 2014 International Society for Hemodialysis.

NLRP3 A439V Mutation in a Large Family with Cryopyrin-associated Periodic Syndrome: Description of Ophthalmologic Symptoms in Correlation with Other Organ Symptoms.

PubMed

Sobolewska, Bianka; Angermair, Eva; Deuter, Christoph; Doycheva, Deshka; Kuemmerle-Deschner, Jasmin; Zierhut, Manfred

2016-06-01

Cryopyrin-associated periodic syndrome (CAPS) is a group of inherited autoinflammatory disorders caused by mutations in the NLRP3 gene resulting in the overproduction of interleukin 1β. NLRP3 mutations cause a broad clinical phenotype of CAPS. The aims of the study were to evaluate clinical, laboratory, and genetic features of a 5-generation family with CAPS focusing in detail on ocular symptoms. In a retrospective observational cohort study, consecutive family members were screened for the presence of the NLRP3 mutation. Patients underwent standardized clinical, laboratory, and ophthalmological assessments. The genotype-specific risk of ophthalmological findings and other organ symptoms was determined. Twenty-nine patients were clinically affected. The A439V mutation encoded by exon 3 of the NLRP3 gene was found in 15 of 37 family members (41%). The most common clinical features were musculoskeletal symptoms, headaches, and ophthalmological symptoms. The mutation-positive patients were characterized by more frequent skin rashes, ocular symptoms, arthralgia, arthritis, and severe Muckle-Wells syndrome (MWS) Disease Activity Score. Rosacea was diagnosed in 8 patients. The NLRP3 mutation A439V is associated with a heterogeneous clinical spectrum of familial cold autoinflammatory syndrome/MWS-overlap syndrome. Skin rash and eye diseases, such as conjunctivitis and uveitis, were positively correlated with this mutation.

A Novel Clinically Translatable Fluorescent Nanoparticle for Targeted Molecular Imaging of Tumors in Living Subjects

PubMed Central

Gao, Jinhao; Chen, Kai; Luong, Richard; Bouley, Donna M.; Mao, Hua; Qiao, Tiecheng; Gambhir, Sanjiv S.; Cheng, Zhen

2011-01-01

The use of quantum dots (QDs) in biomedical research has grown tremendously, yet successful examples of clinical applications are absent due to many clinical concerns. Here, we report on a new type of stable and biocompatible dendron-coated InP/ZnS core/shell QDs as a clinically translatable nanoprobe for molecular imaging applications. The QDs (QD710-Dendron) were demonstrated to hold several significant features: near-infrared (NIR) emission, high stability in biological media, suitable size with possible renal clearance and ability of extravasation. More importantly, a pilot mouse toxicity study confirmed that QD710-Dendron lacks significant toxicity at the doses tested. The acute tumor uptake of QD710-Dendron resulted in good contrast from the surrounding non-tumorous tissues, indicating the possibility of passive targeting of the QDs. The highly specific targeting of QD710-Dendron-RGD2 to integrin αvβ3–positive tumor cells resulted in high tumor uptake and long retention of the nanoprobe at tumor sites. In summary, QD710-Dendron and RGD modified nanoparticles demonstrate small size, high stability, biocompatibility, favorable in vivo pharmacokinetics, and successful tumor imaging properties. These features satisfy the requirements for clinical translation and should promote efforts to further investigate the possibility of using QD710-Dendron based nanoprobes in the clinical setting in the near future. PMID:22172022

A novel clinically translatable fluorescent nanoparticle for targeted molecular imaging of tumors in living subjects.

PubMed

Gao, Jinhao; Chen, Kai; Luong, Richard; Bouley, Donna M; Mao, Hua; Qiao, Tiecheng; Gambhir, Sanjiv S; Cheng, Zhen

2012-01-11

The use of quantum dots (QDs) in biomedical research has grown tremendously, yet successful examples of clinical applications are absent due to many clinical concerns. Here, we report on a new type of stable and biocompatible dendron-coated InP/ZnS core/shell QD as a clinically translatable nanoprobe for molecular imaging applications. The QDs (QD710-Dendron) were demonstrated to hold several significant features: near-infrared (NIR) emission, high stability in biological media, suitable size with possible renal clearance, and ability of extravasation. More importantly, a pilot mouse toxicity study confirmed that QD710-Dendron lacks significant toxicity at the doses tested. The acute tumor uptake of QD710-Dendron resulted in good contrast from the surrounding nontumorous tissues, indicating the possibility of passive targeting of the QDs. The highly specific targeting of QD710-Dendron-RGD(2) to integrin α(v)β(3)-positive tumor cells resulted in high tumor uptake and long retention of the nanoprobe at tumor sites. In summary, QD710-Dendron and RGD-modified nanoparticles demonstrate small size, high stability, biocompatibility, favorable in vivo pharmacokinetics, and successful tumor imaging properties. These features satisfy the requirements for clinical translation and should promote efforts to further investigate the possibility of using QD710-Dendron-based nanoprobes in the clinical setting in the near future. © 2011 American Chemical Society

Bladder cancer treatment response assessment with radiomic, clinical, and radiologist semantic features

NASA Astrophysics Data System (ADS)

Gordon, Marshall N.; Cha, Kenny H.; Hadjiiski, Lubomir M.; Chan, Heang-Ping; Cohan, Richard H.; Caoili, Elaine M.; Paramagul, Chintana; Alva, Ajjai; Weizer, Alon Z.

2018-02-01

We are developing a decision support system for assisting clinicians in assessment of response to neoadjuvant chemotherapy for bladder cancer. Accurate treatment response assessment is crucial for identifying responders and improving quality of life for non-responders. An objective machine learning decision support system may help reduce variability and inaccuracy in treatment response assessment. We developed a predictive model to assess the likelihood that a patient will respond based on image and clinical features. With IRB approval, we retrospectively collected a data set of pre- and post- treatment CT scans along with clinical information from surgical pathology from 98 patients. A linear discriminant analysis (LDA) classifier was used to predict the likelihood that a patient would respond to treatment based on radiomic features extracted from CT urography (CTU), a radiologist's semantic feature, and a clinical feature extracted from surgical and pathology reports. The classification accuracy was evaluated using the area under the ROC curve (AUC) with a leave-one-case-out cross validation. The classification accuracy was compared for the systems based on radiomic features, clinical feature, and radiologist's semantic feature. For the system based on only radiomic features the AUC was 0.75. With the addition of clinical information from examination under anesthesia (EUA) the AUC was improved to 0.78. Our study demonstrated the potential of designing a decision support system to assist in treatment response assessment. The combination of clinical features, radiologist semantic features and CTU radiomic features improved the performance of the classifier and the accuracy of treatment response assessment.

Antibodies to histones in systemic lupus erythematosus: prevalence, specificity, and relationship to clinical and laboratory features.

PubMed Central

Cohen, M G; Pollard, K M; Webb, J

1992-01-01

Antibodies to histones (AHA) are commonly found in patients with systemic lupus erythematosus (SLE). However, the full profile of AHA and their clinical associations remains unclear. A total of 111 patients with SLE were studied, including 13 patients in whom multiple serum samples were available over several years. IgM, IgG, and IgA antibodies to total core histones, histone complexes, and individual histones were determined by highly sensitive enzyme linked immunosorbent assays (ELISAs). Antibodies to histones were detected in 74% of serum samples, though only at low levels in half of these. Antibodies to each of the individual histones (H1, H2A, H2B, H3, H4) occurred with similar frequencies except for IgG and IgA antibodies to H4, which were uncommon. In contrast, antibodies to the histone complexes H2A-H2B and H3-H4 were detected in only two serum samples and thus do not appear to be a feature of SLE. All three major isotypes of AHA were common and usually occurred with similar frequencies to one another for the various histone specificities. There were few clinical or laboratory associations with AHA; the strongest was between IgG antibodies to total core histones and antibodies to native DNA. Similarly, there was no association between the presence of AHA and disease activity. However, for the patients as a group and in one patient alone, periods of SLE disease activity were associated with higher levels of AHA. Although the profile of antibodies to individual histones varied with time, no profile was identified that corresponded with any specific disease manifestations. It is concluded from this study that although AHA are common in patients with SLE, their clinical value in this syndrome must, at present, be considered limited. PMID:1540040

Redefining cerebral malaria by including malaria retinopathy.

PubMed

Beare, Nicholas A V; Lewallen, Susan; Taylor, Terrie E; Molyneux, Malcolm E

2011-03-01

Accurate diagnosis of cerebral malaria (CM) is important for patient management, epidemiological and end point surveillance, and enrolling patients with CM in studies of pathogenesis or therapeutic trials. In malaria-endemic areas, where asymptomatic Plasmodium falciparum parasitemia is common, a positive blood film in a comatose individual does not prove that the coma is due to malaria. A retinopathy consisting of two unique features - patchy retinal whitening and focal changes of vessel color - is highly specific for encephalopathy of malarial etiology. White-centered retinal hemorrhages are a common but less specific feature. Either indirect or direct ophthalmoscopy can be used to identify the changes, and both procedures can be learned and practiced by nonspecialist clinicians. In view of its important contributions to both clinical care and research, examination of the retina should become a routine component of the assessment of a comatose child or adult when CM is a possible diagnosis.

Redefining cerebral malaria by including malaria retinopathy

PubMed Central

Beare, Nicholas AV; Lewallen, Susan; Taylor, Terrie E; Molyneux, Malcolm E

2011-01-01

Accurate diagnosis of cerebral malaria (CM) is important for patient management, epidemiological and end point surveillance, and enrolling patients with CM in studies of pathogenesis or therapeutic trials. In malaria-endemic areas, where asymptomatic Plasmodium falciparum parasitemia is common, a positive blood film in a comatose individual does not prove that the coma is due to malaria. A retinopathy consisting of two unique features – patchy retinal whitening and focal changes of vessel color – is highly specific for encephalopathy of malarial etiology. White-centered retinal hemorrhages are a common but less specific feature. Either indirect or direct ophthalmoscopy can be used to identify the changes, and both procedures can be learned and practiced by nonspecialist clinicians. In view of its important contributions to both clinical care and research, examination of the retina should become a routine component of the assessment of a comatose child or adult when CM is a possible diagnosis. PMID:21449844

Leuloplakia - Review of A Potentially Malignant Disorder

PubMed Central

Abidullah, Mohammed; Gaddikeri, Kavitha; Raghoji, Swetha; Ravishankar T, Shilpa

2014-01-01

Leukoplakias are oral white lesions that have not been diagnosed as any other specific disease. They are grouped under premalignant lesions, now redesignated as potentially malignant disorders. Their significance lies in the fact that they have propensity for malignant transformation at a higher rate when compared to other oral lesions. This article reviews aetiology, epidemiology, clinical characteristics, histopathologic features, malignant potential and treatment of oral leukoplakia. PMID:25302287

Identification of symptom and functional domains that fibromyalgia patients would like to see improved: a cluster analysis.

PubMed

Bennett, Robert M; Russell, Jon; Cappelleri, Joseph C; Bushmakin, Andrew G; Zlateva, Gergana; Sadosky, Alesia

2010-06-28

The purpose of this study was to determine whether some of the clinical features of fibromyalgia (FM) that patients would like to see improved aggregate into definable clusters. Seven hundred and eighty-eight patients with clinically confirmed FM and baseline pain > or =40 mm on a 100 mm visual analogue scale ranked 5 FM clinical features that the subjects would most like to see improved after treatment (one for each priority quintile) from a list of 20 developed during focus groups. For each subject, clinical features were transformed into vectors with rankings assigned values 1-5 (lowest to highest ranking). Logistic analysis was used to create a distance matrix and hierarchical cluster analysis was applied to identify cluster structure. The frequency of cluster selection was determined, and cluster importance was ranked using cluster scores derived from rankings of the clinical features. Multidimensional scaling was used to visualize and conceptualize cluster relationships. Six clinical features clusters were identified and named based on their key characteristics. In order of selection frequency, the clusters were Pain (90%; 4 clinical features), Fatigue (89%; 4 clinical features), Domestic (42%; 4 clinical features), Impairment (29%; 3 functions), Affective (21%; 3 clinical features), and Social (9%; 2 functional). The "Pain Cluster" was ranked of greatest importance by 54% of subjects, followed by Fatigue, which was given the highest ranking by 28% of subjects. Multidimensional scaling mapped these clusters to two dimensions: Status (bounded by Physical and Emotional domains), and Setting (bounded by Individual and Group interactions). Common clinical features of FM could be grouped into 6 clusters (Pain, Fatigue, Domestic, Impairment, Affective, and Social) based on patient perception of relevance to treatment. Furthermore, these 6 clusters could be charted in the 2 dimensions of Status and Setting, thus providing a unique perspective for interpretation of FM symptomatology.

Patient registries: useful tools for clinical research in myasthenia gravis.

PubMed

Baggi, Fulvio; Mantegazza, Renato; Antozzi, Carlo; Sanders, Donald

2012-12-01

Clinical registries may facilitate research on myasthenia gravis (MG) in several ways: as a source of demographic, clinical, biological, and immunological data on large numbers of patients with this rare disease; as a source of referrals for clinical trials; and by allowing rapid identification of MG patients with specific features. Physician-derived registries have the added advantage of incorporating diagnostic and treatment data that may allow comparison of outcomes from different therapeutic approaches, which can be supplemented with patient self-reported data. We report the demographic analysis of MG patients in two large physician-derived registries, the Duke MG Patient Registry, at the Duke University Medical Center, and the INNCB MG Registry, at the Istituto Neurologico Carlo Besta, as a preliminary study to assess the consistency of the two data sets. These registries share a common structure, with an inner core of common data elements (CDE) that facilitate data analysis. The CDEs are concordant with the MG-specific CDEs developed under the National Institute of Neurological Disorders and Stroke Common Data Elements Project. © 2012 New York Academy of Sciences.

Management of inflammatory bowel disease in older persons: evolving paradigms

PubMed Central

Kedia, Saurabh; Limdi, Jimmy K.

2018-01-01

The incidence and prevalence of inflammatory bowel disease (IBD) is increasing, and considering the aging population, this number is set to increase further in the future. The clinical features and natural history of elderly-onset IBD have many similarities with those of IBD in younger patients, but with significant differences including a broader differential diagnosis. The relative lack of data specific to elderly patients with IBD, often stemming from their typical exclusion from clinical trials, has made clinical decision-making somewhat challenging. Treatment decisions in elderly patients with IBD must take into account age-specific concerns such as comorbidities, locomotor and cognitive function, and polypharmacy, to set realistic treatment targets in order to enable personalized treatment and minimize harm. Notwithstanding paucity of clinical data, recent studies have provided valuable insights, which, taken together with information gleaned from previous studies, can broaden our understanding of IBD. These insights may contribute to the development of paradigms for the holistic and, when possible, evidence-based management of this potentially vulnerable population and are the focus of this review. PMID:29743832

IDH mutation assessment of glioma using texture features of multimodal MR images

NASA Astrophysics Data System (ADS)

Zhang, Xi; Tian, Qiang; Wu, Yu-Xia; Xu, Xiao-Pan; Li, Bao-Juan; Liu, Yi-Xiong; Liu, Yang; Lu, Hong-Bing

2017-03-01

Purpose: To 1) find effective texture features from multimodal MRI that can distinguish IDH mutant and wild status, and 2) propose a radiomic strategy for preoperatively detecting IDH mutation patients with glioma. Materials and Methods: 152 patients with glioma were retrospectively included from the Cancer Genome Atlas. Corresponding T1-weighted image before- and post-contrast, T2-weighted image and fluid-attenuation inversion recovery image from the Cancer Imaging Archive were analyzed. Specific statistical tests were applied to analyze the different kind of baseline information of LrGG patients. Finally, 168 texture features were derived from multimodal MRI per patient. Then the support vector machine-based recursive feature elimination (SVM-RFE) and classification strategy was adopted to find the optimal feature subset and build the identification models for detecting the IDH mutation. Results: Among 152 patients, 92 and 60 were confirmed to be IDH-wild and mutant, respectively. Statistical analysis showed that the patients without IDH mutation was significant older than patients with IDH mutation (p<0.01), and the distribution of some histological subtypes was significant different between IDH wild and mutant groups (p<0.01). After SVM-RFE, 15 optimal features were determined for IDH mutation detection. The accuracy, sensitivity, specificity, and AUC after SVM-RFE and parameter optimization were 82.2%, 85.0%, 78.3%, and 0.841, respectively. Conclusion: This study presented a radiomic strategy for noninvasively discriminating IDH mutation of patients with glioma. It effectively incorporated kinds of texture features from multimodal MRI, and SVM-based classification strategy. Results suggested that features selected from SVM-RFE were more potential to identifying IDH mutation. The proposed radiomics strategy could facilitate the clinical decision making in patients with glioma.

A proposal of criteria for the classification of systemic sclerosis.

PubMed

Nadashkevich, Oleg; Davis, Paul; Fritzler, Marvin J

2004-11-01

Sensitive and specific criteria for the classification of systemic sclerosis are required by clinicians and investigators to achieve higher quality clinical studies and approaches to therapy. A clinical study of systemic sclerosis patients in Europe and Canada led to a set of criteria that achieve high sensitivity and specificity. Both clinical and laboratory investigations of patients with systemic sclerosis, related conditions and diseases with clinical features that can be mistaken as part of the systemic sclerosis spectrum were undertaken. Laboratory investigations included the detection of autoantibodies to centromere proteins, Scl-70 (topoisomerase I), and fibrillarin (U3-RNP). Based on the investigation of 269 systemic sclerosis patients and 720 patients presenting with related and confounding conditions, the following set of criteria for the classification of systemic sclerosis was proposed: 1) autoantibodies to: centromere proteins, Scl-70 (topo I), fibrillarin; 2) bibasilar pulmonary fibrosis; 3) contractures of the digital joints or prayer sign; 4) dermal thickening proximal to the wrists; 5) calcinosis cutis; 6) Raynaud's phenomenon; 7) esophageal distal hypomotility or reflux-esophagitis; 8) sclerodactyly or non-pitting digital edema; 9) teleangiectasias. The classification of definite SSc requires at least three of the above criteria. Criteria for the classification of systemic sclerosis have been proposed. Preliminary testing has defined the sensitivity and specificity of these criteria as high as 99% and 100%, respectively. Testing and validation of the proposed criteria by other clinical centers is required.

Patterns of presentation and clinical features of toxicity after reported use of ([2-aminopropyl]-2,3-dihydrobenzofurans), the 'benzofuran' compounds. A report from the United Kingdom National Poisons Information Service.

PubMed

Kamour, Ashraf; James, David; Lupton, David J; Cooper, Gillian; Eddleston, Micheal; Vale, Allister; Thompson, John P; Thanacoody, Ruben; Hill, Simon L; Thomas, Simon H L

2014-12-01

To characterise the patterns of presentation and clinical features of toxicity following reported recreational use of benzofuran compounds ((2-aminopropyl)-2,3-dihydrobenzofurans) in the UK, as reported to the National Poisons Information Service (NPIS), and to compare clinical features of toxicity with those after reported mephedrone use. NPIS patient-specific telephone enquiries and user sessions for TOXBASE(®), the NPIS online information database, related to (2-aminopropyl)-2,3-dihydrobenzofurans and associated synonyms were reviewed from March 2009 to August 2013. These data were compared with those of mephedrone, the recreational substance most frequently reported to NPIS, collected over the same period. There were 63 telephone enquiries concerning 66 patients and 806 TOXBASE(®) user sessions regarding benzofuran compounds during the period of study. The first telephone enquiry was made in July 2010 and the highest numbers of enquiries were received in August 2010 (33 calls, 112 TOXBASE(®) sessions). Patients were predominantly male (82%) with a median age of 29 years; 9 reported co-ingestion of other substances. Comparing the 57 patients who reported ingesting benzofuran compounds alone with 315 patients ingesting mephedrone alone, benzofurans were more often associated with stimulant features, including tachycardia, hypertension, mydriasis, palpitation, fever, increased sweating, and tremor, (72% vs. 38%, odds ratio [OR] 4.2, 95% confidence interval [CI] 2.27-7.85, P < 0.0001) and mental health disturbances (58% vs. 38%, OR 2.3, 95% CI 1.29-4.07, P = 0.006). Other features reported after benzofuran compound ingestion included gastrointestinal symptoms (16%), reduced level of consciousness (9%), chest pain (7%), and creatinine kinase elevation (5%). Reported ingestion of benzofuran compounds is associated with similar toxic effects to those of amphetamines and cathinones. Mental health disturbances and stimulant features were reported more frequently following reported ingestion of benzofuran compounds than after ingestion of mephedrone.

Twists and turns in the body: an imaging spectrum.

PubMed

Luk, Shiobhon Y; Fung, K H

2010-10-01

Life is full of twists and turns. These surprises can sometimes be wonderfully invigorating. Twists and turns can also occur in the body, however, sometimes with dangerous consequences. Torsion and volvulus are important causes of acute abdominal pain. The clinical symptoms and signs associated with torsion and volvulus are often non-specific and are difficult to diagnose clinically. Clinicians frequently rely on imaging methods to make the diagnosis. Prompt and accurate diagnosis is important to avoid the life-threatening complications of torsion and volvulus. Therefore, it is helpful to be familiar with the features of torsion and volvulus.

Ion beams in radiotherapy - from tracks to treatment planning

NASA Astrophysics Data System (ADS)

Krämer, M.; Scifoni, E.; Wälzlein, C.; Durante, M.

2012-07-01

Several dozen clinical sites around the world apply beams of fast light ions for radiotherapeutical purposes. Thus there is a vested interest in the various physical and radiobiological processes governing the interaction of ion beams with matter, specifically living systems. We discuss the various modelling steps which lead from basic interactions to the application in actual patient treatment planning. The nano- and microscopic scale is covered by sample calculations with our TRAX code. On the macroscopic scale we feature the TRiP98 treatment planning system, which was clinically used in GSI's radiotherapy pilot project.

Patterns of clinical nail appearances in patients with cutaneous psoriasis

PubMed Central

MARINA, ELENA MIHAELA; BOTAR-JID, CAROLINA; BOLBOACA, SORANA DANIELA; ROMAN, IULIA IOANA; SENILA, CORINA SIMONA; MIHU, CARMEN MIHAELA; TATARU, DUMITRU ALEXANDRU

2017-01-01

Background and aim Nail manifestations are often an overlooked aspect in psoriatic disease, cutaneous and joint involvement being far more often reported and investigated. The reported prevalence of nail changes varies in literature, specific fingernail clinical features having different degrees of occurrence. The aim of this study was to describe specific clinical patterns of fingernail alterations in adult patients with plaque-type psoriasis in a university hospital in the North-West of Romania. Methods Clinical data of 35 patients with fingernail psoriasis were collected and analyzed. Psoriasis Area and Severity Index (PASI) and Nail Psoriasis Severity Index (NAPSI) scores were used to quantify disease extension in each patient. Results PASI score proved linearly correlated with NAPSI score (p<0.05). The age of onset of fingernail psoriasis was positively correlated with age of onset cutaneous psoriasis (p<0.0001). Furthermore, the duration of cutaneous involvement and NAPSI proved significantly related (p<0.05). The third fingernail in the right hand and first fingernail in the left hand were in most of the cases severely affected. The most common observed nail pattern was pitting, followed by salmon patches and subungual hyperkeratosis. Conclusion Important nail changes appear even in moderate forms of cutaneous psoriasis. Particular localization of specific fingernail psoriasis pattern enables the possibility of detecting early stage disease. PMID:28246493

3D-CAM: Derivation and Validation of a 3-Minute Diagnostic Interview for CAM-defined Delirium

PubMed Central

Marcantonio, Edward R.; Ngo, Long H.; O’Connor, Margaret; Jones, Richard N.; Crane, Paul K.; Metzger, Eran D.; Inouye, Sharon K.

2015-01-01

Background Delirium is common, morbid, and costly, yet remains often unrecognized in most clinical settings. The Confusion Assessment Method (CAM) is the most widely used diagnostic algorithm, and operationalizing its features would represent a substantial advance for clinical care. Objective To derive the 3D-CAM, a new 3-minute diagnostic assessment for CAM-defined delirium, and to validate it against a clinical reference standard. Design Diagnostic test study Setting 4 general medicine units in an academic medical center Participants 201 inpatients aged ≥ 75 years old Measurements We identified 20 items that best operationalized the 4 CAM diagnostic features to create the 3D-CAM. For prospective validation, 3D-CAM assessments were administered by trained research assistants. Independently, clinicians performed an extensive assessment that included patient interviews, family interviews, and review of the medical record. These data were considered by an expert panel to determine the presence or absence of delirium and dementia (reference standard). We compared the 3D-CAM delirium determination to the reference standard in all patients and in subgroups with and without dementia. Results The 201 participants in the prospective validation study had mean age (SD) of 84 (5.5) years, and 27% had dementia. The expert panel identified delirium in 21%. Median administration time for 3D-CAM was 3 minutes (inter-quartile range: 2–5 minutes). The sensitivity [95% CI] of 3D-CAM was 95% [84%, 99%] and the specificity was 94% [90%, 97%]. The 3D-CAM performed well in patients both with dementia (sensitivity=96% [82%, 100%], specificity=86% [67%, 96%]) and without dementia (sensitivity=93% [66%, 100%], specificity=96% [91%,99%]). Limitations Limited to single center, cross-sectional, and medicine patients only Conclusion The 3D-CAM operationalizes the CAM algorithm using a 3-minute structured assessment with high sensitivity and specificity relative to a reference standard and could be an important tool for improving recognition of delirium. PMID:25329203

Clinical and laboratory features of urinary tract infections in young infants.

PubMed

Lo, Denise Swei; Rodrigues, Larissa; Koch, Vera Hermina Kalika; Gilio, Alfredo Elias

2018-04-26

Urinary tract infection (UTI) is the most common serious bacterial infection in young infants. Signs and symptoms are often nonspecific. To describe clinical, demographic and laboratory features of UTI in infants ≤ 3 months old. Cross-sectional study of infants ≤ 3 months old with UTI diagnosed in a pediatric emergency department, for the period 2010-2012. UTI was defined as ≥ 50,000 colony-forming units per milliliter of a single uropathogen isolated from bladder catheterization. Paired urinalysis and urine culture from group culture-positive and group culture-negative were used to determine the sensitivity and specificity of pyuria and nitrite tests in detecting UTI. Of 519 urine cultures collected, UTI was diagnosed in 65 cases (prevalence: 12.5%); with male predominance (77%). The most common etiologies were Escherichia coli (56.9%), Klebsiella pneumoniae (18.5%) and Enterococcus faecalis (7.7%). Frequent clinical manifestations were fever (77.8%), irritability (41.4%) and vomiting (25.4%). The median temperature was 38.7°C. The sensitivity of the nitrite test was 30.8% (95%CI:19.9-43.4%), specificity of 100% (95%CI:99.2-100%). Pyuria ≥ 10,000/mL had a sensitivity of 87.7% (95%CI:77.2-94.5%), specificity of 74.9% (95%CI:70.6 -78.8%). The median peripheral white blood cell count was 13,150/mm3; C-reactive protein levels were normal in 30.5% of cases. The male: female ratio for urinary tract infection was 3.3:1. Non-Escherichia coli etiologies should be considered in empirical treatment. Fever was the main symptom. Positive nitrite is highly suggestive of UTI but has low sensitivity; whereas pyuria ≥ 10,000/mL revealed good sensitivity, but low specificity. Peripheral white blood cell count and C-reactive protein concentration have limited usefulness to suggest UTI.

Clinical and laboratory features of urinary tract infections in young infants.

PubMed

Lo, Denise Swei; Rodrigues, Larissa; Koch, Vera Hermina Kalika; Gilio, Alfredo Elias

2018-01-01

Urinary tract infection (UTI) is the most common serious bacterial infection in young infants. Signs and symptoms are often nonspecific. To describe clinical, demographic and laboratory features of UTI in infants ≤ 3 months old. Cross-sectional study of infants ≤ 3 months old with UTI diagnosed in a pediatric emergency department, for the period 2010-2012. UTI was defined as ≥ 50,000 colony-forming units per milliliter of a single uropathogen isolated from bladder catheterization. Paired urinalysis and urine culture from group culture-positive and group culture-negative were used to determine the sensitivity and specificity of pyuria and nitrite tests in detecting UTI. Of 519 urine cultures collected, UTI was diagnosed in 65 cases (prevalence: 12.5%); with male predominance (77%). The most common etiologies were Escherichia coli (56.9%), Klebsiella pneumoniae (18.5%) and Enterococcus faecalis (7.7%). Frequent clinical manifestations were fever (77.8%), irritability (41.4%) and vomiting (25.4%). The median temperature was 38.7°C. The sensitivity of the nitrite test was 30.8% (95%CI:19.9-43.4%), specificity of 100% (95%CI:99.2-100%). Pyuria ≥ 10,000/mL had a sensitivity of 87.7% (95%CI:77.2-94.5%), specificity of 74.9% (95%CI:70.6 -78.8%). The median peripheral white blood cell count was 13,150/mm3; C-reactive protein levels were normal in 30.5% of cases. The male: female ratio for urinary tract infection was 3.3:1. Non-Escherichia coli etiologies should be considered in empirical treatment. Fever was the main symptom. Positive nitrite is highly suggestive of UTI but has low sensitivity; whereas pyuria ≥ 10,000/mL revealed good sensitivity, but low specificity. Peripheral white blood cell count and C-reactive protein concentration have limited usefulness to suggest UTI.

Infective endocarditis in drug addicts: role of HIV infection and the diagnostic accuracy of Duke criteria.

PubMed

Cecchi, Enrico; Imazio, Massimo; Tidu, Massimo; Forno, Davide; De Rosa, Francesco Giuseppe; Dal Conte, Ivano; Preziosi, Costantina; Lipani, Filippo; Trinchero, Rita

2007-03-01

Intravenous drug users (IVDUs) are at increased risk of infective endocarditis. Moreover, HIV infection is common in IVDUs, with a reported prevalence of 40-90%. The clinical features of IVDUs with infective endocarditis and HIV infection may be peculiar. Few data have been reported on the diagnostic accuracy of Duke criteria in IVDUs with or without HIV infection, and a comparison of these two populations is lacking. The present study aimed to compare prospectively the clinical features of patients with infective endocarditis with or without HIV infection and to evaluate the diagnostic accuracy of Duke criteria in these patients. The study population consisted of 201 consecutive adult IVDUs with a suspected infective endocarditis (102 patients with HIV infection and 99 patients without HIV infection). Infective endocarditis was the final diagnosis in 40 of 102 patients (38.2%) with HIV infection and in 55 of 99 HIV-negative patients (55.6%). Despite similar baseline features, longer vegetations were recorded in infective endocarditis without HIV infection (23.7 +/- 7.1 mm versus 13.6 +/- 6.8 mm; P = 0.001). Patients with infective endocarditis and HIV infection had a higher total mortality at 2 months (respectively 12.5% versus 1.8%; P = 0.09); almost all the deaths were recorded in patients with AIDS or a CD4 cell count below 200 per microl, and no deaths were recorded in patients with HIV infection and a CD4 cell count > 500 per microl. Despite no identical clinical features, Duke criteria had a similar sensitivity, specificity and diagnostic accuracy in IVDUs with and without HIV infection.

Contingent negative variation in patients with deficit schizophrenia or bipolar I disorder with psychotic features: measurement and correlation with clinical characteristics.

PubMed

Li, Zhe; Deng, Wei; Liu, Xiang; Zheng, Zhong; Li, Mingli; Li, Yinfei; Han, Yuanyuan; Ma, Xiaohong; Wang, Qiang; Liu, Xiehe; Li, Tao

2015-04-01

Schizophrenia is a highly heterogeneous disease. Event-related potentials have been regarded to establish intermediate phenotypes of schizophrenia. Our previous study found that patients with deficit schizophrenia (DS) are relatively homogeneous and show a significantly longer onset latency of contingent negative variation (CNV) expectancy wave. To further examine CNV in patients with first-episode and drug-naïve DS or bipolar I disorder (BP I) with psychotic features, and also investigate correlations between CNV and clinical characteristics in DS and BP I. We elicited a CNV using an alarm (S1)-imperative (S2) paradigm in 30 DS patients or 33 BP I with psychotic features as well as 40 healthy controls. CNV amplitude was significantly smaller and reaction time significantly longer in the DS and BP I groups than in healthy controls. Post-imperative negative variation (PINV) interval was significantly shorter in the DS group than in healthy controls. The onset latency of CNV expectancy wave was significantly longer and PINV area significantly smaller in the DS group than in the other groups. In the DS group, CNV amplitude and PINV interval correlated negatively with the subscale of negative symptoms on the Positive and Negative Syndrome Scale (PANSS); CNV amplitude also correlated negatively with disease duration. In the BP I group, CNV amplitude and reaction time showed no correlation with clinical features. CNV amplitude is a common trait marker for psychosis. The onset latency of CNV expectancy wave appears to be a specific trait marker and may be used to identify candidate genes for DS.

Haemochromatosis: unexplained metacarpophalangeal or ankle arthropathy should prompt diagnostic tests: findings from two UK observational cohort studies.

PubMed

Richardson, A; Prideaux, A; Kiely, P

2017-01-01

To examine demographic and clinical features leading to the diagnosis of hereditary haemochromatosis and assess factors that might enhance earlier diagnosis, with particular attention to arthritic symptoms. Diagnostic features were captured directly from patients with haemochromatosis attending a specialist rheumatology clinic (group 1) and from analysis of a specifically designed questionnaire circulated to members of the UK Haemochromatosis Society (group 2). In groups 1 (n = 62) and 2 (n = 470), respectively, the diagnosis of haemochromatosis was made at a mean age of 52.8 and 56.4 years with 77% and 76% reporting joint symptoms with a mean duration of 8.3 and 8.1 years. The first joints to be affected in group 1 were the metacarpophalangeal (MCP; 38.5%) and ankle (29.5%) followed by the knee, hip, and proximal interphalangeal (PIP) joints. At the time of clinical assessment or questionnaire completion, the most prevalent regions with arthropathy in group 1 were PIP (64.5%), knee (64%), ankle (61%), and MCP (60%) and in group 2 the most prevalent joint regions self-reported were the first carpometacarpal (CMC; 59%), wrist (52%), PIP (47%), MCP (46%), knee (42%), and ankle (35%). Data from both cohorts confirm the high prevalence of joint symptoms in haemochromatosis predating the diagnosis by many years. Discriminatory features of the arthropathy include the involvement of MCP joints and ankles at a relatively young age in the absence of trauma, all of which are unusual features of primary osteoarthritis (OA). The finding of this presentation should prompt diagnostic tests for haemochromatosis.

The contribution of the vaccine adverse event text mining system to the classification of possible Guillain-Barré syndrome reports.

PubMed

Botsis, T; Woo, E J; Ball, R

2013-01-01

We previously demonstrated that a general purpose text mining system, the Vaccine adverse event Text Mining (VaeTM) system, could be used to automatically classify reports of an-aphylaxis for post-marketing safety surveillance of vaccines. To evaluate the ability of VaeTM to classify reports to the Vaccine Adverse Event Reporting System (VAERS) of possible Guillain-Barré Syndrome (GBS). We used VaeTM to extract the key diagnostic features from the text of reports in VAERS. Then, we applied the Brighton Collaboration (BC) case definition for GBS, and an information retrieval strategy (i.e. the vector space model) to quantify the specific information that is included in the key features extracted by VaeTM and compared it with the encoded information that is already stored in VAERS as Medical Dictionary for Regulatory Activities (MedDRA) Preferred Terms (PTs). We also evaluated the contribution of the primary (diagnosis and cause of death) and secondary (second level diagnosis and symptoms) diagnostic VaeTM-based features to the total VaeTM-based information. MedDRA captured more information and better supported the classification of reports for GBS than VaeTM (AUC: 0.904 vs. 0.777); the lower performance of VaeTM is likely due to the lack of extraction by VaeTM of specific laboratory results that are included in the BC criteria for GBS. On the other hand, the VaeTM-based classification exhibited greater specificity than the MedDRA-based approach (94.96% vs. 87.65%). Most of the VaeTM-based information was contained in the secondary diagnostic features. For GBS, clinical signs and symptoms alone are not sufficient to match MedDRA coding for purposes of case classification, but are preferred if specificity is the priority.

Clinical Characteristics, Treatments, and Prognosis of Atopic Eczema in the Elderly.

PubMed

Tanei, Ryoji

2015-05-18

Atopic eczema (AE) in the elderly is gradually increasing and has been added to the classification of AE in recent years. This investigation retrospectively analyzed 60 patients with elderly AE. Among the clinical characteristics, a male predominance, existence of several patterns of onset and clinical course, and associations with immunoglobulin (Ig)E-allergic-status and asthmatic complication were observed. The highest positive-rate and positive-score for serum-specific IgE against Dermatophagoides farinae were 83.8% and 2.65 in patients with IgE-allergic AE, and a lower incidence of lichenified eczema in the elbow and knee folds were observed. In terms of treatments and outcomes, clinical improvement and clinical remission were observed in 80.8% and 36.5% of cases, respectively, using standard treatments and combined therapy with oral corticosteroid in severe cases. As for complications and final prognosis, most elderly AE patients reached the end of life with AE, but patients with IgE-allergic AE showed significantly lower incidences of complications of malignancy and death from malignancy. These results indicate that AE in the elderly represents a new subgroup of AE with specific features.

Clinical Characteristics, Treatments, and Prognosis of Atopic Eczema in the Elderly

PubMed Central

Tanei, Ryoji

2015-01-01

Atopic eczema (AE) in the elderly is gradually increasing and has been added to the classification of AE in recent years. This investigation retrospectively analyzed 60 patients with elderly AE. Among the clinical characteristics, a male predominance, existence of several patterns of onset and clinical course, and associations with immunoglobulin (Ig)E-allergic-status and asthmatic complication were observed. The highest positive-rate and positive-score for serum-specific IgE against Dermatophagoides farinae were 83.8% and 2.65 in patients with IgE-allergic AE, and a lower incidence of lichenified eczema in the elbow and knee folds were observed. In terms of treatments and outcomes, clinical improvement and clinical remission were observed in 80.8% and 36.5% of cases, respectively, using standard treatments and combined therapy with oral corticosteroid in severe cases. As for complications and final prognosis, most elderly AE patients reached the end of life with AE, but patients with IgE-allergic AE showed significantly lower incidences of complications of malignancy and death from malignancy. These results indicate that AE in the elderly represents a new subgroup of AE with specific features. PMID:26239460

A diagnostic model for chronic hypersensitivity pneumonitis

PubMed Central

Johannson, Kerri A; Elicker, Brett M; Vittinghoff, Eric; Assayag, Deborah; de Boer, Kaïssa; Golden, Jeffrey A; Jones, Kirk D; King, Talmadge E; Koth, Laura L; Lee, Joyce S; Ley, Brett; Wolters, Paul J; Collard, Harold R

2017-01-01

The objective of this study was to develop a diagnostic model that allows for a highly specific diagnosis of chronic hypersensitivity pneumonitis using clinical and radiological variables alone. Chronic hypersensitivity pneumonitis and other interstitial lung disease cases were retrospectively identified from a longitudinal database. High-resolution CT scans were blindly scored for radiographic features (eg, ground-glass opacity, mosaic perfusion) as well as the radiologist’s diagnostic impression. Candidate models were developed then evaluated using clinical and radiographic variables and assessed by the cross-validated C-statistic. Forty-four chronic hypersensitivity pneumonitis and eighty other interstitial lung disease cases were identified. Two models were selected based on their statistical performance, clinical applicability and face validity. Key model variables included age, down feather and/or bird exposure, radiographic presence of ground-glass opacity and mosaic perfusion and moderate or high confidence in the radiographic impression of chronic hypersensitivity pneumonitis. Models were internally validated with good performance, and cut-off values were established that resulted in high specificity for a diagnosis of chronic hypersensitivity pneumonitis. PMID:27245779

[Malpractice in Urology: lessons of clinical and legal safety.

PubMed

Vargas-Blasco, César; Gómez-Durán, Esperanza L; Martin-Fumadó, Carles; Arimany-Manso, Josep

2018-06-01

Data about urology malpractice claims in our environment are scarce and should be considered a potential opportunity to "learn from errors". We analyzed every claim for alleged malpractice in Urology managed by the Council of Medical Colleges of Catalonia between 1990 and 2012, and specifically evaluated the clinical and medicolegal features of those cases with medical professional responsibility. We identified 182 cases in 22 years, but only the 25,74%showed professional liability. Testicular torsion misdiagnosis, pregnancies after vasectomy and complications of lithiasis should be noted for their frequency of claims and rate of liability. 246 physicians were involved, 89% were males and mean age was 45.6 years. Most cases (n=137, 75.27%) were processed in the courts. Urology has a medium risk of claims, with a moderate rate of medical professional liability and amount of compensation. There are specific actions that would lead to clinical safety improvements, particularly in testicular pathologies, vasectomy and lithiasis. Finally, more attention should be paid to proper patient information.

Development and evaluation of an electronic health record configuration and customization laboratory course for clinical informatics students.

PubMed

Mohan, Vishnu; Hersh, William R

2013-01-01

There is a need for informatics educational programs to develop laboratory courses that facilitate hands-on access to an EHR, and allow students to learn and evaluate functionality and configuration options. This is particularly relevant given the diversity of backgrounds of informatics students. We implemented an EHR laboratory course that allowed students to explore an EHR in both inpatient and outpatient clinical environments. The course focused on specific elements of the EHR including order set development, customization, clinical decision support, ancillary services, and billing and coding functionality. Students were surveyed at the end of the course for their satisfaction with the learning experience. We detailed challenges as well as lessons learned after analyzing student evaluations of this course. Features that promote the successful offering of an online EHR course, include (1) using more than one EHR to allow students to compare functionalities, (2) ensuring appropriate course calibration, (3) countering issues specific to EHR usability, and (4) fostering a fertile environment for rich online conversations are discussed.

Appreciating the broad clinical features of SMAD4 mutation carriers: a multi-center chart review

PubMed Central

Wain, K.E.; Ellingson, M.S.; McDonald, J.; Gammon, A.; Roberts, M.; Pichurin, P.; Winship, I.; Riegert-Johnson, D.; Weitzel, J. N.; Lindor, N.M.

2014-01-01

Heterozygous loss-of-function (LOF) SMAD4 mutations are associated with juvenile polyposis syndrome (JP) and hereditary hemorrhagic telangiectasia (HHT). Some carriers exhibit symptoms of both conditions, leading to the name JP-HHT syndrome. Three families have been reported with connective tissue abnormalities. In order to better understand the spectrum and extent of clinical findings in SMAD4 carriers, medical records of 34 patients (20 families) from five clinical practices were reviewed. Twenty-one percent (7/34) had features suggesting a connective tissue defect: enlarged aortic root (n=3), aortic and mitral insufficiency (n=2), aortic dissection (n=1), retinal detachment (n=1), brain aneurysms (n=1), lax skin and joints (n=1). JP-specific findings were almost uniformly present but variable. Ninety-seven percent had colon polyps that were generally pan-colonic and of variable histology and number. Forty-eight percent (15/31) had extensive gastric polyposis. HHT features were documented in 76% including epistaxis (19/31, 61%), mucocutaneous telangiectases (15/31, 48%), liver arteriovenous malformation (AVM) (6/16, 38%), brain AVM (1/26, 4%), pulmonary AVM (9/17, 53%), and intrapulmonary shunting (14/23, 61%). SMAD4 carriers should be managed for JP and HHT, since symptoms of both are likely yet unpredictable. Connective tissue abnormalities are an emerging component of JP-HHT syndrome, and larger studies are needed to understand these manifestations. PMID:24525918

Clustering Suicide Attempters: Impulsive-Ambivalent, Well-Planned, or Frequent.

PubMed

Lopez-Castroman, Jorge; Nogue, Erika; Guillaume, Sebastien; Picot, Marie Christine; Courtet, Philippe

2016-06-01

Attempts to predict suicidal behavior within high-risk populations have so far shown insufficient accuracy. Although several psychosocial and clinical features have been consistently associated with suicide attempts, investigations of latent structure in well-characterized populations of suicide attempters are lacking. We analyzed a sample of 1,009 hospitalized suicide attempters that were recruited between 1999 and 2012. Eleven clinically relevant items related to the characteristics of suicidal behavior were submitted to a Hierarchical Ascendant Classification. Phenotypic profiles were compared between the resulting clusters. A decisional tree was constructed to facilitate the differentiation of individuals classified within the first 2 clusters. Most individuals were included in a cluster characterized by less lethal means and planning ("impulse-ambivalent"). A second cluster featured more carefully planned attempts ("well-planned"), more alcohol or drug use before the attempt, and more precautions to avoid interruptions. Finally, a small, third cluster included individuals reporting more attempts ("frequent"), more often serious or violent attempts, and an earlier age at first attempt. Differences across clusters by demographic and clinical characteristics were also found, particularly with the third cluster whose participants had experienced high levels of childhood abuse. Cluster analysis consistently supported 3 distinct clusters of individuals with specific features in their suicidal behaviors and phenotypic profiles that could help clinicians to better focus prevention strategies. © Copyright 2016 Physicians Postgraduate Press, Inc.

[Autoimmune hepatitis in a girl with presence of anti-LKM1 antibodies].

PubMed

Larraín, F; Miquel, J F; González, S

1997-06-01

Autoimmune hepatitis is an inflammatory liver disease characterized by dense mononuclear cell infiltrate in the portal tract, and serologically by the presence of non-organ and liver-specific autoantibodies and increased levels of gammaglobulins in the absence of a known etiology. Three subgroups of autoimmune hepatitis have been recognized, depending on the nature of the autoantibody present in the serum: Type 1 autoimmune hepatitis, associated with smooth-muscle (SMA) or antinuclear antibody (ANA) seropositivity; type 2, with anti-liver/kidney microsome antibody (anti-LKM1), and type 3, with the absence of ANA, SMA and anti-LKM1 and presence of other autoantibodies such as anti-soluble liver antigen (SLA). Subtypes of chronic autoimmune hepatitis have clinically different features and prognoses. An 8 year old female patient presented mild jaundice of insidious onset. The liver was tender and enlarged. Serologic markers for A, B, C, E, Epstein Barr and cytomegalovirus were negative. The liver biopsy showed a histological picture consistent with chronic active hepatitis. High titers of anti-liver/kidney-microsome antibody were found by indirect immunofluorescence test, and this finding was confirmed by Western blot against specific liver microsome antigens. Therapy with prednisolone induced a clinical and biochemical remission after four weeks. The suspension of therapy under strict medical control produced a rapid relapse of clinical and biochemical features. The reinitiation of prednisolone was successful, and an alternate-day program was started and maintained until 8 months follow-up.

A process-model based approach to prospective memory impairment in Parkinson's disease.

PubMed

Kliegel, Matthias; Altgassen, Mareike; Hering, Alexandra; Rose, Nathan S

2011-07-01

The present review discusses the current state of research on the clinical neuropsychology of prospective memory in Parkinson's disease. To do so the paper is divided in two sections. In the first section, we briefly outline key features of the (partly implicit) rationale underlying the available literature on the clinical neuropsychology of prospective memory. Here, we present a conceptual model that guides our approach to the clinical neuropsychology of prospective memory in general and to the effects of Parkinson's disease on prospective memory in particular. In the second section, we use this model to guide our review of the available literature and suggest some open issues and future directions motivated by previous findings and the proposed conceptual model. The review suggests that certain phases of the prospective memory process (intention formation und initiation) are particularly impaired by Parkinson's disease. In addition, it is argued that prospective memory may be preserved when tasks involve specific features (e.g., focal cues) that reduce the need for strategic monitoring processes. In terms of suggestions for future directions, it is noted that intervention studies are needed which target the specific phases of the prospective memory process that are impaired in Parkinson's disease, such as planning interventions. Moreover, it is proposed that prospective memory deficits in Parkinson's disease should be explored in the context of a general impairment in the ability to form an intention and plan or coordinate an appropriate series of actions. Copyright © 2011 Elsevier Ltd. All rights reserved.

Clinical variability of Waardenburg-Shah syndrome in patients with proximal 13q deletion syndrome including the endothelin-B receptor locus.

PubMed

Tüysüz, Beyhan; Collin, Anna; Arapoğlu, Müjde; Suyugül, Nezir

2009-10-01

Waardenburg-Shah syndrome (Waardenburg syndrome type IV-WS4) is an auditory-pigmentary disorder that combines clinical features of pigmentary abnormalities of the skin, hair and irides, sensorineural hearing loss, and Hirschsprung disease (HSCR). Mutations in the endothelin-B receptor (EDNRB) gene on 13q22 have been found to cause this syndrome. Mutations in both alleles cause the full phenotype, while heterozygous mutations cause isolated HSCR or HSCR with minor pigmentary anomalies and/or sensorineural deafness. We investigated the status of the EDNRB gene, by FISH analysis, in three patients with de novo proximal 13q deletions detected at cytogenetic analysis and examined the clinical variability of WS4 among these patients. Chromosome 13q was screened with locus specific FISH probes and breakpoints were determined at 13q22.1q31.3 in Patients 1 and 3, and at 13q21.1q31.3 in Patient 2. An EDNRB specific FISH probe was deleted in all three patients. All patients had common facial features seen in proximal 13q deletion syndrome and mild mental retardation. However, findings related to WS4 were variable; Patient 1 had hypopigmentation of the irides and HSCR, Patient 2 had prominent bicolored irides and mild bilateral hearing loss, and Patient 3 had only mild unilateral hearing loss. These data contribute new insights into the pathogenesis of WS4.

Thermography based prescreening software tool for veterinary clinics

NASA Astrophysics Data System (ADS)

Dahal, Rohini; Umbaugh, Scott E.; Mishra, Deependra; Lama, Norsang; Alvandipour, Mehrdad; Umbaugh, David; Marino, Dominic J.; Sackman, Joseph

2017-05-01

Under development is a clinical software tool which can be used in the veterinary clinics as a prescreening tool for these pathologies: anterior cruciate ligament (ACL) disease, bone cancer and feline hyperthyroidism. Currently, veterinary clinical practice uses several imaging techniques including radiology, computed tomography (CT), and magnetic resonance imaging (MRI). But, harmful radiation involved during imaging, expensive equipment setup, excessive time consumption and the need for a cooperative patient during imaging, are major drawbacks of these techniques. In veterinary procedures, it is very difficult for animals to remain still for the time periods necessary for standard imaging without resorting to sedation - which creates another set of complexities. Therefore, clinical application software integrated with a thermal imaging system and the algorithms with high sensitivity and specificity for these pathologies, can address the major drawbacks of the existing imaging techniques. A graphical user interface (GUI) has been created to allow ease of use for the clinical technician. The technician inputs an image, enters patient information, and selects the camera view associated with the image and the pathology to be diagnosed. The software will classify the image using an optimized classification algorithm that has been developed through thousands of experiments. Optimal image features are extracted and the feature vector is then used in conjunction with the stored image database for classification. Classification success rates as high as 88% for bone cancer, 75% for ACL and 90% for feline hyperthyroidism have been achieved. The software is currently undergoing preliminary clinical testing.

Partial dependence of breast tumor malignancy on ultrasound image features derived from boosted trees

NASA Astrophysics Data System (ADS)

Yang, Wei; Zhang, Su; Li, Wenying; Chen, Yaqing; Lu, Hongtao; Chen, Wufan; Chen, Yazhu

2010-04-01

Various computerized features extracted from breast ultrasound images are useful in assessing the malignancy of breast tumors. However, the underlying relationship between the computerized features and tumor malignancy may not be linear in nature. We use the decision tree ensemble trained by the cost-sensitive boosting algorithm to approximate the target function for malignancy assessment and to reflect this relationship qualitatively. Partial dependence plots are employed to explore and visualize the effect of features on the output of the decision tree ensemble. In the experiments, 31 image features are extracted to quantify the sonographic characteristics of breast tumors. Patient age is used as an external feature because of its high clinical importance. The area under the receiver-operating characteristic curve of the tree ensembles can reach 0.95 with sensitivity of 0.95 (61/64) at the associated specificity 0.74 (77/104). The partial dependence plots of the four most important features are demonstrated to show the influence of the features on malignancy, and they are in accord with the empirical observations. The results can provide visual and qualitative references on the computerized image features for physicians, and can be useful for enhancing the interpretability of computer-aided diagnosis systems for breast ultrasound.

Lyme disease: a rigorous review of diagnostic criteria and treatment.

PubMed

Borchers, Andrea T; Keen, Carl L; Huntley, Arthur C; Gershwin, M Eric

2015-02-01

Lyme disease was originally identified in Lyme, Connecticut, based upon an unusual cluster of what appeared to be patients with juvenile rheumatoid arthritis. It was subsequently identified as a new clinical entity originally called Lyme arthritis based on the observation that arthritis was a major clinical feature. However, Lyme arthritis is now called Lyme disease based upon the understanding that the clinical features include not only arthritis, but also potential cardiac, dermatologic and neurologic findings. Lyme disease typically begins with an erythematous rash called erythema migrans (EM). Approximately 4-8% of patients develop cardiac, 11% develop neurologic and 45-60% of patients manifest arthritis. The disease is transmitted following exposure to a tick bite containing a spirochete in a genetically susceptible host. There is considerable data on spirochetes, including Borrelia burgdorferi (Bb), the original bacteria identified in this disease. Lyme disease, if an organism had not been identified, would be considered as a classic autoimmune disease and indeed the effector mechanisms are similar to many human diseases manifest as loss of tolerance. The clinical diagnosis is highly likely based upon appropriate serology and clinical manifestations. However, the serologic features are often misinterpreted and may have false positives if confirmatory laboratory testing is not performed. Antibiotics are routinely and typically used to treat patients with Lyme disease, but there is no evidence that prolonged or recurrent treatment with antibiotics change the natural history of Lyme disease. Although there are animal models of Lyme disease, there is no system that faithfully recapitulates the human disease. Further research on the effector mechanisms that lead to pathology in some individuals should be further explored to develop more specific therapy. Copyright © 2014 Elsevier Ltd. All rights reserved.

Predicting clinical symptoms of attention deficit hyperactivity disorder based on temporal patterns between and within intrinsic connectivity networks.

PubMed

Wang, Xun-Heng; Jiao, Yun; Li, Lihua

2017-10-24

Attention deficit hyperactivity disorder (ADHD) is a common brain disorder with high prevalence in school-age children. Previously developed machine learning-based methods have discriminated patients with ADHD from normal controls by providing label information of the disease for individuals. Inattention and impulsivity are the two most significant clinical symptoms of ADHD. However, predicting clinical symptoms (i.e., inattention and impulsivity) is a challenging task based on neuroimaging data. The goal of this study is twofold: to build predictive models for clinical symptoms of ADHD based on resting-state fMRI and to mine brain networks for predictive patterns of inattention and impulsivity. To achieve this goal, a cohort of 74 boys with ADHD and a cohort of 69 age-matched normal controls were recruited from the ADHD-200 Consortium. Both structural and resting-state fMRI images were obtained for each participant. Temporal patterns between and within intrinsic connectivity networks (ICNs) were applied as raw features in the predictive models. Specifically, sample entropy was taken asan intra-ICN feature, and phase synchronization (PS) was used asan inter-ICN feature. The predictive models were based on the least absolute shrinkage and selectionator operator (LASSO) algorithm. The performance of the predictive model for inattention is r=0.79 (p<10 -8 ), and the performance of the predictive model for impulsivity is r=0.48 (p<10 -8 ). The ICN-related predictive patterns may provide valuable information for investigating the brain network mechanisms of ADHD. In summary, the predictive models for clinical symptoms could be beneficial for personalizing ADHD medications. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Triple-negative breast cancer: the importance of molecular and histologic subtyping, and recognition of low-grade variants.

PubMed

Pareja, Fresia; Geyer, Felipe C; Marchiò, Caterina; Burke, Kathleen A; Weigelt, Britta; Reis-Filho, Jorge S

2016-01-01

Triple-negative breast cancers (TNBCs), defined by lack of expression of estrogen receptor, progesterone receptor and HER2, account for 12-17% of breast cancers and are clinically perceived as a discrete breast cancer subgroup. Nonetheless, TNBC has been shown to constitute a vastly heterogeneous disease encompassing a wide spectrum of entities with marked genetic, transcriptional, histological and clinical differences. Although most TNBCs are high-grade tumors, there are well-characterized low-grade TNBCs that have an indolent clinical course, whose natural history, molecular features and optimal therapy vastly differ from those of high-grade TNBCs. Secretory and adenoid cystic carcinomas are two histologic types of TNBCs underpinned by specific fusion genes; these tumors have an indolent clinical behavior and lack all of the cardinal molecular features of high-grade triple-negative disease. Recent studies of rare entities, including lesions once believed to constitute mere benign breast disease (e.g., microglandular adenosis), have resulted in the identification of potential precursors of TNBC and suggested the existence of a family of low-grade triple-negative lesions that, despite having low-grade morphology and indolent clinical behavior, have been shown to harbor the complex genomic landscape of common forms of TNBC, and may progress to high-grade disease. In this review, we describe the heterogeneity of TNBC and focus on the histologic and molecular features of low-grade forms of TNBC. Germane to addressing the challenges posed by the so-called triple-negative disease is the realization that TNBC is merely a descriptive term, and that low-grade types of TNBC may be driven by distinct sets of genetic alterations.

Triple-negative breast cancer: the importance of molecular and histologic subtyping, and recognition of low-grade variants

PubMed Central

Pareja, Fresia; Geyer, Felipe C; Marchiò, Caterina; Burke, Kathleen A; Weigelt, Britta; Reis-Filho, Jorge S

2016-01-01

Triple-negative breast cancers (TNBCs), defined by lack of expression of estrogen receptor, progesterone receptor and HER2, account for 12–17% of breast cancers and are clinically perceived as a discrete breast cancer subgroup. Nonetheless, TNBC has been shown to constitute a vastly heterogeneous disease encompassing a wide spectrum of entities with marked genetic, transcriptional, histological and clinical differences. Although most TNBCs are high-grade tumors, there are well-characterized low-grade TNBCs that have an indolent clinical course, whose natural history, molecular features and optimal therapy vastly differ from those of high-grade TNBCs. Secretory and adenoid cystic carcinomas are two histologic types of TNBCs underpinned by specific fusion genes; these tumors have an indolent clinical behavior and lack all of the cardinal molecular features of high-grade triple-negative disease. Recent studies of rare entities, including lesions once believed to constitute mere benign breast disease (e.g., microglandular adenosis), have resulted in the identification of potential precursors of TNBC and suggested the existence of a family of low-grade triple-negative lesions that, despite having low-grade morphology and indolent clinical behavior, have been shown to harbor the complex genomic landscape of common forms of TNBC, and may progress to high-grade disease. In this review, we describe the heterogeneity of TNBC and focus on the histologic and molecular features of low-grade forms of TNBC. Germane to addressing the challenges posed by the so-called triple-negative disease is the realization that TNBC is merely a descriptive term, and that low-grade types of TNBC may be driven by distinct sets of genetic alterations. PMID:28721389

Autoimmunity-Associated PTPN22 Polymorphisms in Latent Autoimmune Diabetes of the Adult Differ from Those of Type 1 Diabetes Patients.

PubMed

Heneberg, Petr; Kocková, Lucie; Čecháková, Marie; Daňková, Pavlína; Černá, Marie

2018-06-12

A portion of adults with humoral immune changes have clinical diabetes that is initially not insulin-requiring (latent autoimmune diabetes of the adult, LADA). One of the genes strongly associated with autoimmune diabetes is PTPN22. We hypothesized that the manifestation and clinical features of LADA are linked to functional variants of PTPN22. We genotyped allelic frequencies of 1 protective and 3 risk-associated PTPN22 variants in 156 Czech LADA patients, 194 type 2 diabetes mellitus patients with LADA-like progression to insulinotherapy and 324 type 1 diabetes mellitus patients, and subsequently examined the associations of PTPN22 variants with the expression of autoantibodies and other clinical features of LADA. We challenged the paradigm that stated that the PTPN22 c.1858T allele serves as a risk allele for LADA, although we confirmed its risk status in the geographically matched T1DM cohort. In contrast, the frequencies of other PTPN22 alleles (c.-1123C, c.788A and c.1970-852C) differed significantly from the healthy controls. We confirmed gender-related differences in the frequency of some PTPN22 polymorphisms (but not c.1858C>T) in LADA. The particular PTPN22 alleles and genotypes were associated with specific clinical features of the examined patients (autoantibodies, HbA1c and age at diagnosis of diabetes). The variability in PTPN22 haplotypes suggests that the genetic signature of LADA is independent and should not be considered a hybrid form of T1DM and T2DM. Further studies should elucidate the associations with clinical characteristics of the LADA patients and focus on the newly emerging types of diabetes with the disease onset in early to mid-adulthood. © 2018 S. Karger AG, Basel.

Computer-aided diagnostic method for classification of Alzheimer's disease with atrophic image features on MR images

NASA Astrophysics Data System (ADS)

Arimura, Hidetaka; Yoshiura, Takashi; Kumazawa, Seiji; Tanaka, Kazuhiro; Koga, Hiroshi; Mihara, Futoshi; Honda, Hiroshi; Sakai, Shuji; Toyofuku, Fukai; Higashida, Yoshiharu

2008-03-01

Our goal for this study was to attempt to develop a computer-aided diagnostic (CAD) method for classification of Alzheimer's disease (AD) with atrophic image features derived from specific anatomical regions in three-dimensional (3-D) T1-weighted magnetic resonance (MR) images. Specific regions related to the cerebral atrophy of AD were white matter and gray matter regions, and CSF regions in this study. Cerebral cortical gray matter regions were determined by extracting a brain and white matter regions based on a level set based method, whose speed function depended on gradient vectors in an original image and pixel values in grown regions. The CSF regions in cerebral sulci and lateral ventricles were extracted by wrapping the brain tightly with a zero level set determined from a level set function. Volumes of the specific regions and the cortical thickness were determined as atrophic image features. Average cortical thickness was calculated in 32 subregions, which were obtained by dividing each brain region. Finally, AD patients were classified by using a support vector machine, which was trained by the image features of AD and non-AD cases. We applied our CAD method to MR images of whole brains obtained from 29 clinically diagnosed AD cases and 25 non-AD cases. As a result, the area under a receiver operating characteristic (ROC) curve obtained by our computerized method was 0.901 based on a leave-one-out test in identification of AD cases among 54 cases including 8 AD patients at early stages. The accuracy for discrimination between 29 AD patients and 25 non-AD subjects was 0.840, which was determined at the point where the sensitivity was the same as the specificity on the ROC curve. This result showed that our CAD method based on atrophic image features may be promising for detecting AD patients by using 3-D MR images.

Automated detection of retinal whitening in malarial retinopathy

NASA Astrophysics Data System (ADS)

Joshi, V.; Agurto, C.; Barriga, S.; Nemeth, S.; Soliz, P.; MacCormick, I.; Taylor, T.; Lewallen, S.; Harding, S.

2016-03-01

Cerebral malaria (CM) is a severe neurological complication associated with malarial infection. Malaria affects approximately 200 million people worldwide, and claims 600,000 lives annually, 75% of whom are African children under five years of age. Because most of these mortalities are caused by the high incidence of CM misdiagnosis, there is a need for an accurate diagnostic to confirm the presence of CM. The retinal lesions associated with malarial retinopathy (MR) such as retinal whitening, vessel discoloration, and hemorrhages, are highly specific to CM, and their detection can improve the accuracy of CM diagnosis. This paper will focus on development of an automated method for the detection of retinal whitening which is a unique sign of MR that manifests due to retinal ischemia resulting from CM. We propose to detect the whitening region in retinal color images based on multiple color and textural features. First, we preprocess the image using color and textural features of the CMYK and CIE-XYZ color spaces to minimize camera reflex. Next, we utilize color features of the HSL, CMYK, and CIE-XYZ channels, along with the structural features of difference of Gaussians. A watershed segmentation algorithm is used to assign each image region a probability of being inside the whitening, based on extracted features. The algorithm was applied to a dataset of 54 images (40 with whitening and 14 controls) that resulted in an image-based (binary) classification with an AUC of 0.80. This provides 88% sensitivity at a specificity of 65%. For a clinical application that requires a high specificity setting, the algorithm can be tuned to a specificity of 89% at a sensitivity of 82%. This is the first published method for retinal whitening detection and combining it with the detection methods for vessel discoloration and hemorrhages can further improve the detection accuracy for malarial retinopathy.

Quantitative imaging as cancer biomarker

NASA Astrophysics Data System (ADS)

Mankoff, David A.

2015-03-01

The ability to assay tumor biologic features and the impact of drugs on tumor biology is fundamental to drug development. Advances in our ability to measure genomics, gene expression, protein expression, and cellular biology have led to a host of new targets for anticancer drug therapy. In translating new drugs into clinical trials and clinical practice, these same assays serve to identify patients most likely to benefit from specific anticancer treatments. As cancer therapy becomes more individualized and targeted, there is an increasing need to characterize tumors and identify therapeutic targets to select therapy most likely to be successful in treating the individual patient's cancer. Thus far assays to identify cancer therapeutic targets or anticancer drug pharmacodynamics have been based upon in vitro assay of tissue or blood samples. Advances in molecular imaging, particularly PET, have led to the ability to perform quantitative non-invasive molecular assays. Imaging has traditionally relied on structural and anatomic features to detect cancer and determine its extent. More recently, imaging has expanded to include the ability to image regional biochemistry and molecular biology, often termed molecular imaging. Molecular imaging can be considered an in vivo assay technique, capable of measuring regional tumor biology without perturbing it. This makes molecular imaging a unique tool for cancer drug development, complementary to traditional assay methods, and a potentially powerful method for guiding targeted therapy in clinical trials and clinical practice. The ability to quantify, in absolute measures, regional in vivo biologic parameters strongly supports the use of molecular imaging as a tool to guide therapy. This review summarizes current and future applications of quantitative molecular imaging as a biomarker for cancer therapy, including the use of imaging to (1) identify patients whose tumors express a specific therapeutic target; (2) determine whether the drug reaches the target; (3) identify an early response to treatment; and (4) predict the impact of therapy on long-term outcomes such as survival. The manuscript reviews basic concepts important in the application of molecular imaging to cancer drug therapy, in general, and will discuss specific examples of studies in humans, and highlight future directions, including ongoing multi-center clinical trials using molecular imaging as a cancer biomarker.

Deep learning based classification of breast tumors with shear-wave elastography.

PubMed

Zhang, Qi; Xiao, Yang; Dai, Wei; Suo, Jingfeng; Wang, Congzhi; Shi, Jun; Zheng, Hairong

2016-12-01

This study aims to build a deep learning (DL) architecture for automated extraction of learned-from-data image features from the shear-wave elastography (SWE), and to evaluate the DL architecture in differentiation between benign and malignant breast tumors. We construct a two-layer DL architecture for SWE feature extraction, comprised of the point-wise gated Boltzmann machine (PGBM) and the restricted Boltzmann machine (RBM). The PGBM contains task-relevant and task-irrelevant hidden units, and the task-relevant units are connected to the RBM. Experimental evaluation was performed with five-fold cross validation on a set of 227 SWE images, 135 of benign tumors and 92 of malignant tumors, from 121 patients. The features learned with our DL architecture were compared with the statistical features quantifying image intensity and texture. Results showed that the DL features achieved better classification performance with an accuracy of 93.4%, a sensitivity of 88.6%, a specificity of 97.1%, and an area under the receiver operating characteristic curve of 0.947. The DL-based method integrates feature learning with feature selection on SWE. It may be potentially used in clinical computer-aided diagnosis of breast cancer. Copyright © 2016 Elsevier B.V. All rights reserved.

Anxiety or agitation in mood disorder with mixed features: A review with a focus on validity as a dimensional criterion.

PubMed

Shim, In Hee; Bae, Dong Sik; Bahk, Won-Myong

2016-08-01

The diagnostic validity of mixed features, excluding anxiety or psychomotor agitation in mood disorders, has not yet been fully examined. PubMed and relevant English-language literature (regardless of year) were searched. Keywords were mixed or mixed state or mixed features or mixed episode and anxious or anxiety or agitation and bipolar disorder or depressive disorder or mood disorder or affective disorder. Most studies on anxiety or psychomotor agitation have included a significant correlation relevant to the "with mixed features" specifier, although it is common in both poles of mood episodes regardless of the predominant polarity. There is some confusion between the characteristic of classical mixed states and the definition of the mixed features specifier with the newly added anxious distress specifier in DSM-5, specifically, whether to include anxiety and agitation as significant characteristics. This change is of concern because a large proportion of patients with mixed features are now unspecified, and this may influence treatment planning and prognosis. The findings of our review suggest that anxiety and psychomotor agitation can be core symptoms in mood episodes with mixed features and important clinical clues for prediction of treatment effects and disease course.

Prototype Packaged Databases and Software in Health

PubMed Central

Gardenier, Turkan K.

1980-01-01

This paper describes the recent demand for packaged databases and software for health applications in light of developments in mini-and micro-computer technology. Specific features for defining prospective user groups are discussed; criticisms generated for large-scale epidemiological data use as a means of replacing clinical trials and associated controls are posed to the reader. The available collaborative efforts for access and analysis of jointly structured health data are stressed, with recommendations for new analytical techniques specifically geared to monitoring data such as the CTSS (Cumulative Transitional State Score) generated for tacking ongoing patient status over time in clinical trials. Examples of graphic display are given from the Domestic Information Display System (DIDS) which is a collaborative multi-agency effort to computerize and make accessible user-specified U.S. and local maps relating to health, environment, socio-economic and energy data.

Epidemiology, diagnosis, and antimicrobial treatment of acute bacterial meningitis.

PubMed

Brouwer, Matthijs C; Tunkel, Allan R; van de Beek, Diederik

2010-07-01

The epidemiology of bacterial meningitis has changed as a result of the widespread use of conjugate vaccines and preventive antimicrobial treatment of pregnant women. Given the significant morbidity and mortality associated with bacterial meningitis, accurate information is necessary regarding the important etiological agents and populations at risk to ascertain public health measures and ensure appropriate management. In this review, we describe the changing epidemiology of bacterial meningitis in the United States and throughout the world by reviewing the global changes in etiological agents followed by specific microorganism data on the impact of the development and widespread use of conjugate vaccines. We provide recommendations for empirical antimicrobial and adjunctive treatments for clinical subgroups and review available laboratory methods in making the etiological diagnosis of bacterial meningitis. Finally, we summarize risk factors, clinical features, and microbiological diagnostics for the specific bacteria causing this disease.

Automatic classification of written descriptions by healthy adults: An overview of the application of natural language processing and machine learning techniques to clinical discourse analysis.

PubMed

Toledo, Cíntia Matsuda; Cunha, Andre; Scarton, Carolina; Aluísio, Sandra

2014-01-01

Discourse production is an important aspect in the evaluation of brain-injured individuals. We believe that studies comparing the performance of brain-injured subjects with that of healthy controls must use groups with compatible education. A pioneering application of machine learning methods using Brazilian Portuguese for clinical purposes is described, highlighting education as an important variable in the Brazilian scenario. The aims were to describe how to:(i) develop machine learning classifiers using features generated by natural language processing tools to distinguish descriptions produced by healthy individuals into classes based on their years of education; and(ii) automatically identify the features that best distinguish the groups. The approach proposed here extracts linguistic features automatically from the written descriptions with the aid of two Natural Language Processing tools: Coh-Metrix-Port and AIC. It also includes nine task-specific features (three new ones, two extracted manually, besides description time; type of scene described - simple or complex; presentation order - which type of picture was described first; and age). In this study, the descriptions by 144 of the subjects studied in Toledo 18 were used,which included 200 healthy Brazilians of both genders. A Support Vector Machine (SVM) with a radial basis function (RBF) kernel is the most recommended approach for the binary classification of our data, classifying three of the four initial classes. CfsSubsetEval (CFS) is a strong candidate to replace manual feature selection methods.

Medical Device Guidebook: A browser information resource for medical device users.

PubMed

Clarkson, Douglas M

2017-03-01

A web based information resource - the 'Medical Device Guidebook' - for the enabling of safe use of medical devices is described. Medical devices are described within a 'catalogue' of specific models and information on a specific model is provided within a consistent set of information 'keys'. These include 'user manuals', 'points of caution', 'clinical use framework', 'training/assessment material', 'frequently asked questions', 'authorised user comments' and 'consumables'. The system allows identification of known risk/hazards associated with specific devices, triggered, for example, by national alerts or locally raised safety observations. This provides a mechanism for more effective briefing of equipment users on the associated hazards of equipment. A feature of the system is the inclusion of a specific 'Operational Procedure' for each device, where the lack of this focus is shown in the literature to often be a key factor in equipment misuse and associated patient injury. The 'Guidebook' provides a mechanism for the development of an information resource developed within local clinical networks and encourages a consistent approach to medical device use. Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.

Bowel obstruction complicated by ischemia: analysis of CT findings.

PubMed

Cox, Veronica L; Tahvildari, Ali M; Johnson, Benjamin; Wei, Wei; Jeffrey, R Brooke

2018-06-01

To analyze CT signs of bowel ischemia in patients with surgical bowel obstruction, and thereby improve CT diagnosis in this common clinical scenario. Surgical and histopathological findings were used as the reference standard. We retrospectively analyzed CT findings in patients brought to surgery for bowel obstruction over 13 years. Etiology of obstruction (adhesion, hernia, etc.) was recorded. Specific CT features of acute mesenteric ischemia (AMI) were analyzed, including bowel wall thickening, mucosal hypoenhancement, and others. 173 cases were eligible for analysis. 21% of cases were positive for bowel ischemia. Volvulus, internal hernia, and closed-loop obstructions showed ischemia rates of 60%, 43%, and 43%; ischemia rate in obstruction from simple adhesion was 21%. Patients with bowel obstruction related to malignancy were never ischemic. Sensitivities and specificities for CT features predicting ischemia were calculated, with wall thickening, hypoenhancement, and pneumatosis showing high specificity for ischemia (86%-100%). Wall thickening, hypoenhancement, and pneumatosis are highly specific CT signs of ischemia in the setting of obstruction. None of the evaluated CT signs were found to be highly sensitive. Overall frequency of ischemia in surgical bowel obstruction is 21%, and 2-3 times that for complex obstructions (volvulus, closed loop, etc.). Obstructions related to malignancy virtually never become ischemic.

Catatonia in Psychotic Patients: Clinical Features and Treatment Response

PubMed Central

England, Mary L.; Öngür, Dost; Konopaske, Glenn T.; Karmacharya, Rakesh

2012-01-01

We report clinical features and treatment response in 25 patients with catatonia admitted to an inpatient psychiatric unit specializing in psychotic disorders. ECT, benzodiazepines, and clozapine had beneficial effects on catatonic features, while typical antipsychotics resulted in clinical worsening. PMID:21677256

A machine learning framework involving EEG-based functional connectivity to diagnose major depressive disorder (MDD).

PubMed

Mumtaz, Wajid; Ali, Syed Saad Azhar; Yasin, Mohd Azhar Mohd; Malik, Aamir Saeed

2018-02-01

Major depressive disorder (MDD), a debilitating mental illness, could cause functional disabilities and could become a social problem. An accurate and early diagnosis for depression could become challenging. This paper proposed a machine learning framework involving EEG-derived synchronization likelihood (SL) features as input data for automatic diagnosis of MDD. It was hypothesized that EEG-based SL features could discriminate MDD patients and healthy controls with an acceptable accuracy better than measures such as interhemispheric coherence and mutual information. In this work, classification models such as support vector machine (SVM), logistic regression (LR) and Naïve Bayesian (NB) were employed to model relationship between the EEG features and the study groups (MDD patient and healthy controls) and ultimately achieved discrimination of study participants. The results indicated that the classification rates were better than chance. More specifically, the study resulted into SVM classification accuracy = 98%, sensitivity = 99.9%, specificity = 95% and f-measure = 0.97; LR classification accuracy = 91.7%, sensitivity = 86.66%, specificity = 96.6% and f-measure = 0.90; NB classification accuracy = 93.6%, sensitivity = 100%, specificity = 87.9% and f-measure = 0.95. In conclusion, SL could be a promising method for diagnosing depression. The findings could be generalized to develop a robust CAD-based tool that may help for clinical purposes.

Primary bowing tremor: a task-specific movement disorder of string instrumentalists.

PubMed

Lederman, Richard J

2012-12-01

Fear of a tremulous or unsteady bow is widespread among string instrumentalists. Faulty technique and performance anxiety have generally been blamed. The cases of 4 high-level violinists and 1 violist, 3 women and 2 men, with uncontrollable bow tremor are presented. Age at onset was from 16 to 75 years, and symptom duration 8 months to 20 years at the time of neurological evaluation. The degree of tremor varied with type of bow stroke and even the portion of the bow contacting the string. Only 1 patient had a slight postural tremor of the opposite limb. In 3 of 5 the tremor was task-specific; the other 2 had mild and nontroubling tremor with other activities. The tremor appeared to worsen over time but then seemed to stabilize. The characteristics of this tremor appear to be distinguishable from the features of both essential tremor and focal dystonia; comparison is made with representative string players afflicted by these other disorders. Analogy of this tremor is made with primary writing tremor, a well-defined task-specific movement disorder also sharing at least some features with both essential tremor and writers' cramp, a focal dystonia. Hence, it was decided to call this primary bowing tremor. Clinical features, family history, diagnostic studies, and responsiveness to treatment of primary writing tremor are discussed to emphasize the similarity to primary bowing tremor. This appears to represent a previously unreported form of task-specific movement disorder of string instrumentalists.

Ocular Features in 16 Brazilian Patients with Williams-Beuren Syndrome.

PubMed

Viana, Melissa Machado; Frasson, Maria; Galvão, Henrique; Leão, Letícia Lima; Stofanko, Martin; Gonçalves-Dornelas, Higgor; da Silva Cunha, Pricila; Burle de Aguiar, Marcos José

2015-01-01

Williams-Beuren Syndrome (WBS) is a multisystem disorder caused by the deletion of contiguous genes on chromosome 7q11.23. Ophthalmologic abnormalities and deficits in visual motor integration are important features of WBS. Here we describe our experience with Brazilian WBS patients and their ophthalmologic features. Sixteen patients with confirmed WBS went through thorough ophthalmologic examination. The most frequent ocular findings in our group of patients were stellate iris pattern (81.2%), hyperopic astigmatism (50%), hyperopia (37.5%), tortuosity of retinal vessel (37.5%) and strabismus (18.7%). This is the second report of ophthalmologic abnormalities in a group of Brazilian individuals with WBS. It is extremely valuable that specific populations are studied so that clinical diagnosis can be refined and management of patients can be driven to the most common presentations of the disease.

Cutaneous involvement in multiple myeloma (MM): A case series with clinicopathologic correlation.

PubMed

Malysz, Jozef; Talamo, Giampaolo; Zhu, Junjia; Clarke, Loren E; Bayerl, Michael G; Ali, Liaqat; Helm, Klaus F; Chung, Catherine G

2016-05-01

Disease-specific skin lesions are rare in patients with multiple myeloma (MM). We sought to further characterize the clinical and pathologic features of patients with cutaneous involvement with MM. We identified 13 patients with cutaneous lesions of MM. Cutaneous lesions consisted of pink, red, and violaceous papules, nodules, and/or plaques that varied in size. Histopathology revealed atypical plasma cells with occasional plasmablastic features. MM had aggressive biologic features and was at an advanced stage in the majority of patients. Despite aggressive management, including chemotherapy and stem-cell transplantation, most patients died of progressive disease within a few months after the development of cutaneous lesions. The study group was relatively small. Cutaneous involvement with MM is associated with aggressive biologic behavior and short survival. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

[Clinical characteristics of Rett Syndrome].

PubMed

Abbes, Zeineb; Bouden, Asma; Halayem, Soumaya; Othman, Sami; Bechir Halayem, Mohamed

2011-10-01

Rett Syndrome is a neurodevelopmental disorder, one of the least commonly occurring autism spectrum disorders (ASD),affecting mainly females. To describe features and molecular specificities of Rett syndrome. To identify articles for this review, a Pubmed search was conducted using the following keywords: Rett syndrome, regression,mutation, stereotypes. This syndrome is characterized by cognitive impairment,communication dysfunction, stereotypic movement disorder, and growth failure. It is generally caused by mutations in the MECP2 gene. Rett Syndrome has a prevalence ranging from 10-20 000 females. Specific treatment is not available, but patients need a careful planning for long-term care, with multidisciplinary approaches.

Fat Embolism Syndrome: A Case Report and Review Literature.

PubMed

Uransilp, Nattaphol; Muengtaweepongsa, Sombat; Chanalithichai, Nuttawut; Tammachote, Nattapol

2018-01-01

Fat embolism syndrome (FES) is a life-threatening complication in patients with orthopedic trauma, especially long bone fractures. The diagnosis of fat embolism is made by clinical features alone with no specific laboratory findings. FES has no specific treatment and requires supportive care, although it can be prevented by early fixation of bone fractures. Here, we report a case of FES in a patient with right femoral neck fracture, which was diagnosed initially by Gurd's criteria and subsequently confirmed by typical appearances on magnetic resonance imaging (MRI) of the brain. The patient received supportive management and a short course of intravenous methylprednisolone.

Examination of adipose depot-specific PPAR moieties

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

Dodson, M.V., E-mail: dodson@wsu.edu; Vierck, J.L.; Hausman, G.J.

2010-04-02

Molecular mechanisms of peroxisome proliferator activated receptors (PPARs) are being defined rapidly, as illustrated by the volume of papers published. Much of the research is directed towards a clinical end-point/application; however, the non-homogeneous nature of adipose depots in laboratory animals is spurring similar research in domestic meat animals (such as beef cattle). Moreover, the size of adipose depots in meat animals remains an attractive feature for using them to obtain cells for PPAR research. Examination of meat-animal depot-specific PPAR moieties may provide novel information about adipocyte regulation that might be extrapolated to all animals.

[SPECIFIC CLINICAL FEATURES OF TYPE 1 AUTOIMMUNE POLYGLANDULAR SYNDROME].

PubMed

Mikhina, M S; Molashenko, N V; Troshina, E A; Orlova, E M; Sozaeva, L S; Eystein, S H; Breivik, S

2015-01-01

Autoimmune polyglandular syndrome is a primary autoimmune disorder affecting two or more peripheral endocrine glands and responsible for their incompetence. It is frequently combined with various organ-specific non-endocrine diseases. Patients with this pathology need life-long replacement therapy and dynamic observation by endocrinologists and other specialists to monitor the effectiveness of the treatment and detect new components of the disease. We report a variant of type 1 autoimmune polyglandular syndrome. Special emphasis is laid on the importance of succession of actions of endocrinologists and specialists in related medical disciplines dealing with children and adult patients.

Pick's disease: a modern approach.

PubMed

Dickson, D W

1998-04-01

Pick's disease is a rare dementing disorder that is sometimes familial. The cardinal features are circumscribed cortical atrophy most often affecting the frontal and temporal poles and argyrophilic, round intraneuronal inclusions (Pick bodies). Clinical manifestations reflect the distribution of cortical degeneration, and personality deterioration and memory deficits are often more severe than visuospatial and apraxic disorders that are common in Alzheimer's disease, but clinical overlap with other non-Alzheimer degenerative disorders is increasingly recognized. Neuronal loss and degeneration are usually maximal in the limbic system, including hippocampus, entorhinal cortex and amygdala. Numerous Pick bodies are often present in the dentate fascia of the hippocampus. Less specific features include leukoencephalopathy and ballooned cortical neurons (Pick cells). Glial reaction is often pronounced in affected cerebral gray and white matter. Tau-immunoreactive glial inclusions are a recently recognized finding in Pick's disease, and neuritic changes have also recently been described. Variable involvement of the deep gray matter and the brainstem is typical, with a predilection for the monoaminergic nuclei and nuclei of the pontine base. Neurochemical studies demonstrate deficits in intrinsic cortical neurotransmitter systems (e.g., somatostatin), but inconsistent loss of transmitters in systems projecting to the cortex (e.g., cholinergic neurons of the basal nucleus). Biochemical and immunocytochemical studies have demonstrated that abnormal tau proteins are the major structural components of Pick bodies. A specific tau protein immunoblotting pattern different from that seen in Alzheimer's disease and certain other disorders has been suggested in some studies. A specific molecular marker and a genetic locus for familial cases are not known.

A small and active ring X chromosome in a female with features of Kabuki syndrome.

PubMed

Rodríguez, L; Diego-Alvarez, D; Lorda-Sanchez, I; Gallardo, F L; Martínez-Fernández, M L; Arroyo-Muñoz, M E; Martínez-Frías, M L

2008-11-01

A ring X chromosome is found in about 6% of patients with Turner syndrome (TS), often with mosaicism for a 45,X cell line. Patients with this karyotype are reported to have a higher incidence of a more severe phenotype including mental retardation. In fact, some studies have shown a correlation between this severity and the presence or absence of an intact and functional X inactivation center (XIST). However, the phenotype of the individuals with r(X) cannot be entirely defined in terms of their X-inactivation patterns. Nevertheless, a small group of these patients have been described to manifest clinical features reminiscent of the Kabuki syndrome. Here we present a female patient with clinical features resembling Kabuki syndrome and a mos 45,X/46,X,r(X) karyotype. Methylation analyses of polymorphic alleles of the androgen receptor gene showed that both alleles were unmethylated suggesting an active ring chromosome. A specific X chromosome array CGH was performed estimating the size of the ring to be 17 Mb, lacking the XIST gene, and including some genes with possible implications in the phenotype of the patient. Copyright 2008 Wiley-Liss, Inc.

Breast cancer risk assessment and diagnosis model using fuzzy support vector machine based expert system

NASA Astrophysics Data System (ADS)

Dheeba, J.; Jaya, T.; Singh, N. Albert

2017-09-01

Classification of cancerous masses is a challenging task in many computerised detection systems. Cancerous masses are difficult to detect because these masses are obscured and subtle in mammograms. This paper investigates an intelligent classifier - fuzzy support vector machine (FSVM) applied to classify the tissues containing masses on mammograms for breast cancer diagnosis. The algorithm utilises texture features extracted using Laws texture energy measures and a FSVM to classify the suspicious masses. The new FSVM treats every feature as both normal and abnormal samples, but with different membership. By this way, the new FSVM have more generalisation ability to classify the masses in mammograms. The classifier analysed 219 clinical mammograms collected from breast cancer screening laboratory. The tests made on the real clinical mammograms shows that the proposed detection system has better discriminating power than the conventional support vector machine. With the best combination of FSVM and Laws texture features, the area under the Receiver operating characteristic curve reached .95, which corresponds to a sensitivity of 93.27% with a specificity of 87.17%. The results suggest that detecting masses using FSVM contribute to computer-aided detection of breast cancer and as a decision support system for radiologists.

Lymph node toxoplasmosis. Follow-up of 237 histologically diagnosed and serologically verified cases.

PubMed

Miettinen, M; Saxén, L; Saxén, E

1980-01-01

The clinical features, histology and follow-up of lymph node toxoplasmosis are presented in the light of 237 histologically and serologically verified cases. Lymph node toxoplasmosis is a disease with mild symptoms, and in most patients the enlarged lymph nodes were the only sign. Three fourths of the patients were women and the majority were under 40 years of age. The clinical picture was not specific, but suggestive features included a relatively short history, presence of the nodes in the neck and relative lymphocytosis in peripheral blood. Histological changes in the lymph nodes were characteristic. The most important features were strong hyperplasia but preserved general structure with small groups of epithelioid cells both in the paracortical area and in the germinal centers. Strands of monocytoid cells were usually found. 80% of the cases with typical histology also had high antibody titers, and in more than 85% of the cases with high antibodies, the lymph nodes presented a typical picture of toxoplasmosis. The follow-up revealed that lymph node toxoplasmosis. The follow-up revealed that lymph node toxoplasmosis is a disease without complications, nor is there any connection with malignant lymphomas.

Extending information retrieval methods to personalized genomic-based studies of disease.

PubMed

Ye, Shuyun; Dawson, John A; Kendziorski, Christina

2014-01-01

Genomic-based studies of disease now involve diverse types of data collected on large groups of patients. A major challenge facing statistical scientists is how best to combine the data, extract important features, and comprehensively characterize the ways in which they affect an individual's disease course and likelihood of response to treatment. We have developed a survival-supervised latent Dirichlet allocation (survLDA) modeling framework to address these challenges. Latent Dirichlet allocation (LDA) models have proven extremely effective at identifying themes common across large collections of text, but applications to genomics have been limited. Our framework extends LDA to the genome by considering each patient as a "document" with "text" detailing his/her clinical events and genomic state. We then further extend the framework to allow for supervision by a time-to-event response. The model enables the efficient identification of collections of clinical and genomic features that co-occur within patient subgroups, and then characterizes each patient by those features. An application of survLDA to The Cancer Genome Atlas ovarian project identifies informative patient subgroups showing differential response to treatment, and validation in an independent cohort demonstrates the potential for patient-specific inference.

Biomarkers in Prodromal Parkinson Disease: a Qualitative Review.

PubMed

Cooper, Christine A; Chahine, Lama M

2016-11-01

Over the past several years, the concept of prodromal Parkinson disease (PD) has been increasingly recognized. This term refers to individuals who do not fulfill motor diagnostic criteria for PD, but who have clinical, genetic, or biomarker characteristics suggesting risk of developing PD in the future. Clinical diagnosis of prodromal PD has low specificity, prompting the need for objective biomarkers with higher specificity. In this qualitative review, we discuss objectively defined putative biomarkers for PD and prodromal PD. We searched Pubmed and Embase for articles pertaining to objective biomarkers for PD and their application in prodromal cohorts. Articles were selected based on relevance and methodology. Objective biomarkers of demonstrated utility in prodromal PD include ligand-based imaging and transcranial sonography. Development of serum, cerebrospinal fluid, and tissue-based biomarkers is underway, but their application in prodromal PD has yet to meaningfully occur. Combining objective biomarkers with clinical or genetic prodromal features increases the sensitivity and specificity for identifying prodromal PD. Several objective biomarkers for prodromal PD show promise but require further study, including their application to and validation in prodromal cohorts followed longitudinally. Accurate identification of prodromal PD will likely require a multimodal approach. (JINS, 2016, 22, 956-967).

Organizational culture associated with provider satisfaction

PubMed Central

Scammon, Debra L.; Tabler, Jennifer; Brunisholz, Kimberly; Gren, Lisa H.; Kim, Jaewhan; Tomoaia-Cotisel, Andrada; Day, Julie; Farrell, Timothy W.; Waitzman, Norman J.; Magill, Michael K.

2014-01-01

Objectives Assess 1) provider satisfaction with specific elements of PCMH; 2) clinic organizational cultures; 3) associations between provider satisfaction and clinic culture. Methods Cross sectional study with surveys conducted in 2011 with providers and staff in 10 primary care clinics implementing their version of a PCMH: Care by Design™. Measures included the Organizational Culture Assessment Instrument (OCAI) and the American Medical Group Association provider satisfaction survey. Results Providers were most satisfied with quality of care (M=4.14; scale=1–5) and interactions with patients (M=4.12) and least satisfied with time spent working (M=3.47), paper work (M =3.45) and compensation (M=3.35). Culture profiles differed across clinics with family/clan and hierarchical the most common. Significant correlations (p ≤ 0.05) between provider satisfaction and clinic culture archetypes included: family/clan negatively correlated with administrative work; entrepreneurial positively correlated with the Time Spent Working dimension; market/rational positively correlated with how practices were facing economic and strategic challenges; and hierarchical negatively correlated with Relationships with Staff and Resource dimensions. Discussion Provider satisfaction is an important metric for assessing experiences with features of a PCMH model. Conclusions Identification of clinic-specific culture archetypes and archetype associations with provider satisfaction can help inform practice redesign. Attention to effective methods for changing organizational culture is recommended. PMID:24610184

Actors involved in the regulation of clinical research: comparison of Finland to England, Canada, and the USA.

PubMed

Hemminki, Elina

2015-04-07

The relevance and quantity of clinical research has caused concern and regulation is claimed to hinder clinical research. This paper compares clinical research regulations in Finland to those of England, Canada, and the USA around 2010-2011. Several approaches and data sources were used, including semi- or unstructured interviews of experts. For the analysis, a theoretical framework was made, data from various sources was synthesized, and features of the systems were simplified and classified. The various specific names and terms used in the data were changed into general ones. Common structures for the regulation existed in all four countries, but the details and scope varied. The research regulated within the main system was determined by research type (Finland), the financer of the health system (England), or research site (Canada, USA). Only Finland had specific legislation on medical research. The overriding impression of the regulatory systems was one of complexity. All countries had extra regulation for drug research. The types of drug research covered varied from trials with unlicensed (new) products or new indications (USA and Canada), to all types of interventional drug research (England), where 'interventional' was interpreted broadly (Finland). The complexity of regulations had led to the creation of various big and small businesses to help researchers and sponsors. There was notable variation in the role played by the public research funder. The role played by health care was difficult to study and seemed to involve varying interests as researchers were also health care employees. Research ethics committees were important and their tasks also included aspects other than ethics. This study revealed that a comparison between countries can provide useful insights into the distinctive aspects of each country's system, as well as identifying common features that require international action.

MUC1 Expression by Immunohistochemistry Is Associated with Adverse Pathologic Features in Prostate Cancer: A Multi-Institutional Study.

PubMed

Eminaga, Okyaz; Wei, Wei; Hawley, Sarah J; Auman, Heidi; Newcomb, Lisa F; Simko, Jeff; Hurtado-Coll, Antonio; Troyer, Dean A; Carroll, Peter R; Gleave, Martin E; Lin, Daniel W; Nelson, Peter S; Thompson, Ian M; True, Lawrence D; McKenney, Jesse K; Feng, Ziding; Fazli, Ladan; Brooks, James D

2016-01-01

The uncertainties inherent in clinical measures of prostate cancer (CaP) aggressiveness endorse the investigation of clinically validated tissue biomarkers. MUC1 expression has been previously reported to independently predict aggressive localized prostate cancer. We used a large cohort to validate whether MUC1 protein levels measured by immunohistochemistry (IHC) predict aggressive cancer, recurrence and survival outcomes after radical prostatectomy independent of clinical and pathological parameters. MUC1 IHC was performed on a multi-institutional tissue microarray (TMA) resource including 1,326 men with a median follow-up of 5 years. Associations with clinical and pathological parameters were tested by the Chi-square test and the Wilcoxon rank sum test. Relationships with outcome were assessed with univariable and multivariable Cox proportional hazard models and the Log-rank test. The presence of MUC1 expression was significantly associated with extracapsular extension and higher Gleason score, but not with seminal vesicle invasion, age, positive surgical margins or pre-operative serum PSA levels. In univariable analyses, positive MUC1 staining was significantly associated with a worse recurrence free survival (RFS) (HR: 1.24, CI 1.03-1.49, P = 0.02), although not with disease specific survival (DSS, P>0.5). On multivariable analyses, the presence of positive surgical margins, extracapsular extension, seminal vesicle invasion, as well as higher pre-operative PSA and increasing Gleason score were independently associated with RFS, while MUC1 expression was not. Positive MUC1 expression was not independently associated with disease specific survival (DSS), but was weakly associated with overall survival (OS). In our large, rigorously designed validation cohort, MUC1 protein expression was associated with adverse pathological features, although it was not an independent predictor of outcome after radical prostatectomy.

Report of a new case with pentasomy X and novel clinical findings

PubMed Central

Demirhan, O; Tanriverdi, N; Yilmaz, MB; Kocaturk-Sel, S; Inandiklioglu, N; Luleyap, U; Akbal, E; Comertpay, G; Tufan, T; Dur, O

2015-01-01

Pentasomy X is an extremely rare sex chromosome abnormality, a condition that only affects females, in which three more X chromosomes are added to the normally present two chromosomes in females. We investigated the novel clinical findings in a 1-year-old female baby with pentasomy X, and determined the parental origins of the X chromosomes. Our case had thenar atrophy, postnatal growth deficiency, developmental delay, mongoloid slant, microcephaly, ear anomalies, micrognathia and congenital heart disease. A conventional cytogenetic technique was applied for the diagnosis of the polysomy X, and quantitative fluorescent polymerase chain reaction (QF-PCR) using 11 inherited short tandem repeat (STR) alleles specific to the chromosome X for the determination of parental origin of X chromosomes. A cytogenetic evaluation revealed that the karyotype of the infant was 49,XXXXX. Comparison of the infant’s features with previously reported cases indicated a clinically recognizable specific pattern of malformations referred to as the pentasomy X syndrome. However, to the best of our know-ledge, this is the first report of thenar atrophy in a patient with 49,XXXXX. The molecular analysis suggested that four X chromosomes of the infant originated from the mother as a result of the non disjunction events in meiosis I and meiosis II. We here state that the clinical manifestations seen in our case were consistent with those described previously in patients with pentasomy X. The degree of early hypotonia constitutes an important early prognostic feature in this syndrome. The pathogenesis of pentasomy X is not clear at present, but it is thought to be caused by successive maternal non disjunctions. PMID:26929910

Evaluation of a real-time PCR assay for rectal screening of OXA-48-producing Enterobacteriaceae in a general intensive care unit of an endemic hospital.

PubMed

Fernández, J; Cunningham, S A; Fernández-Verdugo, A; Viña-Soria, L; Martín, L; Rodicio, M R; Escudero, D; Vazquez, F; Mandrekar, J N; Patel, R

2017-07-01

Carbapenemase-producing Enterobacteriaceae are increasing worldwide. Rectal screening for these bacteria can inform the management of infected and colonized patients, especially those admitted to intensive care units (ICUs). A laboratory developed, qualitative duplex real-time polymerase chain reaction assay for rapid detection of OXA-48-like and VIM producing Enterobacteriaceae, performed on rectal swabs, was designed and evaluated in an intensive care unit with endemic presence of OXA-48. During analytical assay validation, no cross-reactivity was observed and 100% sensitivity and specificity were obtained for both bla OXA-48-like and bla VIM in all spiked clinical samples. During the clinical part of the study, the global sensitivity and specificity of the real-time PCR assay for OXA-48 detection were 95.7% and 100% (P=0.1250), respectively, in comparison with culture; no VIM-producing Enterobacteriaceae were detected. Clinical features of patients in the ICU who were colonized or infected with OXA-48 producing Enterobacteriaceae, including outcome, were analyzed. Most had severe underlying conditions, and had risk factors for colonization with carbapenemase-producing Enterobacteriaceae before or during ICU admission, such as receiving previous antimicrobial therapy, prior healthcare exposure (including long-term care), chronic disease, immunosuppression and/or the presence of an intravascular catheter and/or mechanical ventilation device. The described real-time PCR assay is fast (~2-3hours, if DNA extraction is included), simple to perform and results are easy to interpret, features which make it applicable in the routine of clinical microbiology laboratories. Implementation in endemic hospitals could contribute to early detection of patients colonized by OXA-48 producing Enterobacteriaceae and prevention of their spread. Copyright © 2017 Elsevier Inc. All rights reserved.