Organic Nitrate Therapy, Nitrate Tolerance, and Nitrate-Induced Endothelial Dysfunction: Emphasis on Redox Biology and Oxidative Stress.

PubMed

Daiber, Andreas; Münzel, Thomas

2015-10-10

Organic nitrates, such as nitroglycerin (GTN), isosorbide-5-mononitrate and isosorbide dinitrate, and pentaerithrityl tetranitrate (PETN), when given acutely, have potent vasodilator effects improving symptoms in patients with acute and chronic congestive heart failure, stable coronary artery disease, acute coronary syndromes, or arterial hypertension. The mechanisms underlying vasodilation include the release of •NO or a related compound in response to intracellular bioactivation (for GTN, the mitochondrial aldehyde dehydrogenase [ALDH-2]) and activation of the enzyme, soluble guanylyl cyclase. Increasing cyclic guanosine-3',-5'-monophosphate (cGMP) levels lead to an activation of the cGMP-dependent kinase I, thereby causing the relaxation of the vascular smooth muscle by decreasing intracellular calcium concentrations. The hemodynamic and anti-ischemic effects of organic nitrates are rapidly lost upon long-term (low-dose) administration due to the rapid development of tolerance and endothelial dysfunction, which is in most cases linked to increased intracellular oxidative stress. Enzymatic sources of reactive oxygen species under nitrate therapy include mitochondria, NADPH oxidases, and an uncoupled •NO synthase. Acute high-dose challenges with organic nitrates cause a similar loss of potency (tachyphylaxis), but with distinct pathomechanism. The differences among organic nitrates are highlighted regarding their potency to induce oxidative stress and subsequent tolerance and endothelial dysfunction. We also address pleiotropic effects of organic nitrates, for example, their capacity to stimulate antioxidant pathways like those demonstrated for PETN, all of which may prevent adverse effects in response to long-term therapy. Based on these considerations, we will discuss and present some preclinical data on how the nitrate of the future should be designed.

Organic Nitrate Therapy, Nitrate Tolerance, and Nitrate-Induced Endothelial Dysfunction: Emphasis on Redox Biology and Oxidative Stress

PubMed Central

2015-01-01

Abstract Organic nitrates, such as nitroglycerin (GTN), isosorbide-5-mononitrate and isosorbide dinitrate, and pentaerithrityl tetranitrate (PETN), when given acutely, have potent vasodilator effects improving symptoms in patients with acute and chronic congestive heart failure, stable coronary artery disease, acute coronary syndromes, or arterial hypertension. The mechanisms underlying vasodilation include the release of •NO or a related compound in response to intracellular bioactivation (for GTN, the mitochondrial aldehyde dehydrogenase [ALDH-2]) and activation of the enzyme, soluble guanylyl cyclase. Increasing cyclic guanosine-3′,-5′-monophosphate (cGMP) levels lead to an activation of the cGMP-dependent kinase I, thereby causing the relaxation of the vascular smooth muscle by decreasing intracellular calcium concentrations. The hemodynamic and anti-ischemic effects of organic nitrates are rapidly lost upon long-term (low-dose) administration due to the rapid development of tolerance and endothelial dysfunction, which is in most cases linked to increased intracellular oxidative stress. Enzymatic sources of reactive oxygen species under nitrate therapy include mitochondria, NADPH oxidases, and an uncoupled •NO synthase. Acute high-dose challenges with organic nitrates cause a similar loss of potency (tachyphylaxis), but with distinct pathomechanism. The differences among organic nitrates are highlighted regarding their potency to induce oxidative stress and subsequent tolerance and endothelial dysfunction. We also address pleiotropic effects of organic nitrates, for example, their capacity to stimulate antioxidant pathways like those demonstrated for PETN, all of which may prevent adverse effects in response to long-term therapy. Based on these considerations, we will discuss and present some preclinical data on how the nitrate of the future should be designed. Antioxid. Redox Signal. 23, 899–942. PMID:26261901

[Pulmonary-renal crosstalk in the critically ill patient].

PubMed

Donoso F, Alejandro; Arriagada S, Daniela; Cruces R, Pablo

2015-01-01

Despite advances in the development of renal replacement therapy, mortality of acute renal failure remains high, especially when occurring simultaneously with distant organic failure as it is in the case of the acute respiratory distress syndrome. In this update, birideccional deleterious relationship between lung and kidney on the setting of organ dysfunction is reviewed, which presents important clinical aspects of knowing. Specifically, the renal effects of acute respiratory distress syndrome and the use of positive-pressure mechanical ventilation are discussed, being ventilator induced lung injury one of the most common models for studying the lung-kidney crosstalk. The role of renal failure induced by mechanical ventilation (ventilator-induced kidney injury) in the pathogenesis of acute renal failure is emphasized. We also analyze the impact of the acute renal failure in the lung, recognizing an increase in pulmonary vascular permeability, inflammation, and alteration of sodium and water channels in the alveolar epithelial. This conceptual model can be the basis for the development of new therapeutic strategies to use in patients with multiple organ dysfunction syndrome. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Lactate Clearance and Normalization and Prolonged Organ Dysfunction in Pediatric Sepsis.

PubMed

Scott, Halden F; Brou, Lina; Deakyne, Sara J; Fairclough, Diane L; Kempe, Allison; Bajaj, Lalit

2016-03-01

To evaluate whether lactate clearance and normalization during emergency care of pediatric sepsis is associated with lower rates of persistent organ dysfunction. This was a prospective cohort study of 77 children <18 years of age in the emergency department with infection and acute organ dysfunction per consensus definitions. In consented patients, lactate was measured 2 and/or 4 hours after an initial lactate; persistent organ dysfunction was assessed through laboratory and physician evaluation at 48 hours. A decrease of ≥ 10% from initial to final level was considered lactate clearance; a final level < 2 mmol/L was considered lactate normalization. Relative risk (RR) with 95% CIs, adjusted in a log-binomial model, was used to evaluate associations between lactate clearance/normalization and organ dysfunction. Lactate normalized in 62 (81%) patients and cleared in 70 (91%). The primary outcome, persistent 48-hour organ dysfunction, was present in 32 (42%). Lactate normalization was associated with decreased risk of persistent organ dysfunction (RR 0.46, 0.29-0.73; adjusted RR 0.47, 0.29-0.78); lactate clearance was not (RR 0.70, 0.35-1.41; adjusted RR 0.75, 0.38-1.50). The association between lactate normalization and decreased risk of persistent organ dysfunction was retained in the subgroups with initial lactate ≥ 2 mmol/L and hypotension. In children with sepsis and organ dysfunction, lactate normalization within 4 hours was associated with decreased persistent organ dysfunction. Serial lactate level measurement may provide a useful prognostic tool during the first hours of resuscitation in pediatric sepsis. Copyright © 2016 Elsevier Inc. All rights reserved.

Early lactate clearance is associated with biomarkers of inflammation, coagulation, apoptosis, organ dysfunction and mortality in severe sepsis and septic shock

PubMed Central

2010-01-01

Background Lactate clearance, a surrogate for the magnitude and duration of global tissue hypoxia, is used diagnostically, therapeutically and prognostically. This study examined the association of early lactate clearance with selected inflammatory, coagulation, apoptosis response biomarkers and organ dysfunction scores in severe sepsis and septic shock. Methods Measurements of serum arterial lactate, biomarkers (interleukin-1 receptor antagonist, interleukin-6, interleukin-8, interleukin-10, tumor necrosis factor-alpha, intercellular adhesion molecule-1, high mobility group box-1, D-Dimer and caspase-3), and organ dysfunction scores (Acute Physiology and Chronic Health Evaluation II, Simplified Acute Physiology Score II, Multiple Organ Dysfunction Score, and Sequential Organ Failure Assessment) were obtained in conjunction with a prospective, randomized study examining early goal-directed therapy in severe sepsis and septic shock patients presenting to the emergency department (ED). Lactate clearance was defined as the percent change in lactate levels after six hours from a baseline measurement in the ED. Results Two-hundred and twenty patients, age 65.0 +/- 17.1 years, were examined, with an overall lactate clearance of 35.5 +/- 43.1% and in-hospital mortality rate of 35.0%. Patients were divided into four quartiles of lactate clearance, -24.3 +/- 42.3, 30.1 +/- 7.5, 53.4 +/- 6.6, and 75.1 +/- 7.1%, respectively (p < 0.01). The mean levels of all biomarkers and organ dysfunction scores over 72 hours were significantly lower with higher lactate clearance quartiles (p < 0.01). There was a significant decreased in-hospital, 28-day, and 60-day mortality in the higher lactate clearance quartiles (p < 0.01). Conclusions Early lactate clearance as a surrogate for the resolution of global tissue hypoxia is significantly associated with decreased levels of biomarkers, improvement in organ dysfunction and outcome in severe sepsis and septic shock. PMID:20181046

Management of Chronic Kidney Disease Patients in the Intensive Care Unit: Mixing Acute and Chronic Illness.

PubMed

De Rosa, Silvia; Samoni, Sara; Villa, Gianluca; Ronco, Claudio

2017-01-01

Patients with chronic kidney disease (CKD) are at high risk for developing critical illness and for admission to intensive care units (ICU). 'Critically ill CKD patients' frequently develop an acute worsening of renal function (i.e. acute-on-chronic, AoC) that contributes to long-term kidney dysfunction, potentially leading to end-stage kidney disease (ESKD). An integrated multidisciplinary effort is thus necessary to adequately manage the multi-organ damage of those kidney patients and contemporaneously reduce the progression of kidney dysfunction when they are critically ill. The aim of this review is to describe (1) the pathophysiological mechanisms underlying the development of AoC kidney dysfunction and its role in the progression toward ESKD; (2) the most common clinical presentations of critical illness among CKD/ESKD patients; and (3) the continuum of care for CKD/ESKD patients from maintenance hemodialysis/peritoneal dialysis to acute renal replacement therapy performed in ICU and, vice-versa, for AoC patients who develop ESKD. © 2017 S. Karger AG, Basel.

Hybrid Revascularization for Critical Limb Ischemia Triggered by Multiple Organ Dysfunction Due to Acute Pneumonia; Urgent Catheter Intervention Followed by Low-Density-Lipoprotein Apheresis and Elective Peripheral Bypass Surgery

PubMed Central

2014-01-01

A 66-year-old man was referred for treatment of critical limb ischemia arising with multiple organ dysfunction due to acute pneumonia. Angiographic examinations demonstrated total obstruction of the bilateral external iliac arteries and the bilateral superficial femoral arteries with collateral circulation to the distal vessels. Urgent percutaneous transluminal angioplasty dissolved the obstruction of the left external iliac artery, and subsequent low-density-lipoprotein apheresis ameliorated his progressive ischemia in the lower extremities. Femoro-femoral and bilateral femoro-popliteal bypasses were performed 31 days after the endovascular intervention, which achieved successful limb salvage with the relief of ischemic symptoms related to arteriosclerotic obliterans. PMID:24995063

[PATHOPHYSIOLOGY OF THE CARDIORENAL SYNDROME].

PubMed

Balint, I; Vučak, J; Bašić-Marković, N; Klarić, D; Šakić, V Amerl

2016-12-01

Cardiorenal syndrome, a complex pathophysiological disorder of both the heart and kidneys, is a condition in which acute or chronic damage to one organ can lead to acute or chronic dysfunction of the other organ. Depending on primary organ dysfunction and disease duration, there are five different types of cardiorenal syndrome. Type 1 cardiorenal syndrome (acute cardiorenal syndrome) is defined as acute kidney injury caused by sudden decrease in heart function. Type 2 cardiorenal syndrome (chronic cardiorenal syndrome) refers to chronic kidney disease linked to chronic heart failure. Type 3 cardiorenal syndrome (acute renocardial syndrome) is caused by acute kidney injury that leads to heart failure. Type 4 cardiorenal syndrome (chronic renocardial syndrome) includes chronic heart failure due to chronic kidney disease. Type 5 cardiorenal syndrome (secondary cardiorenal syndrome) is reversible or irreversible condition marked by simultaneous heart and kidney insufficiency, as a result of multiorgan disease such as sepsis, diabetes mellitus, sarcoidosis, amyloidosis, etc. The pathophysiological patterns of cardiorenal syndrome are extremely complicated. Despite numerous publications, perplexed physiological, biochemical and hormonal disturbances as parts of the main pathogenic mechanisms of cardiorenal syndrome remain obscure. Even though there are guidelines for the treatment of patients with heart failure and chronic kidney disease, similar guidelines for the treatment of cardiorenal syndrome are lacking. In everyday practice, it is crucial to diagnose cardiorenal syndrome and use all diagnostic and therapeutic procedures available to prevent or alleviate kidney and heart failure.

High-volume plasma exchange in a patient with acute liver failure due to non-exertional heat stroke in a sauna.

PubMed

Chen, Kuan-Jung; Chen, Tso-Hsiao; Sue, Yuh-Mou; Chen, Tzay-Jinn; Cheng, Chung-Yi

2014-10-01

Heat stroke is a life-threatening condition characterized by an increased core body temperature (over 40°C) and a systemic inflammatory response, which may lead to a syndrome of multiple organ dysfunction. Heat stroke may be due to either strenuous exercise or non-exercise-induced exposure to a high environmental temperature. Current management of heat stroke is mostly supportive, with an emphasis on cooling the core body temperature and preventing the development of multiple organ dysfunction. Prognosis of heat stroke depends on the severity of organ involvement. Here, we report a rare case of non-exercise-induced heat stroke in a 73-year-old male patient who was suffering from acute liver failure after prolonged exposure in a hot sauna room. We successfully managed this patient by administering high-volume plasma exchange, and the patient recovered completely after treatment. © 2014 Wiley Periodicals, Inc.

[An analysis of the clinical and epidemiological characteristics of acute poisoning patients in a general hospital].

PubMed

Hou, Y H; Zhao, Q; Wu, Y X; Hu, T T; Chen, Y; You, Y T; Kang, X W; Hong, G L; Lu, Z Q

2016-07-20

Objective: To analyze the clinical and epidemiological characteristics of acute poisoning patients in a general hospital, then to provide a reference for the prevention and treatment of acute poisoning in the future. Methods: A retrospective analysis was made on the clinical data of 660 patients with acute poisoning admitted in emergency medical center of the First Affiliated Hospital of Wenzhou Medical University from July 2009 to May 2015. Results: More men than women in 660 cases with acute poisoning(the ratio of male to female was 1.36∶1) ; ≥30 years old was the high incidence age (78.79%) ; The top occupation was farmers (39.70%) ; Most were life poisoning (88.18%) , suicide was the main reason (62.42%) especially happened in women, and the main cause of suicide was family conflicts; Toxic species dominated by pesticide (67.58%) , most were severe poisoning (81.82%) ; The top two pesticide poisoning were organic phosphorus and paraquat, and the proportion of blood purification in paraquat was significantly higher (χ 2 =105.21, P =0.00) ; There were 212 cases with organ dysfunction, main were pesticide poisoning patients, and the proportionof organ dysfunction in paraquat was significantly higher than the rest allpesticide poisoning (χ 2 =45.09, P =0.00) ; The general fatal rate of acute poisoning was 2.27%, and the proportion in paraquat poisoning was .higher than the rest pesticide poisoning who were death and give up when discharged (χ 2 =56.83, P =0.00) . Conclusion: The focus of acute poisoning in the general hospital is still pesticide (especially organic phosphorus and paraquat) , and most were severe poisoning.

The Epidemiology of Hospital Death Following Pediatric Severe Sepsis: When, Why, and How Children With Sepsis Die.

PubMed

Weiss, Scott L; Balamuth, Fran; Hensley, Josey; Fitzgerald, Julie C; Bush, Jenny; Nadkarni, Vinay M; Thomas, Neal J; Hall, Mark; Muszynski, Jennifer

2017-09-01

The epidemiology of in-hospital death after pediatric sepsis has not been well characterized. We investigated the timing, cause, mode, and attribution of death in children with severe sepsis, hypothesizing that refractory shock leading to early death is rare in the current era. Retrospective observational study. Emergency departments and ICUs at two academic children's hospitals. Seventy-nine patients less than 18 years old treated for severe sepsis/septic shock in 2012-2013 who died prior to hospital discharge. None. Time to death from sepsis recognition, cause and mode of death, and attribution of death to sepsis were determined from medical records. Organ dysfunction was assessed via daily Pediatric Logistic Organ Dysfunction-2 scores for 7 days preceding death with an increase greater than or equal to 5 defined as worsening organ dysfunction. The median time to death was 8 days (interquartile range, 1-12 d) with 25%, 35%, and 49% of cumulative deaths within 1, 3, and 7 days of sepsis recognition, respectively. The most common cause of death was refractory shock (34%), then multiple organ dysfunction syndrome after shock recovery (27%), neurologic injury (19%), single-organ respiratory failure (9%), and nonseptic comorbidity (6%). Early deaths (≤ 3 d) were mostly due to refractory shock in young, previously healthy patients while multiple organ dysfunction syndrome predominated after 3 days. Mode of death was withdrawal in 72%, unsuccessful cardiopulmonary resuscitation in 22%, and irreversible loss of neurologic function in 6%. Ninety percent of deaths were attributable to acute or chronic manifestations of sepsis. Only 23% had a rise in Pediatric Logistic Organ Dysfunction-2 that indicated worsening organ dysfunction. Refractory shock remains a common cause of death in pediatric sepsis, especially for early deaths. Later deaths were mostly attributable to multiple organ dysfunction syndrome, neurologic, and respiratory failure after life-sustaining therapies were limited. A pattern of persistent, rather than worsening, organ dysfunction preceded most deaths.

Rhabdomyolysis and acute kidney injury in patients with traumatic spinal cord injury

PubMed Central

Galeiras, Rita; Mourelo, Mónica; Pértega, Sonia; Lista, Amanda; Ferreiro, Mª Elena; Salvador, Sebastián; Montoto, Antonio; Rodríguez, Antonio

2016-01-01

Background: Patients with acute traumatic spinal cord injuries (SCIs) exhibit factors that, in other populations, have been associated with rhabdomyolysis. Purpose: The aim of the study is to determine the incidence of rhabdomyolysis in patients with acute traumatic SCI admitted to the Intensive Care Unit (ICU), as well as the development of secondary acute kidney injury and associated factors. Study Design and Setting: This was an observational, retrospective study. Patient Sample: All adult patients admitted to the ICU with acute traumatic SCI who presented rhabdomyolysis, diagnosed through creatine phosphokinase (CPK) levels >500 IU/L. Outcome Measures: Incidence of rhabdomyolysis and subsequent renal dysfunction was calculated. Materials and Methods: Data about demographic variables, comorbidity, rhabdomyolysis risk factors, and variables involving SCI, severity scores, and laboratory parameters were obtained from clinical records. Multivariate logistic regression was used to identify renal injury risk factors. Results: In 2006–2014, 200 patients with acute SCI were admitted to ICU. Of these, 103 had rhabdomyolysis (incidence = 51.5%; 95% confidence interval [CI]: 44.3%–58.7%). The most typical American Spinal Injury Association classification was A (70.3%). The injury severity score was 30.3 ± 12.1 and sequential organ failure assessment (SOFA) score was 5.6 ± 3.3 points. During their stay, 57 patients (55.3%; 95% CI: 45.2%–65.4%) presented renal dysfunction (creatinine ≥1.2 mg/dL). In the multivariate analysis, variables associated with renal dysfunction were creatinine at admission (odds ratio [OR] = 9.20; P = 0.006) and hemodynamic SOFA score the day following admission (OR = 1.33; P = 0.024). Creatinine was a better predictor of renal dysfunction than the peak CPK value during the rhabdomyolysis (area under the receiver operating characteristic curve: 0.91 vs. 0.63, respectively). Conclusions: Rhabdomyolysis is a frequent condition in patients with acute traumatic SCI admitted to the ICU, and renal dysfunction occurs in half of the cases. Creatinine values should be requested starting at the admission while neither the peak CPK values nor the hemodynamic SOFA scores could be used to properly discriminate between patients with and without renal dysfunction. PMID:27688625

Bioartificial organ support for hepatic, renal, and hematologic failure.

PubMed

Maguire, P J; Stevens, C; Humes, H D; Shander, A; Halpern, N A; Pastores, S M

2000-10-01

The current strategy to the treatment of SIRS and MODS uses a multidisciplinary approach that emphasizes supportive therapy. Herein, we have presented a futuristic approach that focuses on replacing the function of failed organs using bioartificial technology (Table 1). Bioartificial organ technology may allow the intensivist to provide physiologic organ replacement either as a bridge to transplantation or as a "time-buying" element until native organs that have become acutely dysfunctional or nonfunctional in a variety of clinical settings, can recover their function or regenerate their mass. As bioartificial organ technology matures, it is conceivable as an ultimate goal that non-immunogenic bioartificial organs would be miniaturized or redesigned and acutely placed within the intracorporeal space as replacement organs.

Thrombopoietin as Early Biomarker of Disease Severity in Patients With Acute Pancreatitis.

PubMed

Lupia, Enrico; Pigozzi, Luca; Pivetta, Emanuele; Bosco, Ornella; Vizio, Barbara; Loiacono, Maria; Lucchiari, Manuela; Battista, Stefania; Morello, Fulvio; Moiraghi, Corrado; Mengozzi, Giulio; Montrucchio, Giuseppe

2017-02-01

To study the concentrations of thrombopoietin (TPO), a growth factor recently involved in the pathogenesis of experimental acute pancreatitis (AP), and its potential role as an early diagnostic and prognostic biomarker in patients with AP. Thrombopoietin was measured in 44 AP patients, 18 patients with nonpancreatic acute abdominal pain, and 18 healthy volunteers. Acute pancreatitis severity was classified on the basis of the 2012 International Atlanta Symposium on Acute Pancreatitis criteria. Thrombopoietin levels did not differ between AP patients and control subjects, whereas these were higher in patients with moderately severe or severe AP compared with those with mild AP. Receiver operating characteristic curve analysis of TPO for severe AP diagnosis showed an area under the curve of 0.80. A cutoff value of 31.48 pg/mL showed the highest sensitivity, allowing to rule out severe AP when TPO was lower, whereas TPO higher than 98.23 pg/mL was associated with severe AP with high specificity (93.5%). Furthermore, TPO levels were greater in AP patients developing organ dysfunction or sepsis and in nonsurvivors compared with survivors. Our data provide the first evidence for TPO as potential early prognostic biomarker in AP patients. High TPO levels at hospital admission may predict organ dysfunction, sepsis, and fatal outcome in AP patients.

Kidney-Heart Interactions in Acute Kidney Injury.

PubMed

Doi, Kent

2016-01-01

Acute kidney injury (AKI) is a common complication in critically ill patients treated in intensive care units. Renal replacement therapy (RRT)-requiring AKI occurs in approximately 5-10% patients in intensive care unit and their mortality rate is unacceptably high (50-60%), despite sufficient control of uremia using remarkably advanced modern RRT techniques. This suggests that there are unrecognized organ interactions following AKI that could worsen the outcomes. Cardiorenal syndrome has been defined based on clinical observations that acute and chronic heart failure causes kidney injury and AKI and that chronic kidney disease worsens heart diseases. Possible pathways that connect these 2 organs have been suggested; however, the precise mechanisms are yet to be clarified, particularly in AKI-induced cardiac dysfunction. This review focuses on acute cardiac dysfunction in the setting of AKI. A recent animal study demonstrated the dysregulation of mitochondrial dynamics caused by an increased dynamin-related protein 1 expression and cellular apoptosis of the heart in a renal ischemia reperfusion model. Although the precise mechanisms that induce cardiac mitochondrial injury in AKI remain unclear, cardiac mitochondria injury could be a novel candidate of drug targets against high mortality in severe AKI. © 2016 S. Karger AG, Basel.

Skeletal Muscle and Lymphocyte Mitochondrial Dysfunctions in Septic Shock Trigger ICU-Acquired Weakness and Sepsis-Induced Immunoparalysis.

PubMed

Maestraggi, Quentin; Lebas, Benjamin; Clere-Jehl, Raphaël; Ludes, Pierre-Olivier; Chamaraux-Tran, Thiên-Nga; Schneider, Francis; Diemunsch, Pierre; Geny, Bernard; Pottecher, Julien

2017-01-01

Fundamental events driving the pathological processes of septic shock-induced multiorgan failure (MOF) at the cellular and subcellular levels remain debated. Emerging data implicate mitochondrial dysfunction as a critical factor in the pathogenesis of sepsis-associated MOF. If macrocirculatory and microcirculatory dysfunctions undoubtedly participate in organ dysfunction at the early stage of septic shock, an intrinsic bioenergetic failure, sometimes called "cytopathic hypoxia," perpetuates cellular dysfunction. Short-term failure of vital organs immediately threatens patient survival but long-term recovery is also severely hindered by persistent dysfunction of organs traditionally described as nonvital, such as skeletal muscle and peripheral blood mononuclear cells (PBMCs). In this review, we will stress how and why a persistent mitochondrial dysfunction in skeletal muscles and PBMC could impair survival in patients who overcome the first acute phase of their septic episode. First, muscle wasting protracts weaning from mechanical ventilation, increases the risk of mechanical ventilator-associated pneumonia, and creates a state of ICU-acquired muscle weakness, compelling the patient to bed. Second, failure of the immune system ("immunoparalysis") translates into its inability to clear infectious foci and predisposes the patient to recurrent nosocomial infections. We will finally emphasize how mitochondrial-targeted therapies could represent a realistic strategy to promote long-term recovery after sepsis.

Triage of patients with acute gastrointestinal bleeding for intensive care unit admission based on risk factors for poor outcome.

PubMed

Afessa, B

2000-04-01

This study's aim was to determine the prognostic factors and to develop a triage system for intensive care unit (ICU) admission of patients with gastrointestinal bleeding (GIB). This prospective, observational study included 411 adults consecutively hospitalized for GIB. Each patient's selected clinical findings and laboratory values at presentation were obtained. The Acute Physiology and Chronic Health Evaluation (APACHE) II scores were calculated from the initial findings in the emergency department. Poor outcome was defined as recurrent GIB, emergency surgery, or death. The role of hepatic cirrhosis, APACHE II score, active GIB, end-organ dysfunction, and hypotension in predicting outcome was evaluated. Chi-square, Student's t, Mann-Whitney U, and logistic regression analysis tests were used for statistical comparisons. Poor outcome developed in 81 (20%) patients; 39 died, 23 underwent emergency surgery, and 47 rebled. End-organ dysfunction, active bleeding, hepatic cirrhosis, and high APACHE II scores were independent predictors of poor outcome with odds ratios of 3:1, 3:1, 2:3, and 1:1, respectively. The ICU admission rate was 37%. High APACHE II score, active bleeding, end-organ dysfunction, and hepatic cirrhosis are independent predictors of poor outcome in patients with GIB and can be used in the triage of these patients for ICU admission.

Serial evaluation of the MODS, SOFA and LOD scores to predict ICU mortality in mixed critically ill patients.

PubMed

Khwannimit, Bodin

2008-09-01

To perform a serial assessment and compare ability in predicting the intensive care unit (ICU) mortality of the multiple organ dysfunction score (MODS), sequential organ failure assessment (SOFA) and logistic organ dysfunction (LOD) score. The data were collected prospectively on consecutive ICU admissions over a 24-month period at a tertiary referral university hospital. The MODS, SOFA, and LOD scores were calculated on initial and repeated every 24 hrs. Two thousand fifty four patients were enrolled in the present study. The maximum and delta-scores of all the organ dysfunction scores correlated with ICU mortality. The maximum score of all models had better ability for predicting ICU mortality than initial or delta score. The areas under the receiver operating characteristic curve (AUC) for maximum scores was 0.892 for the MODS, 0.907 for the SOFA, and 0.92for the LOD. No statistical difference existed between all maximum scores and Acute Physiology and Chronic Health Evaluation II (APACHE II) score. Serial assessment of organ dysfunction during the ICU stay is reliable with ICU mortality. The maximum scores is the best discrimination comparable with APACHE II score in predicting ICU mortality.

Renal Hypoxia and Dysoxia After Reperfusion of the Ischemic Kidney

PubMed Central

Legrand, Matthieu; Mik, Egbert G; Johannes, Tanja; Payen, Didier; Ince, Can

2008-01-01

Ischemia is the most common cause of acute renal failure. Ischemic-induced renal tissue hypoxia is thought to be a major component in the development of acute renal failure in promoting the initial tubular damage. Renal oxygenation originates from a balance between oxygen supply and consumption. Recent investigations have provided new insights into alterations in oxygenation pathways in the ischemic kidney. These findings have identified a central role of microvascular dysfunction related to an imbalance between vasoconstrictors and vasodilators, endothelial damage and endothelium–leukocyte interactions, leading to decreased renal oxygen supply. Reduced microcirculatory oxygen supply may be associated with altered cellular oxygen consumption (dysoxia), because of mitochondrial dysfunction and activity of alternative oxygen-consuming pathways. Alterations in oxygen utilization and/or supply might therefore contribute to the occurrence of organ dysfunction. This view places oxygen pathways’ alterations as a potential central player in the pathogenesis of acute kidney injury. Both in regulation of oxygen supply and consumption, nitric oxide seems to play a pivotal role. Furthermore, recent studies suggest that, following acute ischemic renal injury, persistent tissue hypoxia contributes to the development of chronic renal dysfunction. Adaptative mechanisms to renal hypoxia may be ineffective in more severe cases and lead to the development of chronic renal failure following ischemia-reperfusion. This paper is aimed at reviewing the current insights into oxygen transport pathways, from oxygen supply to oxygen consumption in the kidney and from the adaptation mechanisms to renal hypoxia. Their role in the development of ischemia-induced renal damage and ischemic acute renal failure are discussed. PMID:18488066

Exertional heat stroke and acute liver failure: a late dysfunction

PubMed Central

Carvalho, Ana Sofia; Rodeia, Simão C; Silvestre, Joana; Póvoa, Pedro

2016-01-01

Heat stroke (HS) is defined as a severe elevation of core body temperature along with central nervous system dysfunction. Exertional heat stroke (EHS) with acute liver failure (ALF) is a rare condition. The authors report the case of a 25-year-old man with a history of cognitive enhancers’ intake who developed hyperthermia and neurological impairment while running an outdoor marathon. The patient was cooled and returned to normal body temperature after 6 h. He subsequently developed ALF and was transferred to the intensive care unit. Over-the-counter drug intake may have been related to heat intolerance and contributed to the event. The patient was successfully treated with conservative measures. In the presence of EHS, it is crucial to act promptly with aggressive total body cooling, in order to prevent progression of the clinical syndrome. Liver function must also be monitored, since it can be a late organ dysfunction. PMID:26969359

Randomised, double blind, placebo controlled trial of intravenous antioxidant (n‐acetylcysteine, selenium, vitamin C) therapy in severe acute pancreatitis

PubMed Central

Siriwardena, Ajith K; Mason, James M; Balachandra, Srinivasan; Bagul, Anil; Galloway, Simon; Formela, Laura; Hardman, Jonathan G; Jamdar, Saurabh

2007-01-01

Background Based on equivocal clinical data, intravenous antioxidant therapy has been used for the treatment of severe acute pancreatitis. To date there is no randomised comparison of this therapy in severe acute pancreatitis. Methods We conducted a randomised, double blind, placebo controlled trial of intravenous antioxidant (n‐acetylcysteine, selenium, vitamin C) therapy in patients with predicted severe acute pancreatitis. Forty‐three patients were enrolled from three hospitals in the Manchester (UK) area over the period June 2001 to November 2004. Randomisation stratified for APACHE‐II score and hospital site, and delivered groups that were similar at baseline. Results Relative serum levels of antioxidants rose while markers of oxidative stress fell in the active treatment group during the course of the trial. However, at 7 days, there was no statistically significant difference in the primary end point, organ dysfunction (antioxidant vs placebo: 32% vs 17%, p = 0.33) or any secondary end point of organ dysfunction or patient outcome. Conclusions This study provides no evidence to justify continued use of n‐acetylcysteine, selenium, vitamin C based antioxidant therapy in severe acute pancreatitis. In the context of any future trial design, careful consideration must be given to the risks raised by the greater trend towards adverse outcome in patients in the treatment arm of this study. PMID:17356040

Effects of disease severity and necrosis on pancreatic dysfunction after acute pancreatitis.

PubMed

Garip, Gokhan; Sarandöl, Emre; Kaya, Ekrem

2013-11-28

To evaluate the effects of disease severity and necrosis on organ dysfunctions in acute pancreatitis (AP). One hundred and nine patients treated as AP between March 2003 and September 2007 with at least 6 mo follow-up were included. Patients were classified according to severity of the disease, necrosis ratio and localization. Subjective clinical evaluation and fecal pancreatic elastase-I (FPE-I) were used for exocrine dysfunction evaluation, and oral glucose tolerance test was completed for endocrine dysfunction. The correlation of disease severity, necrosis ratio and localization with exocrine and endocrine dysfunction were investigated. There were 58 male and 51 female patients, and mean age was 56.5 ± 15.7. Of the patients, 35.8% had severe AP (SAP) and 27.5% had pancreatic necrosis. Exocrine dysfunction was identified in 13.7% of the patients [17.9% were in SAP, 11.4% were in mild AP (MAP)] and 34.7% of all of the patients had endocrine dysfunction (56.4% in SAP and 23.2% in MAP). In patients with SAP and necrotizing AP (NAP), FPE-Ilevels were lower than the others (P < 0.05 and 0.001 respectively) and in patients having pancreatic head necrosis or near total necrosis, FPE-1 levels were lower than 200 μg/g stool. Forty percent of the patients who had undergone necrosectomy developed exocrine dysfunction. Endocrine dysfunction was more significant in patients with SAP and NAP (P < 0.001). All of the patients in the necrosectomy group had endocrine dysfunction. Patients with SAP, NAP, pancreatic head necrosis and necrosectomy should be followed for pancreatic functions.

Practice patterns, outcomes, and end-organ dysfunction for patients with acute severe hypertension: the Studying the Treatment of Acute hyperTension (STAT) registry.

PubMed

Katz, Jason N; Gore, Joel M; Amin, Alpesh; Anderson, Frederick A; Dasta, Joseph F; Ferguson, James J; Kleinschmidt, Kurt; Mayer, Stephan A; Multz, Alan S; Peacock, W Frank; Peterson, Eric; Pollack, Charles; Sung, Gene Yong; Shorr, Andrew; Varon, Joseph; Wyman, Allison; Emery, Leigh A; Granger, Christopher B

2009-10-01

Limited data are available on the care of patients with acute severe hypertension requiring hospitalization. We characterized contemporary practice patterns and outcomes for this population. STAT is a 25-institution, US registry of consecutive patients with acute severe hypertension (>180 mm Hg systolic and/or >110 mm Hg diastolic; >140 and/or >90 for subarachnoid hemorrhage) treated with intravenous therapy in a critical care setting. One thousand five hundred eighty-eight patients were enrolled (January 2007 to April 2008). Median age was 58 years (interquartile range 49-70 years), 779 (49%) were women, and 892 (56%) were African American; 27% (n = 425) had a prior admission for acute hypertension and 486 (31%) had chronic kidney disease. Median qualifying blood pressure (BP) was 200 (186, 220) systolic and 110 (93, 123) mm Hg diastolic. Initial intravenous antihypertensive therapies used to control BP varied, with 1,009 (64%) patients requiring multiple drugs. Median time to achieve a systolic BP <160 mm Hg (<140 mm Hg for subarachnoid hemorrhage) was 4.0 (0.8, 12) hours; 893 (60%) had reelevation to >180 (>140 for subarachnoid hemorrhage) after initial control; and 63 (4.0%) developed iatrogenic hypotension. Hospital mortality was 6.9% (n = 109) with an aggregate 90-day mortality rate of 11% (174/1,588); 59% (n = 943) had acute/worsening end-organ dysfunction during hospitalization. The 90-day readmission rate was 37% (523/1,415), of which one quarter (132/523) was due to recurrent acute severe hypertension. This study highlights heterogeneity in care, BP control, and outcomes of patients hospitalized with acute severe hypertension.

Immune thrombocytopenia with multi-organ dysfunction syndrome as a rare presentation of scrub typhus: a case report.

PubMed

Ittyachen, Abraham M; Abraham, Saramma P; Krishnamoorthy, Smitha; Vijayan, Anuroopa; Kokkat, Jayamohan

2017-10-06

Scrub typhus is an acute infectious illness caused by Orientia tsutsugamushi. It is endemic to a part of the world known as the "tsutsugamushi triangle". Humans are accidental hosts in this zoonotic disease. About a third of patients admitted with scrub typhus have evidence of multi-organ dysfunction. Multi-organ dysfunction secondary to scrub typhus carries a high mortality rate. We report a 65-year old lady who was admitted in a Tertiary Care Center in the state of Kerala in India, with 7 day history of fever, myalgia and reduced urine output. Head to foot examination revealed the presence of an eschar on her chest. One week prior to the onset of her illness she had gone trekking through a hilly forest area. She was clinically suspected to have scrub typhus, which was later confirmed with laboratory tests. She developed multi-organ dysfunction syndrome secondary to this illness. Though there was an improvement in the multi-organ dysfunction, thrombocytopenia alone failed to improve. Bone marrow study was done which was suggestive of immune thrombocytopenia. Patient was given a course of steroids with which the thrombocytopenia improved. Failure of platelet count to normalize even after there has been a general improvement of other markers of multi-organ dysfunction in scrub typhus should prompt the clinician to consider other potential causes of thrombocytopenia. An unusual finding as this calls for further research to understand the molecular mechanisms behind such an event. Further, considering the close similarity in clinical presentation of several tropical illnesses, meticulous history taking and a detailed physical examination needs to be emphasized.

Acute Right Ventricular Dysfunction in Intensive Care Unit

PubMed Central

Domingo, Enric

2017-01-01

The role of the left ventricle in ICU patients with circulatory shock has long been considered. However, acute right ventricle (RV) dysfunction causes and aggravates many common critical diseases (acute respiratory distress syndrome, pulmonary embolism, acute myocardial infarction, and postoperative cardiac surgery). Several supportive therapies, including mechanical ventilation and fluid management, can make RV dysfunction worse, potentially exacerbating shock. We briefly review the epidemiology, pathophysiology, diagnosis, and recommendations to guide management of acute RV dysfunction in ICU patients. Our aim is to clarify the complex effects of mechanical ventilation, fluid therapy, vasoactive drug infusions, and other therapies to resuscitate the critical patient optimally. PMID:29201914

Acute allograft failure in thoracic organ transplantation.

PubMed

Jahania, M S; Mullett, T W; Sanchez, J A; Narayan, P; Lasley, R D; Mentzer, R M

2000-01-01

Thoracic organ transplantation is an effective form of treatment for end-stage heart and lung disease. Despite major advances in the field, transplant patients remain at risk for acute allograft dysfunction, a major cause of early and late mortality. The most common causes of allograft failure include primary graft failure secondary to inadequate heart and lung preservation during cold storage, cellular rejection, and various donor-recipient-related factors. During cold storage and early reperfusion, heart and lung allografts are vulnerable to intracellular calcium overload, acidosis, cell swelling, injury mediated by reactive oxygen species, and the inflammatory response. Brain death itself is associated with a reduction in myocardial contractility, and recipient-related factors such as preexisting pulmonary hypertension can lead to acute right heart failure and the pulmonary reimplantation response. The development of new methods to prevent or treat these various causes of acute graft failure could lead to a marked improvement in short- and long-term survival of patients undergoing thoracic organ transplantation.

[Epithelial dysfunction associated with pyo-inflammatory diseases of the ENT organs].

PubMed

Petukhova, N A

The modern concept of epithelial-endothelial dysfunction and epithelial-endothelial distress-syndrome associated with pyo-inflammatory ENT diseases is presented. It has provided a basis for the analysis of the initial stages of etiopathogenesis of acute and chronic inflammation in the ENT system including the mucous and associated lymphoid tissues as well as the Pirogov-Waldeyer limphopharyngeal ring making up the first protective barrier. The leading role of dysbiosis of synanthropic microflora and endotoxins of the Gram-negative bacteria in the mechanisms of regional responsiveness of the organism to the infection and chronic endotoxic aggression is demonstrated. The regional and synthetic mechanisms underlying the interaction between the external and internal media of the organism are subjected to the analysis with special reference to those operating in epithelium. The possible variants of the outcome of these processes are considered including both the recovery and the development of chronic inflammation. It has been proved that the exhaustion of the internal reserves for the stabilization of the epithelium-associated lymphoid tissue system including the Pirogov-Waldeyer limphopharyngeal ring leads to the formation of epithelial dysfunction as the initial stage of epithelial-endothelial dysfunction and epithelial-endothelial distress-syndrome. It is concluded that the modern concept of epithelial-endothelial dysfunction and epithelial-endothelial distress-syndrome is a fundamental interdisciplinary phenomenon.

Experimental evidence of obesity as a risk factor for severe acute pancreatitis.

PubMed

Frossard, Jean-Louis; Lescuyer, Pierre; Pastor, Catherine M

2009-11-14

The incidence of acute pancreatitis, an inflammation of the pancreas, is increasing worldwide. Pancreatic injury is mild in 80%-90% of patients who recover without complications. The remaining patients may develop a severe disease with local complications such as acinar cell necrosis, abscess and remote organ injury including lung injury. The early prediction of the severity of the disease is an important goal for physicians in management of patients with acute pancreatitis in order to optimize the therapy and to prevent organ dysfunction and local complications. For that purpose, multiple clinical scale scores have been applied to patients with acute pancreatitis. Recently, a new problem has emerged: the increased severity of the disease in obese patients. However, the mechanisms by which obesity increases the severity of acute pancreatitis are unclear. Several hypotheses have been suggested: (1) obese patients have an increased inflammation within the pancreas; (2) obese patients have an increased accumulation of fat within and around the pancreas where necrosis is often located; (3) increase in both peri- and intra-pancreatic fat and inflammatory cells explain the high incidence of pancreatic inflammation and necrosis in obese patients; (4) hepatic dysfunction associated with obesity might enhance the systemic inflammatory response by altering the detoxification of inflammatory mediators; and (5) ventilation/perfusion mismatch leading to hypoxia associated with a low pancreatic flow might reduce the pancreatic oxygenation and further enhance pancreatic injury. Recent experimental investigations also show an increased mortality and morbidity in obese rodents with acute pancreatitis and the implication of the adipokines leptin and adiponectin. Such models are important to investigate whether the inflammatory response of the disease is enhanced by obesity. It is exciting to speculate that manipulation of the adipokine milieu has the potential to influence the severity of acute pancreatitis.

Cardiovascular and systemic effects of gastric dilatation and volvulus in dogs.

PubMed

Sharp, Claire R; Rozanski, Elizabeth A

2014-09-01

Gastric dilatation and volvulus (GDV) is a common emergency condition in large and giant breed dogs that is associated with high morbidity and mortality. Dogs with GDV classically fulfill the criteria for the systemic inflammatory response syndrome (SIRS) and can go on to develop multiple organ dysfunction syndrome (MODS). Previously reported organ dysfunctions in dogs with GDV include cardiovascular, respiratory, gastrointestinal, coagulation and renal dysfunction. Cardiovascular manifestations of GDV include shock, cardiac arrhythmias and myocardial dysfunction. Respiratory dysfunction is also multifactorial, with contributory factors including decreased respiratory excursion due to gastric dilatation, decreased pulmonary perfusion and aspiration pneumonia. Gastrointestinal dysfunction includes gastric necrosis and post-operative gastrointestinal upset such as regurgitation, vomiting, and ileus. Coagulation dysfunction is another common feature of MODS in dogs with GDV. Disseminated intravascular coagulation can occur, putting them at risk of complications associated with thrombosis in the early hypercoagulable state and hemorrhage in the subsequent hypocoagulable state. Acute kidney injury, acid-base and electrolyte disturbances are also reported in dogs with GDV. Understanding the potential for systemic effects of GDV allows the clinician to monitor patients astutely and detect such complications early, facilitating early intervention to maximize the chance of successful management. Copyright © 2014 Elsevier Inc. All rights reserved.

Development of a novel score for the prediction of hospital mortality in patients with severe sepsis: the use of electronic healthcare records with LASSO regression.

PubMed

Zhang, Zhongheng; Hong, Yucai

2017-07-25

There are several disease severity scores being used for the prediction of mortality in critically ill patients. However, none of them was developed and validated specifically for patients with severe sepsis. The present study aimed to develop a novel prediction score for severe sepsis. A total of 3206 patients with severe sepsis were enrolled, including 1054 non-survivors and 2152 survivors. The LASSO score showed the best discrimination (area under curve: 0.772; 95% confidence interval: 0.735-0.810) in the validation cohort as compared with other scores such as simplified acute physiology score II, acute physiological score III, Logistic organ dysfunction system, sequential organ failure assessment score, and Oxford Acute Severity of Illness Score. The calibration slope was 0.889 and Brier value was 0.173. The study employed a single center database called Medical Information Mart for Intensive Care-III) MIMIC-III for analysis. Severe sepsis was defined as infection and acute organ dysfunction. Clinical and laboratory variables used in clinical routines were included for screening. Subjects without missing values were included, and the whole dataset was split into training and validation cohorts. The score was coined LASSO score because variable selection was performed using the least absolute shrinkage and selection operator (LASSO) technique. Finally, the LASSO score was evaluated for its discrimination and calibration in the validation cohort. The study developed the LASSO score for mortality prediction in patients with severe sepsis. Although the score had good discrimination and calibration in a randomly selected subsample, external validations are still required.

[Successful continuous renal replacement therapy in a neonate with early-onset group B streptococcal sepsis and multi-organ dysfunction syndrome].

PubMed

von Schnakenburg, C; Hufnagel, M; Superti-Furga, A; Rieger-Fackeldey, E; Berner, R

2009-01-01

Group B streptococcal early-onset sepsis (GBS EOS) in neonates has a mortality rate of approximately 5%, particularly in the presence of multi-organ dysfunction. Fluid management is crucial in these patients, and continuous venovenous haemofiltration (CVVH) should be considered a therapeutic option even in newborn babies. After an uneventful pregnancy within hours after birth, a female term infant presented with dyspnoea, irritability and cyanosis. The systemic inflammatory response syndrome (SIRS) progressed to multi-organ dysfunction with acute respiratory distress syndrome (ARDS), impaired myocardial contractility, pulmonary hypertension and fluid overload. The maximum PRISM score was 51. The child required maximal respiratory and inotropic support with high volume intravenous fluid administration. However, only by using of CVVH from day 5 to 14, we successfully resolved progressive pulmonary and cardiovascular dysfunction. The child improved directly after initiation of fluid removal, was extubated on day 17 and discharged without obvious sequelae on day 57. All microbiology studies revealed GBS. Perinatal GBS-infections remain a major life-threatening event for newborn babies. CVVH should be considered an option for reversing fluid overload even in neonates with overwhelming SIRS. Alternatively, extracorporeal membrane oxygenation (ECMO) is discussed.

New insights into bioactivation of organic nitrates, nitrate tolerance and cross-tolerance.

PubMed

Daiber, A; Wenzel, P; Oelze, M; Münzel, T

2008-01-01

Organic nitrates still represent a group of very effective anti-ischemic drugs used for the treatment of patients with stable angina, acute myocardial infarction and chronic congestive heart failure. Long-term therapy with organic nitrates, however, results in a rapid development of nitrate tolerance blunting their hemodynamic and antiischemic efficacy. Recent studies revealed that mitochondrial reactive oxygen species (ROS) formation and a subsequent oxidative inactivation of nitrate reductase, the mitochondrial aldehyde dehydrogenase (ALDH-2), play an important role for the development of nitrate and crosstolerance. The present review focuses firstly on the role of ALDH-2 for organic nitrate bioactivation and secondly on the role of oxidative stress in the development of tolerance and cross-tolerance (endothelial dysfunction) in response to various organic nitrates. Finally, we would like to draw the reader's attention to the protective properties of the organic nitrate pentaerithrityl tetranitrate (PETN), which, in contrast to all other organic nitrates, is able to upregulate enzymes with a strong antioxidative capacity thereby preventing tolerance and the development of endothelial dysfunction.

The prognostic and risk-stratified value of heart-type fatty acid-binding protein in septic patients in the emergency department.

PubMed

Chen, Yun-Xia; Li, Chun-Sheng

2014-08-01

To evaluate the prognostic and risk-stratified ability of heart-type fatty acid-binding protein (H-FABP) in septic patients in the emergency department (ED). From August to November 2012, 295 consecutive septic patients were enrolled. Circulating H-FABP was measured. The predictive value of H-FABP for 28-day mortality, organ dysfunction on ED arrival, and requirement for mechanical ventilation or a vasopressor within 6 hours after ED arrival was assessed by the receiver operating characteristic curve and logistic regression and was compared with Acute Physiology and Chronic Health Evaluation (APACHE) II score, Mortality in Emergency Department Sepsis (MEDS) score, and Sequential Organ Failure Assessment score. The 28-day mortality, APACHE II, MEDS, and Sequential Organ Failure Assessment scores were much higher in H-FABP-positive patients. The incidence of organ dysfunction at ED arrival and requirement for mechanical ventilation or a vasopressor within 6 hours after ED arrival was higher in H-FABP-positive patients. Heart-type fatty acid-binding protein was an independent predictor of 28-day mortality and organ dysfunction. The area under the receiver operating characteristic curve for H-FABP predicting 28-day mortality and organ dysfunction was 0.784 and 0.755, respectively. Combination of H-FABP and MEDS improved the performance of MEDS in predicting organ dysfunction, and the difference of AUC was statistically significant (P<.05). The combinations of H-FABP and MEDS or H-FABP and APACHE II also improved the prognostic value of MEDS and APACHE II, but the areas under the curve were not statistically different. Heart-type fatty acid-binding protein was helpful for prognosis and risk stratification of septic patients in the ED. Copyright © 2014 Elsevier Inc. All rights reserved.

Consensus Report by the Pediatric Acute Lung Injury and Sepsis Investigators and Pediatric Blood and Marrow Transplantation Consortium Joint Working Committees on Supportive Care Guidelines for Management of Veno-Occlusive Disease in Children and Adolescents, Part 3: Focus on Cardiorespiratory Dysfunction, Infections, Liver Dysfunction, and Delirium.

PubMed

Ovchinsky, Nadia; Frazier, Warren; Auletta, Jeffery J; Dvorak, Christopher C; Ardura, Monica; Song, Enkyung; McArthur, Jennifer; Jeyapalan, Asumthia; Tamburro, Robert; Mahadeo, Kris M; Traube, Chani; Duncan, Christine N; Bajwa, Rajinder P S

2018-02-01

Some patients with veno-occlusive disease (VOD) have multiorgan dysfunction, and multiple teams are involved in their daily care in the pediatric intensive care unit. Cardiorespiratory dysfunction is critical in these patients, requiring immediate action. The decision of whether to use a noninvasive or an invasive ventilation strategy may be difficult in the setting of mucositis or other comorbidities in patients with VOD. Similarly, monitoring of organ functions may be very challenging in these patients, who may have fulminant hepatic failure with or without hepatic encephalopathy complicated by delirium and/or infections. In this final guideline of our series on supportive care in patients with VOD, we address some of these questions and provide evidence-based recommendations on behalf of the Pediatric Acute Lung Injury and Sepsis Investigators and Pediatric Blood and Marrow Transplantation Consortium Joint Working Committees. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Immunologic alterations and the pathogenesis of organ failure in the ICU.

PubMed

Opal, Steven M

2011-10-01

Rapid and marked alterations of innate and adaptive immunity typify the host response to systemic infection and acute inflammatory states. Immune dysfunction contributes to the development of organ failure in most patients with critical illness. The molecular mechanisms by which microbial pathogens and tissue injury activate myeloid cells and prime cellular and humoral immunity are increasingly understood. An early and effective immune response to microbial invasion is essential to mount an effective antimicrobial response. However, unchecked and nonresolving inflammation can induce diffuse vasodilation, increased capillary permeability, microvascular damage, coagulation activation, and organ dysfunction. Control of the inflammatory response to limit tissue damage, yet retain the antimicrobial responses in critically ill patients with severe infection, has been sought for decades. Anti-inflammatory approaches might be beneficial in some patients but detrimental in others. It is now clear that a state of sepsis-induced immune suppression can follow the immune activation phase of sepsis. In carefully selected patients, a better therapeutic strategy might be to provide immunoadjuvants to reconstitute immune function in intensive care unit (ICU) patients. Proresolving agents are also in development to terminate acute inflammatory reactions without immune suppression. This brief review summarizes the current understanding of the fundamental immune alterations in critical illness that lead to organ failure in critical illness. © Thieme Medical Publishers.

Transient ventricular dysfunction after an asphyxiation event: stress or hypoxia?

PubMed

Valletta, Mary E; Haque, Ikram; Al-Mousily, Faris; Udassi, Jai; Saidi, Arwa

2008-11-01

This report of a pediatric patient with acute upper airway obstruction causing asphyxiation emphasizes the need to maintain clinical suspicion for acquired myocardial dysfunction, despite the presumed role of noncardiogenic causes for pulmonary edema after an acute upper airway obstruction. Case report. A tertiary pediatric intensive care unit. A 10-year-old girl with no significant medical history who developed flash pulmonary edema and acute myocardial dysfunction after an acute upper airway obstruction. Serial echocardiograms, exercise stress test, and coronary angiography were performed. Serial pro-brain natriuretic peptide, troponins, and CK-MB levels were also followed. Troponin level normalized approximately 7 days after the acute event. CK-MB and pro-brain natriuretic peptide levels decreased but had not completely normalized by time of discharge. The patient was discharged home 10 days after the event on an anticipated 6-month course of metoprolol without any signs or symptoms of cardiac dysfunction. Myocardial dysfunction is rarely documented in children after an acute upper airway obstruction or an asphyxiation event. Pediatric intensivists and hospitalists should maintain a high degree of clinical suspicion and screen for possible myocardial dysfunction in the pediatric patient with an acute severe hypoxic event especially when accompanied by pulmonary edema. Prompt evaluation ensures appropriate support. Additionally, some role may exist for early adrenergic receptor blockade.

Successful treatment of extreme acute lead intoxication.

PubMed

Mikler, J; Banovcin, P; Jesenak, M; Hamzikova, J; Statelova, D

2009-03-01

Severe acute lead intoxications are rare and are associated with accidental or purposeful ingestion. There were only few cases of severe to fatal poisonings reported in literature in children. We report a case of acute lead intoxication in a child with extremely high lead blood level of 20.4 micromol/L (422.7 microg/dL), who was treated with chelation and in whom significant organ dysfunction did not develop. Documented significant high level above 3.37 micromol/L (corresponding to 70 microg/dL) in this patient persisted for approximately 24 h. Adequate, single or combined chelatation therapy in early phase of acute lead poisoning is essential for the further patient's outcome.

The gut in trauma.

PubMed

Patel, Jayshil J; Rosenthal, Martin D; Miller, Keith R; Martindale, Robert G

2016-08-01

The purpose of this review is to describe established and emerging mechanisms of gut injury and dysfunction in trauma, describe emerging strategies to improve gut dysfunction, detail the effect of trauma on the gut microbiome, and describe the gut-brain connection in traumatic brain injury. Newer data suggest intraluminal contents, pancreatic enzymes, and hepatobiliary factors disrupt the intestinal mucosal layer. These mechanisms serve to perpetuate the inflammatory response leading to multiple organ dysfunction syndrome (MODS). To date, therapies to mitigate acute gut dysfunction have included enteral nutrition and immunonutrition; emerging therapies aimed to intestinal mucosal layer disruption, however, include protease inhibitors such as tranexamic acid, parenteral nutrition-supplemented bombesin, and hypothermia. Clinical trials to demonstrate benefit in humans are needed before widespread applications can be recommended. Despite resuscitation, gut dysfunction promotes distant organ injury. In addition, postresuscitation nosocomial and iatrogenic 'hits' exaggerate the immune response, contributing to MODS. This was a provocative concept, suggesting infectious and noninfectious causes of inflammation may trigger, heighten, and perpetuate an inflammatory response culminating in MODS and death. Emerging evidence suggests posttraumatic injury mechanisms, such as intestinal mucosal disruption and shifting of the gut microbiome to a pathobiome. In addition, traumatic brain injury activates the gut-brain axis and increases intestinal permeability.

RIPHeart (Remote Ischemic Preconditioning for Heart Surgery) Study: Myocardial Dysfunction, Postoperative Neurocognitive Dysfunction, and 1 Year Follow-Up.

PubMed

Meybohm, Patrick; Kohlhaas, Madeline; Stoppe, Christian; Gruenewald, Matthias; Renner, Jochen; Bein, Berthold; Albrecht, Martin; Cremer, Jochen; Coburn, Mark; Schaelte, Gereon; Boening, Andreas; Niemann, Bernd; Sander, Michael; Roesner, Jan; Kletzin, Frank; Mutlak, Haitham; Westphal, Sabine; Laufenberg-Feldmann, Rita; Ferner, Marion; Brandes, Ivo F; Bauer, Martin; Stehr, Sebastian N; Kortgen, Andreas; Wittmann, Maria; Baumgarten, Georg; Meyer-Treschan, Tanja; Kienbaum, Peter; Heringlake, Matthias; Schoen, Julika; Treskatsch, Sascha; Smul, Thorsten; Wolwender, Ewa; Schilling, Thomas; Fuernau, Georg; Bogatsch, Holger; Brosteanu, Oana; Hasenclever, Dirk; Zacharowski, Kai

2018-03-26

Remote ischemic preconditioning (RIPC) has been suggested to protect against certain forms of organ injury after cardiac surgery. Previously, we reported the main results of RIPHeart (Remote Ischemic Preconditioning for Heart Surgery) Study, a multicenter trial randomizing 1403 cardiac surgery patients receiving either RIPC or sham-RIPC. In this follow-up paper, we present 1-year follow-up of the composite primary end point and its individual components (all-cause mortality, myocardial infarction, stroke and acute renal failure), in a sub-group of patients, intraoperative myocardial dysfunction assessed by transesophageal echocardiography and the incidence of postoperative neurocognitive dysfunction 5 to 7 days and 3 months after surgery. RIPC neither showed any beneficial effect on the 1-year composite primary end point (RIPC versus sham-RIPC 16.4% versus 16.9%) and its individual components (all-cause mortality [3.4% versus 2.5%], myocardial infarction [7.0% versus 9.4%], stroke [2.2% versus 3.1%], acute renal failure [7.0% versus 5.7%]) nor improved intraoperative myocardial dysfunction or incidence of postoperative neurocognitive dysfunction 5 to 7 days (67 [47.5%] versus 71 [53.8%] patients) and 3 months after surgery (17 [27.9%] versus 18 [27.7%] patients), respectively. Similar to our main study, RIPC had no effect on intraoperative myocardial dysfunction, neurocognitive function and long-term outcome in cardiac surgery patients undergoing propofol anesthesia. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01067703. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Mechanical ventilation interacts with endotoxemia to induce extrapulmonary organ dysfunction

PubMed Central

O'Mahony, D Shane; Liles, W Conrad; Altemeier, William A; Dhanireddy, Shireesha; Frevert, Charles W; Liggitt, Denny; Martin, Thomas R; Matute-Bello, Gustavo

2006-01-01

Introduction Multiple organ dysfunction syndrome (MODS) is a common complication of sepsis in mechanically ventilated patients with acute respiratory distress syndrome, but the links between mechanical ventilation and MODS are unclear. Our goal was to determine whether a minimally injurious mechanical ventilation strategy synergizes with low-dose endotoxemia to induce the activation of pro-inflammatory pathways in the lungs and in the systemic circulation, resulting in distal organ dysfunction and/or injury. Methods We administered intraperitoneal Escherichia coli lipopolysaccharide (LPS; 1 μg/g) to C57BL/6 mice, and 14 hours later subjected the mice to 6 hours of mechanical ventilation with tidal volumes of 10 ml/kg (LPS + MV). Comparison groups received ventilation but no LPS (MV), LPS but no ventilation (LPS), or neither LPS nor ventilation (phosphate-buffered saline; PBS). Results Myeloperoxidase activity and the concentrations of the chemokines macrophage inflammatory protein-2 (MIP-2) and KC were significantly increased in the lungs of mice in the LPS + MV group, in comparison with mice in the PBS group. Interestingly, permeability changes across the alveolar epithelium and histological changes suggestive of lung injury were minimal in mice in the LPS + MV group. However, despite the minimal lung injury, the combination of mechanical ventilation and LPS resulted in chemical and histological evidence of liver and kidney injury, and this was associated with increases in the plasma concentrations of KC, MIP-2, IL-6, and TNF-α. Conclusion Non-injurious mechanical ventilation strategies interact with endotoxemia in mice to enhance pro-inflammatory mechanisms in the lungs and promote extra-pulmonary end-organ injury, even in the absence of demonstrable acute lung injury. PMID:16995930

Catastrophic antiphospholipid antibody syndrome presenting as acute vascular occlusion in a young female patient.

PubMed

Alonso, Joaquín Valle; Del Pozo, Francisco Javier Fonseca; Álvarez, Manuel Vaquero; Pedraza, Jorge; Aguayo, Miguel Angel; Sanchez, Almudena

Acquired thrombotic and thromboembolic disorders may be presented initially with symptoms and signs of acute ischaemia or organ dysfunction that will lead many of these patients to seek care in the emergency department. We report a case of a 19-year-old female patient who developed catastrophic antiphospholipid syndrome (CAPS syndrome or Asherson syndrome) 6 weeks post stillbirth with an initial presentation of acute vascular occlusion. The patient was immediately operated and anticoagulated with significant improvement. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Case report: severe heat stroke with multiple organ dysfunction – a novel intravascular treatment approach

PubMed Central

Broessner, Gregor; Beer, Ronny; Franz, Gerhard; Lackner, Peter; Engelhardt, Klaus; Brenneis, Christian; Pfausler, Bettina; Schmutzhard, Erich

2005-01-01

Introduction We report the case of a patient who developed a severe post-exertional heat stroke with consecutive multiple organ dysfunction resistant to conventional antipyretic treatment, necessitating the use of a novel endovascular device to combat hyperthermia and maintain normothermia. Methods A 38-year-old male suffering from severe heat stroke with predominant signs and symptoms of encephalopathy requiring acute admission to an intensive care unit, was admitted to a ten-bed neurological intensive care unit of a tertiary care hospital. The patient developed consecutive multiple organ dysfunction with rhabdomyolysis, and hepatic and respiratory failure. Temperature elevation was resistant to conventional treatment measures. Aggressive intensive care treatment included forced diuresis and endovascular cooling to combat hyperthermia and maintain normothermia. Results Analyses of serum revealed elevation of proinflammatory cytokines (TNF alpha, IL-6), cytokines (IL-2R), anti-inflammatory cytokines (IL-4) and chemokines (IL-8) as well as signs of rhabdomyolysis and hepatic failure. Aggressive intensive care treatment as forced diuresis and endovascular cooling (CoolGard® and CoolLine®) to combat hyperthermia and maintain normothermia were used successfully to treat this severe heat stroke. Conclusion In this case of severe heat stroke, presenting with multiple organ dysfunction and elevation of cytokines and chemokines, which was resistant to conventional cooling therapies, endovascular cooling may have contributed significantly to the reduction of body temperature and, possibly, avoided a fatal result. PMID:16285034

A multicenter randomised controlled trial of hydroxyurea (hydroxycarbamide) in very young children with sickle cell anaemia

PubMed Central

Wang, Winfred C; Ware, Russell E; Miller, Scott T; Iyer, Rathi V; Casella, James F; Minniti, Caterina P; Rana, Sohail; Thornburg, Courtney D; Rogers, Zora R; Kalpatthi, Ram V; Barredo, Julio C; Brown, R Clark; Sarnaik, Sharada A; Howard, Thomas H; Wynn, Lynn W; Kutlar, Abdullah; Armstrong, F Daniel; Files, Beatrice A; Goldsmith, Jonathan C; Waclawiw, Myron A; Huang, Xiangke; Thompson, Bruce W

2011-01-01

Background Sickle cell anaemia (SCA) is associated with significant morbidity from acute complications and organ dysfunction beginning in the first year of life. In the first multicenter randomised double-blinded trial in very young children with SCA, the impact of hydroxyurea (hydroxycarbamide) therapy on organ dysfunction, clinical complications, and laboratory findings, and its toxicity, were examined. Methods Eligible subjects had HbSS or Sβ0thalassaemia, were age 9–18 months at randomisation, and were not selected for clinical severity. Subjects received liquid hydroxyurea, 20 mg/kg/day, or placebo for two years. Primary study endpoints were splenic function (qualitative uptake on 99Tc spleen scan) and renal function (glomerular filtration rate by 99mTc-DTPA clearance). Additional evaluations included: blood counts, HbF, chemistry profiles, spleen function biomarkers, urine osmolality, neurodevelopment, transcranial Doppler ultrasonography, growth, and mutagenicity. Study visits occurred every two to four weeks. Findings Ninety-six subjects received hydroxyurea and 97 placebo; 86% completed the study. Significant differences were not seen for the primary endpoints, but suggestive benefit was noted in quantitative measures of spleen function. Hydroxyurea significantly decreased pain and dactylitis with trends for decreased acute chest syndrome, hospitalisation and transfusion. Hydroxyurea increased haemoglobin and HbF and decreased WBC count. Toxicity was limited to mild-moderate neutropaenia. Interpretation Although hydroxyurea treatment did not reduce splenic and renal dysfunction assessed by primary endpoint measures, it resulted in major clinical benefit because of diminished acute complications, favorable haematologic results, and a lack of unexpected toxicities. Based on the safety and efficacy data from this trial, hydroxyurea can now be considered for all very young children with SCA. PMID:21571150

CT abdominal imaging findings in patients with sickle cell disease: acute vaso-occlusive crisis, complications, and chronic sequelae.

PubMed

Gardner, Carly S; Boll, Daniel T; Bhosale, Priya; Jaffe, Tracy A

2016-12-01

Sickle cell disease (SCD) is the most prevalent hemoglobinopathy. Survival in patients with SCD has improved over the past few decades. These patients experience a lifetime of repeated acute pain crises, which are thought to result from sickling and microvascular occlusions; acute abdominal pain is common. Moreover, repeated crises often lead to organ dysfunction, such as asplenia, hepatic failure, and renal failure. The spleen, liver, biliary system, kidneys, and gastrointestinal tract can all be affected. Patients may undergo CT to further direct clinical management. We review the spectrum of CT imaging findings of abdominal manifestations in patients with SCD, from the acute microvascular occlusive pain crisis to the potential complications and chronic sequelae.

[Cardio-hepatic Syndrome in Heart Failure: Prevalence, Pathogenesis and Prognostic Significance].

PubMed

Kobalava, Zh D; Villevalde, S V; Soloveva, A E

2016-12-01

In a framework of the concept of organ interactions great attention has been paid during recent years to interaction of the heart and liver. The term cardio-hepatic syndrome (CHS) designates the combination of clinical-laboratory signs of liver dysfunction and acute or chronic cardiac pathology. In this article, we present mechanisms and characteristics of CHS in acute and chronic heart failure (HF), data of large clinical studies and registries on prevalence, associations, and prognostic significance of cardiogenic disturbances of liver function in patients with HF.

Acute transient cognitive dysfunction and acute brain injury induced by systemic inflammation occur by dissociable IL-1-dependent mechanisms.

PubMed

Skelly, Donal T; Griffin, Éadaoin W; Murray, Carol L; Harney, Sarah; O'Boyle, Conor; Hennessy, Edel; Dansereau, Marc-Andre; Nazmi, Arshed; Tortorelli, Lucas; Rawlins, J Nicholas; Bannerman, David M; Cunningham, Colm

2018-06-06

Systemic inflammation can impair cognition with relevance to dementia, delirium and post-operative cognitive dysfunction. Episodes of delirium also contribute to rates of long-term cognitive decline, implying that these acute events induce injury. Whether systemic inflammation-induced acute dysfunction and acute brain injury occur by overlapping or discrete mechanisms remains unexplored. Here we show that systemic inflammation, induced by bacterial LPS, produces both working-memory deficits and acute brain injury in the degenerating brain and that these occur by dissociable IL-1-dependent processes. In normal C57BL/6 mice, LPS (100 µg/kg) did not affect working memory but impaired long-term memory consoliodation. However prior hippocampal synaptic loss left mice selectively vulnerable to LPS-induced working memory deficits. Systemically administered IL-1 receptor antagonist (IL-1RA) was protective against, and systemic IL-1β replicated, these working memory deficits. Dexamethasone abolished systemic cytokine synthesis and was protective against working memory deficits, without blocking brain IL-1β synthesis. Direct application of IL-1β to ex vivo hippocampal slices induced non-synaptic depolarisation and irrevesible loss of membrane potential in CA1 neurons from diseased animals and systemic LPS increased apoptosis in the degenerating brain, in an IL-1RI -/- -dependent fashion. The data suggest that LPS induces working memory dysfunction via circulating IL-1β but direct hippocampal action of IL-1β causes neuronal dysfunction and may drive neuronal death. The data suggest that acute systemic inflammation produces both reversible cognitive deficits, resembling delirium, and acute brain injury contributing to long-term cognitive impairment but that these events are mechanistically dissociable. These data have significant implications for management of cognitive dysfunction during acute illness.

Deciphering the complexity of acute inflammation using mathematical models.

PubMed

Vodovotz, Yoram

2006-01-01

Various stresses elicit an acute, complex inflammatory response, leading to healing but sometimes also to organ dysfunction and death. We constructed both equation-based models (EBM) and agent-based models (ABM) of various degrees of granularity--which encompass the dynamics of relevant cells, cytokines, and the resulting global tissue dysfunction--in order to begin to unravel these inflammatory interactions. The EBMs describe and predict various features of septic shock and trauma/hemorrhage (including the response to anthrax, preconditioning phenomena, and irreversible hemorrhage) and were used to simulate anti-inflammatory strategies in clinical trials. The ABMs that describe the interrelationship between inflammation and wound healing yielded insights into intestinal healing in necrotizing enterocolitis, vocal fold healing during phonotrauma, and skin healing in the setting of diabetic foot ulcers. Modeling may help in understanding the complex interactions among the components of inflammation and response to stress, and therefore aid in the development of novel therapies and diagnostics.

Life-threatening heat stroke presenting with ST elevations: a report of consecutive cases during the heat wave in Austria in July 2013.

PubMed

Lassnig, Elisabeth; Dinkhauser, Patrick; Maurer, Edwin; Eber, Bernd

2014-08-01

Heat stroke is a life-threatening condition due to an acute thermoregulatory failure during exposure to high environmental temperatures. We report a series of four cases (three exertional, one classic heat stroke) during the heat wave of July 2013 in Austria. All of them presented with a core temperature > 41 °C, central nervous dysfunction, acute respiratory and renal failure, disseminated intravascular coagulation, rhabdomyolysis, and severe electrocardiographic changes, two cases even mimicking ST-elevation myocardial infarction. The patients were cooled to normal temperature with the "Arctic sun" external cooling system within hours. Electrocardiographic changes resolved quickly. All patients primarily recovered from multiple organ dysfunction and could be discharged from intensive care unit. Unfortunately, the two elder patients died 1 week and 5 weeks later because of late complications.

Fast simultaneous assessment of renal and liver function using polymethine dyes in animal models of chronic and acute organ injury.

PubMed

Press, A T; Butans, M J; Haider, T P; Weber, C; Neugebauer, S; Kiehntopf, M; Schubert, U S; Clemens, M G; Bauer, M; Kortgen, A

2017-11-13

Simultaneous assessment of excretory liver and kidney function is still an unmet need in experimental stress models as well as in critical care. The aim of the study was to characterize two polymethine-dyes potentially suitable for this purpose in vivo. Plasma disappearance rate and elimination measurements of simultaneously injected fluorescent dyes DY-780 (hepato-biliary elimination) and DY-654(renal elimination) were conducted using catheter techniques and intravital microscopy in animals subjected to different organ injuries, i.e. polymicrobial sepsis by peritoneal contamination and infection, ischemia-reperfusion-injury and glycerol-induced acute kidney-injury. DY-780 and DY-654 showed organ specific and determined elimination routes in both healthy and diseased animals. They can be measured simultaneously using near-infrared imaging and spectrophotometry. Plasma-disappearance rates of DY-780 and DY-654 are superior to conventional biomarkers in indicating hepatic or kidney dysfunction in different animal models. Greatest impact on liver function was found in animals with polymicrobial sepsis whereas glomerular damage due to glycerol-induced kidney-injury had strongest impact on DY-654 elimination. We therefore conclude that hepatic elimination and renal filtration can be assessed in rodents measuring plasma-disappearance rates of both dyes. Further, assessment of organ dysfunction by polymethine dyes correlates with, but outperforms conventional biomarkers regarding sensitivity and the option of spatial resolution if biophotonic strategies are applied. Polymethine-dye clearance thereby allows sensitive point-of-care assessment of both organ functions simultaneously.

Glutaric Aciduria Type 1 and Acute Renal Failure: Case Report and Suggested Pathomechanisms.

PubMed

du Moulin, Marcel; Thies, Bastian; Blohm, Martin; Oh, Jun; Kemper, Markus J; Santer, René; Mühlhausen, Chris

2018-01-01

Glutaric aciduria type 1 (GA1) is caused by deficiency of the mitochondrial matrix enzyme glutaryl-CoA dehydrogenase (GCDH), leading to accumulation of glutaric acid (GA) and 3-hydroxyglutaric acid (3OHGA) in tissues and body fluids. During catabolic crises, GA1 patients are prone to the development of striatal necrosis and a subsequent irreversible movement disorder during a time window of vulnerability in early infancy. Thus, GA1 had been considered a pure "cerebral organic aciduria" in the past. Single case reports have indicated the occurrence of acute renal dysfunction in children affected by GA1. In addition, growing evidence arises that GA1 patients may develop chronic renal failure during adulthood independent of the previous occurrence of encephalopathic crises. The underlying mechanisms are yet unknown. Here we report on a 3-year-old GA1 patient who died following the development of acute renal failure most likely due to haemolytic uraemic syndrome associated with a pneumococcal infection. We hypothesise that known GA1 pathomechanisms, namely the endothelial dysfunction mediated by 3OHGA, as well as the transporter mechanisms for the urinary excretion of GA and 3OHGA, are involved in the development of glomerular and tubular dysfunction, respectively, and may contribute to a pre-disposition of GA1 patients to renal disease. We recommend careful differential monitoring of glomerular and tubular renal function in GA1 patients.

Acute kidney injury in acute liver failure: a review.

PubMed

Moore, Joanna K; Love, Eleanor; Craig, Darren G; Hayes, Peter C; Simpson, Kenneth J

2013-11-01

Acute liver failure is a rare and often devastating condition consequent on massive liver cell necrosis that frequently affects young, previously healthy individuals resulting in altered cognitive function, coagulopathy and peripheral vasodilation. These patients frequently develop concurrent acute kidney injury (AKI). This abrupt and sustained decline in renal function, through a number of pathogenic mechanisms such as renal hypoperfusion, direct drug-induced nephrotoxicity or sepsis/systemic inflammatory response contributes to increased morbidity and is strongly associated with a worse prognosis. Improved understanding of the pathophysiology AKI in the context of acute liver failure may be beneficial in a number of areas; the development of new and sensitive biomarkers of renal dysfunction, refining prognosis and organ allocation, and ultimately leading to the development of novel treatment strategies, these issues are discussed in more detail in this expert review.

Acute complications of sickle cell disease in children.

PubMed

2001-05-01

Sickle cell disease is a recessively inherited condition in which synthesis of haemoglobin is abnormal. The disease, which occurs mainly in people of African, African-Caribbean, Indian, Mediterranean and Middle Eastern descent, is characterised by chronic anaemia, susceptibility to infection, bouts of severe pain and organ dysfunction. While the life expectancy for patients has improved, from a median survival age of 14 years in the 1970s among those homozygous for the sickle haemoglobin gene to survival into the mid-40s, childhood remains a period of peak mortality and morbidity. Here, we discuss the acute complications of sickle cell disease in children, concentrating on the management of the acutely unwell child.

Detrimental role of humoral signalling in cardio-renal cross-talk.

PubMed

Cantaluppi, Vincenzo; Dellepiane, Sergio; Quercia, Alessandro D; Ferrario, Silvia

2014-01-22

In critically ill patients, any acute organ injury is associated with a sudden change of circulating factors that may play a role in distant organ dysfunction through a complex cross-talk. In this issue, Virzì and colleagues discuss the relevance of humoral signalling between heart and kidney, focusing on type 1 and type 3 cardio-renal syndrome. We herein review the mechanisms of heart-kidney cross-talk, discussing the role of circulating detrimental mediators in the pathogenetic mechanisms of cardio-renal syndrome.

Urgent Chemotherapy in Sepsis-Like Shock Related to Hematologic Malignancies.

PubMed

Cherruault, Marlène; Le Goff, Marielle; Tamburini, Jérôme; Pène, Frédéric

2018-05-01

Hematologic malignancies may result in multiple organ involvement including pulmonary and renal dysfunctions, and the less common acute circulatory failure. We herein addressed the outcome of patients with sepsis-like shock related to aggressive hematologic malignancies. A 10-year (2007-2016) monocenter retrospective study. A medical ICU in a tertiary care center. Patients with circulatory shock requiring vasopressors and who subsequently received chemotherapy. Shock was presumably related to the underlying malignancy after ruling out an ongoing or new-onset infectious process. The extent and time course of organ failures was assessed by a modified Sequential Organ Failure Assessment score devoid of the platelet component. None. Seventeen patients were included, including 13 with non-Hodgkin lymphoma, two with hyperleukocytic acute myeloid leukemia, and two with "Human Herpes virus 8"-associated multicentric Castleman's disease. The following associated conditions prompted urgent administration of chemotherapy: tumor lysis syndrome (n = 10), hemophagocytic lymphohistiocytosis (n = 3), compressive bulky tumor (n = 3), pulmonary involvement (n = 3), and disseminated intravascular coagulation (n = 1). Following the initiation of chemotherapy, a number of patients died rapidly from untractable multiple organ failure. In contrast, chemotherapy led to a fast and dramatic improvement in organ failures in early survivors, as shown by the decrease in the modified Sequential Organ Failure Assessment score. However, the overall outcome was poor since only four and three patients could be discharged alive from the ICU and the hospital, and three and two patients remained alive at 6 months and 1 year. Multiple organ dysfunction syndrome related to hematologic malignancies is associated with a dismal outcome. A chemotherapy trial may provide a fast prognostic assessment of the reversibility of organ failure.

Perioperative management of liver surgery-review on pathophysiology of liver disease and liver failure.

PubMed

Gasteiger, Lukas; Eschertzhuber, Stephan; Tiefenthaler, Werner

2018-01-01

An increasing number of patients present for liver surgery. Given the complex pathophysiological changes in chronic liver disease (CLD), it is pivotal to understand the fundamentals of chronic and acute liver failure. This review will give an overview on related organ dysfunction as well as recommendations for perioperative management and treatment of liver failure-related symptoms.

Plasma cystatin C is a predictor of renal dysfunction, acute-on-chronic liver failure, and mortality in patients with acutely decompensated liver cirrhosis.

PubMed

Markwardt, Daniel; Holdt, Lesca; Steib, Christian; Benesic, Andreas; Bendtsen, Flemming; Bernardi, Mauro; Moreau, Richard; Teupser, Daniel; Wendon, Julia; Nevens, Frederik; Trebicka, Jonel; Garcia, Elisabet; Pavesi, Marco; Arroyo, Vicente; Gerbes, Alexander L

2017-10-01

The development of acute-on-chronic liver failure (ACLF) in patients with liver cirrhosis is associated with high mortality rates. Renal failure is the most significant organ dysfunction that occurs in ACLF. So far there are no biomarkers predicting ACLF. We investigated whether cystatin C (CysC) and neutrophil gelatinase-associated lipocalin (NGAL) can predict development of renal dysfunction (RD), hepatorenal syndrome (HRS), ACLF, and mortality. We determined the plasma levels of CysC and NGAL in 429 patients hospitalized for acute decompensation of cirrhosis in the EASL-CLIF Acute-on-Chronic Liver Failure in Cirrhosis (CANONIC) study. The patients were followed for 90 days. Patients without RD or ACLF at inclusion but with development of either had significantly higher baseline concentrations of CysC and NGAL compared to patients without. CysC, but not NGAL, was found to be predictive of RD (odds ratio, 9.4; 95% confidence interval [CI], 1.8-49.7), HRS (odds ratio, 4.2; 95% CI, 1.2-14.8), and ACLF (odds ratio, 5.9; 95% CI, 1.3-25.9). CysC at day 3 was not found to be a better predictor than baseline CysC. CysC and NGAL were both predictive of 90-day mortality, with hazard ratios for CysC of 3.1 (95% CI, 2.1-4.7) and for NGAL of 1.9 (95% CI, 1.5-2.4). Baseline CysC is a biomarker of RD, HRS, and ACLF and an independent predictor of mortality in patients with acutely decompensated liver cirrhosis, though determining CysC at day 3 did not provide any benefit; while NGAL is also associated with short-term mortality, it fails to predict development of RD, HRS, and ACLF. Baseline CysC may help to identify patients at risk earlier and improve clinical management. (Hepatology 2017;66:1232-1241). © 2017 by the American Association for the Study of Liver Diseases.

4G/5G polymorphism of PAI-1 gene is associated with multiple organ dysfunction and septic shock in pneumonia induced severe sepsis: prospective, observational, genetic study.

PubMed

Madách, Krisztina; Aladzsity, István; Szilágyi, Agnes; Fust, George; Gál, János; Pénzes, István; Prohászka, Zoltán

2010-01-01

Activation of inflammation and coagulation are closely related and mutually interdependent in sepsis. The acute-phase protein, plasminogen activator inhibitor-1 (PAI-1) is a key element in the inhibition of fibrinolysis. Elevated levels of PAI-1 have been related to worse outcome in pneumonia. We aimed to evaluate the effect of functionally relevant 4G/5G polymorphism of PAI-1 gene in pneumonia induced sepsis. We enrolled 208 Caucasian patients with severe sepsis due to pneumonia admitted to an intensive care unit (ICU). Patients were followed up until ICU discharge or death. Clinical data were collected prospectively and the PAI-1 4G/5G polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism technique. Patients were stratified according to the occurrence of multiple organ dysfunction syndrome, septic shock or death. We found that carriers of the PAI-1 4G/4G and 4G/5G genotypes have a 2.74-fold higher risk for multiple organ dysfunction syndrome (odds ratio [OR] 95% confidence interval [CI] = 1.335 - 5.604; p = 0.006) and a 2.57-fold higher risk for septic shock (OR 95%CI = 1.180 - 5.615; p = 0.018) than 5G/5G carriers. The multivariate logistic regression analysis adjusted for independent predictors, such as age, nosocomial pneumonia and positive microbiological culture also supported that carriers of the 4G allele have a higher prevalence of multiple organ dysfunction syndrome (adjusted odds ratio [aOR] = 2.957; 95%CI = 1.306 -6.698; p = 0.009) and septic shock (aOR = 2.603; 95%CI = 1.137 - 5.959; p = 0.024). However, genotype and allele analyses have not shown any significant difference regarding mortality in models non-adjusted or adjusted for acute physiology and chronic health evaluation (APACHE) II. Patients bearing the 4G allele had higher disseminated intravascular coagulation (DIC) score at admission (p = 0.007) than 5G/5G carriers. Moreover, in 4G allele carriers the length of ICU stay of non-survivors was longer (p = 0.091), fewer ventilation-free days (p = 0.008) and days without septic shock (p = 0.095) were observed during the first 28 days. In Caucasian patients with severe sepsis due to pneumonia carriers of the 4G allele of PAI-1 polymorphism have higher risk for multiple organ dysfunction syndrome and septic shock and in agreement they showed more fulminant disease progression based on continuous clinical variables.

Echocardiographic parameters of right ventricular function predict mortality in acute respiratory distress syndrome: a pilot study

PubMed Central

Wadia, Subeer K.; Kovach, Julie; Fogg, Louis; Tandon, Rajive

2016-01-01

Abstract Right ventricular (RV) dysfunction in acute respiratory distress syndrome (ARDS) contributes to increased mortality. Our aim is to identify reproducible transthoracic echocardiography (TTE) parameters of RV dysfunction that can be used to predict outcomes in ARDS. We performed a retrospective single-center cohort pilot study measuring tricuspid annular plane systolic excursion (TAPSE), Tei index, RV-fractional area change (RV-FAC), pulmonary artery systolic pressure (PASP), and septal shift, reevaluated by an independent blinded cardiologist (JK). Thirty-eight patients were included. Patients were divided on the basis of 30-day survival. Thirty-day mortality was 47%. Survivors were younger than nonsurvivors. Survivors had a higher pH, PaO2∶FiO2 ratio, and TAPSE. Acute Physiology and Chronic Health Evaluation II (APACHE II), Simplified Acute Physiology Score II (SAPS II), and Sequential Organ Failure Assessment (SOFA) scores were lower in survivors. TAPSE has the strongest association with increased 30-day mortality from date of TTE. Accordingly, TAPSE has a strong positive correlation with PaO2∶FiO2 ratios, and Tei index has a strong negative correlation with PaO2∶FiO2 ratios. Septal shift was associated with lower PaO2∶FiO2 ratios. Decrease in TAPSE, increase in Tei index, and septal shift were seen in the severe ARDS group. In multivariate logistic regression models, TAPSE maintained a significant association with mortality independent of age, pH, PaO2∶FiO2 ratios, positive end expiratory pressure, PCO2, serum bicarbonate, plateau pressures, driving pressures, APACHE II, SAPS II, and SOFA scores. In conclusion, TAPSE and other TTE parameters should be used as novel predictive indicators for RV dysfunction in ARDS. These parameters can be used as surrogate noninvasive RV hemodynamic measurements to be manipulated to improve mortality in patients with ARDS and contributory RV dysfunction. PMID:27252840

Clinical features, complications and mortality in critically ill patients with 2009 influenza A(H1N1) in Sfax,Tunisia.

PubMed

Damak, Hassen; Chtara, Kamilia; Bahloul, Mabrouk; Kallel, Hatem; Chaari, Anis; Ksibi, Hichem; Chaari, Adel; Chelly, Hedi; Rekik, Noureddine; Ben Hamida, Chokri; Bouaziz, Mounir

2011-07-01

Africa, as the rest of the world, was touched by the 2009 pandemic influenza A(H1N1). In the literature, a few publications covering this subject emerged from this continent. We prospectively describe baseline characteristics, treatment and outcomes of consecutive critically ill patients with confirmed 2009 influenza A(H1N1) in the intensive care unit (ICU) of Sfax hospital. From 29 November 2009 through 21 January 2010, 32 patients with confirmed 2009 influenza A(H1N1) were admitted to our ICU. We prospectively analysed data and outcomes of these patients and compared survivors and dead patients to identify any predictors of death. Patients were young (mean, 36·1 [SD], 20·7 years) and 21 (65·6%) of whom had co-morbidities. During ICU care, 29 (90·6%) patients had respiratory failure; among these, 15 (46·9%) patients required invasive ventilation with a median duration of 9 (IQR 3-12) days. In our experience, respiratory dysfunction can remain isolated but may also be associated with other dysfunctions or complications, such as, septic shock, seizures, myasthenia gravis exacerbation, Guillan-Barre syndrome, acute renal failure, nosocomial infections and biological disturbances. The nine patients (28·1%) who died had greater initial severity of illness (SAPS II and sequential organ failure assessment (SOFA) scores) but also a higher SOFA score and increasing severity of organ dysfunction during their ICU evolution. Critical illness from the 2009 influenza A(H1N1) in Sfax occurred in young individuals and was associated with severe acute respiratory and additional organ system failure. SAPS II and SOFA scores at ICU admission, and also during evolution, constitute a good predictor of death. © 2011 Blackwell Publishing Ltd.

Successful use of high-dose cytarabine in a patient with acute myeloid leukemia and severe hepatic dysfunction.

PubMed

Barker, Jacob A; Marini, Bernard L; Bixby, Dale; Perissinotti, Anthony J

2016-12-01

Acute myeloid leukemia is a hematologic malignancy characterized by the clonal expansion of myeloid blasts in the peripheral blood, bone marrow, and other tissues. Prognosis is poor with 5-year survival rates ranging from 5-65% depending on demographic and clinical features. Outcomes are worse for patients that have an antecedent myeloproliferative neoplasm that evolves to acute myeloid leukemia, with a survival rate of <10%. Treatment for acute myeloid leukemia has remained cytarabine and an anthracycline given in the standard 3 + 7 regimen. However, for patients with liver dysfunction this regimen, among many others, cannot be given safely. There is currently a lack of data regarding the use of cytarabine in patients with severe hepatic dysfunction. In this case report, we present a patient with secondary acute myeloid leukemia who successfully received a modified regimen of high-dose cytarabine while in severe hepatic dysfunction (bilirubin >15 mg/dL). © The Author(s) 2015.

Right ventricular dysfunction in acute pulmonary embolism: NT-proBNP vs. troponin T.

PubMed

Cotugno, Marilena; Orgaz-Molina, Jacinto; Rosa-Salazar, Vladimir; Guirado-Torrecillas, Leticia; García-Pérez, Bartolomé

2017-04-21

Dysfunction of the right ventricle (RV) is a parameter of severity in acute pulmonary embolism (PE). Echocardiographic assessment is not always possible in accident and emergency, hence the need to predict the presence of RV dysfunction using easily measurable parameters. To analyse the value of NT-proBNP and troponin T as markers of RV dysfunction in patients with acute PE. Secondarily, to assess the relationship between RV failure and clinical parameters related to PE. Analytical, observational, cross-sectional and retrospective study comparing the values NT-proBNP, troponin T and presenting symptoms of PE among patients with and without RV dysfunction. One hundred seventy-two patients (52 with RV failure,120 without) were included. All symptoms occurred with similar frequency between the 2groups except dyspnea and syncope (more common in the group with RV failure). Both NT-proBNP and troponin T had significantly higher values in the group of patients with RV dysfunction. However, in the multivariate analysis, NT-proBNP had a higher explanatory value for RV failure than troponin T. NT-proBNP is a diagnostic parameter of RV dysfunction with higher sensitivity in the context of acute PE. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Temporary Decompression in Critically Ill Patients: Retrospective Comparison of Ileostomy and Colostomy.

PubMed

Lin, Zhi-Liang; Yu, Wen-Kui; Shi, Jia-Liang; Chen, Qi-Yi; Tan, Shan-Jun; Li, Ning

2014-05-01

In critically ill patients, gastrointestinal function plays an important role in multiple organ dysfunction syndrome. Patients suffering from acute lower gastrointestinal dysfunction need to be performed a temporary fecal diversion after the failure of conservative treatment. This study aims to determine which type of fecal diversion is associated with better clinical outcomes in critically ill patients. Data of critically ill patients requiring surgical decompression following acute lower gastrointestinal dysfunction between January 2008 and June 2013 were retrospectively analyzed. Comparison was made between ileostomy group and colostomy group regarding the stoma-related complications and the recovery after stoma creation. 63 patients consisted of temporary ileostomy group (n = 35) and temporary colostomy group (n = 28) were included in this study. First bowel movement and length of enteral nutrition intolerance after fecal diversion were both significantly shorter in the ileostomy group than in the colostomy group (1.70 ± 0.95 vs. 3.04 ± 1.40; p < 0.001 and 3.96 ± 2.84 vs. 8.12 ± 7.05; p = 0.009). In comparison of the complication rates, we found a significantly higher incidence of dermatitis (31.43% vs. 7.14%; p = 0.017), hypokalemia (25.71 vs. 3.57; p = 0.017) and hypocalcemia (28.57 vs. 7.14; p = 0.031), and slightly lower incidence of stoma prolapse (0% vs. 10.71%; p = 0.082) in the ileostomy group than in the colostomy group. Both procedures provide an effective defunctioning of the distant gastrointestinal tract with a low complication incidence. We prefer a temporary ileostomy to temporary colostomy for acute lower gastrointestinal dysfunction in critically ill patients.

Spontaneous acute subdural hematoma and intracerebral hemorrhage in a patient with thrombotic microangiopathy during pregnancy.

PubMed

Wayhs, Sâmia Yasin; Wottrich, Joise; Uggeri, Douglas Prestes; Dias, Fernando Suparregui

2013-01-01

Preeclampsia, HELLP syndrome (hemolysis, elevated liver enzymes, and low-platelet count), and acute fatty liver of pregnancy are the main causes of thrombotic microangiopathy and evere liver dysfunction during pregnancy and represent different manifestations of the same pathological continuum. The case of a 35-week pregnant woman who was admitted to an intensive care unit immediately after a Cesarean section due to fetal death and the presence of nausea, vomiting, and jaundice is reported. Postpartum preeclampsia and acute fatty liver of pregnancy were diagnosed. The patient developed an acute subdural hematoma and an intracerebral hemorrhage, which were subjected to neurosurgical treatment. The patient died from refractory hemolytic anemia and spontaneous bleeding of multiple organs. Preeclampsia HELLP syndrome, and acute fatty liver of pregnancy might overlap and be associated with potentially fatal complications, including intracranial hemorrhage, as in the present case. Early detection and diagnosis are crucial to ensure management and treatment success.

Inclusion and definition of acute renal dysfunction in critically ill patients in randomized controlled trials: a systematic review.

PubMed

da Hora Passos, Rogerio; Ramos, Joao Gabriel Rosa; Gobatto, André; Caldas, Juliana; Macedo, Etienne; Batista, Paulo Benigno

2018-04-24

In evidence-based medicine, multicenter, prospective, randomized controlled trials (RCTs) are the gold standard for evaluating treatment benefits and ensuring the effectiveness of interventions. Patient-centered outcomes, such as mortality, are most often the preferred evaluated outcomes. While there is currently agreement on how to classify renal dysfunction in critically ill patients , the application frequency of this new classification system in RCTs has not previously been evaluated. In this study, we aim to assess the definition of renal dysfunction in multicenter RCTs involving critically ill patients that included mortality as a primary endpoint. A comprehensive search was conducted for publications reporting multicenter randomized controlled trials (RCTs) involving adult patients in intensive care units (ICUs) that included mortality as a primary outcome. MEDLINE and PUBMED were queried for relevant articles in core clinical journals published between May 2004 and December 2017. Of 418 articles reviewed, 46 multicenter RCTs with a primary endpoint related to mortality were included. Thirty-six (78.3%) of the trial reports provided information on renal function in the participants. Only seven articles (15.2%) included mean or median serum creatinine levels, mean creatinine clearance or estimated glomerular filtration rates. Sequential organ failure assessment (SOFA) score was the most commonly used definition of renal dysfunction (20 studies; 43.5%). Risk, Injury, Failure, Loss, End-stage renal disease (RIFLE), Acute Kidney Injury Network (AKIN) and Kidney Disease Improving Global Outcomes (KDIGO) criteria were used in five (10.9%) trials. In thirteen trials (28.3%), no renal dysfunction criteria were reported. Only one trial excluded patients with renal dysfunction, and it used urinary output or need for renal replacement therapy (RRT) as criteria for this diagnosis. The presence of renal dysfunction was included as a baseline patient characteristic in most RCTs. The RIFLE, AKIN and KDIGO classification systems were infrequently used; renal dysfunction was generally defined using the SOFA score.

Intratracheal Milrinone Bolus Administration During Acute Right Ventricular Dysfunction After Cardiopulmonary Bypass.

PubMed

Gebhard, Caroline Eva; Desjardins, Georges; Gebhard, Cathérine; Gavra, Paul; Denault, André Y

2017-04-01

To evaluate intratracheal milrinone (tMil) administration for rapid treatment of right ventricular (RV) dysfunction as a novel route after cardiopulmonary bypass. Retrospective analysis. Single-center study. The study comprised 7 patients undergoing cardiac surgery who exhibited acute RV dysfunction after cardiopulmonary bypass. After difficult weaning caused by cardiopulmonary bypass-induced acute RV dysfunction, milrinone was administered as a 5-mg bolus inside the endotracheal tube. RV function improvement, as indicated by decreasing pulmonary artery pressure and changes of RV waveforms, was observed in all 7 patients. Adverse effects of tMil included dynamic RV outflow tract obstruction (2 patients) and a decrease in systemic mean arterial pressure (1 patient). tMil may be an effective, rapid, and easily applicable therapeutic alternative to inhaled milrinone for the treatment of acute RV failure during cardiac surgery. However, sufficiently powered clinical trials are needed to confirm these findings. Copyright © 2017 Elsevier Inc. All rights reserved.

Downregulation of Glutathione Biosynthesis Contributes to Oxidative Stress and Liver Dysfunction in Acute Kidney Injury

PubMed Central

Siow, Yaw L.; Isaak, Cara K.

2016-01-01

Ischemia-reperfusion is a common cause for acute kidney injury and can lead to distant organ dysfunction. Glutathione is a major endogenous antioxidant and its depletion directly correlates to ischemia-reperfusion injury. The liver has high capacity for producing glutathione and is a key organ in modulating local and systemic redox balance. In the present study, we investigated the mechanism by which kidney ischemia-reperfusion led to glutathione depletion and oxidative stress. The left kidney of Sprague-Dawley rats was subjected to 45 min ischemia followed by 6 h reperfusion. Ischemia-reperfusion impaired kidney and liver function. This was accompanied by a decrease in glutathione levels in the liver and plasma and increased hepatic lipid peroxidation and plasma homocysteine levels. Ischemia-reperfusion caused a significant decrease in mRNA and protein levels of hepatic glutamate-cysteine ligase mediated through the inhibition of transcription factor Nrf2. Ischemia-reperfusion inhibited hepatic expression of cystathionine γ-lyase, an enzyme responsible for producing cysteine (an essential precursor for glutathione synthesis) through the transsulfuration pathway. These results suggest that inhibition of glutamate-cysteine ligase expression and downregulation of the transsulfuration pathway lead to reduced hepatic glutathione biosynthesis and elevation of plasma homocysteine levels, which, in turn, may contribute to oxidative stress and distant organ injury during renal ischemia-reperfusion. PMID:27872680

Three Hypothetical Inflammation Pathobiology Phenotypes and Pediatric Sepsis-Induced Multiple Organ Failure Outcome.

PubMed

Carcillo, Joseph A; Halstead, E Scott; Hall, Mark W; Nguyen, Trung C; Reeder, Ron; Aneja, Rajesh; Shakoory, Bita; Simon, Dennis

2017-06-01

We hypothesize that three inflammation pathobiology phenotypes are associated with increased inflammation, proclivity to develop features of macrophage activation syndrome, and multiple organ failure-related death in pediatric severe sepsis. Prospective cohort study comparing children with severe sepsis and any of three phenotypes: 1) immunoparalysis-associated multiple organ failure (whole blood ex vivo tumor necrosis factor response to endotoxin < 200 pg/mL), 2) thrombocytopenia-associated multiple organ failure (new onset thrombocytopenia with acute kidney injury and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 activity < 57%), and/or 3) sequential multiple organ failure with hepatobiliary dysfunction (respiratory distress followed by liver dysfunction with soluble Fas ligand > 200 pg/mL), to those without any of these phenotypes. Tertiary children's hospital PICU. One hundred consecutive severe sepsis admissions. Clinical data were recorded daily, and blood was collected twice weekly. Multiple organ failure developed in 75 cases and eight died. Multiple organ failure cases with any of the three inflammation phenotypes (n = 37) had higher inflammation (C-reactive protein, p = 0.009 and ferritin, p < 0.001) than multiple organ failure cases without any of these phenotypes (n = 38) or cases with only single organ failure (n = 25). Development of features of macrophage activation syndrome and death were more common among multiple organ failure cases with any of the phenotypes (macrophage activation syndrome: 10/37, 27%; death: 8/37, 22%) compared to multiple organ failure cases without any phenotype (macrophage activation syndrome: 1/38, 3%; p = 0.003 and death: 0/38, 0%; p = 0.002). Our approach to phenotype categorization remains hypothetical, and the phenotypes identified need to be confirmed in multicenter studies of pediatric multiple organ dysfunction syndrome.

Prefrontal Cortex Corticotropin-Releasing Factor Receptor 1 Conveys Acute Stress-Induced Executive Dysfunction.

PubMed

Uribe-Mariño, Andrés; Gassen, Nils C; Wiesbeck, Maximilian F; Balsevich, Georgia; Santarelli, Sara; Solfrank, Beate; Dournes, Carine; Fries, Gabriel R; Masana, Merce; Labermeier, Christiana; Wang, Xiao-Dong; Hafner, Kathrin; Schmid, Bianca; Rein, Theo; Chen, Alon; Deussing, Jan M; Schmidt, Mathias V

2016-11-15

The medial prefrontal cortex (mPFC) subserves complex cognition and is impaired by stress. Corticotropin-releasing factor (CRF), through CRF receptor 1 (CRFR1), constitutes a key element of the stress response. However, its contribution to the effects of stress in the mPFC remains unclear. Mice were exposed to acute social defeat stress and subsequently to either the temporal order memory (n = 11-12) or reversal learning (n = 9-11) behavioral test. Changes in mPFC Crhr1 messenger RNA levels were measured in acutely stressed mice (n = 12). Crhr1 loxP/loxP mice received either intra-mPFC adeno-associated virus-Cre or empty microinjections (n = 17-20) and then were submitted to acute stress and later to the behavioral tests. Co-immunoprecipitation was used to detect activation of the protein kinase A (PKA) signaling pathway in the mPFC of acutely stressed mice (n = 8) or intra-mPFC CRF injected mice (n = 7). Finally, mice received intra-mPFC CRF (n = 11) and/or Rp-isomer cyclic adenosine 3',5' monophosphorothioate (Rp-cAMPS) (n = 12) microinjections and underwent behavioral testing. We report acute stress-induced effects on mPFC-mediated cognition, identify CRF-CRFR1-containing microcircuits within the mPFC, and demonstrate stress-induced changes in Crhr1 messenger RNA expression. Importantly, intra-mPFC CRFR1 deletion abolishes acute stress-induced executive dysfunction, whereas intra-mPFC CRF mimics acute stress-induced mPFC dysfunction. Acute stress and intra-mPFC CRF activate the PKA signaling pathway in the mPFC, leading to cyclic AMP response element binding protein phosphorylation in intra-mPFC CRFR1-expressing neurons. Finally, PKA blockade reverses the intra-mPFC CRF-induced executive dysfunction. Taken together, these results unravel a molecular mechanism linking acute stress to executive dysfunction via CRFR1. This will aid in the development of novel therapeutic targets for stress-induced cognitive dysfunction. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Liver proteomics for therapeutic drug discovery: inhibition of the cyclophilin receptor CD147 attenuates sepsis-induced acute renal failure

PubMed Central

Dear, James W.; Leelahavanichkul, Asada; Aponte, Angel; Hu, Xuzhen; Constant, Stephanie L.; Hewitt, Stephen M.; Yuen, Peter S.T.; Star, Robert A.

2008-01-01

Objective Sepsis-induced multi-organ failure continues to have a high mortality. The liver is an organ central to the disease pathogenesis. The objective of this study was to identify the liver proteins that change in abundance with sepsis and, therefore, identify new drug targets. Design Proteomic discovery study and drug target validation Setting Research institute laboratory Subjects Three month old C57BL/6 mice Interventions We used a mouse model of sepsis based on cecal ligation and puncture (CLP) but with fluid and antibiotic resuscitation. Liver proteins that changed in abundance were identified by difference in-gel electrophoresis (DIGE). We compared liver proteins from 6 hr post-CLP to sham-operated mice (‘early proteins’) and 24 hr post-CLP with 6 hr post-CLP (‘late proteins’). Proteins that changed in abundance were identified by tandem mass spectrometry. We then inhibited the receptor for one protein and determined the effect on sepsis-induced organ dysfunction. Results The liver proteins that changed in abundance after sepsis had a range of functions such as acute phase proteins, coagulation, ER stress, oxidative stress, apoptosis, mitochondrial proteins and nitric oxide metabolism. We found that cyclophilin increased in abundance after CLP. When the receptor for this protein, CD147, was inhibited sepsis-induced renal dysfunction was reduced. There was also a significant reduction in serum cytokine production when CD147 was inhibited. Conclusion By applying proteomics to a clinically relevant mouse model of sepsis we identified a number of novel proteins that changed in abundance. The inhibition of the receptor for one of these proteins, cyclophilin, attenuated sepsis-induced acute renal failure. The application of proteomics to sepsis research can facilitate the discovery of new therapeutic targets. PMID:17944020

Management of fever, hyperglycemia, and swallowing dysfunction following hospital admission for acute stroke in New South Wales, Australia.

PubMed

Drury, Peta; Levi, Christopher; McInnes, Elizabeth; Hardy, Jennifer; Ward, Jeanette; Grimshaw, Jeremy M; D' Este, Catherine; Dale, Simeon; McElduff, Patrick; Cheung, N Wah; Quinn, Clare; Griffiths, Rhonda; Evans, Malcolm; Cadilhac, Dominique; Middleton, Sandy

2014-01-01

Fever, hyperglycemia, and swallow dysfunction poststroke are associated with significantly worse outcomes. We report treatment and monitoring practices for these three items from a cohort of acute stroke patients prior to randomization in the Quality in Acute Stroke Care trial. Retrospective medical record audits were undertaken for prospective patients from 19 stroke units. For the first three-days following stroke, we recorded all temperature readings and administration of paracetamol for fever (≥37·5°C) and all glucose readings and administration of insulin for hyperglycemia (>11 mmol/L). We also recorded swallow screening and assessment during the first 24 h of admission. Data for 718 (98%) patients were available; 138 (19%) had four hourly or more temperature readings and 204 patients (29%) had a fever, with 44 (22%) receiving paracetamol. A quarter of patients (n = 102/412, 25%) had six hourly or more glucose readings and 23% (95/412) had hyperglycemia, with 31% (29/95) of these treated with insulin. The majority of patients received a swallow assessment (n = 562, 78%) by a speech pathologist in the first instance rather than a swallow screen by a nonspeech pathologist (n = 156, 22%). Of those who passed a screen (n = 108 of 156, 69%), 68% (n = 73) were reassessed by a speech pathologist and 97% (n = 71) were reconfirmed to be able to swallow safely. Our results showed that acute stroke patients were: undermonitored and undertreated for fever and hyperglycemia; and underscreened for swallowing dysfunction and unnecessarily reassessed by a speech pathologist, indicating the need for urgent behavior change. © 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.

Plasma granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor levels in critical illness including sepsis and septic shock: relation to disease severity, multiple organ dysfunction, and mortality.

PubMed

Presneill, J J; Waring, P M; Layton, J E; Maher, D W; Cebon, J; Harley, N S; Wilson, J W; Cade, J F

2000-07-01

To define the circulating levels of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) during critical illness and to determine their relationship to the severity of illness as measured by the Acute Physiology and Chronic Health Evaluation (APACHE) II score, the development of multiple organ dysfunction, or mortality. Prospective cohort study. University hospital intensive care unit. A total of 82 critically ill adult patients in four clinically defined groups, namely septic shock (n = 29), sepsis without shock (n = 17), shock without sepsis (n = 22), and nonseptic, nonshock controls (n = 14). None. During day 1 of septic shock, peak plasma levels of G-CSF, interleukin (IL)-6, and leukemia inhibitory factor (LIF), but not GM-CSF, were greater than in sepsis or shock alone (p < .001), and were correlated among themselves (rs = 0.44-0.77; p < .02) and with the APACHE II score (rs = 0.25-0.40; p = .03 to .18). G-CSF, IL-6, and UF, and sepsis, shock, septic shock, and APACHE II scores were strongly associated with organ dysfunction or 5-day mortality by univariate analysis. However, multiple logistic regression analysis showed that only septic shock remained significantly associated with organ dysfunction and only APACHE II scores and shock with 5-day mortality. Similarly, peak G-CSF, IL-6, and LIF were poorly predictive of 30-day mortality. Plasma levels of G-CSF, IL-6, and LIF are greatly elevated in critical illness, including septic shock, and are correlated with one another and with the severity of illness. However, they are not independently predictive of mortality, or the development of multiple organ dysfunction. GM-CSF was rarely elevated, suggesting different roles for G-CSF and GM-CSF in human septic shock.

Intravascular lymphomatosis presenting as acute hemispheric dysfunction.

PubMed

Hwang, Woo Sub; Jung, Chul Won; Ko, Young Hye; Seo, Sang Won; Na, Duk L

2012-11-01

Intravascular lymphomatosis (IVL) is known to affect both hemispheres of the brain and manifests clinically as seizures or dementia. To our knowledge, there have been no cases in which acute hemispheric dysfunction is manifested in IVL. We present a 54-year-old man who showed steroid responsive acute hemispheric dysfunction. A technetium 99m-ethyl cysteinate dimer single-photon emission computed tomographic scan of the brain revealed hypoperfusion in the right hemisphere. The bone marrow biopsy specimen confirmed malignant lymphoid cells in vessels, which suggested IVL. Our case signifies the diversity of clinical manifestations in IVL. Copyright © 2012. Published by Elsevier Inc.

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

Massa, Christopher B.; Scott, Pamela; Abramova, Elena

Acute Cl{sub 2} exposure following industrial accidents or military/terrorist activity causes pulmonary injury and severe acute respiratory distress. Prior studies suggest that antioxidant depletion is important in producing dysfunction, however a pathophysiologic mechanism has not been elucidated. We propose that acute Cl{sub 2} inhalation leads to oxidative modification of lung lining fluid, producing surfactant inactivation, inflammation and mechanical respiratory dysfunction at the organ level. C57BL/6J mice underwent whole-body exposure to an effective 60 ppm-hour Cl{sub 2} dose, and were euthanized 3, 24 and 48 h later. Whereas pulmonary architecture and endothelial barrier function were preserved, transient neutrophilia, peaking at 24more » h, was noted. Increased expression of ARG1, CCL2, RETLNA, IL-1b, and PTGS2 genes was observed in bronchoalveolar lavage (BAL) cells with peak change in all genes at 24 h. Cl{sub 2} exposure had no effect on NOS2 mRNA or iNOS protein expression, nor on BAL NO{sub 3}{sup −} or NO{sub 2}{sup −}. Expression of the alternative macrophage activation markers, Relm-α and mannose receptor was increased in alveolar macrophages and pulmonary epithelium. Capillary surfactometry demonstrated impaired surfactant function, and altered BAL phospholipid and surfactant protein content following exposure. Organ level respiratory function was assessed by forced oscillation technique at 5 end expiratory pressures. Cl{sub 2} exposure had no significant effect on either airway or tissue resistance. Pulmonary elastance was elevated with time following exposure and demonstrated PEEP refractory derecruitment at 48 h, despite waning inflammation. These data support a role for surfactant inactivation as a physiologic mechanism underlying respiratory dysfunction following Cl{sub 2} inhalation. - Highlights: • Effect of 60 ppm*hr Cl{sub 2} gas on lung inflammation and mechanical function examined. • Pulmonary inflammation is transient and minor. • Alterations in surfactant homeostasis and pulmonary mechanics are noted. • No increase in the caliber of larger airways was suggested. • Small airways stability appears impaired based on PEEP response of mechanics.« less

Use of a novel hemoadsorption device for cytokine removal as adjuvant therapy in a patient with septic shock with multi-organ dysfunction: A case study.

PubMed

Basu, Reshma; Pathak, Sunjay; Goyal, Jyoti; Chaudhry, Rajeev; Goel, Rati B; Barwal, Anil

2014-12-01

CytoSorb(®) (CytoSorbents Corporation, USA) is a novel sorbent hemoadsorption device for cytokine removal. The aim of this study was to examine the clinical use of CytoSorb(®) in the management of patient with septic shock. We used this device as an adjuvant to stabilize a young patient with multi-organ failure and severe sepsis with septic shock. A 36-year-old female patient was hospitalized with the complaints of malaise, general body ache, and breathing difficulty and had a medical history of diabetes mellitus type II, hypertension, obstructive sleep apnea, hypothyroidism and morbid obesity. She was diagnosed to have septic shock with multi-organ dysfunction (MODS) and a low perfusion state. CytoSorb(®) hemoadsorption column was used as an attempt at blood purification. Acute physiology and chronic health evaluation score, MODS score, and sequential organ failure assessment score were measured before and after the device application. CytoSorb application as an adjuvant therapy could be considered in septic shock.

Use of a novel hemoadsorption device for cytokine removal as adjuvant therapy in a patient with septic shock with multi-organ dysfunction: A case study

PubMed Central

Basu, Reshma; Pathak, Sunjay; Goyal, Jyoti; Chaudhry, Rajeev; Goel, Rati B.; Barwal, Anil

2014-01-01

CytoSorb® (CytoSorbents Corporation, USA) is a novel sorbent hemoadsorption device for cytokine removal. The aim of this study was to examine the clinical use of CytoSorb® in the management of patient with septic shock. We used this device as an adjuvant to stabilize a young patient with multi-organ failure and severe sepsis with septic shock. A 36-year-old female patient was hospitalized with the complaints of malaise, general body ache, and breathing difficulty and had a medical history of diabetes mellitus type II, hypertension, obstructive sleep apnea, hypothyroidism and morbid obesity. She was diagnosed to have septic shock with multi-organ dysfunction (MODS) and a low perfusion state. CytoSorb® hemoadsorption column was used as an attempt at blood purification. Acute physiology and chronic health evaluation score, MODS score, and sequential organ failure assessment score were measured before and after the device application. CytoSorb application as an adjuvant therapy could be considered in septic shock. PMID:25538418

Acute hypopituitarism associated with periorbital swelling and cardiac dysfunction in a patient with pituitary tumor apoplexy: a case report.

PubMed

Ohara, Nobumasa; Yoneoka, Yuichiro; Seki, Yasuhiro; Akiyama, Katsuhiko; Arita, Masataka; Ohashi, Kazumasa; Suzuki, Kazuo; Takada, Toshinori

2017-08-24

Pituitary tumor apoplexy is a rare clinical syndrome caused by acute hemorrhage or infarction in a preexisting pituitary adenoma. It typically manifests as an acute episode of headache, visual disturbance, mental status changes, cranial nerve palsy, and endocrine pituitary dysfunction. However, not all patients present with classical symptoms, so it is pertinent to appreciate the clinical spectrum of pituitary tumor apoplexy presentation. We report an unusual case of a patient with pituitary tumor apoplexy who presented with periorbital edema associated with hypopituitarism. An 83-year-old Japanese man developed acute anterior hypopituitarism; he showed anorexia, fatigue, lethargy, severe bilateral periorbital edema, and mild cardiac dysfunction in the absence of headache, visual disturbance, altered mental status, and cranial nerve palsy. Magnetic resonance imaging showed a 2.5-cm pituitary tumor containing a mixed pattern of solid and liquid components indicating pituitary tumor apoplexy due to hemorrhage in a preexisting pituitary adenoma. Replacement therapy with oral hydrocortisone and levothyroxine relieved his symptoms of central adrenal insufficiency, central hypothyroidism, periorbital edema, and cardiac dysfunction. Common causes of periorbital edema include infections, inflammation, trauma, allergy, kidney or cardiac dysfunction, and endocrine disorders such as primary hypothyroidism. In the present case, the patient's acute central hypothyroidism was probably involved in the development of both periorbital edema and cardiac dysfunction. The present case highlights the need for physicians to consider periorbital edema as an unusual predominant manifestation of pituitary tumor apoplexy.

Heat stroke induced cerebellar dysfunction: A “forgotten syndrome”

PubMed Central

Kosgallana, Athula D; Mallik, Shreyashee; Patel, Vishal; Beran, Roy G

2013-01-01

We report a case of heat stroke induced acute cerebellar dysfunction, a rare neurological disease characterized by gross cerebellar dysfunction with no acute radiographic changes, in a 61 years old ship captain presenting with slurred speech and gait ataxia. A systematic review of the literature on heat stroke induced cerebellar dysfunction was performed, with a focus on investigations, treatment and outcomes. After review of the literature and detailed patient investigation it was concluded that this patient suffered heat stroke at a temperature less than that quoted in the literature. PMID:24340279

Peripheral blood sampling for the detection of allograft rejection: biomarker identification and validation.

PubMed

Heidt, Sebastiaan; San Segundo, David; Shankar, Sushma; Mittal, Shruti; Muthusamy, Anand S R; Friend, Peter J; Fuggle, Susan V; Wood, Kathryn J

2011-07-15

Currently, acute allograft rejection can only be detected reliably by deterioration of graft function confirmed by allograft biopsy. A huge drawback of this method of diagnosis is that substantial organ damage has already taken place at the time that rejection is diagnosed. Discovering and validating noninvasive biomarkers that predict acute rejection, and chronic allograft dysfunction, is of great importance. Many studies have investigated changes in the peripheral blood in an attempt to find biomarkers that reflect changes in the graft directly or indirectly. Herein, we will review the promises and limitations of the peripheral blood biomarkers that have been described in the literature so far.

Acute kidney injury and cardiovascular outcomes in acute severe hypertension.

PubMed

Szczech, Lynda A; Granger, Christopher B; Dasta, Joseph F; Amin, Alpesh; Peacock, W Frank; McCullough, Peter A; Devlin, John W; Weir, Matthew R; Katz, Jason N; Anderson, Frederick A; Wyman, Allison; Varon, Joseph

2010-05-25

Little is known about the association of kidney dysfunction and outcome in acute severe hypertension. This study aimed to measure the association between baseline chronic kidney disease (estimated glomerular filtration rate), acute kidney injury (AKI, decrease in estimated glomerular filtration rate > or =25% from baseline) and outcome in patients hospitalized with acute severe hypertension. The Studying the Treatment of Acute Hypertension (STAT) registry enrolled patients with acute severe hypertension, defined as > or =1 blood pressure measurement >180 mm Hg systolic and/or >110 mm Hg diastolic and treated with intravenous antihypertensive therapy. Data were compared across groups categorized by admission estimated glomerular filtration rate and AKI during admission. On admission, 79% of the cohort (n=1566) had at least mild chronic kidney disease (estimated glomerular filtration rate <60 mL/min in 46%, <30 mL/min in 22%). Chronic kidney disease patients were more likely to develop heart failure (P<0.0001), non-ST-elevation myocardial infarction (P=0.003), and AKI (P<0.007). AKI patients were at greater risk of heart failure and cardiac arrest (P< or =0.0001 for both). Subjects with AKI experienced higher mortality at 90 days (P=0.003). Any acute loss of estimated glomerular filtration rate during hospitalization was independently associated with an increased risk of death (odds ratio, 1.05; P=0.03 per 10-mL/min decline). Other independent predictors of mortality included increasing age (P<0.0001), male gender (P=0.016), white versus black race (P=0.003), and worse baseline kidney function (P=0.003). Chronic kidney disease is a common comorbidity among patients admitted with acute severe hypertension, and AKI is a frequent form of acute target organ dysfunction, particularly in those with baseline chronic kidney disease. Any degree of AKI is associated with a greater risk of morbidity and mortality.

ACUTE DIALYSIS QUALITY INITIATIVE (ADQI) XIV SEPSIS PHENOTYPES AND TARGETS FOR BLOOD PURIFICATION IN SEPSIS: THE BOGOTÁ CONSENSUS.

PubMed

Kellum, John A; Gómez, Hernando; Gómez, Alonso; Murray, Patrick; Ronco, Claudio

2016-03-01

Despite widespread use, there is currently no consensus on how extracorporeal blood purification therapies should be applied or studied in patients with sepsis. One major obstacle has been the lack of clear descriptions of specific sepsis phenotypes tied to mechanisms that would permit the identification of molecular targets. Current evidence suggests that sepsis-related morbidity and mortality involve widely different clinical phenotypes that variably include mitochondrial dysfunction, abnormalities of vascular biology including endothelial dysfunction and coagulopathy, epithelial dysfunction, and immune suppression and dysregulation. While most cases of sepsis involve some element of all of these pathobiologic processes, the magnitude of each varies greatly from patient to patient in part as a result of the pathogen and in part related to host-specific factors. Thus, the purpose of the fourteenth international consensus conference of acute dialysis quality initiative was to develop consensus for a conceptual model of sepsis-induced organ failure that can be treated by extracorporeal blood purification and possibly also with drugs or other therapies. We assembled a group of experts from around the world and used a modified Delphi method to reach consensus. Specific findings and recommendations for future research are provided in the four accompanying papers.

4G/5G polymorphism of PAI-1 gene is associated with multiple organ dysfunction and septic shock in pneumonia induced severe sepsis: prospective, observational, genetic study

PubMed Central

2010-01-01

Introduction Activation of inflammation and coagulation are closely related and mutually interdependent in sepsis. The acute-phase protein, plasminogen activator inhibitor-1 (PAI-1) is a key element in the inhibition of fibrinolysis. Elevated levels of PAI-1 have been related to worse outcome in pneumonia. We aimed to evaluate the effect of functionally relevant 4G/5G polymorphism of PAI-1 gene in pneumonia induced sepsis. Methods We enrolled 208 Caucasian patients with severe sepsis due to pneumonia admitted to an intensive care unit (ICU). Patients were followed up until ICU discharge or death. Clinical data were collected prospectively and the PAI-1 4G/5G polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism technique. Patients were stratified according to the occurrence of multiple organ dysfunction syndrome, septic shock or death. Results We found that carriers of the PAI-1 4G/4G and 4G/5G genotypes have a 2.74-fold higher risk for multiple organ dysfunction syndrome (odds ratio [OR] 95% confidence interval [CI] = 1.335 - 5.604; p = 0.006) and a 2.57-fold higher risk for septic shock (OR 95%CI = 1.180 - 5.615; p = 0.018) than 5G/5G carriers. The multivariate logistic regression analysis adjusted for independent predictors, such as age, nosocomial pneumonia and positive microbiological culture also supported that carriers of the 4G allele have a higher prevalence of multiple organ dysfunction syndrome (adjusted odds ratio [aOR] = 2.957; 95%CI = 1.306 -6.698; p = 0.009) and septic shock (aOR = 2.603; 95%CI = 1.137 - 5.959; p = 0.024). However, genotype and allele analyses have not shown any significant difference regarding mortality in models non-adjusted or adjusted for acute physiology and chronic health evaluation (APACHE) II. Patients bearing the 4G allele had higher disseminated intravascular coagulation (DIC) score at admission (p = 0.007) than 5G/5G carriers. Moreover, in 4G allele carriers the length of ICU stay of non-survivors was longer (p = 0.091), fewer ventilation-free days (p = 0.008) and days without septic shock (p = 0.095) were observed during the first 28 days. Conclusions In Caucasian patients with severe sepsis due to pneumonia carriers of the 4G allele of PAI-1 polymorphism have higher risk for multiple organ dysfunction syndrome and septic shock and in agreement they showed more fulminant disease progression based on continuous clinical variables. PMID:20429897

Acute suppurative parotitis: a dreadful complication in elderly surgical patients.

PubMed

Lampropoulos, Pavlos; Rizos, Spyros; Marinis, Athanasios

2012-08-01

Acute suppurative parotitis (ASP) is a severe infection seen particularly in elderly surgical patients. Factors that increase the risk of ASP include post-operative dehydration, debilitating conditions, and immunosuppressed states. Case report and literature review. An 82-year-old female patient was admitted because of paralytic ileus, dehydration, and poor oral hygiene, and was in distress. After two days of hospitalization, the patient developed a progressive painful swelling of her right parotid gland and fever up to 39.0°C. Computed tomography scanning showed an abscess in the parotid gland. Because of her progressive clinical deterioration, the patient underwent operative drainage of the abscess and removal of the necrotic material. Unfortunately, she suffered multiple organ dysfunction syndrome and died. Acute suppurative parotitis requires prompt aggressive treatment that nevertheless may fail.

Post-operative cognitive dysfunction after knee arthroplasty: a diagnostic dilemma

PubMed Central

Yap, Kiryu K.; Joyner, Peter

2014-01-01

Post-operative cognitive dysfunction (POCD) is common in the elderly, and significantly impacts their recovery. We present an unusual diagnostic challenge where a 65-year-old male presented 4-week post-total knee arthroplasty with acute cognitive dysfunction lasting 19 days. Curiously, there were no findings uncovering a specific cause, but during investigation underlying predisposing factors such as depression, mild memory deficits and generalized brain volume loss were identified. The impression after psychogeriatric review was that of an organic brain syndrome with overlay of depression, with a complex presentation as POCD. After escalation of behavioural disturbance, he was commenced on anti-psychotic/depressant, with immediate response. We emphasize the importance of pre-operative evaluation of cognitive function and risk factors in all geriatric patients undergoing elective surgery, and the need for further characterization of POCD, as well as experimental research elucidating the underlying mechanisms to better identify and treat this important post-surgical phenomenon. PMID:25988029

Neurologic Complications of Transplantation.

PubMed

Dhar, Rajat

2018-02-01

Neurologic disturbances including encephalopathy, seizures, and focal deficits complicate the course 10-30% of patients undergoing organ or stem cell transplantation. While much or this morbidity is multifactorial and often associated with extra-cerebral dysfunction (e.g., graft dysfunction, metabolic derangements), immunosuppressive drugs also contribute significantly. This can either be through direct toxicity (e.g., posterior reversible encephalopathy syndrome from calcineurin inhibitors such as tacrolimus in the acute postoperative period) or by facilitating opportunistic infections in the months after transplantation. Other neurologic syndromes such as akinetic mutism and osmotic demyelination may also occur. While much of this neurologic dysfunction may be reversible if related to metabolic factors or drug toxicity (and the etiology is recognized and reversed), cases of multifocal cerebral infarction, hemorrhage, or infection may have poor outcomes. As transplant patients survive longer, delayed infections (such as progressive multifocal leukoencephalopathy) and post-transplant malignancies are increasingly reported.

Upregulation of microRNA 142-3p in the peripheral blood and urinary cells of kidney transplant recipients with post-transplant graft dysfunction

PubMed Central

Domenico, T.D.; Joelsons, G.; Montenegro, R.M.; Manfro, R.C.

2017-01-01

We analyzed microRNA (miR)-142-3p expression in leucocytes of the peripheral blood and urinary sediment cell samples obtained from kidney transplant recipients who developed graft dysfunction. Forty-one kidney transplant recipients with kidney graft dysfunction and 8 stable patients were included in the study. The groups were divided according to histological analysis into acute rejection group (n=23), acute tubular necrosis group (n=18) and stable patients group used as a control for gene expression (n=8). Percutaneous biopsies were performed and peripheral blood samples and urine samples were obtained. miR-142-3p was analyzed by real-time polymerase chain reaction. The group of patients with acute tubular necrosis presented significantly higher expressions in peripheral blood (P<0.05) and urine (P<0.001) compared to the stable patients group. Also, in the peripheral blood, miR-142-3p expression was significantly higher in the acute tubular necrosis group compared to the acute rejection group (P<0.05). Urine samples of the acute rejection group presented higher expression compared to the stable patients group (P<0.001) but the difference between acute tubular necrosis and acute rejection groups was not significant in the urinary analyzes (P=0.079). miR-142-3p expression has a distinct pattern of expression in the setting of post-operative acute tubular necrosis after kidney transplantation and may potentially be used as a non-invasive biomarker for renal graft dysfunction. PMID:28380212

Upregulation of microRNA 142-3p in the peripheral blood and urinary cells of kidney transplant recipients with post-transplant graft dysfunction.

PubMed

Domenico, T D; Joelsons, G; Montenegro, R M; Manfro, R C

2017-04-03

We analyzed microRNA (miR)-142-3p expression in leucocytes of the peripheral blood and urinary sediment cell samples obtained from kidney transplant recipients who developed graft dysfunction. Forty-one kidney transplant recipients with kidney graft dysfunction and 8 stable patients were included in the study. The groups were divided according to histological analysis into acute rejection group (n=23), acute tubular necrosis group (n=18) and stable patients group used as a control for gene expression (n=8). Percutaneous biopsies were performed and peripheral blood samples and urine samples were obtained. miR-142-3p was analyzed by real-time polymerase chain reaction. The group of patients with acute tubular necrosis presented significantly higher expressions in peripheral blood (P<0.05) and urine (P<0.001) compared to the stable patients group. Also, in the peripheral blood, miR-142-3p expression was significantly higher in the acute tubular necrosis group compared to the acute rejection group (P<0.05). Urine samples of the acute rejection group presented higher expression compared to the stable patients group (P<0.001) but the difference between acute tubular necrosis and acute rejection groups was not significant in the urinary analyzes (P=0.079). miR-142-3p expression has a distinct pattern of expression in the setting of post-operative acute tubular necrosis after kidney transplantation and may potentially be used as a non-invasive biomarker for renal graft dysfunction.

Spontaneous acute subdural hematoma and intracerebral hemorrhage in a patient with thrombotic microangiopathy during pregnancy

PubMed Central

Wayhs, Sâmia Yasin; Wottrich, Joise; Uggeri, Douglas Prestes; Dias, Fernando Suparregui

2013-01-01

Preeclampsia, HELLP syndrome (hemolysis, elevated liver enzymes, and low-platelet count), and acute fatty liver of pregnancy are the main causes of thrombotic microangiopathy and severe liver dysfunction during pregnancy and represent different manifestations of the same pathological continuum. The case of a 35-week pregnant woman who was admitted to an intensive care unit immediately after a Cesarean section due to fetal death and the presence of nausea, vomiting, and jaundice is reported. Postpartum preeclampsia and acute fatty liver of pregnancy were diagnosed. The patient developed an acute subdural hematoma and an intracerebral hemorrhage, which were subjected to neurosurgical treatment. The patient died from refractory hemolytic anemia and spontaneous bleeding of multiple organs. Preeclampsia, HELLP syndrome, and acute fatty liver of pregnancy might overlap and be associated with potentially fatal complications, including intracranial hemorrhage, as in the present case. Early detection and diagnosis are crucial to ensure appropriate management and treatment success. PMID:23917984

Annual literature review of donor-specific HLA antibodies after organ transplantation.

PubMed

Kaneku, Hugo

2011-01-01

The literature review of post-transplant DSA published in 2011 shows: Observations after kidney and lung transplant in non-sensitized transplant recipients show that monitoring post-transplant HLA antibodies offers limited benefit in predicting acute rejection episodes. It remains to be seen if a different monitoring schedule and/ or studying other organs may show otherwise. Nevertheless, others have shown that monitoring post-transplant antibodies does identify patients at higher risk for chronic rejection. Studies in kidney, heart, and liver patients transplanted in the presence of preformed DSA show that detecting these antibodies early after transplant identifies a group of patients with greater risk for allograft dysfunction. New and larger studies using bortezomib and eculizumab to treat acute antibody-mediated rejection confirm earlier observations that these two therapies are effective in treating and preventing rejections. In general, identification of HLAantibodies and DSA after transplant is associated with higher rates of rejection and poor allograft survival in all organs examined. IgM antibodies appear to play an important role after lung transplants.

Alcohol-related dysfunction in working-age men in Izhevsk, Russia: an application of structural equation models to study the association with education.

PubMed

Cook, Sarah; Leon, David A; Kiryanov, Nikolay; Ploubidis, George B; De Stavola, Bianca L

2013-01-01

Acute alcohol-related dysfunctional behaviours, such as hangover, are predictive of poor health and mortality. Although much is known about the association of education with alcohol consumption, little is known about its association with these dysfunctional behaviours. The study population was 1,705 male drinkers aged 25-54 years resident in the city of Izhevsk, Russia who participated in a cross-sectional survey (2003-6). Structural equation modelling was used to examine the relationships between education, beverage and non-beverage alcohol intake, drinking patterns, and acute alcohol-related dysfunction score among these drinkers. Dysfunction was related to all other drinking variables, with the strongest predictors being spirit intake, non-beverage alcohol consumption and drinking patterns. There was a strong relationship between education and acute dysfunction which was not explained by adjusting for alcohol intake and drinking patterns (mean adjusted dysfunction score 0.35 SD (95% CI 0.10, 0.61) lower in men with higher versus secondary education). Although by definition one or more aspects of alcohol consumption should explain the educational differences in alcohol-related dysfunction, detailed information on drinking only partly accounted for the observed patterns. Thus beyond their intrinsic interest, these results illustrate the challenges in constructing statistical models that convincingly identify the pathways that link educational differences to health-related outcomes.

The mitochondria-targeted antioxidant MitoQ protects against organ damage in a lipopolysaccharide-peptidoglycan model of sepsis.

PubMed

Lowes, Damon A; Thottakam, Bensita M V; Webster, Nigel R; Murphy, Michael P; Galley, Helen F

2008-12-01

Sepsis is characterised by a systemic dysregulated inflammatory response and oxidative stress, often leading to organ failure and death. Development of organ dysfunction associated with sepsis is now accepted to be due at least in part to oxidative damage to mitochondria. MitoQ is an antioxidant selectively targeted to mitochondria that protects mitochondria from oxidative damage and which has been shown to decrease mitochondrial damage in animal models of oxidative stress. We hypothesised that if oxidative damage to mitochondria does play a significant role in sepsis-induced organ failure, then MitoQ should modulate inflammatory responses, reduce mitochondrial oxidative damage, and thereby ameliorate organ damage. To assess this, we investigated the effects of MitoQ in vitro in an endothelial cell model of sepsis and in vivo in a rat model of sepsis. In vitro MitoQ decreased oxidative stress and protected mitochondria from damage as indicated by a lower rate of reactive oxygen species formation (P=0.01) and by maintenance of the mitochondrial membrane potential (P<0.005). MitoQ also suppressed proinflammatory cytokine release from the cells (P<0.05) while the production of the anti-inflammatory cytokine interleukin-10 was increased by MitoQ (P<0.001). In a lipopolysaccharide-peptidoglycan rat model of the organ dysfunction that occurs during sepsis, MitoQ treatment resulted in lower levels of biochemical markers of acute liver and renal dysfunction (P<0.05), and mitochondrial membrane potential was augmented (P<0.01) in most organs. These findings suggest that the use of mitochondria-targeted antioxidants such as MitoQ may be beneficial in sepsis.

Management of sepsis: a 47-year-old woman with an indwelling intravenous catheter and sepsis.

PubMed

Angus, Derek C

2011-04-13

Severe sepsis is the term used to describe the host response to infection when complicated by acute organ dysfunction. Severe sepsis occurs in more than 750,000 individuals in the United States each year, with a hospital mortality of about 30%. Although the classic presentation is of florid shock with frank hypotension, fever, and elevated white blood cell count, many patients can present with cryptogenic shock (shock without hypotension) with more subtle signs of vital organ compromise. Using the case of Ms C, a 47-year-old woman with short gut syndrome and an indwelling intravenous catheter who developed an episode of severe sepsis secondary to a central line infection, treatment of sepsis is discussed. Management consists of prompt intervention with broad-spectrum antibiotics and fluid resuscitation, even in the absence of hypotension, and institution of a variety of strategies in the emergency setting to prevent development or worsening of vital organ dysfunction. Although advances in understanding the host immune response have fueled considerable interest in immunomodulatory therapy, the role of such agents in clinical practice remains limited and controversial.

Acute obstruction by Pannus in patients with aortic medtronic-hall valves: 30 years of experience.

PubMed

Ellensen, Vegard Skalstad; Andersen, Knut Sverre; Vitale, Nicola; Davidsen, Einar Skulstad; Segadal, Leidulf; Haaverstad, Rune

2013-12-01

Acute dysfunction of mechanical aortic valve prostheses is a life-threatening adverse event. Pannus overgrowth, which is fibroelastic hyperplasia originating from the periannular area, is one cause of dysfunction. The aim of this study was to determine the annual incidence of readmittance resulting from acute obstruction caused by pannus during 30 years of observation in patients with Medtronic-Hall aortic valve prostheses and to analyze the risk factors associated with pannus development. From 1982 to 2004, 1,187 patients in our department underwent aortic valve replacement with Medtronic-Hall mechanical monoleaflet valve prostheses. As of December 31, 2012, 27 of these patients (2.3%) had presented with acute valve dysfunction caused by pannus obstruction. The annual incidence of pannus was 0.7 per 1,000. The median time from the primary operation to prosthetic dysfunction was 11.1 years (range, 1.2 to 26.8 years). Of the 20 patients who underwent reoperation, 2 died. Seven patients died before reoperation. Women had a higher risk for the development of obstructing pannus, and patients with pannus obstruction were younger. Valve size was not an independent risk factor. Women and younger patients are at higher risk for pannus development. When acute dysfunction by pannus is suspected in a mechanical aortic valve, an immediate echocardiogram and an emergency aortic valve replacement should be carried out because of the potential of a fatal outcome. Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Multiorgan failure following mass wasp stings.

PubMed

Lin, Cheng-Jui; Wu, Chih-Jen; Chen, Han-Hsiang; Lin, Hsin-Chang

2011-05-01

Wasp bites usually bring temporary discomfort and pain, but on occasion, they can cause serious infections and fatal allergic reactions. We report on a patient who experienced massive wasp stings and developed multiple organ failure, including acute kidney, hepatic failure, and circulatory collapse 4 days later. He was treated with aggressive fluid resuscitation, inotropic agent, intravenous injection of steroids, broad-spectrum antibiotics, and hemodialysis. After intensive treatment, his liver function recovered one month later. Recovery of renal function was delayed, and the patient needed temporary regular hemodialysis. The pathology of kidney biopsy showed acute tubulointerstitial nephritis. This case shows that toxic reactions following massive wasp attacks may happen several days after the fact and result in severe, multiorgan system dysfunction.

Regeneration of the Exocrine Pancreas Is Delayed in Telomere-Dysfunctional Mice

PubMed Central

von Figura, Guido; Wagner, Martin; Nalapareddy, Kodandaramireddy; Hartmann, Daniel; Kleger, Alexander; Guachalla, Luis Miguel; Rolyan, Harshvardhan; Adler, Guido; Rudolph, Karl Lenhard

2011-01-01

Introduction Telomere shortening is a cell-intrinsic mechanism that limits cell proliferation by induction of DNA damage responses resulting either in apoptosis or cellular senescence. Shortening of telomeres has been shown to occur during human aging and in chronic diseases that accelerate cell turnover, such as chronic hepatitis. Telomere shortening can limit organ homeostasis and regeneration in response to injury. Whether the same holds true for pancreas regeneration in response to injury is not known. Methods In the present study, pancreatic regeneration after acute cerulein-induced pancreatitis was studied in late generation telomerase knockout mice with short telomeres compared to telomerase wild-type mice with long telomeres. Results Late generation telomerase knockout mice exhibited impaired exocrine pancreatic regeneration after acute pancreatitis as seen by persistence of metaplastic acinar cells and markedly reduced proliferation. The expression levels of p53 and p21 were not significantly increased in regenerating pancreas of late generation telomerase knockout mice compared to wild-type mice. Conclusion Our results indicate that pancreatic regeneration is limited in the context of telomere dysfunction without evidence for p53 checkpoint activation. PMID:21364961

Mechanisms of MDMA (Ecstasy)-Induced Oxidative Stress, Mitochondrial Dysfunction, and Organ Damage

PubMed Central

Song, Byoung-Joon; Moon, Kwan-Hoon; Upreti, Vijay V.; Eddington, Natalie D.; Lee, Insong J.

2010-01-01

Despite numerous reports about the acute and sub-chronic toxicities caused by MDMA (3,4-methylenedioxymethamphetamine, ecstasy), the underlying mechanism of organ damage is poorly understood. The aim of this review is to present an update of the mechanistic studies on MDMA-mediated organ damage partly caused by increased oxidative/nitrosative stress. Because of the extensive reviews on MDMA-mediated oxidative stress and tissue damage, we specifically focus on the mechanisms and consequences of oxidative-modifications of mitochondrial proteins, leading to mitochondrial dysfunction. We briefly describe a method to systematically identify oxidatively-modified mitochondrial proteins in control and MDMA-exposed rats by using biotin-N-maleimide (biotin-NM) as a sensitive probe for oxidized proteins. We also describe various applications and advantages of this Cys-targeted proteomics method and alternative approaches to overcome potential limitations of this method in studying oxidized proteins from MDMA-exposed tissues. Finally we discuss the mechanism of synergistic drug-interaction between MDMA and other abused substances including alcohol (ethanol) as well as application of this redox-based proteomics method in translational studies for developing effective preventive and therapeutic agents against MDMA-induced organ damage. PMID:20420575

Abrupt reflow enhances cytokine-induced proinflammatory activation of endothelial cells during simulated shock and resuscitation.

PubMed

Li, Ranran; Zijlstra, Jan G; Kamps, Jan A A M; van Meurs, Matijs; Molema, Grietje

2014-10-01

Circulatory shock and resuscitation are associated with systemic hemodynamic changes, which may contribute to the development of MODS (multiple organ dysfunction syndrome). In this study, we used an in vitro flow system to simulate the consecutive changes in blood flow as occurring during hemorrhagic shock and resuscitation in vivo. We examined the kinetic responses of different endothelial genes in human umbilical vein endothelial cells preconditioned to 20 dyne/cm unidirectional laminar shear stress for 48 h to flow cessation and abrupt reflow, respectively, as well as the effect of flow cessation and reflow on tumor necrosis factor-α (TNF-α)-induced endothelial proinflammatory activation. Endothelial CD31 and VE-cadherin were not affected by the changes in flow in the absence or presence of TNF-α. The messenger RNA levels of proinflammatory molecules E-selectin, VCAM-1 (vascular cell adhesion molecule 1), and IL-8 (interleukin 8) were significantly induced by flow cessation respectively acute reflow, whereas ICAM-1 (intercellular adhesion molecule 1) was downregulated on flow cessation and induced by subsequent acute reflow. Flow cessation also affected the Ang/Tie2 (Angiopoietin/Tie2 receptor tyrosine kinase) system by downregulating Tie2 and inducing its endothelial ligand Ang2, an effect that was further extended on acute reflow. Furthermore, the induction of proinflammatory adhesion molecules by TNF-α under flow cessation was significantly enhanced on subsequent acute reflow. This study demonstrated that flow alterations per se during shock and resuscitation contribute to endothelial activation and that these alterations interact with proinflammatory factors coexisting in vivo such as TNF-α. The abrupt reflow-related enhancement of cytokine-induced endothelial proinflammatory activation supports the concept that sudden regain of flow during resuscitation has an aggravating effect on endothelial activation, which may play a significant role in vascular dysfunction and consequent organ injury. This study implies that the improvement of resuscitation strategies and the pharmacological interference with proinflammatory signaling cascades at the right time of resuscitation of shock patients may be beneficial to regain and/or maintain organ function in patients after circulatory shock.

A comparison of toxicities in acute myeloid leukemia patients with and without renal impairment treated with decitabine.

PubMed

Levine, Lauren B; Roddy, Julianna Vf; Kim, Miryoung; Li, Junan; Phillips, Gary; Walker, Alison R

2018-06-01

Purpose There are limited data regarding the clinical use of decitabine for the treatment of acute myeloid leukemia in patients with a serum creatinine of 2 mg/dL or greater. Methods We retrospectively evaluated 111 patients with acute myeloid leukemia who had been treated with decitabine and compared the development of toxicities during cycle 1 in those with normal renal function (creatinine clearance greater than or equal to 60 mL/min) to those with renal dysfunction (creatinine clearance less than 60 mL/min). Results Notable differences in the incidence of grade ≥3 cardiotoxicity (33% of renal dysfunction patients vs. 16% of normal renal function patients, p = 0.042) and respiratory toxicity (40% of renal dysfunction patients vs. 14% of normal renal function patients, p = 0.0037) were observed. The majority of heart failure, myocardial infarction, and atrial fibrillation cases occurred in the renal dysfunction group. The odds of developing grade ≥3 cardiotoxicity did not differ significantly between patients with and without baseline cardiac comorbidities (OR 1.43, p = 0.43). Conclusions This study noted a higher incidence of grade ≥3 cardiac and respiratory toxicities in decitabine-treated acute myeloid leukemia patients with renal dysfunction compared to normal renal function. This may prompt closer monitoring, regardless of baseline cardiac comorbidities. Further evaluation of decitabine in patients with renal dysfunction is needed.

Pulmonary function test findings in patients with acute inhalation injury caused by smoke bombs

PubMed Central

Cao, Lu; Zhang, Xin-Gang; Wang, Jian-Guo; Wang, Han-Bin; Chen, Yi-Bing; Zhao, Da-Hui; Shi, Wen-Fang

2016-01-01

Background This study aimed to determine the effects of smoke bomb-induced acute inhalation injury on pulmonary function at different stages of lung injury. Methods We performed pulmonary function tests (PFTs) in 15 patients with acute inhalation injury from days 3 to 180 after smoke inhalation. We measured the trace element zinc in whole blood on days 4 and 17, and correlations of zinc levels with PFTs were performed. Results In the acute stage of lung injury (day 3), 3 of 11 patients with mild symptoms had normal pulmonary function and 8 patients with restrictive ventilatory dysfunction and reduced diffusing capacity. Some patients also had mild obstructive ventilatory dysfunction (5 patients) and a decline in small airway function (6 patients). For patients with severe symptoms, PFT results showed moderate to severe restrictive ventilatory dysfunction and reduced diffusing capacity. PaCO2 was significantly higher (P=0.047) in patients with reduced small airway function compared with those with normal small airway function. Whole blood zinc levels in the convalescence stage (day 17) were significantly lower than those in the acute stage (day 4). Zinc in the acute stage was negatively correlated with DLCO/VA on days 3, 10, and 46 (r=−0.633, −0.676, and −0.675 respectively, P<0.05). Conclusions Smoke inhalation injury mainly causes restrictive ventilatory dysfunction and reduced diffusing capacity, and causes mild obstructive ventilatory dysfunction and small airway function decline in some patients. Zinc is negatively correlated with DLCO/VA. Zinc levels may be able to predict prognosis and indicate the degree of lung injury. PMID:28066595

Increased levels of 3-hydroxykynurenine parallel disease severity in human acute pancreatitis.

PubMed

Skouras, Christos; Zheng, Xiaozhong; Binnie, Margaret; Homer, Natalie Z M; Murray, Toby B J; Robertson, Darren; Briody, Lesley; Paterson, Finny; Spence, Heather; Derr, Lisa; Hayes, Alastair J; Tsoumanis, Andreas; Lyster, Dawn; Parks, Rowan W; Garden, O James; Iredale, John P; Uings, Iain J; Liddle, John; Wright, Wayne L; Dukes, George; Webster, Scott P; Mole, Damian J

2016-09-27

Inhibition of kynurenine 3-monooxygenase (KMO) protects against multiple organ dysfunction (MODS) in experimental acute pancreatitis (AP). We aimed to precisely define the kynurenine pathway activation in relation to AP and AP-MODS in humans, by carrying out a prospective observational study of all persons presenting with a potential diagnosis of AP for 90 days. We sampled peripheral venous blood at 0, 3, 6, 12, 24, 48, 72 and 168 hours post-recruitment. We measured tryptophan metabolite concentrations and analysed these in the context of clinical data and disease severity indices, cytokine profiles and C-reactive protein (CRP) concentrations. 79 individuals were recruited (median age: 59.6 years; 47 males, 59.5%). 57 met the revised Atlanta definition of AP: 25 had mild, 23 moderate, and 9 severe AP. Plasma 3-hydroxykynurenine concentrations correlated with contemporaneous APACHE II scores (R 2  = 0.273; Spearman rho = 0.581; P < 0.001) and CRP (R 2  = 0.132; Spearman rho = 0.455, P < 0.001). Temporal profiling showed early tryptophan depletion and contemporaneous 3-hydroxykynurenine elevation. Furthermore, plasma concentrations of 3-hydroxykynurenine paralleled systemic inflammation and AP severity. These findings support the rationale for investigating early intervention with a KMO inhibitor, with the aim of reducing the incidence and severity of AP-associated organ dysfunction.

Increased levels of 3-hydroxykynurenine parallel disease severity in human acute pancreatitis

PubMed Central

Skouras, Christos; Zheng, Xiaozhong; Binnie, Margaret; Homer, Natalie Z. M.; Murray, Toby B. J.; Robertson, Darren; Briody, Lesley; Paterson, Finny; Spence, Heather; Derr, Lisa; Hayes, Alastair J.; Tsoumanis, Andreas; Lyster, Dawn; Parks, Rowan W.; Garden, O. James; Iredale, John P.; Uings, Iain J.; Liddle, John; Wright, Wayne L.; Dukes, George; Webster, Scott P.; Mole, Damian J.

2016-01-01

Inhibition of kynurenine 3-monooxygenase (KMO) protects against multiple organ dysfunction (MODS) in experimental acute pancreatitis (AP). We aimed to precisely define the kynurenine pathway activation in relation to AP and AP-MODS in humans, by carrying out a prospective observational study of all persons presenting with a potential diagnosis of AP for 90 days. We sampled peripheral venous blood at 0, 3, 6, 12, 24, 48, 72 and 168 hours post-recruitment. We measured tryptophan metabolite concentrations and analysed these in the context of clinical data and disease severity indices, cytokine profiles and C-reactive protein (CRP) concentrations. 79 individuals were recruited (median age: 59.6 years; 47 males, 59.5%). 57 met the revised Atlanta definition of AP: 25 had mild, 23 moderate, and 9 severe AP. Plasma 3-hydroxykynurenine concentrations correlated with contemporaneous APACHE II scores (R2 = 0.273; Spearman rho = 0.581; P < 0.001) and CRP (R2 = 0.132; Spearman rho = 0.455, P < 0.001). Temporal profiling showed early tryptophan depletion and contemporaneous 3-hydroxykynurenine elevation. Furthermore, plasma concentrations of 3-hydroxykynurenine paralleled systemic inflammation and AP severity. These findings support the rationale for investigating early intervention with a KMO inhibitor, with the aim of reducing the incidence and severity of AP-associated organ dysfunction. PMID:27669975

New or Progressive Multiple Organ Dysfunction Syndrome in Pediatric Severe Sepsis: A Sepsis Phenotype With Higher Morbidity and Mortality.

PubMed

Lin, John C; Spinella, Philip C; Fitzgerald, Julie C; Tucci, Marisa; Bush, Jenny L; Nadkarni, Vinay M; Thomas, Neal J; Weiss, Scott L

2017-01-01

To describe the epidemiology, morbidity, and mortality of new or progressive multiple organ dysfunction syndrome in children with severe sepsis. Secondary analysis of a prospective, cross-sectional, point prevalence study. International, multicenter PICUs. Pediatric patients with severe sepsis identified on five separate days over a 1-year period. None. Of 567 patients from 128 PICUs in 26 countries enrolled, 384 (68%) developed multiple organ dysfunction syndrome within 7 days of severe sepsis recognition. Three hundred twenty-seven had multiple organ dysfunction syndrome on the day of sepsis recognition. Ninety-one of these patients developed progressive multiple organ dysfunction syndrome, whereas an additional 57 patients subsequently developed new multiple organ dysfunction syndrome, yielding a total proportion with severe sepsis-associated new or progressive multiple organ dysfunction syndrome of 26%. Hospital mortality in patients with progressive multiple organ dysfunction syndrome was 51% compared with patients with new multiple organ dysfunction syndrome (28%) and those with single-organ dysfunction without multiple organ dysfunction syndrome (10%) (p < 0.001). Survivors of new or progressive multiple organ dysfunction syndrome also had a higher frequency of moderate to severe disability defined as a Pediatric Overall Performance Category score of greater than or equal to 3 and an increase of greater than or equal to 1 from baseline: 22% versus 29% versus 11% for progressive, new, and no multiple organ dysfunction syndrome, respectively (p < 0.001). Development of new or progressive multiple organ dysfunction syndrome is common (26%) in severe sepsis and is associated with a higher risk of morbidity and mortality than severe sepsis without new or progressive multiple organ dysfunction syndrome. Our data support the use of new or progressive multiple organ dysfunction syndrome as an important outcome in trials of pediatric severe sepsis although efforts are needed to validate whether reducing new or progressive multiple organ dysfunction syndrome leads to improvements in more definitive morbidity and mortality endpoints.

RAAS inhibition and cardiorenal syndrome.

PubMed

Onuigbo, Macaulay Amechi C

2014-01-01

The consensus conference on cardio-renal syndromes (2008) defined 'cardio-renal syndromes' as 'disorders of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other' and identified five subtypes of the syndromes. Various pathophysiologic mechanisms underlie cardiorenal syndrome including hemodynamic derangements, reduced cardiac output leading to impaired renal perfusion, reduced stroke volume, raised atrial filling pressures, elevated atrial pressures, sodium and water retention, venous congestion, right ventricular dysfunction and venous hypertension causing increased renal venous pressure, intra-abdominal hypertension, various neurohormonal adaptations including activation of the renin-angiotensin-aldosterone system, adaptive activation of the sympathetic nervous system, cytokine release and oxidative stress. Although there are standardized clinical guidelines for the management of heart failure, and chronic kidney disease, respectively, there are no similar consensus clinical guidelines for the management of the cardiorenal syndromes. RAAS inhibition is advocated in treating systolic heart failure. There is evidence that RAAS inhibition is also useful in cardiorenal syndrome. However, RAAS inhibition, while potentially useful in the management of cardiorenal syndrome, is not the 'magic bullet', is sometimes limited by adverse renal events, is not applicable to all patients, and must be applied by physicians with due diligence and caution. Nevertheless, a more comprehensive multidisciplinary multipronged approach to managing patients with cardiorenal syndrome is even more pragmatic and commonsense given the multiple mechanisms and pathogenetic pathways implicated in the causation and perpetuation of cardiorenal syndrome.

The Emerging Importance of Non-HLA Autoantibodies in Kidney Transplant Complications.

PubMed

Cardinal, Héloise; Dieudé, Mélanie; Hébert, Marie-Josée

2017-02-01

Antibodies that are specific to organ donor HLA have been involved in the majority of cases of antibody-mediated rejection in solid organ transplant recipients. However, recent data show that production of non-HLA autoantibodies can occur before transplant in the form of natural autoantibodies. In contrast to HLAs, which are constitutively expressed on the cell surface of the allograft endothelium, autoantigens are usually cryptic. Tissue damage associated with ischemia-reperfusion, vascular injury, and/or rejection creates permissive conditions for the expression of cryptic autoantigens, allowing these autoantibodies to bind antigenic targets and further enhance vascular inflammation and renal dysfunction. Antiperlecan/LG3 antibodies and antiangiotensin II type 1 receptor antibodies have been found before transplant in patients with de novo transplants and portend negative long-term outcome in patients with renal transplants. Here, we review mounting evidence suggesting an important role for autoantibodies to cryptic antigens as novel accelerators of kidney dysfunction and acute or chronic allograft rejection. Copyright © 2017 by the American Society of Nephrology.

Patent foramen ovale increases the risk of acute ischemic stroke in patients with acute pulmonary embolism leading to right ventricular dysfunction.

PubMed

Goliszek, Sylwia; Wiśniewska, Małgorzata; Kurnicka, Katarzyna; Lichodziejewska, Barbara; Ciurzyński, Michał; Kostrubiec, Maciej; Gołębiowski, Marek; Babiuch, Marek; Paczynska, Marzanna; Koć, Marcin; Palczewski, Piotr; Wyzgał, Anna; Pruszczyk, Piotr

2014-11-01

Patent foramen ovale (PFO) is an established risk factor for ischemic stroke. Since acute right ventricular dysfunction (RVD) observed in patients with PE can lead to right-to-left inter-atrial shunt via PFO, we hypothesized that PFO is a risk factor for ischemic stroke in PE with significant right ventricular dysfunction. 55 patients (31 F, 24M), median age 49 years (range 19-83 years) with confirmed PE underwent echocardiography for RVD and PFO assessment. High risk acute PE was diagnosed in 3 (5.5%) patients, while 16 (29%) hemodynamically stable with RVD patients formed a group with intermediate-risk PE. PFO was diagnosed in 19 patients (34.5%). Diffusion-weighted MRI of the brain for acute ischemic stroke (AIS) was performed in all patients 4.91 ± 4.1 days after admission. AIS was detected by MRI in 4 patients (7.3%). Only one stroke was clinically overt and resulted in hemiplegia. All 4 AIS occurred in the PFO positive group (4 of 19 patients), and none in subjects without PFO (21.0% vs 0%, p=0.02). Moreover, all AIS occurred in patients with RVD and PFO, and none in patients with PFO without RVD (50% vs 0%, p=0.038). Our data suggest that acute pulmonary embolism resulting in right ventricular dysfunction may lead to acute ischemic stroke in patients with patent foramen ovale. However, the clinical significance of such lesions remains to be determined. Copyright © 2014 Elsevier Ltd. All rights reserved.

After the bomb drops: A new look at radiation-induced multiple organ dysfunction syndrome (MODS)

PubMed Central

Williams, Jacqueline P.; McBride, William H.

2012-01-01

Purpose There is increasing concern that, since the Cold War era, there has been little progress regarding the availability of medical countermeasures in the event of either a radiological or nuclear incident. Fortunately, since much is known about the acute consequences that are likely to be experienced by an exposed population, the probability of survival from the immediate hematological crises after total body irradiation (TBI) has improved in recent years. Therefore focus has begun to shift towards later down-stream effects, seen in such organs as the gastrointestinal tract (GI), skin, and lung. However, the mechanisms underlying therapy-related normal tissue late effects, resulting from localised irradiation, have remained somewhat elusive and even less is known about the development of the delayed syndrome seen in the context of whole body exposures, when it is likely that systemic perturbations may alter tissue microenvironments and homeostasis. Conclusions The sequence of organ failures observed after near-lethal TBI doses are similar in many ways to that of multiple organ dysfunction syndrome (MODS), leading to multiple organ failure (MOF). In this review, we compare the mechanistic pathways that underlie both MODS and delayed normal tissue effects since these may impact on strategies to identify radiation countermeasures. PMID:21417595

Mitochondrial DNA Damage Initiates Acute Lung Injury and Multi-Organ System Failure Evoked in Rats by Intra-Tracheal Pseudomonas Aeruginosa.

PubMed

Lee, Yann-Leei; Obiako, Boniface; Gorodnya, Olena M; Ruchko, Mykhaylo V; Kuck, Jamie L; Pastukh, Viktor M; Wilson, Glenn L; Simmons, Jon D; Gillespie, Mark N

2017-07-01

Although studies in rat cultured pulmonary artery endothelial cells, perfused lungs, and intact mice support the concept that oxidative mitochondrial (mt) DNA damage triggers acute lung injury (ALI), it has not yet been determined whether enhanced mtDNA repair forestalls development of ALI and its progression to multiple organ system failure (MOSF). Accordingly, here we examined the effect of a fusion protein construct targeting the DNA glycosylase, Ogg1, to mitochondria in a rat model intra-tracheal Pseudomonas aeruginosa (strain 103; PA103)-induced ALI and MOSF. Relative to controls, animals given PA103 displayed increases in lung vascular filtration coefficient accompanied by transient lung tissue oxidative mtDNA damage and variable changes in mtDNA copy number without evidence of nuclear DNA damage. The approximate 40% of animals surviving 24 h after bacterial administration exhibited multiple organ dysfunction, manifest as increased serum and tissue-specific indices of kidney and liver failure, along with depressed heart rate and blood pressure. While administration of mt-targeted Ogg1 to control animals was innocuous, the active fusion protein, but not a DNA repair-deficient mutant, prevented bacteria-induced increases in lung tissue oxidative mtDNA damage, failed to alter mtDNA copy number, and attenuated lung endothelial barrier degradation. These changes were associated with suppression of liver, kidney, and cardiovascular dysfunction and with decreased 24 h mortality. Collectively, the present findings indicate that oxidative mtDNA damage to lung tissue initiates PA103-induced ALI and MOSF in rats.

A randomized clinical trial of hydroxymethylglutaryl- coenzyme a reductase inhibition for acute lung injury (The HARP Study).

PubMed

Craig, Thelma R; Duffy, Martin J; Shyamsundar, Murali; McDowell, Cliona; O'Kane, Cecilia M; Elborn, J Stuart; McAuley, Daniel F

2011-03-01

There is no effective pharmacological treatment for acute lung injury (ALI). Statins are a potential new therapy because they modify many of the underlying processes important in ALI. To test whether simvastatin improves physiological and biological outcomes in ALI. We conducted a randomized, double-blinded, placebo-controlled trial in patients with ALI. Patients received 80 mg simvastatin or placebo until cessation of mechanical ventilation or up to 14 days. Extravascular lung water was measured using thermodilution. Measures of pulmonary and nonpulmonary organ function were assessed daily. Pulmonary and systemic inflammation was assessed by bronchoalveolar lavage fluid and plasma cytokines. Systemic inflammation was also measured by plasma C-reactive protein. Sixty patients were recruited. Baseline characteristics, including demographics and severity of illness scores, were similar in both groups. At Day 7, there was no difference in extravascular lung water. By Day 14, the simvastatin-treated group had improvements in nonpulmonary organ dysfunction. Oxygenation and respiratory mechanics improved, although these parameters failed to reach statistical significance. Intensive care unit mortality was 30% in both groups. Simvastatin was well tolerated, with no increase in adverse events. Simvastatin decreased bronchoalveolar lavage IL-8 by 2.5-fold (P = 0.04). Plasma C-reactive protein decreased in both groups but failed to achieve significance in the placebo-treated group. Treatment with simvastatin appears to be safe and may be associated with an improvement in organ dysfunction in ALI. These clinical effects may be mediated by a reduction in pulmonary and systemic inflammation. Clinical trial registered with www.controlled-trials.com (ISRCTN70127774).

Characteristics, Outcomes, and Predictability of Critically Ill Obstetric Patients: A Multicenter Prospective Cohort Study.

PubMed

Vasquez, Daniela N; Das Neves, Andrea V; Vidal, Laura; Moseinco, Miriam; Lapadula, Jorge; Zakalik, Graciela; Santa-Maria, Analía; Gomez, Raúl A; Capalbo, Mónica; Fernandez, Claudia; Agüero-Villareal, Enrique; Vommaro, Santiago; Moretti, Marcelo; Soli, Silvana B; Ballestero, Florencia; Sottile, Juan P; Chapier, Viviana; Lovesio, Carlos; Santos, José; Bertoletti, Fernando; Intile, Alfredo D; Desmery, Pablo M; Estenssoro, Elisa

2015-09-01

To evaluate pregnant/postpartum patients requiring ICUs admission in Argentina, describe characteristics of mothers and outcomes for mothers/babies, evaluate risk factors for maternal-fetal-neonatal mortality; and compare outcomes between patients admitted to public and private health sectors. Multicenter, prospective, national cohort study. Twenty ICUs in Argentina (public, 8 and private, 12). Pregnant/postpartum (< 42 d) patients admitted to ICU. None. Three hundred sixty-two patients were recruited, 51% from the public health sector and 49% from the private. Acute Physiology and Chronic Health Evaluation II was 8 (4-12); predicted/observed mortality, 7.6%/3.6%; hospital length of stay, 7 days (5-13 d); and fetal-neonatal losses, 17%. Public versus private health sector patients: years of education, 9 ± 3 versus 15 ± 3; transferred from another hospital, 43% versus 12%; Acute Physiology and Chronic Health Evaluation II, 9 (5-13.75) versus 7 (4-9); hospital length of stay, 10 days (6-17 d) versus 6 days (4-9 d); prenatal care, 75% versus 99.4%; fetal-neonatal losses, 25% versus 9% (p = 0.000 for all); and mortality, 5.4% versus 1.7% (p = 0.09). Complications in ICU were multiple-organ dysfunction syndrome (34%), shock (28%), renal dysfunction (25%), and acute respiratory distress syndrome (20%); all predominated in the public sector. Sequential Organ Failure Assessment (during first 24 hr of admission) score of at least 6.5 presented the best discriminative power for maternal mortality. Independent predictors of maternal-fetal-neonatal mortality were Acute Physiology and Chronic Health Evaluation II, education level, prenatal care, and admission to tertiary hospitals. Patients spent a median of 7 days in hospital; 3.6% died. Maternal-fetal-neonatal mortality was determined not only by acuteness of illness but to social and healthcare aspects like education, prenatal control, and being cared in specialized hospitals. Sequential Organ Failure Assessment (during first 24 hr of admission), easier to calculate than Acute Physiology and Chronic Health Evaluation II, was a better predictor of maternal outcome. Evident health disparities existed between patients admitted to public versus private hospitals: the former received less prenatal care, were less educated, were more frequently transferred from other hospitals, were sicker at admission, and developed more complications; maternal and fetal-neonatal mortality were higher. These findings point to the need of redesigning healthcare services to account for these inequities.

Enterovirus-related diarrhoea in Guangdong, China: clinical features and implications in hand, foot and mouth disease and herpangina.

PubMed

Zhou, Hong-Tao; Yi, Hai-Su; Guo, Yong-Hui; Pan, Yu-Xian; Tao, Shao-Hua; Wang, Bin; Chen, Man-Jun; Yang, Mei; Yu, Nan

2016-03-16

A series of complications caused by enteroviruses, including meningitis, encephalitis, acute flaccid paralysis, acute cardiopulmonary failure, respiratory infection, and myocardial injury have been reported in hand, foot and mouth disease/herpangina (HFMD/HA). However, the complication of diarrhoea caused by enteroviruses has been neglected, and a summary of its clinical features and impact on HFMD/HA is unavailable. We included inpatients with HFMD/HA admitted to the Paediatric Department of Zhujiang Hospital during 2009-2012. We summarised and compared clinical data for cases with and without diarrhoea, and determined enterovirus serotypes by reverse transcriptase polymerase chain reaction and genotyping based on a partial-length fragment of viral protein 1 or the 5'-untranslated region. There were 804 inpatients with HFMD/HA and 28 (3.5%) presented with diarrhoea. Gastrointestinal symptoms were mild in most cases of diarrhoea (82.1%), with high prevalence of no dehydration (82.1%), short duration of diarrhoea (78.6%) and watery stools (75.0%). The prevalence of multi-organ dysfunction syndrome (10.7 vs 0.40%) (p = 0.001), hepatic injury (14.3 vs 3.4%) (p = 0.019), myocardial injury (21.4 vs 6.1%) (p = 0.002) and convulsion (21.4 vs 7.2%) (p = 0.016) was significantly higher in the diarrhoea than no diarrhoea group. There was no significant difference between the two groups regarding prevalence of death, altered consciousness, paralysis, central nervous system involvement, or acute respiratory infection. Most patients with diarrhoea caused by enteroviruses circulating in Guangdong Province in 2009-2012 had mild or moderate gastrointestinal symptoms. Although enterovirus-related diarrhoea caused additional multi-organ dysfunction syndrome, hepatic injury and myocardial injury in children with HFMD/HA, timely intervention efficiently reduced disease severity and improved outcome.

Synthetic Marijuana Induced Acute Nonischemic Left Ventricular Dysfunction.

PubMed

Elsheshtawy, Moustafa; Sriganesh, Priatharsini; Virparia, Vasudev; Patel, Falgun; Khanna, Ashok

2016-01-01

Synthetic marijuana is an uptrending designer drug currently widely spread in the US. We report a case of acute deterioration of nonischemic left ventricular dysfunction after exposure to synthetic marijuana. This case illustrates the importance of history taking in cardiac patients and identifies a negative cardiovascular effect of synthetic marijuana known as K2, not yet well detected by urine toxicology screening tools.

Current Review of Iron Overload and Related Complications in Hematopoietic Stem Cell Transplantation

PubMed Central

Atilla, Erden; Toprak, Selami K.; Demirer, Taner

2017-01-01

Iron overload is an adverse prognostic factor for patients undergoing hematopoietic stem cell transplantation (HSCT). In the HSCT setting, pretransplant and early posttransplant ferritin and transferrin saturation were found to be highly elevated due to high transfusion requirements. In addition to that, post-HSCT iron overload was shown to be related to infections, hepatic sinusoidal obstruction syndrome, mucositis, liver dysfunction, and acute graft-versus-host disease. Hyperferritinemia causes decreased survival rates in both pre- and posttransplant settings. Serum ferritin levels, magnetic resonance imaging, and liver biopsy are diagnostic tools for iron overload. Organ dysfunction due to iron overload may cause high mortality rates and therefore sufficient iron chelation therapy is recommended in this setting. In this review the management of iron overload in adult HSCT is discussed. PMID:27956374

SIRS score on admission and initial concentration of IL-6 as severe acute pancreatitis outcome predictors.

PubMed

Gregoric, Pavle; Pavle, Gregoric; Sijacki, Ana; Ana, Sijacki; Stankovic, Sanja; Sanja, Stankovic; Radenkovic, Dejan; Dejan, Radenkovic; Ivancevic, Nenad; Nenad, Ivancevic; Karamarkovic, Aleksandar; Aleksandar, Karamarkovic; Popovic, Nada; Nada, Popovic; Karadzic, Borivoje; Borivoje, Karadzic; Stijak, Lazar; Stefanovic, Branislav; Branislav, Stefanovic; Milosevic, Zoran; Zoran, Milosević; Bajec, Djordje; Djordje, Bajec

2010-01-01

Early recognition of severe form of acute pancreatitis is important because these patients need more agressive diagnostic and therapeutical approach an can develope systemic complications such as: sepsis, coagulopathy, Acute Lung Injury (ALI), Acute Respiratory Distress Syndrome (ARDS), Multiple Organ Dysfunction Syndrome (MODS), Multiple Organ Failure (MOF). To determine role of the combination of Systemic Inflammatory Response Syndrome (SIRS) score and serum Interleukin-6 (IL-6) level on admission as predictor of illness severity and outcome of Severe Acute Pancreatitis (SAP). We evaluated 234 patients with first onset of SAP appears in last twenty four hours. A total of 77 (33%) patients died. SIRS score and serum IL-6 concentration were measured in first hour after admission. In 105 patients with SIRS score 3 and higher, initial measured IL-6 levels were significantly higher than in the group of remaining 129 patients (72 +/- 67 pg/mL, vs 18 +/- 15 pg/mL). All nonsurvivals were in the first group, with SIRS score 3 and 4 and initial IL-6 concentration 113 +/- 27 pg/mL. The values of C-reactive Protein (CRP) measured after 48h, Acute Physiology and Chronic Health Evaluation (APACHE II) score on admission and Ranson score showed the similar correlation, but serum amylase level did not correlate significantly with Ranson score, IL-6 concentration and APACHE II score. The combination of SIRS score on admission and IL-6 serum concentration can be early, predictor of illness severity and outcome in SAP.

Evaluation of cerebral-cardiac syndrome using echocardiography in a canine model of acute traumatic brain injury.

PubMed

Qian, Rong; Yang, Weizhong; Wang, Xiumei; Xu, Zhen; Liu, Xiaodong; Sun, Bing

2015-01-01

Previous studies have confirmed that traumatic brain injury (TBI) can induce general adaptation syndrome (GAS), which subsequently results in myocardial dysfunction and damage in some patients with acute TBI; this condition is also termed as cerebral-cardiac syndrome. However, most clinicians ignore the detection and treatment of myocardial dysfunction, and instead concentrate only on the serious neural damage that is observed in acute TBI, which is one of the most important fatal factors. Therefore, clarification is urgently needed regarding the relationship between TBI and myocardial dysfunction. In the present study, we evaluated 18 canine models of acute TBI, by using real-time myocardial contrast echocardiography and strain rate imaging to accurately evaluate myocardial function and regional microcirculation, including the strain rate of the different myocardial segments, time-amplitude curves, mean ascending slope of the curve, and local myocardial blood flow. Our results suggest that acute TBI often results in cerebral-cardiac syndrome, which rapidly progresses to the serious stage within 3 days. This study is the first to provide comprehensive ultrasonic characteristics of cerebral-cardiac syndrome in an animal model of TBI.

[Clinical case of acute renal failure revealing an autoimmune hypothyroidism].

PubMed

Montasser, Dina Ibrahim; Hassani, Mohamed; Zajjari, Yassir; Bahadi, Abdelali; Alayoud, Ahmed; Hamzi, Amine; Hassani, Kawtar; Moujoud, Omar; Asseraji, Mohamed; Kadiri, Moncif; Aatif, Taoufik; El Kabbaj, Driss; Benyahia, Mohamed; Allam, Mustapha; Akhmouch, Ismail; Oualim, Zouhir

2010-04-01

Although the clinic picture is often indicative of muscle manifestations in patients with hypothyroidism, signs and symptoms of this condition are variable from simple elevation of serum muscle enzymes with myalgia, muscle weakness, cramps to rhabdomyolysis with acute renal failure which remains a rare event. Thyroid hormones affect the function of almost every body organ, and thyroid dysfunction produces a wide range of metabolic disturbances. Hypothyroidism is associated with significant effects on the kidney which the pathophysiology seems to be multifactorial, but the exact mechanisms remain poorly understood. Hypothyroidism as a cause of renal impairment is usually overlooked, leading to unnecessary diagnostic procedures. The main objective of our observation is to report a case of acute renal failure revealing an autoimmune hypothyroidism in which thyroid hormone substitution led to a significant improvement in muscular, thyroid and renal disorders. Copyright 2010 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

Delayed Consequences of Acute Kidney Injury

PubMed Central

Parr, Sharidan K; Siew, Edward D

2016-01-01

Acute kidney injury (AKI) is an increasingly common complication of hospitalization and acute illness. Experimental data indicate that AKI may cause permanent kidney damage through tubulointerstitial fibrosis and progressive nephron loss, while also lowering the threshold for subsequent injury. Furthermore, preclinical data suggest that AKI may also cause distant organ dysfunction. The extension of these findings to human studies suggests long-term consequences of AKI including, but not limited to recurrent AKI, progressive kidney disease, elevated blood pressure, cardiovascular events, and mortality. As the number of AKI survivors increases, the need to better understand the mechanisms driving these processes becomes paramount. Optimizing care for AKI survivors will require understanding the short- and long-term risks associated with AKI, identifying patients at highest risk for poor outcomes, and testing interventions that target modifiable risk factors. In this review, we examine the literature describing the association between AKI and long-term outcomes and highlight opportunities for further research and potential intervention. PMID:27113695

Risk stratification and prognostic performance of the predisposition, infection, response, and organ dysfunction (PIRO) scoring system in septic patients in the emergency department: a cohort study.

PubMed

Chen, Yun-Xia; Li, Chun-Sheng

2014-04-16

The predisposition, infection, response and organ dysfunction (PIRO) staging system was designed as a stratification tool to deal with the inherent heterogeneity of septic patients. The present study was conducted to assess the performance of PIRO in predicting multiple organ dysfunction (MOD), intensive care unit (ICU) admission, and 28-day mortality in septic patients in the emergency department (ED), and to compare this scoring system with the Mortality in Emergency Department Sepsis (MEDS) and Acute Physiology and Chronic Health Evaluation (APACHE II) scores. Consecutive septic patients (n = 680) admitted to the ED of Beijing Chao-Yang Hospital were enrolled. PIRO, MEDS, and APACHE II scores were calculated for each patient on ED arrival. Organ function was reassessed within 3 days of enrollment. All patients were followed up for 28 days. Outcome criteria were the development of MOD within 3 days, ICU admission or death within 28 days after enrollment. The predictive ability of the four components of PIRO was analyzed separately. Receiver operating characteristic (ROC) curve and logistic regression analysis were used to assess the prognostic and risk stratification value of the scoring systems. Organ dysfunction independently predicted ICU admission, MOD, and 28-day mortality, with areas under the ROC curve (AUC) of 0.888, 0.851, and 0.816, respectively. The predictive value of predisposition, infection, and response was weaker than that of organ dysfunction. A negative correlation was found between the response component and MOD, as well as mortality. PIRO, MEDS, and APACHE II scores significantly differed between patients who did and did not meet the outcome criteria (P < 0.001). PIRO and APACHE II independently predicted ICU admission and MOD, but MEDS did not. All three systems were independent predictors of 28-day mortality with similar AUC values. The AUC of PIRO was 0.889 for ICU admission, 0.817 for MOD, and 0.744 for 28-day mortality. The AUCs of PIRO were significantly greater than those of APACHE II and MEDS (P < 0.05) in predicting ICU admission and MOD. The study indicates that PIRO is helpful for risk stratification and prognostic determinations in septic patients in the ED.

Perioperative Management of Sickle Cell Disease

PubMed Central

Adjepong, Kwame Ofori; Otegbeye, Folashade

2018-01-01

Over 30 million people worldwide have sickle cell disease (SCD). Emergent and non-emergent surgical procedures in SCD have been associated with relatively increased risks of peri-operative mortality, vaso-occlusive (painful) crisis, acute chest syndrome, post-operative infections, congestive heart failure, cerebrovascular accident and acute kidney injury. Pre-operative assessment must include a careful review of the patient’s known crisis triggers, baseline hematologic profile, usual transfusion requirements, pre-existing organ dysfunction and opioid use. Use of preoperative blood transfusions should be selective and decisions individualized based on the baseline hemoglobin, surgical procedure and anticipated volume of blood loss. Intra- and post-operative management should focus on minimizing hypoxia, hypothermia, acidosis, and intravascular volume depletion. Pre- and post-operative incentive spirometry use should be encouraged. PMID:29755709

Diagnosis and treatment of bacterial prostatitis.

PubMed

Videčnik Zorman, Jerneja; Matičič, Mojca; Jeverica, Samo; Smrkolj, Tomaž

2015-01-01

Prostate inflammation is a common syndrome, especially in men under 50. It usually presents with voiding symptoms and pain in the genitourinary area, and sometimes as sexual dysfunction. Based on clinical and laboratory characteristics, prostatitis is classified as acute bacterial prostatitis, chronic bacterial prostatitis, chronic inflammatory and non-inflammatory prostatitis or chronic pelvic pain syndrome, and asymptomatic inflammatory prostatitis. Bacterial prostatitis is most often caused by infection with uropathogens, mainly Gram-negative bacilli, but Gram-positive and atypical microorganisms have also been identified as causative organisms of chronic prostatitis. According to reports by several authors, Chlamydia trachomatis and Trichomonas vaginalis are some of the most common pathogens, making chronic prostatitis a sexually transmitted disease. Diagnosis and treatment of acute and chronic bacterial prostatitis in particular can be challenging.

Perioperative Management of Sickle Cell Disease.

PubMed

Adjepong, Kwame Ofori; Otegbeye, Folashade; Adjepong, Yaw Amoateng

2018-01-01

Over 30 million people worldwide have sickle cell disease (SCD). Emergent and non-emergent surgical procedures in SCD have been associated with relatively increased risks of peri-operative mortality, vaso-occlusive (painful) crisis, acute chest syndrome, post-operative infections, congestive heart failure, cerebrovascular accident and acute kidney injury. Pre-operative assessment must include a careful review of the patient's known crisis triggers, baseline hematologic profile, usual transfusion requirements, pre-existing organ dysfunction and opioid use. Use of preoperative blood transfusions should be selective and decisions individualized based on the baseline hemoglobin, surgical procedure and anticipated volume of blood loss. Intra- and post-operative management should focus on minimizing hypoxia, hypothermia, acidosis, and intravascular volume depletion. Pre- and post-operative incentive spirometry use should be encouraged.

Lung-Kidney Cross-Talk in the Critically Ill Patient.

PubMed

Husain-Syed, Faeq; Slutsky, Arthur S; Ronco, Claudio

2016-08-15

Discoveries have emerged highlighting the complex nature of the interorgan cross-talk between the kidney and the lung. Vascular rigidity, neurohormonal activation, tissue hypoxia, and abnormal immune cell signaling have been identified as common pathways leading to the development and progression of chronic kidney disease. However, our understanding of the causal relationships between lung injury and kidney injury is not precise. This review discusses a number of features and mechanisms of renal dysfunction in pulmonary disorders in relation to respiratory acidosis, impaired gas exchange, systemic congestion, respiratory support/replacement therapies, and other issues relevant to the clinical care of these patients. Biotrauma due to injurious ventilatory strategies can lead to the release of mediators into the lung, which may then translocate into the systemic circulation and cause end-organ dysfunction, including renal dysfunction. Right ventricular dysfunction and congestive states may contribute to alterations of renal perfusion and oxygenation, leading to diuretic resistance and recurrent hospitalization. In patients with concomitant respiratory failure, noninvasive ventilation represents a promising treatment option for the correction of impaired renal microcirculation and endothelial dysfunction. In patients requiring extracorporeal membrane oxygenation, short- and long-term monitoring of kidney function is warranted, as they are at highest risk of developing acute kidney injury and fluid overload.

The Immune System’s Role in Sepsis Progression, Resolution and Long-Term Outcome

PubMed Central

Delano, Matthew J.; Ward, Peter A.

2016-01-01

SUMMARY Sepsis occurs when an infection exceeds local tissue containment and induces a series of dysregulated physiologic responses that result in organ dysfunction. A subset of patients with sepsis progress to septic shock, defined by profound circulatory, cellular, and metabolic abnormalities, and associated with a greater mortality. Historically, sepsis-induced organ dysfunction and lethality were attributed to the complex interplay between the initial inflammatory and later anti-inflammatory responses. With advances in intensive care medicine and goal-directed interventions, early 30-day sepsis mortality has diminished, only to steadily escalate long after “recovery” from acute events. Since so many sepsis survivors succumb later to persistent, recurrent, nosocomial and secondary infections, many investigators have turned their attention to the long-term sepsis-induced alterations in cellular immune function. Sepsis clearly alters the innate and adaptive immune responses for sustained periods of time after clinical recovery, with immune suppression, chronic inflammation, and persistence of bacterial representing such alterations. Understanding that sepsis-associated immune cell defects correlate with long-term mortality, more investigations have centered on the potential for immune modulatory therapy to improve long term patient outcomes. These efforts are focused on more clearly defining and effectively reversing the persistent immune cell dysfunction associated with long-term sepsis mortality. PMID:27782333

Autonomic Dysfunction Predicts Clinical Outcomes After Acute Ischemic Stroke: A Prospective Observational Study.

PubMed

Xiong, Li; Tian, Ge; Leung, Howan; Soo, Yannie O Y; Chen, Xiangyan; Ip, Vincent H L; Mok, Vincent C T; Chu, Winnie C W; Wong, Ka Sing; Leung, Thomas W H

2018-01-01

Central autonomic dysfunction increases stroke morbidity and mortality. We aimed to investigate whether poststroke autonomic dysfunction graded by Ewing battery can predict clinical outcome. In this prospective observational study, we assessed autonomic function of ischemic stroke patients within 7 days from symptom onset by Ewing battery. On the basis of the magnitude of autonomic dysfunction, we stratified patients into significant (definite, severe, or atypical) or minor (normal or early) autonomic function impairment groups and correlated the impairment with the 3-month modified Rankin Scale score (good outcome: modified Rankin Scale score 0≈2; poor outcome: modified Rankin Scale score 3≈6). Among the 150 patients enrolled (mean age, 66.4±9.9 years; 70.7% males), minor autonomic dysfunction was identified in 36 patients (24.0%), and significant autonomic dysfunction was identified in 114 patients (76.0%) based on Ewing battery. In 3 months, a poor functional outcome was found in 32.5% of significant group patients compared with 13.9% in the minor group ( P =0.031). Crude odds ratios of the magnitude of autonomic dysfunction and 3-month unfavorable functional outcome after acute ischemic stroke were 2.979 (95% confidence interval, 1.071-8.284; P =0.036). After adjusting for confounding variables with statistical significance between the 2 functional outcome subgroups identified in univariate analysis (including sex and National Institutes of Health Stroke Scale score on admission), the magnitude of autonomic dysfunction still independently predicted an unfavorable outcome, with an odds ratio of 3.263 (95% confidence interval, 1.141-9.335; P =0.027). Autonomic dysfunction gauged by Ewing battery predicts poor functional outcome after acute ischemic stroke. © 2017 American Heart Association, Inc.

Pseudo-acute myocardial infarction due to transient apical ventricular dysfunction syndrome (Takotsubo syndrome).

PubMed

Maciel, Bruno Araújo; Cidrão, Alan Alves de Lima; Sousa, Italo Bruno Dos Santos; Ferreira, José Adailson da Silva; Messias Neto, Valdevino Pedro

2013-03-01

Takotsubo syndrome is characterized by predominantly medial-apical transient left ventricular dysfunction, which is typically triggered by physical or emotional stress. The present article reports the case of a 61-year-old female patient presenting with dizziness, excessive sweating, and sudden state of ill feeling following an episode involving intense emotional stress. The physical examination and electrocardiogram were normal upon admission, but the troponin I and creatine kinase-MB concentrations were increased. Acute myocardial infarction without ST segment elevation was suspected, and coronary angiography was immediately performed, which showed severe diffuse left ventricular hypokinesia, medial-apical systolic ballooning, and a lack of significant coronary injury. The patient was referred to the intensive care unit and was successfully treated with supportive therapy. As this case shows, Takotsubo syndrome might simulate the clinical manifestations of acute myocardial infarction, and coronary angiography is necessary to distinguish between both myocardial infarction and myocardial infarction in the acute stage. The present patient progressed with spontaneous resolution of the ventricular dysfunction without any sequelae.

Pseudo-acute myocardial infarction due to transient apical ventricular dysfunction syndrome (Takotsubo syndrome)

PubMed Central

Maciel, Bruno Araújo; Cidrão, Alan Alves de Lima; Sousa, Ítalo Bruno dos Santos; Ferreira, José Adailson da Silva; Messias Neto, Valdevino Pedro

2013-01-01

Takotsubo syndrome is characterized by predominantly medial-apical transient left ventricular dysfunction, which is typically triggered by physical or emotional stress. The present article reports the case of a 61-year-old female patient presenting with dizziness, excessive sweating, and sudden state of ill feeling following an episode involving intense emotional stress. The physical examination and electrocardiogram were normal upon admission, but the troponin I and creatine kinase-MB concentrations were increased. Acute myocardial infarction without ST segment elevation was suspected, and coronary angiography was immediately performed, which showed severe diffuse left ventricular hypokinesia, medial-apical systolic ballooning, and a lack of significant coronary injury. The patient was referred to the intensive care unit and was successfully treated with supportive therapy. As this case shows, Takotsubo syndrome might simulate the clinical manifestations of acute myocardial infarction, and coronary angiography is necessary to distinguish between both myocardial infarction and myocardial infarction in the acute stage. The present patient progressed with spontaneous resolution of the ventricular dysfunction without any sequelae. PMID:23887762

Systemic Inflammatory Response Syndrome, Quick Sequential Organ Function Assessment, and Organ Dysfunction: Insights From a Prospective Database of ED Patients With Infection.

PubMed

Williams, Julian M; Greenslade, Jaimi H; McKenzie, Juliet V; Chu, Kevin; Brown, Anthony F T; Lipman, Jeffrey

2017-03-01

A proposed revision of sepsis definitions has abandoned the systemic inflammatory response syndrome (SIRS), defined organ dysfunction as an increase in total Sequential Organ Function Assessment (SOFA) score of ≥ 2, and conceived "qSOFA" (quick SOFA) as a bedside indicator of organ dysfunction. We aimed to (1) determine the prognostic impact of SIRS, (2) compare the diagnostic accuracy of SIRS and qSOFA for organ dysfunction, and (3) compare standard (Sepsis-2) and revised (Sepsis-3) definitions for organ dysfunction in ED patients with infection. Consecutive ED patients admitted with presumed infection were prospectively enrolled over 3 years. Sufficient observational data were collected to calculate SIRS, qSOFA, SOFA, comorbidity, and mortality. We enrolled 8,871 patients, with SIRS present in 4,176 (47.1%). SIRS was associated with increased risk of organ dysfunction (relative risk [RR] 3.5) and mortality in patients without organ dysfunction (OR 3.2). SIRS and qSOFA showed similar discrimination for organ dysfunction (area under the receiver operating characteristic curve, 0.72 vs 0.73). qSOFA was specific but poorly sensitive for organ dysfunction (96.1% and 29.7%, respectively). Mortality for patients with organ dysfunction was similar for Sepsis-2 and Sepsis-3 (12.5% and 11.4%, respectively), although 29% of patients with Sepsis-3 organ dysfunction did not meet Sepsis-2 criteria. Increasing numbers of Sepsis-2 organ system dysfunctions were associated with greater mortality. SIRS was associated with organ dysfunction and mortality, and abandoning the concept appears premature. A qSOFA score ≥ 2 showed high specificity, but poor sensitivity may limit utility as a bedside screening method. Although mortality for organ dysfunction was comparable between Sepsis-2 and Sepsis-3, more prognostic and clinical information is conveyed using Sepsis-2 regarding number and type of organ dysfunctions. The SOFA score may require recalibration. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Linking Inflammation, Cardiorespiratory Variability, and Neural Control in Acute Inflammation via Computational Modeling

PubMed Central

Dick, Thomas E.; Molkov, Yaroslav I.; Nieman, Gary; Hsieh, Yee-Hsee; Jacono, Frank J.; Doyle, John; Scheff, Jeremy D.; Calvano, Steve E.; Androulakis, Ioannis P.; An, Gary; Vodovotz, Yoram

2012-01-01

Acute inflammation leads to organ failure by engaging catastrophic feedback loops in which stressed tissue evokes an inflammatory response and, in turn, inflammation damages tissue. Manifestations of this maladaptive inflammatory response include cardio-respiratory dysfunction that may be reflected in reduced heart rate and ventilatory pattern variabilities. We have developed signal-processing algorithms that quantify non-linear deterministic characteristics of variability in biologic signals. Now, coalescing under the aegis of the NIH Computational Biology Program and the Society for Complexity in Acute Illness, two research teams performed iterative experiments and computational modeling on inflammation and cardio-pulmonary dysfunction in sepsis as well as on neural control of respiration and ventilatory pattern variability. These teams, with additional collaborators, have recently formed a multi-institutional, interdisciplinary consortium, whose goal is to delineate the fundamental interrelationship between the inflammatory response and physiologic variability. Multi-scale mathematical modeling and complementary physiological experiments will provide insight into autonomic neural mechanisms that may modulate the inflammatory response to sepsis and simultaneously reduce heart rate and ventilatory pattern variabilities associated with sepsis. This approach integrates computational models of neural control of breathing and cardio-respiratory coupling with models that combine inflammation, cardiovascular function, and heart rate variability. The resulting integrated model will provide mechanistic explanations for the phenomena of respiratory sinus-arrhythmia and cardio-ventilatory coupling observed under normal conditions, and the loss of these properties during sepsis. This approach holds the potential of modeling cross-scale physiological interactions to improve both basic knowledge and clinical management of acute inflammatory diseases such as sepsis and trauma. PMID:22783197

Cardiorenal Syndrome in Western Countries: Epidemiology, Diagnosis and Management Approaches.

PubMed

Ronco, Claudio; Di Lullo, Luca

2017-01-01

It is well established that a large number of hospitalized patients present various degrees of heart and kidney dysfunction; primary disease of the heart or kidney often involves dysfunction or injury to the other. Based on above-cited organ cross-talk, the term cardiorenal syndrome (CRS) was proposed. Although CRS was usually referred to as abruption of kidney function following heart injury, it is now clearly established that it can describe negative effects of an impaired renal function on the heart and circulation. The historical lack of clear syndrome definition and complexity of diseases contributed to a waste of precious time especially concerning diagnosis and therapeutic strategies. The effective classification of CRS proposed in a Consensus Conference by the Acute Dialysis Quality Group essentially divides CRS into two main groups, cardiorenal and renocardiac CRS, on the basis of primum movens of disease (cardiac or renal); both cardiorenal and renocardiac CRS are then divided into acute and chronic according to disease onset. Type 5 CRS integrates all cardiorenal involvement induced by systemic disease. Prevalence and incidence data show a widespread increase of CRS also due to an increasing incidence of acute and chronic cardiovascular disease, such as acute decompensated heart failure, arterial hypertension and valvular heart disease. Patients with chronic kidney disease present various degrees of cardiovascular involvement especially due to chronic inflammatory status, volume and pressure overload and secondary hyperparathyroidism leading to a higher incidence of calcific heart disease. The following review will focus on the main aspects (epidemiology, risk factors, diagnostic tools and protocols, therapeutic approaches) of CRS in Western countries (Europe and United States).

Linking Inflammation, Cardiorespiratory Variability, and Neural Control in Acute Inflammation via Computational Modeling.

PubMed

Dick, Thomas E; Molkov, Yaroslav I; Nieman, Gary; Hsieh, Yee-Hsee; Jacono, Frank J; Doyle, John; Scheff, Jeremy D; Calvano, Steve E; Androulakis, Ioannis P; An, Gary; Vodovotz, Yoram

2012-01-01

Acute inflammation leads to organ failure by engaging catastrophic feedback loops in which stressed tissue evokes an inflammatory response and, in turn, inflammation damages tissue. Manifestations of this maladaptive inflammatory response include cardio-respiratory dysfunction that may be reflected in reduced heart rate and ventilatory pattern variabilities. We have developed signal-processing algorithms that quantify non-linear deterministic characteristics of variability in biologic signals. Now, coalescing under the aegis of the NIH Computational Biology Program and the Society for Complexity in Acute Illness, two research teams performed iterative experiments and computational modeling on inflammation and cardio-pulmonary dysfunction in sepsis as well as on neural control of respiration and ventilatory pattern variability. These teams, with additional collaborators, have recently formed a multi-institutional, interdisciplinary consortium, whose goal is to delineate the fundamental interrelationship between the inflammatory response and physiologic variability. Multi-scale mathematical modeling and complementary physiological experiments will provide insight into autonomic neural mechanisms that may modulate the inflammatory response to sepsis and simultaneously reduce heart rate and ventilatory pattern variabilities associated with sepsis. This approach integrates computational models of neural control of breathing and cardio-respiratory coupling with models that combine inflammation, cardiovascular function, and heart rate variability. The resulting integrated model will provide mechanistic explanations for the phenomena of respiratory sinus-arrhythmia and cardio-ventilatory coupling observed under normal conditions, and the loss of these properties during sepsis. This approach holds the potential of modeling cross-scale physiological interactions to improve both basic knowledge and clinical management of acute inflammatory diseases such as sepsis and trauma.

Obesity-Induced Endoplasmic Reticulum Stress Causes Lung Endothelial Dysfunction and Promotes Acute Lung Injury.

PubMed

Shah, Dilip; Romero, Freddy; Guo, Zhi; Sun, Jianxin; Li, Jonathan; Kallen, Caleb B; Naik, Ulhas P; Summer, Ross

2017-08-01

Obesity is a significant risk factor for acute respiratory distress syndrome. The mechanisms underlying this association are unknown. We recently showed that diet-induced obese mice exhibit pulmonary vascular endothelial dysfunction, which is associated with enhanced susceptibility to LPS-induced acute lung injury. Here, we demonstrate that lung endothelial dysfunction in diet-induced obese mice coincides with increased endoplasmic reticulum (ER) stress. Specifically, we observed enhanced expression of the major sensors of misfolded proteins, including protein kinase R-like ER kinase, inositol-requiring enzyme α, and activating transcription factor 6, in whole lung and in primary lung endothelial cells isolated from diet-induced obese mice. Furthermore, we found that primary lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of diet-induced obese mice, including an increase in expression of endothelial adhesion molecules and a decrease in expression of endothelial cell-cell junctional proteins. Similar changes were observed in lung endothelial cells and in whole-lung tissue after exposure to tunicamycin, a compound that causes ER stress by blocking N-linked glycosylation, indicating that ER stress causes endothelial dysfunction in the lung. Treatment with 4-phenylbutyric acid, a chemical protein chaperone that reduces ER stress, restored vascular endothelial cell expression of adhesion molecules and protected against LPS-induced acute lung injury in diet-induced obese mice. Our work indicates that fatty acids in obese serum induce ER stress in the pulmonary endothelium, leading to pulmonary endothelial cell dysfunction. Our work suggests that reducing protein load in the ER of pulmonary endothelial cells might protect against acute respiratory distress syndrome in obese individuals.

Hexamethonium reverses the lethal cardiopulmonary damages in a rat model of brainstem lesions mimicking fatal enterovirus 71 encephalitis.

PubMed

Lu, Wen-Hsien; Hsieh, Kai-Sheng; Lu, Pei-Jung; Wu, Yi-Shan; Ho, Wen-Yu; Lai, Chi-Cheng; Wang, Jyh-Seng; Ger, Luo-Ping; Hsiao, Michael; Tseng, Ching-Jiunn

2013-05-01

Among enterovirus 71 infections, brainstem encephalitis progressing abruptly to cardiac dysfunction and pulmonary edema causes rapid death within several hours. However, no currently known early indicators and treatments can monitor or prevent the unexpectedly fulminant course. We investigate the possible mechanisms and treatment of fatal enterovirus 71 infections to prevent the abrupt progression to cardiac dysfunction and pulmonary edema by using an animal model. Treatment study. Research laboratory. Sprague-Dawley rats. We microinjected 6-hydroxydopamine or vitamin C into nucleus tractus solitarii of the rat and evaluated the cardiopulmonary changes after treatment with ganglionic blocker. The time course of changes in the heart and lungs of rats with brainstem lesions were investigated. Rats were administered 6-hydroxydopamine to induce brainstem lesions, causing acute hypertension in 10 minutes and acute elevations of catecholamines accompanied by acute cardiac dysfunction and increased strong expressions of connexin 43 gap junction protein in heart and lung specimens by immunohistochemical staining within 3 hours. Severe pulmonary hemorrhagic edema was produced within 6 hours, and the rats expired rapidly within 7 hours. After hexamethonium treatment, it was found that the acute hypertension induced by 6-hydroxydopamine lesions was immediately reversed and the acute high rise of catecholamine serum level was significantly attenuated within 3 hours, accompanied by preserved cardiac output and decreased expressions of connexin 43 in the heart and lungs. No pulmonary edema occurred and the rats survived for more than 14 hours. Early hexamethonium treatment attenuates acute excessive release of catecholamines to prevent cardiac dysfunction and pulmonary edema for increasing survival rate.

Predictors and outcomes of acute pancreatitis in critically ill patients presenting to the emergency department of a tertiary referral centre in Australia.

PubMed

Sundararajan, Krishnaswamy; Schoeman, Tom; Hughes, Lara; Edwards, Suzanne; Reddi, Benjamin

2017-04-01

To provide a current review of the clinical characteristics, predictors and outcomes in critically ill patients presenting to the ED with acute pancreatitis and subsequently admitted to an intensive care unit (ICU) of a tertiary referral centre in Australia. A retrospective single-centre study of adult patients admitted with pancreatitis. Severe acute pancreatitis defined by Bedside Index of Severity in Acute Pancreatitis (BISAP) score ≥2. Eighty-seven patients fulfilled criteria for inclusion during the study period, representing 0.9% of all ICU admissions. The median age of patients was 54. Survival was independent of patients' age, sex, aetiology and comorbidities. Mortality was 30.8% for both inpatient referrals to the ICU and for direct referrals via the ED. Higher mortality was identified among patients requiring mechanical ventilation (74.2 vs 24.6% in survivors; P < 0.0001), vasopressor support (85.7 vs 33.8% in survivors; P < 0.0001) or renal replacement therapy (60 vs 16.9% in survivors; P < 0.002). BISAP score surpasses Ranson's and Acute Physiological and Chronic Health Examination (APACHE) II scores in discriminating between survivors and non-survivors among unselected patients with acute pancreatitis admitted to ICU, whereas APACHE II discriminates better in the cohort admitted from ED. Severe acute pancreatitis is associated with high mortality. Aetiology and comorbidity did not predict adverse outcomes in this population. BISAP score is non-inferior to APACHE II score as a prognostic tool in critically ill patients with acute pancreatitis and could be used to triage admission. Evidence of persistent organ dysfunction and requirements for organ support reliably identify patients at high-risk of death. © 2017 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

Acute Kidney Injury as a Risk Factor for Delirium and Coma during Critical Illness.

PubMed

Siew, Edward D; Fissell, William H; Tripp, Christina M; Blume, Jeffrey D; Wilson, Matthew D; Clark, Amanda J; Vincz, Andrew J; Ely, E Wesley; Pandharipande, Pratik P; Girard, Timothy D

2017-06-15

Acute kidney injury may contribute to distant organ dysfunction. Few studies have examined kidney injury as a risk factor for delirium and coma. To examine whether acute kidney injury is associated with delirium and coma in critically ill adults. In a prospective cohort study of intensive care unit patients with respiratory failure and/or shock, we examined the association between acute kidney injury and daily mental status using multinomial transition models adjusting for demographics, nonrenal organ failure, sepsis, prior mental status, and sedative exposure. Acute kidney injury was characterized daily using the difference between baseline and peak serum creatinine and staged according to Kidney Disease Improving Global Outcomes criteria. Mental status (normal vs. delirium vs. coma) was assessed daily with the Confusion Assessment Method for the ICU and Richmond Agitation-Sedation Scale. Among 466 patients, stage 2 acute kidney injury was a risk factor for delirium (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.07-2.26) and coma (OR, 2.04; 95% CI, 1.25-3.34) as was stage 3 injury (OR for delirium, 2.56; 95% CI, 1.57-4.16) (OR for coma, 3.34; 95% CI, 1.85-6.03). Daily peak serum creatinine (adjusted for baseline) values were also associated with delirium (OR, 1.35; 95% CI, 1.18-1.55) and coma (OR, 1.44; 95% CI, 1.20-1.74). Renal replacement therapy modified the association between stage 3 acute kidney injury and daily peak serum creatinine and both delirium and coma. Acute kidney injury is a risk factor for delirium and coma during critical illness.

Ionizing radiation regulates cardiac Ca handling via increased ROS and activated CaMKII.

PubMed

Sag, Can M; Wolff, Hendrik A; Neumann, Kay; Opiela, Marie-Kristin; Zhang, Juqian; Steuer, Felicia; Sowa, Thomas; Gupta, Shamindra; Schirmer, Markus; Hünlich, Mark; Rave-Fränk, Margret; Hess, Clemens F; Anderson, Mark E; Shah, Ajay M; Christiansen, Hans; Maier, Lars S

2013-11-01

Ionizing radiation (IR) is an integral part of modern multimodal anti-cancer therapies. IR involves the formation of reactive oxygen species (ROS) in targeted tissues. This is associated with subsequent cardiac dysfunction when applied during chest radiotherapy. We hypothesized that IR (i.e., ROS)-dependently impaired cardiac myocytes' Ca handling might contribute to IR-dependent cardiocellular dysfunction. Isolated ventricular mouse myocytes and the mediastinal area of anaesthetized mice (that included the heart) were exposed to graded doses of irradiation (sham 4 and 20 Gy) and investigated acutely (after ~1 h) as well as chronically (after ~1 week). IR induced a dose-dependent effect on myocytes' systolic function with acutely increased, but chronically decreased Ca transient amplitudes, which was associated with an acutely unaltered but chronically decreased sarcoplasmic reticulum (SR) Ca load. Likewise, in vivo echocardiography of anaesthetized mice revealed acutely enhanced left ventricular contractility (strain analysis) that declined after 1 week. Irradiated myocytes showed persistently increased diastolic SR Ca leakage, which was acutely compensated by an increase in SR Ca reuptake. This was reversed in the chronic setting in the face of slowed relaxation kinetics. As underlying cause, acutely increased ROS levels were identified to activate Ca/calmodulin-dependent protein kinase II (CaMKII). Accordingly, CaMKII-, but not PKA-dependent phosphorylation sites of the SR Ca release channels (RyR2, at Ser-2814) and phospholamban (at Thr-17) were found to be hyperphosphorylated following IR. Conversely, ROS-scavenging as well as CaMKII-inhibition significantly attenuated CaMKII-activation, disturbed Ca handling, and subsequent cellular dysfunction upon irradiation. Targeted cardiac irradiation induces a biphasic effect on cardiac myocytes Ca handling that is associated with chronic cardiocellular dysfunction. This appears to be mediated by increased oxidative stress and persistently activated CaMKII. Our findings suggest impaired cardiac myocytes Ca handling as a so far unknown mediator of IR-dependent cardiac damage that might be of relevance for radiation-induced cardiac dysfunction.

Endothelial glycocalyx degradation is more severe in patients with non-pulmonary sepsis compared to pulmonary sepsis and associates with risk of ARDS and other organ dysfunction.

PubMed

Murphy, Laura S; Wickersham, Nancy; McNeil, J Brennan; Shaver, Ciara M; May, Addison K; Bastarache, Julie A; Ware, Lorraine B

2017-10-06

Disruption of the endothelial glycocalyx contributes to acute lung injury in experimental sepsis but has not been well studied in humans. To study glycocalyx degradation in sepsis-induced ARDS, we measured plasma levels of syndecan-1, a marker for glycocalyx degradation. The present study is a retrospective observational study of 262 ventilated medical ICU patients at risk of ARDS due to severe sepsis and APACHE II ≥ 25. Plasma syndecan-1 was measured at study enrollment. Primary analysis focused on the association between syndecan-1 levels and the development of ARDS, other organ dysfunction (Brussels criteria), or in-hospital mortality. Overall, 135 (52%) patients developed ARDS. In patients with non-pulmonary sepsis, syndecan-1 levels were associated with ARDS (p = 0.05). Regardless of etiology of sepsis, higher syndecan-1 levels were associated with hepatic (p < 0.001), renal (p = 0.003), coagulation (p = 0.001), and circulatory (p = 0.02) failure as well as in-hospital mortality (p = 0.001), and there was a significant association between syndecan-1 levels and the number of vasopressors required in the first 24 h (p < 0.001). In addition, elevated syndecan levels were independently predictive of mortality in multivariable logistic regression adjusted for age and APACHE II score (odds ratio 1.85 per log increase in syndecan-1, 95% CI 1.056-3.241, p = 0.03). The extent of endothelial glycocalyx degradation is associated with non-pulmonary organ dysfunction in subjects with sepsis and is associated with ARDS but only in the subgroup with non-pulmonary sepsis. Measurement of syndecan-1 levels in sepsis patients might be useful for identifying patients at high risk of organ dysfunction and mortality as well as those who could benefit from therapies targeted at protecting or restoring the glycocalyx.

Acute diffuse alveolar haemorrhage accompanied by gastrointestinal bleeding in a patient with serious systemic lupus erythematosus: A case report.

PubMed

Du, Jing; Wang, Ying; Li, Yan-Chun; Wang, Tong-Tong; Zhou, Yong-Lie; Ying, Zhen-Hua

2018-05-01

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects many organs, but multisystem dysfunction is rare. Here, we report a case of a 29-year-old woman who was initially diagnosed with SLE complications including lupus nephritis, lupus encephalopathy, renal hypertension, thrombocytopenia, anaemia and hyperkalaemia. She recovered following treatment with high dose methylprednisolone, intravenous immunoglobulin (IVIG) and continuous renal replacement therapy (CRRT). However, a few days after hospital discharge, she developed gastrointestinal bleeding. Although intensive treatment was administered, the patient deteriorated rapidly and had a progressive decline in oxygen saturation followed by diffuse alveolar haemorrhage and acute left heart failure. Inotropic therapy, mechanical ventilation, blood transfusion, CRRT, antibiotics, intravenous glucocorticoids and other support therapies were initiated and gradually the patient's vital signs stabilized and haemoptysis subsided. This case report emphasises that complications of SLE can occur at any stage of the disease, especially in patients with active SLE. Therefore, it is important for clinicians to be aware of the rare presentations of SLE and its complex management. For multisystem dysfunction, early intensive treatment with high dose corticosteroids and cyclophosphamide is advocated.

Liver - guardian, modifier and target of sepsis.

PubMed

Strnad, Pavel; Tacke, Frank; Koch, Alexander; Trautwein, Christian

2017-01-01

Sepsis and septic shock are characterized by life-threatening organ dysfunction caused by a dysregulated host response to infection. The liver has a central role during sepsis, and is essential to the regulation of immune defence during systemic infections by mechanisms such as bacterial clearance, acute-phase protein or cytokine production and metabolic adaptation to inflammation. However, the liver is also a target for sepsis-related injury, including hypoxic hepatitis due to ischaemia and shock, cholestasis due to altered bile metabolism, hepatocellular injury due to drug toxicity or overwhelming inflammation, as well as distinct pathologies such as secondary sclerosing cholangitis in critically ill patients. Hence, hepatic dysfunction substantially impairs the prognosis of sepsis and serves as a powerful independent predictor of mortality in the intensive care unit. Sepsis is particularly problematic in patients with liver cirrhosis (who experience increased bacterial translocation from the gut and impaired microbial defence) as it can trigger acute-on-chronic liver failure - a syndrome with high short-term mortality. Here, we review the importance of the liver as a guardian, modifier and target of sepsis, the factors that contribute to sepsis in patients with liver cirrhosis and new therapeutic strategies.

GSK-3α directly regulates β-adrenergic signaling and the response of the heart to hemodynamic stress in mice

PubMed Central

Zhou, Jibin; Lal, Hind; Chen, Xiongwen; Shang, Xiying; Song, Jianliang; Li, Yingxin; Kerkela, Risto; Doble, Bradley W.; MacAulay, Katrina; DeCaul, Morgan; Koch, Walter J.; Farber, John; Woodgett, James; Gao, Erhe; Force, Thomas

2010-01-01

The glycogen synthase kinase-3 (GSK-3) family of serine/threonine kinases consists of 2 highly related isoforms, α and β. Although GSK-3β has an important role in cardiac development, much remains unknown about the function of either GSK-3 isoform in the postnatal heart. Herein, we present what we believe to be the first studies defining the role of GSK-3α in the mouse heart using gene targeting. Gsk3a–/– mice over 2 months of age developed progressive cardiomyocyte and cardiac hypertrophy and contractile dysfunction. Following thoracic aortic constriction in young mice, we observed enhanced hypertrophy that rapidly transitioned to ventricular dilatation and contractile dysfunction. Surprisingly, markedly impaired β-adrenergic responsiveness was found at both the organ and cellular level. This phenotype was reproduced by acute treatment of WT cardiomyocytes with a small molecule GSK-3 inhibitor, confirming that the response was not due to a chronic adaptation to LV dysfunction. Thus, GSK-3α appears to be the central regulator of a striking range of essential processes, including acute and direct positive regulation of β-adrenergic responsiveness. In the absence of GSK-3α, the heart cannot respond effectively to hemodynamic stress and rapidly fails. Our findings identify what we believe to be a new paradigm of regulation of β-adrenergic signaling and raise concerns given the rapid expansion of drug development targeting GSK-3. PMID:20516643

Acute Kidney Injury: Definition, Pathophysiology and Clinical Phenotypes

PubMed Central

Makris, Konstantinos; Spanou, Loukia

2016-01-01

Acute kidney injury (AKI) is a clinical syndrome that complicates the course and worsens the outcome in a significant number of hospitalised patients. Recent advances in clinical and basic research will help with a more accurate definition of this syndrome and in the elucidation of its pathogenesis. With this knowledge we will be able to conduct more accurate epidemiologic studies in an effort to gain a better understanding of the impact of this syndrome. AKI is a syndrome that rarely has a sole and distinct pathophysiology. Recent evidence, in both basic science and clinical research, is beginning to change our view for AKI from a single organ failure syndrome to a syndrome where the kidney plays an active role in the progress of multi-organ dysfunction. Accurate and prompt recognition of AKI and better understanding of the pathophysiologic mechanisms underlying the various clinical phenotypes are of great importance to research for effective therapeutic interventions. In this review we provide the most recent updates in the definition, epidemiology and pathophysiology of AKI. PMID:28303073

Acute Kidney Injury: Definition, Pathophysiology and Clinical Phenotypes.

PubMed

Makris, Konstantinos; Spanou, Loukia

2016-05-01

Acute kidney injury (AKI) is a clinical syndrome that complicates the course and worsens the outcome in a significant number of hospitalised patients. Recent advances in clinical and basic research will help with a more accurate definition of this syndrome and in the elucidation of its pathogenesis. With this knowledge we will be able to conduct more accurate epidemiologic studies in an effort to gain a better understanding of the impact of this syndrome. AKI is a syndrome that rarely has a sole and distinct pathophysiology. Recent evidence, in both basic science and clinical research, is beginning to change our view for AKI from a single organ failure syndrome to a syndrome where the kidney plays an active role in the progress of multi-organ dysfunction. Accurate and prompt recognition of AKI and better understanding of the pathophysiologic mechanisms underlying the various clinical phenotypes are of great importance to research for effective therapeutic interventions. In this review we provide the most recent updates in the definition, epidemiology and pathophysiology of AKI.

Comparison of the Nosocomial Pneumonia Mortality Prediction (NPMP) model with standard mortality prediction tools.

PubMed

Srinivasan, M; Shetty, N; Gadekari, S; Thunga, G; Rao, K; Kunhikatta, V

2017-07-01

Severity or mortality prediction of nosocomial pneumonia could aid in the effective triage of patients and assisting physicians. To compare various severity assessment scoring systems for predicting intensive care unit (ICU) mortality in nosocomial pneumonia patients. A prospective cohort study was conducted in a tertiary care university-affiliated hospital in Manipal, India. One hundred patients with nosocomial pneumonia, admitted in the ICUs who developed pneumonia after >48h of admission, were included. The Nosocomial Pneumonia Mortality Prediction (NPMP) model, developed in our hospital, was compared with Acute Physiology and Chronic Health Evaluation II (APACHE II), Mortality Probability Model II (MPM 72  II), Simplified Acute Physiology Score II (SAPS II), Multiple Organ Dysfunction Score (MODS), Sequential Organ Failure Assessment (SOFA), Clinical Pulmonary Infection Score (CPIS), Ventilator-Associated Pneumonia Predisposition, Insult, Response, Organ dysfunction (VAP-PIRO). Data and clinical variables were collected on the day of pneumonia diagnosis. The outcome for the study was ICU mortality. The sensitivity and specificity of the various scoring systems was analysed by plotting receiver operating characteristic (ROC) curves and computing the area under the curve for each of the mortality predicting tools. NPMP, APACHE II, SAPS II, MPM 72  II, SOFA, and VAP-PIRO were found to have similar and acceptable discrimination power as assessed by the area under the ROC curve. The AUC values for the above scores ranged from 0.735 to 0.762. CPIS and MODS showed least discrimination. NPMP is a specific tool to predict mortality in nosocomial pneumonia and is comparable to other standard scores. Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

PVCM, PVCD, EPL, and irritable larynx syndrome: what are we talking about and how do we treat it?

PubMed

Andrianopoulos, M V; Gallivan, G J; Gallivan, K H

2000-12-01

Paroxysmal vocal cord movement/motion (PVCM), paroxysmal vocal cord dysfunction (PVCD), episodic paroxysmal laryngospasm (EPL), and irritable larynx syndrome (ILS) are terms used to describe laryngeal dysfunction masquerading as asthma, upper airway obstruction, or functional and organic voice disorders. The differential diagnosis of PVCM, PVCD, EPL, and ILS is critical to successful medical and behavioral management of the patient. During the past 10 years, 27 subjects, ages 15-79 years, were identified to have paroxysms of inspiratory stridor, acute respiratory distress, associated aphonia and dysphonia, resulting in misdiagnosis and unnecessary emergency treatments, including endotracheal intubation, cardiopulmonary resuscitation, massive pharmacotherapy, or tracheostomy. A multifactorial management program is proposed utilizing principles of motor learning, neurolinguistic programming model, respiratory and phonatory synchronization, relaxation techniques, concurrent monitoring of behavioral adjustments, and formal psychological counseling.

[Immunological Markers in Organ Transplantation].

PubMed

Beckmann, J H; Heits, N; Braun, F; Becker, T

2017-04-01

The immunological monitoring in organ transplantation is based mainly on the determination of laboratory parameters as surrogate markers of organ dysfunction. Structural damage, caused by alloreactivity, can only be detected by invasive biopsy of the graft, which is why inevitably rejection episodes are diagnosed at a rather progressive stage. New non-invasive specific markers that enable transplant clinicians to identify rejection episodes at an earlier stage, on the molecular level, are needed. The accurate identification of rejection episodes and the establishment of operational tolerance permit early treatment or, respectively, a controlled cessation of immunosuppression. In addition, new prognostic biological markers are expected to allow a pre-transplant risk stratification thus having an impact on organ allocation and immunosuppressive regimen. New high-throughput screening methods allow simultaneous examination of hundreds of characteristics and the generation of specific biological signatures, which might give concrete information about acute rejection, chronic dysfunction as well as operational tolerance. Even though multiple studies and a variety of publications report about important advances on this subject, almost no new biological marker has been implemented in clinical practice as yet. Nevertheless, new technologies, in particular analysis of the genome, transcriptome, proteome and metabolome will make personalised transplantation medicine possible and will further improve the long-term results and graft survival rates. This article gives a survey of the limitations and possibilities of new immunological markers in organ transplantation. Georg Thieme Verlag KG Stuttgart · New York.

Acute Pancreatitis Complicated with Diabetic Ketoacidosis in a Young Adult without Hypertriglyceridemia: A Case Report.

PubMed

Kim, Jung Hyun; Oh, Myung Jin

2016-11-25

Systemic complications related to acute pancreatitis include acute respiratory distress syndrome, multiple organ dysfunction syndrome, disseminated intravascular coagulation, hypocalcemia, hyperglycemia, and insulin dependent diabetes or diabetic ketoacidosis. In practice, the development of diabetic ketoacidosis induced by acute pancreatitis is rare and generally associated with hypertriglyceridemia. However, herein we report a case of a 34-year-old female without hypertriglyceridemia, who was diagnosed with acute pancreatitis complicated with diabetic ketoacidosis. The patient was admitted with complaints of febrile sensation, back pain, and abdominal pain around the epigastric area. Levels of serum amylase and lipase were elevated to 663 U/L and 3,232 U/L. Contrast-enhanced abdominal CT showed pancreatic swelling, peri-pancreatic fat infiltration and fluid collection. The patient was initially diagnosed with simple acute pancreatitis. Though the symptoms were rapidly relieved after initiation of treatment, severe hyperglycemia (575 mg/dL), severe metabolic acidosis (pH 6.9), and ketonuria developed at four days after hospitalization. However, serum triglyceride levels remained within the normal range (134 mg/dL). Finally, the patient was diagnosed with acute pancreatitis complicated with diabetic ketoacidosis unrelated to hypertriglyceridemia. She recovered through insulin and fluid therapy, and receives insulin therapy at the outpatient clinic.

History of erectile dysfunction as a predictor of poor physical performance after an acute myocardial infarction.

PubMed

Compostella, Leonida; Compostella, Caterina; Truong, Li Van Stella; Russo, Nicola; Setzu, Tiziana; Iliceto, Sabino; Bellotto, Fabio

2017-03-01

Background Erectile dysfunction may predict future cardiovascular events and indicate the severity of coronary artery disease in middle-aged men. The aim of this study was to evaluate whether erectile dysfunction (expression of generalized macro- and micro-vascular pathology) could predict reduced effort tolerance in patients after an acute myocardial infarction. Patients and methods One hundred and thirty-nine male patients (60 ± 12 years old), admitted to intensive cardiac rehabilitation 13 days after a complicated acute myocardial infarction, were evaluated for history of erectile dysfunction using the International Index of Erectile Function questionnaire. Their physical performance was assessed by means of two six-minute walk tests (performed two weeks apart) and by a symptom limited cardiopulmonary exercise test (CPET). Results Patients with erectile dysfunction (57% of cases) demonstrated poorer physical performance, significantly correlated to the degree of erectile dysfunction. After cardiac rehabilitation, they walked shorter distances at the final six-minute walk test (490 ± 119 vs. 564 ± 94 m; p < 0.001); at CPET they sustained lower workload (79 ± 28 vs. 109 ± 34 W; p < 0.001) and reached lower oxygen uptake at peak effort (18 ± 5 vs. 21 ± 5 ml/kg per min; p = 0.003) and at anaerobic threshold (13 ± 3 vs.16 ± 4 ml/kg per min; p = 0.001). The positive predictive value of presence of erectile dysfunction was 0.71 for low peak oxygen uptake (<20 ml/kg per min) and 0.69 for reduced effort capacity (W-max <100 W). Conclusions As indicators of generalized underlying vascular pathology, presence and degree of erectile dysfunction may predict the severity of deterioration of effort tolerance in post-acute myocardial infarction patients. In the attempt to reduce the possibly associated long-term risk, an optimization of type, intensity and duration of cardiac rehabilitation should be considered.

Inhibition of nuclear factor-κB signal by pyrrolidine dithiocarbamate alleviates lipopolysaccharide-induced acute lung injury

PubMed Central

Yang, Hongfu; Sun, Rongqing; Ma, Ning; Liu, Qilong; Sun, Xiaoge; Zi, Panpan; Wang, Junsheng; Chao, Ke; Yu, Lei

2017-01-01

This study mainly studied the effect of inhibition of nuclear factor-κB (NF-κB) signal by pyrrolidine dithiocarbamate (PDTC) on lipopolysaccharide (LPS)-induced inflammatory response, oxidative stress, and mitochondrial dysfunction in a murine acute lung injury model. The results showed that LPS exposure activated NF-κB and its upstream proteins and caused lung inflammation, oxidative stress, and mitochondrial dysfunction in mice. While inhibition of NF-κB by PDTC adminstration alleviated LPS-induced generation of lymphocytes, IL-1β, and TNF-α. Malondialdehyde, a common oxidative product, was markedly reduced after PDTC treatment in LPS-challenged mice. Furthermore, PDTC alleviated LPS-induced mitochondrial dysfunction via improving ATP synthesis and uncoupling protein 2 expression. In conclusion, inhibition of NF-κB by PDTC alleviated LPS-induced acute lung injury via maintaining inflammatory status, oxidative balance, and mitochondrial function in mice. PMID:28521300

Treatment of severe fluoroacetamide poisoning in patient with combined multiple organ dysfunction syndrome by evidence-based integrated Chinese and Western medicines: A case report.

PubMed

Wen, Wanxin; Gao, Hongxia; Kang, Nini; Lu, Aili; Qian, Caiwen; Zhao, Yuanqi

2017-07-01

Fluoroacetamide poisoning is the acute and severe disease of human, which leads to nervous, digestive, and cardiovascular system damage or even death in a short period of time. We report a case of a 65-year-old woman with loss of consciousness, nausea, and vomiting who was sent to the hospital by passers-by. She was diagnosed with severe fluoroacetamide poisoning with combined multiple organ dysfunction syndrome. When the diagnosis was unclear, we gave gastric lavage, support and symptomatic treatment, and closely with the vital sign. When the diagnosis was clear, based on the evidence of retrieved, muscle injection of acetamide, calcium gluconate, and vitamin C. Traditional Chinese medicine aspect, oral administration of mung bean soup of glycyrrhizae and Da-Cheng-Qi decoction enema. By setting reasonable treatment for patients, she had no special discomfort and complications after treatment. Besides, through 1-month follow-up, it was confirmed that the treatments were effective. Evidence-based integrated Chinese and Western medicines can effectively improve the therapeutic effects in severe fluoroacetamide-poisoned patients with combined MODS.

Stress hormonal changes in the brain and plasma after acute noise exposure in mice.

PubMed

Jin, Sang Gyun; Kim, Min Jung; Park, So Young; Park, Shi Nae

2017-06-01

To investigate the effects of acute noise stress on two amine stress hormones, norepinephrine (NE) and 5-hydroxyindoleacetic acid (5-HIAA) in the brain and plasma of mice after noise exposure. Mice were grouped into the control and noise groups. Mice in the noise group were exposed to white noise of 110dB sound pressure level for 60min. Auditory brainstem response thresholds, distortion product otoacoustic emissions, the organ of Corti grading scores, western blots of NE/5-HIAA in the whole brain and hippocampus, and the plasma levels of NE/5-HIAA were compared between the two groups. Significant hearing loss and cochlear damage were demonstrated in the noise group. NE and 5-HIAA in the hippocampus were elevated in the noise group (p=0.019/0.022 for NE/5-HIAA vs. the control). Plasma levels of NE and 5-HIAA were not statistically different between the groups (p=0.052/0.671 for NE/5-HIAA). Hearing loss with outer hair cell dysfunction and morphological changes of the organ of Corti after noise exposure in C57BL/6 mice proved the reliability of our animal model as an acute noise stress model. NE and 5-HIAA are suggested to be the potential biomarkers for acute noise stress in the hippocampus. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Abnormal troponin I levels in a thalassemia major patient with high ferritin concentration, permanent atrial fibrillation and without acute coronary syndrome.

PubMed

Patanè, Salvatore; Marte, Filippo

2010-01-21

Thalassemia is a congenital hemoglobinopathy leading to anemia because of impaired erythropoiesis and peripheral hemolysis. Thalassemia major patients are transfusion dependent and it results in iron accumulation. The heart is one of the major organs affected with iron overload and iron induced cardiac dysfunction (pump and conduction abnormalities) remains the number one cause of death among thalassemia major patients. It has been reported that a high ferritin concentration is related to high troponin levels in hemodialysis patients receiving more intravenous iron sucrose. Abnormal troponin I levels have also been reported without acute coronary syndrome. We present a case of abnormal troponin I levels in Thalassemia major patient with high ferritin concentration, permanent atrial fibrillation and without acute coronary syndrome. To our knowledge, this is the first report of abnormal troponin I levels in a Thalassemia major patient with high ferritin concentration and without acute coronary syndrome and also this case focuses attention on the importance of the correct evaluation of abnormal troponin I levels. Copyright (c) 2008 Elsevier Ireland Ltd. All rights reserved.

The impact of extracerebral organ failure on outcome of patients after cardiac arrest: an observational study from the ICON database.

PubMed

Nobile, Leda; Taccone, Fabio S; Szakmany, Tamas; Sakr, Yasser; Jakob, Stephan M; Pellis, Tommaso; Antonelli, Massimo; Leone, Marc; Wittebole, Xavier; Pickkers, Peter; Vincent, Jean-Louis

2016-11-14

We used data from a large international database to assess the incidence and impact of extracerebral organ dysfunction on prognosis of patients admitted after cardiac arrest (CA). This was a sub-analysis of the Intensive Care Over Nations (ICON) database, which contains data from all adult patients admitted to one of 730 participating intensive care units (ICUs) in 84 countries from 8-18 May 2012, except admissions for routine postoperative surveillance. For this analysis, patients admitted after CA (defined as those with "post-anoxic coma" or "cardiac arrest" as the reason for ICU admission) were included. Data were collected daily in the ICU for a maximum of 28 days; patients were followed up for outcome data until death, hospital discharge, or a maximum of 60 days in-hospital. Favorable neurological outcome was defined as alive at hospital discharge with a last available neurological Sequential Organ Failure Assessment (SOFA) subscore of 0-2. Among the 469 patients admitted after CA, 250 (53 %) had had out-of-hospital CA; 210 (45 %) patients died in the ICU and 357 (76 %) had an unfavorable neurological outcome. Non-survivors had a higher incidence of renal (43 vs. 16 %), cardiovascular (56 vs. 45 %), and respiratory (62 vs. 48 %) failure on admission and during the ICU stay than survivors (all p < 0.05). Similar results were found for patients with unfavorable vs. favorable neurological outcomes. In multivariable analysis, independent predictors of ICU mortality were renal failure on admission, high admission Simplified Acute Physiology Score (SAPS) II, high maximum serum lactate levels within the first 24 h after ICU admission, and development of sepsis. Independent predictors of unfavorable neurological outcome were mechanical ventilation on admission, high admission SAPS II score, and neurological dysfunction on admission. In this multicenter cohort, extracerebral organ dysfunction was common in CA patients. Renal failure on admission was the only extracerebral organ dysfunction independently associated with higher ICU mortality.

As in Real Estate, Location Is What Matters: A Case Report of Transplant Ureteral Obstruction Due to an Inguinal Hernia.

PubMed

Bugeja, Ann; Clark, Edward G; Sood, Manish M; Ali, Sohrab N

2018-01-01

Kidney allograft dysfunction is common and often reversible but can lead to allograft loss if not promptly evaluated. Transplant ureteral obstruction in an inguinal hernia is a rare cause of allograft dysfunction, but early recognition may prevent allograft loss. We present a case of a man with acute kidney allograft dysfunction who received a deceased donor kidney transplant 6 years earlier for end-stage kidney disease secondary to polycystic kidney disease. Abdominal ultrasounds revealed hydronephrosis without full visualization of the transplant ureter. Abdominal computed tomography revealed moderate hydronephrosis of the transplant kidney due to obstructed herniation of the transplant ureter in a right inguinal hernia. A stent was inserted into the transplant ureter to prevent further allograft dysfunction and facilitate hernia repair. Transplant ureteral obstruction is a rare cause of acute kidney allograft dysfunction, and its detection can be challenging. The recognition of transplant ureteral obstruction is vital to timely management for preventing allograft loss.

Vasculoprotective Effects of Dietary Cocoa Flavanols in Patients on Hemodialysis: A Double-Blind, Randomized, Placebo-Controlled Trial.

PubMed

Rassaf, Tienush; Rammos, Christos; Hendgen-Cotta, Ulrike B; Heiss, Christian; Kleophas, Werner; Dellanna, Frank; Floege, Jürgen; Hetzel, Gerd R; Kelm, Malte

2016-01-07

Hemodialysis (HD) per se entails vascular dysfunction in patients with ESRD. Endothelial dysfunction is a key step in atherosclerosis and is characterized by impaired flow-mediated dilation (FMD). Interventional studies have shown that cocoa flavanol (CF)-rich supplements improve vascular function. Aim of this study was to investigate the effect of flavanol-rich bioactive food ingredients on acute and chronic HD-induced vascular dysfunction in ESRD. We conducted a randomized, double-blind, placebo-controlled trial from 2012 to 2013. Fifty-seven participants were enrolled, ingested CF-rich beverages (900 mg CF per study day), and were compared with those ingesting CF-free placebo. This included (1) a baseline cross-over acute study to determine safety and efficacy of CF and (2) a subsequent chronic parallel group study with a 30-day follow-up period to study effects of CF on HD-mediated vascular dysfunction entailing (3) an acute substudy during HD in flavanol-naive patients and (4) an acute on chronic study during HD. Primary and secondary outcome measures included changes in FMD and hemodynamics. CF ingestion was well tolerated. Acute ingestion improved FMD by 53% (3.2±0.6% to 4.8±0.9% versus placebo, 3.2±0.7% to 3.3±0.8%; P<0.001), with no effects on BP or heart rate. A 30-day ingestion of CF led to an increase in baseline FMD by 18% (3.4±0.9% to 3.9±0.8% versus placebo, 3.5±0.7% to 3.5±0.7%; P<0.001), with reduced diastolic BP (73±12 to 69±11 mmHg versus placebo, 70±11 to 73±13 mmHg; P=0.03) and increased heart rate (70±12 to 74±13 bpm versus placebo, 75±15 to 74±13 bpm; P=0.01). No effects were observed for placebo. Acute ingestion of CF during HD alleviated HD-induced vascular dysfunction (3.4±0.9% to 2.7±0.6% versus placebo, 3.5±0.7% to 2.0±0.6%; P<0.001). This effect was sustained throughout the study (acute on chronic, 3.9±0.9% to 3.0±0.7% versus placebo, 3.5±0.7% to 2.2±0.6; P=0.01). Dietary CF ingestion mitigates acute HD-induced and chronic endothelial dysfunction in patients with ESRD and thus, improves vascular function in this high-risk population. Larger clinical trials are warranted to test whether this translates into an improved cardiovascular prognosis in patients with ESRD. Copyright © 2016 by the American Society of Nephrology.

Fractal Dimension of EEG Activity Senses Neuronal Impairment in Acute Stroke

PubMed Central

Zappasodi, Filippo; Olejarczyk, Elzbieta; Marzetti, Laura; Assenza, Giovanni; Pizzella, Vittorio; Tecchio, Franca

2014-01-01

The brain is a self-organizing system which displays self-similarities at different spatial and temporal scales. Thus, the complexity of its dynamics, associated to efficient processing and functional advantages, is expected to be captured by a measure of its scale-free (fractal) properties. Under the hypothesis that the fractal dimension (FD) of the electroencephalographic signal (EEG) is optimally sensitive to the neuronal dysfunction secondary to a brain lesion, we tested the FD’s ability in assessing two key processes in acute stroke: the clinical impairment and the recovery prognosis. Resting EEG was collected in 36 patients 4–10 days after a unilateral ischemic stroke in the middle cerebral artery territory and 19 healthy controls. National Health Institute Stroke Scale (NIHss) was collected at T0 and 6 months later. Highuchi FD, its inter-hemispheric asymmetry (FDasy) and spectral band powers were calculated for EEG signals. FD was smaller in patients than in controls (1.447±0.092 vs 1.525±0.105) and its reduction was paired to a worse acute clinical status. FD decrease was associated to alpha increase and beta decrease of oscillatory activity power. Larger FDasy in acute phase was paired to a worse clinical recovery at six months. FD in our patients captured the loss of complexity reflecting the global system dysfunction resulting from the structural damage. This decrease seems to reveal the intimate nature of structure-function unity, where the regional neural multi-scale self-similar activity is impaired by the anatomical lesion. This picture is coherent with neuronal activity complexity decrease paired to a reduced repertoire of functional abilities. FDasy result highlights the functional relevance of the balance between homologous brain structures’ activities in stroke recovery. PMID:24967904

Fractal dimension of EEG activity senses neuronal impairment in acute stroke.

PubMed

Zappasodi, Filippo; Olejarczyk, Elzbieta; Marzetti, Laura; Assenza, Giovanni; Pizzella, Vittorio; Tecchio, Franca

2014-01-01

The brain is a self-organizing system which displays self-similarities at different spatial and temporal scales. Thus, the complexity of its dynamics, associated to efficient processing and functional advantages, is expected to be captured by a measure of its scale-free (fractal) properties. Under the hypothesis that the fractal dimension (FD) of the electroencephalographic signal (EEG) is optimally sensitive to the neuronal dysfunction secondary to a brain lesion, we tested the FD's ability in assessing two key processes in acute stroke: the clinical impairment and the recovery prognosis. Resting EEG was collected in 36 patients 4-10 days after a unilateral ischemic stroke in the middle cerebral artery territory and 19 healthy controls. National Health Institute Stroke Scale (NIHss) was collected at T0 and 6 months later. Highuchi FD, its inter-hemispheric asymmetry (FDasy) and spectral band powers were calculated for EEG signals. FD was smaller in patients than in controls (1.447±0.092 vs 1.525±0.105) and its reduction was paired to a worse acute clinical status. FD decrease was associated to alpha increase and beta decrease of oscillatory activity power. Larger FDasy in acute phase was paired to a worse clinical recovery at six months. FD in our patients captured the loss of complexity reflecting the global system dysfunction resulting from the structural damage. This decrease seems to reveal the intimate nature of structure-function unity, where the regional neural multi-scale self-similar activity is impaired by the anatomical lesion. This picture is coherent with neuronal activity complexity decrease paired to a reduced repertoire of functional abilities. FDasy result highlights the functional relevance of the balance between homologous brain structures' activities in stroke recovery.

Impact of acute lung injury and acute respiratory distress syndrome after traumatic brain injury in the United States.

PubMed

Rincon, Fred; Ghosh, Sayantani; Dey, Saugat; Maltenfort, Mitchell; Vibbert, Matthew; Urtecho, Jacqueline; McBride, William; Moussouttas, Michael; Bell, Rodney; Ratliff, John K; Jallo, Jack

2012-10-01

Traumatic brain injury (TBI) is a major cause of disability, morbidity, and mortality. The effect of the acute respiratory distress syndrome and acute lung injury (ARDS/ALI) on in-hospital mortality after TBI remains controversial. To determine the epidemiology of ARDS/ALI, the prevalence of risk factors, and impact on in-hospital mortality after TBI in the United States. Retrospective cohort study of admissions of adult patients>18 years with a diagnosis of TBI and ARDS/ALI from 1988 to 2008 identified through the Nationwide Inpatient Sample. During the 20-year study period, the prevalence of ARDS/ALI increased from 2% (95% confidence interval [CI], 2.1%-2.4%) in 1988 to 22% (95% CI, 21%-22%) in 2008 (P<.001). ARDS/ALI was more common in younger age; males; white race; later year of admission; in conjunction with comorbidities such as congestive heart failure, hypertension, chronic obstructive pulmonary disease, chronic renal and liver failure, sepsis, multiorgan dysfunction; and nonrural, medium/large hospitals, located in the Midwest, South, and West continental US location. Mortality after TBI decreased from 13% (95% CI, 12%-14%) in 1988 to 9% (95% CI, 9%-10%) in 2008 (P<.001). ARDS/ALI-related mortality after TBI decreased from 33% (95% CI, 33%-34%) in 1988 to 28% (95% CI, 28%-29%) in 2008 (P<.001). Predictors of in-hospital mortality after TBI were older age, male sex, white race, cancer, chronic kidney disease, hypertension, chronic liver disease, congestive heart failure, ARDS/ALI, and organ dysfunctions. Our analysis demonstrates that ARDS/ALI is common after TBI. Despite an overall reduction of in-hospital mortality, ARDS/ALI carries a higher risk of in-hospital death after TBI.

New-Onset Heart Failure and Mortality in Hospital Survivors of Sepsis-Related Left Ventricular Dysfunction.

PubMed

Vallabhajosyula, Saraschandra; Jentzer, Jacob C; Geske, Jeffrey B; Kumar, Mukesh; Sakhuja, Ankit; Singhal, Akhil; Poterucha, Joseph T; Kashani, Kianoush; Murphy, Joseph G; Gajic, Ognjen; Kashyap, Rahul

2018-02-01

The association between new-onset left ventricular (LV) dysfunction during sepsis with long-term heart failure outcomes is lesser understood. Retrospective cohort study of all adult patients with severe sepsis and septic shock between 2007 and 2014 who underwent echocardiography within 72 h of admission to the intensive care unit. Patients with prior heart failure, LV dysfunction, and structural heart disease were excluded. LV systolic dysfunction was defined as LV ejection fraction <50% and LV diastolic dysfunction as ≥grade II. Primary composite outcome included new hospitalization for acute decompensated heart failure and all-cause mortality at 2-year follow-up. Secondary outcomes included persistent LV dysfunction, and hospital mortality and length of stay. During this 8-year period, 434 patients with 206 (48%) patients having LV dysfunction were included. The two groups had similar baseline characteristics, but those with LV dysfunction had worse function as demonstrated by worse LV ejection fraction, cardiac index, and LV diastolic dysfunction. In the 331 hospital survivors, new-onset acute decompensated heart failure hospitalization did not differ between the two cohorts (15% vs. 11%). The primary composite outcome was comparable at 2-year follow-up between the groups with and without LV dysfunction (P = 0.24). Persistent LV dysfunction was noted in 28% hospital survivors on follow-up echocardiography. Other secondary outcomes were similar between the two groups. In patients with severe sepsis and septic shock, the presence of new-onset LV dysfunction did not increase the risk of long-term adverse heart failure outcomes.

Acute and chronic hepatobiliary manifestations of sickle cell disease: A review

PubMed Central

Shah, Rushikesh; Taborda, Cesar; Chawla, Saurabh

2017-01-01

Sickle cell disease (SCD) is a common hemoglobinopathy which can affect multiple organ systems in the body. Within the digestive tract, the hepatobiliary system is most commonly affected in SCD. The manifestations range from benign hyperbilirubinemia to overt liver failure, with the spectrum of acute clinical presentations often referred to as “sickle cell hepatopathy”. This is an umbrella term referring to liver dysfunction and hyperbilirubinemia due to intrahepatic sickling process during SCD crisis leading to ischemia, sequestration and cholestasis. In this review, we detail the pathophysiology, clinical presentation and biochemical features of various acute and chronic hepatobiliary manifestations of SCD and present and evaluate existing evidence with regards to management of this disease process. We also discuss recent advances and controversies such as the role of liver transplantation in sickle cell hepatopathy and highlight important questions in this field which would require further research. Our aim with this review is to help increase the understanding, aid in early diagnosis and improve management of this important disease process. PMID:28868180

Acute alcohol intoxication-induced microvascular leakage.

PubMed

Doggett, Travis M; Breslin, Jerome W

2014-09-01

Alcohol intoxication can increase inflammation and worsen injury, yet the mechanisms involved are not clear. We investigated whether acute alcohol intoxication increases microvascular permeability and investigated potential signaling mechanisms in endothelial cells that may be involved. Conscious rats received a 2.5 g/kg alcohol bolus via gastric catheters to produce acute intoxication. Microvascular leakage of intravenously administered fluorescein isothiocyanate (FITC)-conjugated albumin (FITC-albumin) from the mesenteric microcirculation was assessed by intravital microscopy. Endothelial-specific mechanisms were studied using cultured endothelial cell monolayers. Transendothelial electrical resistance (TER) served as an index of barrier function, before and after treatment with alcohol or its metabolite acetaldehyde. Pharmacologic agents were used to test the roles of alcohol metabolism, oxidative stress, p38 mitogen-activated protein kinase (MAPK), myosin light-chain kinase (MLCK), rho kinase (ROCK), and exchange protein activated by cAMP (Epac). VE-cadherin localization was investigated to assess junctional integrity. Rac1 and RhoA activation was assessed by ELISA assays. Alcohol significantly increased FITC-albumin extravasation from the mesenteric microcirculation. Alcohol also significantly decreased TER and disrupted VE-cadherin organization at junctions. Acetaldehyde significantly decreased TER, but inhibition of alcohol dehydrogenase or application of a superoxide dismutase mimetic failed to prevent alcohol-induced decreases in TER. Inhibition of p38 MAPK, but not MLCK or ROCK, significantly attenuated the alcohol-induced barrier dysfunction. Alcohol rapidly decreased GTP-bound Rac1 but not RhoA during the drop in TER. Activation of Epac increased TER, but did not prevent alcohol from decreasing TER. However, activation of Epac after initiation of alcohol-induced barrier dysfunction quickly resolved TER to baseline levels. Our results suggest that alcohol intoxication increases microvascular permeability to plasma proteins. The data also suggest the endothelial-specific mechanism involves the p38 MAPK, Rac1, and reorganization of VE-cadherin at junctions. Last, activation of Epac can quickly resolve alcohol-induced endothelial barrier dysfunction. Copyright © 2014 by the Research Society on Alcoholism.

Hypopituitarism after acute brain injury.

PubMed

Urban, Randall J

2006-07-01

Acute brain injury has many causes, but the most common is trauma. There are 1.5-2.0 million traumatic brain injuries (TBI) in the United States yearly, with an associated cost exceeding 10 billion dollars. TBI is the most common cause of death and disability in young adults less than 35 years of age. The consequences of TBI can be severe, including disability in motor function, speech, cognition, and psychosocial and emotional skills. Recently, clinical studies have documented the occurrence of pituitary dysfunction after TBI and another cause of acute brain injury, subarachnoid hemorrhage (SAH). These studies have consistently demonstrated a 30-40% occurrence of pituitary dysfunction involving at least one anterior pituitary hormone following a moderate to severe TBI or SAH. Growth hormone (GH) deficiency is the most common pituitary hormone disorder, occurring in approximately 20% of patients when multiple tests of GH deficiency are used. Within 7-21 days of acute brain injury, adrenal insufficiency is the primary concern. Pituitary function can fluctuate over the first year after TBI, but it is well established by 1 year. Studies are ongoing to assess the effects of hormone replacement on motor function and cognition in TBI patients. Any subject with a moderate to severe acute brain injury should be screened for pituitary dysfunction.

Overlap of Post-obstructive Diuresis and Unmasked Diabetes Insipidus in a Case of IgG4-related Retroperitoneal Fibrosis and Tuberoinfundibular Hypophysitis: A Case Report and Review of the Literature

PubMed Central

Sasaki Yatabe, Midori; Watanabe, Kimio; Hayashi, Yoshimitsu; Yatabe, Junichi; Morimoto, Satoshi; Ichihara, Atsuhiro; Nakayama, Masaaki; Watanabe, Tsuyoshi

2017-01-01

The clinical picture of IgG4-related disease (IgG4-RD) is diverse because various organs can be affected. We describe the case of a 56-year-old man with acute renal failure and tuberoinfundibular hypophysitis due to IgG4-RD. Steroid therapy lowered the serum IgG4 level and ameliorated renal dysfunction, bilateral hydronephrosis and retroperitoneal fibrosis. However, polyuria from post-obstructive diuresis and unmasked central diabetes insipidus ensued. The patient's polyuria continued despite the administration of a therapeutic dose of glucocorticoid; the patient's pituitary swelling and anterior pituitary dysfunction were partially ameliorated. The pituitary swelling recurred seven months later. In patients with IgG4-RD, the manifestation of polyuria after steroid therapy should prompt suspicion of post-obstructive diuresis and the unmasking of central diabetes insipidus. PMID:28049999

Overlap of Post-obstructive Diuresis and Unmasked Diabetes Insipidus in a Case of IgG4-related Retroperitoneal Fibrosis and Tuberoinfundibular Hypophysitis: A Case Report and Review of the Literature.

PubMed

Sasaki Yatabe, Midori; Watanabe, Kimio; Hayashi, Yoshimitsu; Yatabe, Junichi; Morimoto, Satoshi; Ichihara, Atsuhiro; Nakayama, Masaaki; Watanabe, Tsuyoshi

The clinical picture of IgG4-related disease (IgG4-RD) is diverse because various organs can be affected. We describe the case of a 56-year-old man with acute renal failure and tuberoinfundibular hypophysitis due to IgG4-RD. Steroid therapy lowered the serum IgG4 level and ameliorated renal dysfunction, bilateral hydronephrosis and retroperitoneal fibrosis. However, polyuria from post-obstructive diuresis and unmasked central diabetes insipidus ensued. The patient's polyuria continued despite the administration of a therapeutic dose of glucocorticoid; the patient's pituitary swelling and anterior pituitary dysfunction were partially ameliorated. The pituitary swelling recurred seven months later. In patients with IgG4-RD, the manifestation of polyuria after steroid therapy should prompt suspicion of post-obstructive diuresis and the unmasking of central diabetes insipidus.

Takotsubo-like Myocardial Dysfunction in a Patient with Botulism.

PubMed

Tonomura, Shuichi; Kakehi, Yoshiaki; Sato, Masatoshi; Naito, Yuki; Shimizu, Hisao; Goto, Yasunobu; Takahashi, Nobuyuki

2017-11-01

Botulinum toxin A (BTXA) can disrupt the neuromuscular and autonomic functions. We herein report a case of autonomic system dysfunction that manifested as Takotsubo-like myocardial dysfunction in a patient with botulism. Takotsubo syndrome results in acute cardiac insufficiency, another fatal complication of botulism in addition to respiratory muscle paralysis, particularly in patients with cardiovascular disease.

Takotsubo-like Myocardial Dysfunction in a Patient with Botulism

PubMed Central

Tonomura, Shuichi; Kakehi, Yoshiaki; Sato, Masatoshi; Naito, Yuki; Shimizu, Hisao; Goto, Yasunobu; Takahashi, Nobuyuki

2017-01-01

Botulinum toxin A (BTXA) can disrupt the neuromuscular and autonomic functions. We herein report a case of autonomic system dysfunction that manifested as Takotsubo-like myocardial dysfunction in a patient with botulism. Takotsubo syndrome results in acute cardiac insufficiency, another fatal complication of botulism in addition to respiratory muscle paralysis, particularly in patients with cardiovascular disease. PMID:28924131

Clinical and billing review of extracorporeal membrane oxygenation.

PubMed

Blum, James M; Lynch, William R; Coopersmith, Craig M

2015-06-01

Extracorporeal membrane oxygenation (ECMO) is a temporary technique for providing life support for cardiac dysfunction, pulmonary dysfunction, or both. The two forms of ECMO, veno-arterial (VA) and veno-venous (VV), are used to support cardiopulmonary and pulmonary dysfunction, respectively. Historically, ECMO was predominantly used in the neonatal and pediatric populations, as early adult studies failed to improve outcomes. ECMO has become far more common in the adult population because of positive results in published case series and clinical trials during the 2009 influenza A(H1N1) pandemic in 2009 to 2010. Advances in technology that make the technique much easier to implement likely fueled the renewed interest. Although exact criteria for ECMO are not available, patients who are good candidates are generally considered to be relatively young and suffering from acute illness that is believed to be reversible or organ dysfunction that is otherwise treatable. With the increase in the use in the adult population, a number of different codes have been generated to better identify the method of support with distinctly different relative value units assigned to each code from a very simple prior coding scheme. To effectively be reimbursed for use of the technique, it is imperative that the clinician understands the new coding scheme and works with payers to determine what is incorporated into each specific code.

Regional Brain Dysfunction Associated with Semantic Errors in Comprehension.

PubMed

Shahid, Hinna; Sebastian, Rajani; Tippett, Donna C; Saxena, Sadhvi; Wright, Amy; Hanayik, Taylor; Breining, Bonnie; Bonilha, Leonardo; Fridriksson, Julius; Rorden, Chris; Hillis, Argye E

2018-02-01

Here we illustrate how investigation of individuals acutely after stroke, before structure/function reorganization through recovery or rehabilitation, can be helpful in answering questions about the role of specific brain regions in language functions. Although there is converging evidence from a variety of sources that the left posterior-superior temporal gyrus plays some role in spoken word comprehension, its precise role in this function has not been established. We hypothesized that this region is essential for distinguishing between semantically related words, because it is critical for linking the spoken word to the complete semantic representation. We tested this hypothesis in 127 individuals with 48 hours of acute ischemic stroke, before the opportunity for reorganization or recovery. We identified tissue dysfunction (acute infarct and/or hypoperfusion) in gray and white matter parcels of the left hemisphere, and we evaluated the association between rate of semantic errors in a word-picture verification tasks and extent of tissue dysfunction in each region. We found that after correcting for lesion volume and multiple comparisons, the rate of semantic errors correlated with the extent of tissue dysfunction in left posterior-superior temporal gyrus and retrolenticular white matter. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Number of organ dysfunctions predicts mortality in emergency department patients with suspected infection: a multicenter validation study.

PubMed

Jessen, Marie K; Skibsted, Simon; Shapiro, Nathan I

2017-06-01

The aim of this study was to validate the association between number of organ dysfunctions and mortality in emergency department (ED) patients with suspected infection. This study was conducted at two medical care center EDs. The internal validation set was a prospective cohort study conducted in Boston, USA. The external validation set was a retrospective case-control study conducted in Aarhus, Denmark. The study included adult patients (>18 years) with clinically suspected infection. Laboratory results and clinical data were used to assess organ dysfunctions. Inhospital mortality was the outcome measure. Multivariate logistic regression was used to determine the independent mortality odds for number and types of organ dysfunctions. We enrolled 4952 (internal) and 483 (external) patients. The mortality rate significantly increased with increasing number of organ dysfunctions: internal validation: 0 organ dysfunctions: 0.5% mortality, 1: 3.6%, 2: 9.5%, 3: 17%, and 4 or more: 37%; external validation: 2.2, 6.7, 17, 41, and 57% mortality (both P<0.001 for trend). Age-adjusted and comorbidity-adjusted number of organ dysfunctions remained an independent predictor. The effect of specific types of organ dysfunction on mortality was most pronounced for hematologic [odds ratio (OR) 3.3 (95% confidence interval (CI) 2.0-5.4)], metabolic [OR 3.3 (95% CI 2.4-4.6); internal validation], and cardiovascular dysfunctions [OR 14 (95% CI 3.7-50); external validation]. The number of organ dysfunctions predicts sepsis mortality.

Heme Oxygenase-1 Induction and Organic Nitrate Therapy: Beneficial Effects on Endothelial Dysfunction, Nitrate Tolerance, and Vascular Oxidative Stress

PubMed Central

Daiber, Andreas; Oelze, Matthias; Wenzel, Philip; Bollmann, Franziska; Pautz, Andrea; Kleinert, Hartmut

2012-01-01

Organic nitrates are a group of very effective anti-ischemic drugs. They are used for the treatment of patients with stable angina, acute myocardial infarction, and chronic congestive heart failure. A major therapeutic limitation inherent to organic nitrates is the development of tolerance, which occurs during chronic treatment with these agents, and this phenomenon is largely based on induction of oxidative stress with subsequent endothelial dysfunction. We therefore speculated that induction of heme oxygenase-1 (HO-1) could be an efficient strategy to overcome nitrate tolerance and the associated side effects. Indeed, we found that hemin cotreatment prevented the development of nitrate tolerance and vascular oxidative stress in response to chronic nitroglycerin therapy. Vice versa, pentaerithrityl tetranitrate (PETN), a nitrate that was previously reported to be devoid of adverse side effects, displayed tolerance and oxidative stress when the HO-1 pathway was blocked pharmacologically or genetically by using HO-1+/– mice. Recently, we identified activation of Nrf2 and HuR as a principle mechanism of HO-1 induction by PETN. With the present paper, we present and discuss our recent and previous findings on the role of HO-1 for the prevention of nitroglycerin-induced nitrate tolerance and for the beneficial effects of PETN therapy. PMID:22506100

A Case Report of Parvovirus B19 Infection in a Renal Allograft.

PubMed

Oramas, Diana M; Setty, Suman; Yeldandi, Vijay; Cabrera, Julio; Patel, Tushar

2017-10-01

Parvovirus B19 infection is undiagnosed in recipients undergoing solid organ transplantation. It is usually responsible for unexplained acute and chronic red blood cell aplasia that does not respond to erythropoietin therapy. Cases of parvovirus B19 infection associated with pancytopenia, solid organ dysfunction, and allograft rejection have been described in the literature. The deterioration of the immune system as a result of severe immunotherapy favors the reactivation of a previous infection or the acquisition of a new one. We present a case of a 32-year-old woman with a 1-year history of renal allograft transplant and previous cytomegalovirus (CMV) infection who presented with chest pain, polyarthritis, pancytopenia, and renal dysfunction. A serum sample using polymerase chain reaction showed a parvovirus titer of 13.8 trillion IU/mL and a CMV titer of 800 IU/mL. The renal biopsy revealed nucleomegaly with focal viral inclusions, along with changes associated with immunotherapy toxicity. Electron microscopy demonstrated capillary and tubular epithelial cells with "viral factories," thereby confirming the diagnosis. Thus, screening for parvovirus B19 is advised in high-risk patients who present with refractory anemia to avoid the complications of a chronic infection associated with the fatal rejection of the transplanted organ.

Spinal Cord Injury Causes Chronic Liver Pathology in Rats

PubMed Central

Sauerbeck, Andrew D.; Laws, J. Lukas; Bandaru, Veera V.R.; Popovich, Phillip G.; Haughey, Norman J.

2015-01-01

Abstract Traumatic spinal cord injury (SCI) causes major disruption to peripheral organ innervation and regulation. Relatively little work has investigated these post-SCI systemic changes, however, despite considerable evidence that multiple organ system dysfunction contributes to chronic impairments in health. Because metabolic dysfunction is common after SCI and the liver is a pivotal site for metabolic homeostasis, we sought to determine if liver pathology occurs as a result of SCI in a rat spinal contusion model. Histologic evidence showed excess lipid accumulation in the liver for at least 21 days post-injury after cervical or midthoracic SCI. Lipidomic analysis revealed an acute increase in hepatic ceramides as well as chronically elevated lactosylceramide. Post-SCI hepatic changes also included increased proinflammatory gene expression, including interleukin (IL)-1α, IL-1β, chemokine ligand-2, and tumor necrosis factor-α mRNA. These were coincident with increased CD68+ macrophages in the liver through 21 days post-injury. Serum alanine transaminase, used clinically to detect liver damage, was significantly increased at 21 days post-injury, suggesting that early metabolic and inflammatory damage preceded overt liver pathology. Surprisingly, liver inflammation was even detected after lumbar SCI. Collectively, these results suggest that SCI produces chronic liver injury with symptoms strikingly similar to those of nonalcoholic steatohepatitis (fatty liver disease). These clinically significant hepatic changes after SCI are known to contribute to systemic inflammation, cardiovascular disease, and metabolic syndrome, all of which are more prevalent in persons with SCI. Targeting acute and prolonged hepatic pathology may improve recovery and reduce long-term complications after SCI. PMID:25036371

Specific Etiologies Associated With the Multiple Organ Dysfunction Syndrome in Children: Part 2.

PubMed

Upperman, Jeffrey S; Bucuvalas, John C; Williams, Felicia N; Cairns, Bruce A; Cox, Charles S; Doctor, Allan; Tamburro, Robert F

2017-03-01

To describe a number of conditions and therapies associated with multiple organ dysfunction syndrome presented as part of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Multiple Organ Dysfunction Workshop (March 26-27, 2015). In addition, the relationship between burn injuries and multiple organ dysfunction syndrome is also included although it was not discussed at the workshop. Literature review, research data, and expert opinion. Not applicable. Moderated by an expert from the field, issues relevant to the association of multiple organ dysfunction syndrome with a variety of conditions and therapies were presented, discussed, and debated with a focus on identifying knowledge gaps and the research priorities. Summary of presentations and discussion supported and supplemented by relevant literature. Sepsis and trauma are the two conditions most commonly associated with multiple organ dysfunction syndrome both in children and adults. However, many other pathophysiologic processes may result in multiple organ dysfunction syndrome. In this article, we discuss conditions such as liver failure and pancreatitis, pathophysiologic processes such as ischemia and hypoxia, and injuries such as trauma and burns. Additionally, therapeutic interventions such as medications, blood transfusions, transplantation may also precipitate and contribute to multiple organ dysfunction syndrome. The purpose of this article is to describe the association of multiple organ dysfunction syndrome with a variety of conditions and therapies in an attempt to identify similarities, differences, and opportunities for therapeutic intervention.

A dual role of p21 in stem cell aging.

PubMed

Ju, Zhenyu; Choudhury, Aaheli Roy; Rudolph, K Lenhard

2007-04-01

A decline in adult stem cell function occurs during aging, likely contributing to the decline in organ homeostasis and regeneration with age. An emerging field in aging research is to analyze molecular pathways limiting adult stem cell function in response to macromolecular damage accumulation during aging. Current data suggest that the p21 cell cycle inhibitor has a dual role in stem cell aging: On one hand, p21 protects adult stem cells from acute genotoxic stress by preventing inappropriate cycling of acutely damaged stem cells. On the other hand, p21 activation impairs stem cell function and survival of aging telomere dysfunctional mice indicating that p21 checkpoint function is disadvantageous in the context of chronic and persistent damage, which accumulates during aging. This article focuses on these dual roles of p21 in aging stem cells.

Immunosuppression after Sepsis: Systemic Inflammation and Sepsis Induce a Loss of Naïve T-Cells but No Enduring Cell-Autonomous Defects in T-Cell Function

PubMed Central

Markwart, Robby; Condotta, Stephanie A.; Requardt, Robert P.; Borken, Farina; Schubert, Katja; Weigel, Cynthia; Bauer, Michael; Griffith, Thomas S.; Förster, Martin; Brunkhorst, Frank M.; Badovinac, Vladimir P.; Rubio, Ignacio

2014-01-01

Sepsis describes the life-threatening systemic inflammatory response (SIRS) of an organism to an infection and is the leading cause of mortality on intensive care units (ICU) worldwide. An acute episode of sepsis is characterized by the extensive release of cytokines and other mediators resulting in a dysregulated immune response leading to organ damage and/or death. This initial pro-inflammatory burst often transits into a state of immune suppression characterised by loss of immune cells and T-cell dysfunction at later disease stages in sepsis survivors. However, despite these appreciations, the precise nature of the evoked defect in T-cell immunity in post-acute phases of SIRS remains unknown. Here we present an in-depth functional analysis of T-cell function in post-acute SIRS/sepsis. We document that T-cell function is not compromised on a per cell basis in experimental rodent models of infection-free SIRS (LPS or CpG) or septic peritonitis. Transgenic antigen-specific T-cells feature an unaltered cytokine response if challenged in vivo and ex vivo with cognate antigens. Isolated CD4+/CD8+ T-cells from post-acute septic animals do not exhibit defects in T-cell receptor-mediated activation at the the level of receptor-proximal signalling, activation marker upregulation or expansion. However, SIRS/sepsis induced transient lymphopenia and gave rise to an environment of immune attenuation at post acute disease stages. Thus, systemic inflammation has an acute impact on T-cell numbers and adaptive immunity, but does not cause major cell-autonomous enduring functional defects in T-cells. PMID:25541945

Acute Frontal Lobe Dysfunction Following Prefrontal Low-Frequency Repetitive Transcranial Magnetic Stimulation in a Patient with Treatment-Resistant Depression

PubMed Central

Carle, Guilhem; Touat, Mehdi; Bruno, Nicolas; Galanaud, Damien; Peretti, Charles-Siegfried; Valero-Cabré, Antoni; Levy, Richard; Azuar, Carole

2017-01-01

The potential of repetitive transcranial magnetic stimulation (rTMS) to treat numerous neurological and psychiatric disorders has been thoroughly studied for the last two decades. Here, we report for the first time, the case of a 65-year-old woman suffering from treatment-resistant depression who developed an acute frontal lobe syndrome following eight sessions of low-frequency rTMS (LF-rTMS) to the right dorsolateral prefrontal cortex while also treated with sertraline and mianserin. The pathophysiological mechanisms underlying such an unexpected acute frontal lobe dysfunction are discussed in relation to the therapeutic use of LF-rTMS in combination with pharmacotherapy in depressed patients. PMID:28611694

Long lasting dysautonomia due to botulinum toxin B poisoning: clinical-laboratory follow up and difficulties in initial diagnosis.

PubMed

Potulska-Chromik, Anna; Zakrzewska-Pniewska, Beata; Szmidt-Sałkowska, Elżbieta; Lewandowski, Jacek; Siński, Maciej; Przyjałkowski, Witold; Kostera-Pruszczyk, Anna

2013-10-30

Botulism is an acute form of poisoning caused by one of four types (A, B, E, F) toxins produced by Clostridium botulinum, ananaerobic, spore forming bacillus. Usually diagnosis of botulism is considered in patients with predominant motor symptoms: muscle weakness with intact sensation and preserved mental function. We report a case of 56-year-old Caucasian female with a history of arterial hypertension, who presented with acute respiratory failure and bilateral ptosis misdiagnosed as brainstem ischemia. She had severe external and internal ophtalmoplegia, and autonomic dysfunction with neither motor nor sensory symptoms from upper and lower limbs. Diagnosis of botulinum toxin poisoning was made and confirmed by serum antibody testing in the mouse inoculation test. Ophtalmoplegia, autonomic dysfunction and respiratory failure can be caused by botulism. Early treatment and intensive care is essential for survival and recovery. The electrophysiological tests are crucial to correct and rapid diagnosis. Botulism (especially type B) should be considered in any case of acute or predominant isolated autonomic dysfunction.

Telomere length in patients with pulmonary fibrosis associated with chronic lung allograft dysfunction and post-lung transplantation survival.

PubMed

Newton, Chad A; Kozlitina, Julia; Lines, Jefferson R; Kaza, Vaidehi; Torres, Fernando; Garcia, Christine Kim

2017-08-01

Prior studies have shown that patients with pulmonary fibrosis with mutations in the telomerase genes have a high rate of certain complications after lung transplantation. However, few studies have investigated clinical outcomes based on leukocyte telomere length. We conducted an observational cohort study of all patients with pulmonary fibrosis who underwent lung transplantation at a single center between January 1, 2007, and December 31, 2014. Leukocyte telomere length was measured from a blood sample collected before lung transplantation, and subjects were stratified into 2 groups (telomere length <10th percentile vs ≥10th percentile). Primary outcome was post-lung transplant survival. Secondary outcomes included incidence of allograft dysfunction, non-pulmonary organ dysfunction, and infection. Approximately 32% of subjects had a telomere length <10th percentile. Telomere length <10th percentile was independently associated with worse survival (hazard ratio 10.9, 95% confidence interval 2.7-44.8, p = 0.001). Telomere length <10th percentile was also independently associated with a shorter time to onset of chronic lung allograft dysfunction (hazard ratio 6.3, 95% confidence interval 2.0-20.0, p = 0.002). Grade 3 primary graft dysfunction occurred more frequently in the <10th percentile group compared with the ≥10th percentile group (28% vs 7%; p = 0.034). There was no difference between the 2 groups in incidence of acute cellular rejection, cytopenias, infection, or renal dysfunction. Telomere length <10th percentile was associated with worse survival and shorter time to onset of chronic lung allograft dysfunction and thus represents a biomarker that may aid in risk stratification of patients with pulmonary fibrosis before lung transplantation. Copyright © 2017 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Albumin infusion improves renal blood flow autoregulation in patients with acute decompensation of cirrhosis and acute kidney injury.

PubMed

Garcia-Martinez, Rita; Noiret, Lorette; Sen, Sambit; Mookerjee, Rajeshwar; Jalan, Rajiv

2015-02-01

In cirrhotic patients with renal failure, renal blood flow autoregulation curve is shifted to the right, which is consequent upon sympathetic nervous system activation and endothelial dysfunction. Albumin infusion improves renal function in cirrhosis by mechanisms that are incompletely understood. We aimed to determine the effect of albumin infusion on systemic haemodynamics, renal blood flow, renal function and endothelial function in patients with acute decompensation of cirrhosis and acute kidney injury. Twelve patients with refractory ascites and 10 patients with acute decompensation of cirrhosis and acute kidney injury were studied. Both groups were treated with intravenous albumin infusion, 40-60 g/days over 3-4 days. Cardiac and renal haemodynamics were measured. Endothelial activation/dysfunction was assessed using von Willebrand factor and serum nitrite levels. F2α Isoprostanes, resting neutrophil burst and noradrenaline levels were quantified as markers of oxidative stress, endotoxemia and sympathetic activation respectively. Albumin infusion leads to a shift in the renal blood flow autoregulation curve towards normalization, which resulted in a significant increase in renal blood flow. Accordingly, improvement of renal function was observed. In parallel, a significant decrease in sympathetic activation, inflammation/oxidative stress and endothelial activation/dysfunction was documented. Improvement of renal blood flow correlated with improvement in endothelial activation (r = 0.741, P < 0.001). The data suggest that albumin infusion improves renal function in acutely decompensated cirrhotic patients with acute kidney injury by impacting on renal blood flow autoregulation. This is possibly achieved through endothelial stabilization and a reduction in the sympathetic tone, endotoxemia and oxidative stress. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Acute Kidney Injury in Pediatric Severe Sepsis: An Independent Risk Factor for Death and New Disability.

PubMed

Fitzgerald, Julie C; Basu, Rajit K; Akcan-Arikan, Ayse; Izquierdo, Ledys M; Piñeres Olave, Byron E; Hassinger, Amanda B; Szczepanska, Maria; Deep, Akash; Williams, Duane; Sapru, Anil; Roy, Jason A; Nadkarni, Vinay M; Thomas, Neal J; Weiss, Scott L; Furth, Susan

2016-12-01

The prevalence of septic acute kidney injury and impact on functional status of PICU survivors are unknown. We used data from an international prospective severe sepsis study to elucidate functional outcomes of children suffering septic acute kidney injury. Secondary analysis of patients in the Sepsis PRevalence, OUtcomes, and Therapies point prevalence study: acute kidney injury was defined on the study day using Kidney Disease Improving Global Outcomes definitions. Patients with no acute kidney injury or stage 1 acute kidney injury ("no/mild acute kidney injury") were compared with those with stage 2 or 3 acute kidney injury ("severe acute kidney injury"). The primary outcome was a composite of death or new moderate disability at discharge defined as a Pediatric Overall Performance Category score of 3 or higher and increased by 1 from baseline. One hundred twenty-eight PICUs in 26 countries. Children with severe sepsis in the Sepsis PRevalence, OUtcomes, and Therapies study. None. One hundred two (21%) of 493 patients had severe acute kidney injury. More than twice as many patients with severe acute kidney injury died or developed new moderate disability compared with those with no/mild acute kidney injury (64% vs 30%; p < 0.001). Severe acute kidney injury was independently associated with death or new moderate disability (adjusted odds ratio, 2.5; 95% CI, 1.5-4.2; p = 0.001) after adjustment for age, region, baseline disability, malignancy, invasive mechanical ventilation, albumin administration, and the pediatric logistic organ dysfunction score. In a multinational cohort of critically ill children with severe sepsis and high mortality rates, septic acute kidney injury is independently associated with further increased death or new disability.

Bacterial infection causes stress-induced memory dysfunction in mice.

PubMed

Gareau, Mélanie G; Wine, Eytan; Rodrigues, David M; Cho, Joon Ho; Whary, Mark T; Philpott, Dana J; Macqueen, Glenda; Sherman, Philip M

2011-03-01

The brain-gut axis is a key regulator of normal intestinal physiology; for example, psychological stress is linked to altered gut barrier function, development of food allergies and changes in behaviour. Whether intestinal events, such as enteric bacterial infections and bacterial colonisation, exert a reciprocal effect on stress-associated behaviour is not well established. To determine the effects of either acute enteric infection or absence of gut microbiota on behaviour, including anxiety and non-spatial memory formation. Behaviour was assessed following infection with the non-invasive enteric pathogen, Citrobacter rodentium in both C57BL/6 mice and germ-free Swiss-Webster mice, in the presence or absence of acute water avoidance stress. Whether daily treatment with probiotics normalised behaviour was assessed, and potential mechanisms of action evaluated. No behavioural abnormalities were observed, either at the height of infection (10 days) or following bacterial clearance (30 days), in C rodentium-infected C57BL/6 mice. When infected mice were exposed to acute stress, however, memory dysfunction was apparent after infection (10 days and 30 days). Memory dysfunction was prevented by daily treatment of infected mice with probiotics. Memory was impaired in germ-free mice, with or without exposure to stress, in contrast to conventionally reared, control Swiss-Webster mice with an intact intestinal microbiota. The intestinal microbiota influences the ability to form memory. Memory dysfunction occurs in infected mice exposed to acute stress, while in the germ-free setting memory is altered at baseline.

SOD1 overexpression prevents acute hyperglycemia-induced cerebral myogenic dysfunction: relevance to contralateral hemisphere and stroke outcomes

PubMed Central

Coucha, Maha; Li, Weiguo; Hafez, Sherif; Abdelsaid, Mohammed; Johnson, Maribeth H.; Fagan, Susan C.

2014-01-01

Admission hyperglycemia (HG) amplifies vascular injury and neurological deficits in acute ischemic stroke, but the mechanisms remain controversial. We recently reported that ischemia-reperfusion (I/R) injury impairs the myogenic response in both hemispheres via increased nitration. However, whether HG amplifies contralateral myogenic dysfunction and whether loss of tone in the contralateral hemisphere contributes to stroke outcomes remain to be determined. Our hypothesis was that contralateral myogenic dysfunction worsens stroke outcomes after acute hyperglycemic stroke in an oxidative stress-dependent manner. Male wild-type or SOD1 transgenic rats were injected with saline or 40% glucose solution 10 min before surgery and then subjected to 30 min of ischemia/45 min or 24 h of reperfusion. In another set of animals (n = 5), SOD1 was overexpressed only in the contralateral hemisphere by stereotaxic adenovirus injection 2–3 wk before I/R. Myogenic tone and neurovascular outcomes were determined. HG exacerbated myogenic dysfunction in contralateral side only, which was associated with infarct size expansion, increased edema, and more pronounced neurological deficit. Global and selective SOD1 overexpression restored myogenic reactivity in ipsilateral and contralateral sides, respectively, and enhanced neurovascular outcomes. In conclusion, our results show that SOD1 overexpression nullified the detrimental effects of HG on myogenic tone and stroke outcomes and that the contralateral hemisphere may be a novel target for the management of acute hyperglycemic stroke. PMID:25552308

Interpretation and use of natriuretic peptides in non-congestive heart failure settings.

PubMed

Tsai, Shih-Hung; Lin, Yen-Yue; Chu, Shi-Jye; Hsu, Ching-Wang; Cheng, Shu-Meng

2010-03-01

Natriuretic peptides (NPs) have been found to be useful markers in differentiating acute dyspneic patients presenting to the emergency department (ED) and emerged as potent prognostic markers for patients with congestive heart failure (CHF). The best-established and widely used clinical application of BNP and NT-proBNP testing is for the emergent diagnosis of CHF in patients presenting with acute dyspnea. Nevertheless, elevated NPs levels can be found in many circumstances involving left ventricular (LV) dysfunction or hypertrophy; right ventricular (RV) dysfunction secondary to pulmonary diseases; cardiac inflammatory or infectious diseases; endocrinology diseases and high output status without decreased LV ejection fraction. Even in the absence of significant clinical evidence of volume overload or LV dysfunction, markedly elevated NP levels can be found in patients with multiple comorbidities with a certain degree of prognostic value. Potential clinical applications of NPs are expanded accompanied by emerging reports regarding screening the presence of secondary cardiac dysfunction; monitoring the therapeutic responses, risk stratifications and providing prognostic values in many settings. Clinicians need to have expanded knowledge regarding the interpretation of elevated NPs levels and potential clinical applications of NPs. Clinicians should recognize that currently the only reasonable application for routine practice is limited to differentiation of acute dyspnea, rule-out-diagnostic-tests, monitoring of therapeutic responses and prognosis of acute or decompensated CHF. The rationales as well the potential applications of NPs in these settings are discussed in this review article.

Interpretation and Use of Natriuretic Peptides in Non-Congestive Heart Failure Settings

PubMed Central

Lin, Yen-Yue; Chu, Shi-Jye; Hsu, Ching-Wang; Cheng, Shu-Meng

2010-01-01

Natriuretic peptides (NPs) have been found to be useful markers in differentiating acute dyspneic patients presenting to the emergency department (ED) and emerged as potent prognostic markers for patients with congestive heart failure (CHF). The best-established and widely used clinical application of BNP and NT-proBNP testing is for the emergent diagnosis of CHF in patients presenting with acute dyspnea. Nevertheless, elevated NPs levels can be found in many circumstances involving left ventricular (LV) dysfunction or hypertrophy; right ventricular (RV) dysfunction secondary to pulmonary diseases; cardiac inflammatory or infectious diseases; endocrinology diseases and high output status without decreased LV ejection fraction. Even in the absence of significant clinical evidence of volume overload or LV dysfunction, markedly elevated NP levels can be found in patients with multiple comorbidities with a certain degree of prognostic value. Potential clinical applications of NPs are expanded accompanied by emerging reports regarding screening the presence of secondary cardiac dysfunction; monitoring the therapeutic responses, risk stratifications and providing prognostic values in many settings. Clinicians need to have expanded knowledge regarding the interpretation of elevated NPs levels and potential clinical applications of NPs. Clinicians should recognize that currently the only reasonable application for routine practice is limited to differentiation of acute dyspnea, rule-out-diagnostic-tests, monitoring of therapeutic responses and prognosis of acute or decompensated CHF. The rationales as well the potential applications of NPs in these settings are discussed in this review article. PMID:20191004

Endocrine and metabolic dysfunction in yellow perch, Perca flavescens, exposed to organic contaminants and heavy metals in the St. Lawrence River

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

Hontela, A.; Duclos, D.; Fortin, R.

1995-04-01

The endocrine and biochemical responses to the acute stress of capture and handling were investigated in sexually mature and in immature male and female yellow perch, Perca flavescens, from a site contaminated by organic contaminants (PAHs and PCBs) and heavy metals (Hg, Cd, As, and Zn) and from a reference site in the St. Lawrence River. Following a standardized capture and handling stress, fish from the contaminated site did not exhibit the expected physiological stress response observed in fish from the reference site. Blood cortisol and thyroxine levels were lower, and liver glycogen stores were greater in mature males andmore » females, as well as in the immature fish from the contaminated site, compared to the reference site. Fish from the contaminated site also had smaller gonads and lower condition factor. The impaired ability to elevate blood cortisol in response to an acute stress may be used as a biomarker of toxic stress in health assessment of feral fish from polluted environments.« less

Clinical and Radiological Profile of Acute Fibrinous and Organizing Pneumonia: A Retrospective Study.

PubMed

Dai, Jing-Hong; Li, Hui; Shen, Wei; Miao, Li-Yun; Xiao, Yong-Long; Huang, Mei; Cao, Meng-Shu; Wang, Yang; Zhu, Bin; Meng, Fan-Qing; Cai, Hou-Rong

2015-10-20

Acute fibrinous and organizing pneumonia (AFOP) is a unique pathological entity with intra-alveolar fibrin in the form of "fibrin balls" and organizing pneumonia. It was divided into rare idiopathic interstitial pneumonia according to the classification notified by American Thoracic Society/European Respiratory Society in 2013. As a rare pathological entity, it is still not well known and recognized by clinicians. We reviewed the clinical features of 20 patients with AFOP diagnosed in a teaching hospital. The medical records of 20 patients with biopsy-proven diagnosis of AFOP were retrospectively reviewed. The patients' symptoms, duration of the disease, comorbidities, clinical laboratory data, pulmonary function testing, radiographic studies, and the response to treatment were extracted and analyzed. Fever was the most common symptom and was manifested in 90% of AFOP patients. For clinical laboratory findings, systematic inflammatory indicators, including C-reactive protein and erythrocyte sedimentation rate, were significantly higher than normal in AFOP patients. In accordance with this increased indicators, injured liver functions were common in AFOP patients. Inversely, AFOP patients had worse clinical conditions including anemia and hypoalbuminemia. For pulmonary function testing, AFOP patients showed the pattern of restrictive mixed with obstructive ventilation dysfunction. For high-resolution computerized tomography (HRCT) findings, the most common pattern for AFOP patients was lobar consolidation which was very similar to pneumonia. However, unlike pneumonia, AFOP patients responded well to glucocorticoids. Patients with AFOP manifest as acute inflammatory-like clinical laboratory parameters and lobar consolidation on HRCT, but respond well to steroid.

Two cases of Kawasaki disease presented with acute febrile jaundice.

PubMed

Kaman, Ayşe; Aydın-Teke, Türkan; Gayretli-Aydın, Zeynep Gökçe; Öz, Fatma Nur; Metin-Akcan, Özge; Eriş, Deniz; Tanır, Gönül

2017-01-01

Kawasaki disease is an acute, systemic vasculitis of unknown etiology. Although gastrointestinal involvement does not belong to the classic diagnostic criteria; diarrhea, abdominal pain, hepatic dysfunction, hydrops of gallbladder, and acute febrile cholestatic jaundice are reported in patients with Kawasaki disease. We describe here two cases presented with fever, and acute jaundice as initial features of Kawasaki disease.

New insights into environmental enteric dysfunction

USDA-ARS?s Scientific Manuscript database

Environmental enteric dysfunction (EED) has been recognised as an important contributing factor to physical and cognitive stunting, poor response to oral vaccines, limited resilience to acute infections and ultimately global childhood mortality. The aetiology of EED remains poorly defined but the ep...

Immuno-therapy of Acute Radiation Syndromes : Extracorporeal Immuno-Lympho-Plasmo-Sorption.

NASA Astrophysics Data System (ADS)

Popov, Dmitri; Maliev, Slava

Methods Results Summary and conclusions Introduction: Existing Medical Management of the Acute Radiation Syndromes (ARS) does not include methods of specific immunotherapy and active detoxication. Though the Acute Radiation Syndromes were defined as an acute toxic poisonous with development of pathological processes: Systemic Inflammatory Response Syndrome (SIRS), Toxic Multiple Organ Injury (TMOI), Toxic Multiple Organ Dysfunction Syndrome(TMODS), Toxic Multiple Organ Failure (TMOF). Radiation Toxins of SRD Group play an important role as the trigger mechanisms in development of the ARS clinical symptoms. Methods: Immuno-Lympho-Plasmo-Sorption is a type of Immuno-therapy which includes prin-ciples of immunochromato-graphy, plasmopheresis, and hemodialysis. Specific Antiradiation Antitoxic Antibodies are the active pharmacological agents of immunotherapy . Antiradia-tion Antitoxic Antibodies bind selectively to Radiation Neurotoxins, Cytotoxins, Hematotox-ins and neutralize their toxic activity. We have developed the highly sensitive method and system for extracorporeal-immune-lypmh-plasmo-sorption with antigen-specific IgG which is clinically important for treatment of the toxic and immunologic phases of the ARS. The method of extracorporeal-immune-lypmh-plasmo-sorption includes Antiradiation Antitoxic Antibodies (AAA) immobilized on microporous polymeric membranes with a pore size that is capable to provide diffusion of blood-lymph plasma. Plasma of blood or lymph of irradiated mammals contains Radiation Toxins (RT) that have toxic and antigenic properties. Radiation Toxins are Antigen-specific to Antitoxic blocking antibodies (Immunoglobulin G). Plasma diffuses through membranes with immobilized AAA and AA-antibodies bind to the polysaccharide chain of tox-ins molecules and complexes of AAA-RT that are captured on membrane surfaces. RT were removed from plasma. Re-transfusion of plasma of blood and lymph had been provided. We show a statistical significant reduction in postradiation lethality.

FC-99 ameliorates sepsis-induced liver dysfunction by modulating monocyte/macrophage differentiation via Let-7a related monocytes apoptosis.

PubMed

Zhao, Yarong; Zhu, Haiyan; Wang, Haining; Ding, Liang; Xu, Lizhi; Chen, Dai; Shen, Sunan; Hou, Yayi; Dou, Huan

2018-03-13

The liver is a vital target for sepsis-related injury, leading to inflammatory pathogenesis, multiple organ dysfunction and high mortality rates. Monocyte-derived macrophage transformations are key events in hepatic inflammation. N 1 -[(4-methoxy)methyl]-4-methyl-1,2-benzenediamine (FC-99) previously displayed therapeutic potential on experimental sepsis. However, the underlying mechanism of this protective effect is still not clear. FC-99 treatment attenuated the liver dysfunction in septic mice that was accompanied with reduced numbers of pro-inflammatory Ly6C hi monocytes in the peripheral blood and CD11b + F4/80 lo monocyte-derived macrophages in the liver. These effects were attributed to the FC-99-induced apoptosis of CD11b + cells. In PMA-differentiated THP-1 cells, FC-99 repressed the expression of CD11b, CD14 and caspase3 and resulted in a high proportion of Annexin V + cells. Moreover, let-7a-5p expression was abrogated upon CLP stimulation in vivo , whereas it was restored by FC-99 treatment. TargetScan analysis and luciferase assays indicated that the anti-apoptotic protein BCL-XL was targeted by let-7a-5p. BCL-XL was inhibited by FC-99 in order to induce monocyte apoptosis, leading to the impaired monocyte-to-macrophage differentiation. Murine acute liver failure was generated by caecal ligation puncture surgery after FC-99 administration; Blood samples and liver tissues were collected to determine the monocyte/macrophage subsets and the induction of apoptosis. Human acute monocytic leukemia cell line (THP-1) cells were pretreated with FC-99 followed by phorbol-12-myristate-13-acetate (PMA) stimulation, in order to induce monocyte-to-macrophage differentiation. The target of FC-99 and the mechanistic analyses were conducted by microarrays, qRT-PCR validation, TargetScan algorithms and a luciferase report assay. FC-99 exhibits potential therapeutic effects on CLP-induced liver dysfunction by restoring let-7a-5p levels.

Immunotherapy in the management of sepsis.

PubMed Central

Fagan, E. A.; Singer, M.

1995-01-01

The pathophysiological effects of severe sepsis, septic shock and related syndromes result from tissues damaged by the uncontrolled production of the mediators of inflammation. Early deaths are related primarily to the acute effects of the systemic inflammatory response. Later deaths are related more closely to the consequences of multiple organ dysfunction. Monoclonal antibodies and other immunotherapies have been developed against bacterial products, cytokines and other mediators involved in this systemic inflammatory response. Immunotherapies may improve outcome in the critically ill with sepsis if used early and as part of the therapeutic regimen of antimicrobial agents and intensive care support. PMID:7724438

Recent advances in the pathogenetic mechanisms of sepsis-associated acute kidney injury.

PubMed

Fani, Filippo; Regolisti, Giuseppe; Delsante, Marco; Cantaluppi, Vincenzo; Castellano, Giuseppe; Gesualdo, Loreto; Villa, Gianluca; Fiaccadori, Enrico

2018-06-01

Sepsis is a serious medical condition that can lead to multi-organ failure and shock, and it is associated with increased mortality. Acute kidney injury (AKI) is a frequent complication of sepsis in critically ill patients, and often requires renal replacement therapy. The pathophysiology of AKI in sepsis has not yet been fully defined. In the past, classic theories were mainly focused on systemic hemodynamic derangements, underscoring the key role of whole kidney hypoperfusion due to reduced renal blood flow. However, a growing body of experimental and clinical evidence now shows that, at least in the early phase of sepsis-associated AKI, renal blood flow is normal, or even increased. This could suggest a dissociation between renal blood flow and kidney function. In addition, the scant data available from kidney biopsies in human studies do not support diffuse acute tubular necrosis as the predominant lesion. Instead, increasing importance is now attributed to kidney damage resulting from a complex interaction between immunologic mechanisms, inflammatory cascade activation, and deranged coagulation pathways, leading to microvascular dysfunction, endothelial damage, leukocyte/platelet activation with the formation of micro-thrombi, epithelial tubular cell injury and dysfunction. Moreover, the same processes, through maladaptive responses leading to fibrosis acting from the very beginning, may set the stage for progression to chronic kidney disease in survivors from sepsis-associated AKI episodes. The aim of this narrative review is to summarize and discuss the latest evidence on the pathophysiological mechanisms involved in septic AKI, based on the most recent data from the literature.

Urinary retention associated with herpes zoster infection.

PubMed

Cohen, L M; Fowler, J F; Owen, L G; Callen, J P

1993-01-01

Herpes zoster infection particularly involving the sacral dermatomes has been associated with bladder and bowel dysfunction, most commonly urinary retention. We report two patients who developed acute urinary retention, one of whom also had constipation, within days of herpes zoster skin lesions of the S2-S4 dermatomes. Herpes zoster is a reversible cause of neurogenic bladder and bowel dysfunction and should be considered in a patient that presents with acute urinary retention and/or constipation. Sensory abnormalities and flaccid detrusor paralysis are most likely involved in the pathogenesis.

[Cyclic vomiting with ketosis as a cause of acute kidney dysfunction: own clinical experience].

PubMed

Ostrowska-Nawarycz, L; Rapacka, E; Baszczyński, J; Górski, P; Czajka, J; Makowski, M; Kudzin, A

2000-04-01

The aim of the study was to evaluate renal activity during cyclic vomiting with ketosis. The clinical material was obtained from 50 cases of children hospitalized in Department of Pediatrics Military Medical University within 1993-1999 what makes about 1% of all patients. The examined group consisted of 26 boys (52%) and 24 girls (48%). Three of the children were repeatedly hospitalized (3 to 8 times) because of acetonemic vomiting. The special attention during the laboratory studies was paid to evaluation of renal activity. Vomiting with ketosis were associated with temporary kidneys acute dysfunction in 46% of cases. In 98% of cases the parenteral hydration was necessary. Ketonemic vomiting with kidneys dysfunction was observed mainly with the children in pre-school age.

Association Between Severity and the Determinant-Based Classification, Atlanta 2012 and Atlanta 1992, in Acute Pancreatitis

PubMed Central

Chen, Yuhui; Ke, Lu; Tong, Zhihui; Li, Weiqin; Li, Jieshou

2015-01-01

Abstract Recently, the determinant-based classification (DBC) and the Atlanta 2012 have been proposed to provide a basis for study and treatment of acute pancreatitis (AP). The present study aimed to evaluate the association between severity and the DBC, the Atlanta 2012 and the Atlanta 1992, in AP. Patients admitted to our center with AP from January 2007 to July 2013 were reviewed retrospectively. Patients were assigned to severity categories for all the 3 classification systems. The primary outcomes include long-term clinical prognosis (mortality and length-of-hospital stay), major complications (intraabdominal hemorrhage, multiple-organ dysfunction, single organ failure [OF], and sepsis) and clinical interventions (surgical drainage, continuous renal replace therapy [CRRT] lasting time, and mechanical ventilation [MV] lasting time). The classification systems were validated and compared in terms of these abovementioned primary outcomes. A total of 395 patients were enrolled in this retrospective study with an overall 8.86% in-hospital mortality. Intraabdominal hemorrhage was present in 27 (6.84%) of the patients, multiple-organ dysfunction in 73(18.48%), single OF in 67 (16.96%), and sepsis in 73(18.48%). For each classification system, different categories regarding severity were associated with statistically different clinical mortality, major complications, and clinical interventions (P < 0.05). However, the Atlanta 2012 and the DBC performed better than the Atlanta 1992, and they were comparable in predicting mortality (area under curve [AUC] 0.899 and 0.955 vs 0.585, P < 0.05); intraabdominal hemorrhage (AUC 0.930 and 0.961 vs 0.583, P < 0.05), multiple-organ dysfunction (AUC 0.858 and 0.881 vs 0.595, P < 0.05), sepsis (AUC 0.826 and 0.879 vs 0.590, P < 0.05), and surgical drainage (AUC 0.900 and 0.847 vs 0.606, P < 0.05). For continuous variables, the Atlanta 2012 and the DBC were also better than the Atlanta 1992, and they were similar in predicting CRRT lasting time (Somer D 0.379 and 0.360 vs 0.210, P < 0.05) and MV lasting time (Somer D 0.344 and 0.336 vs 0.186, P < 0.05). All the 3 classification systems accurately classify the severity of AP. However, the Atlanta 2012 and the DBC performed better than the Atlanta 1992, and they were comparable in predicting long-term clinical prognosis, major complications, and clinical interventions. PMID:25837754

Challenges and Rewards on the Road to Translational Systems Biology in Acute Illness: Four Case Reports from Interdisciplinary Teams

PubMed Central

An, Gary; Hunt, C. Anthony; Clermont, Gilles; Neugebauer, Edmund; Vodovotz, Yoram

2007-01-01

Introduction Translational systems biology approaches can be distinguished from mainstream systems biology in that their goal is to drive novel therapies and streamline clinical trials in critical illness. One systems biology approach, dynamic mathematical modeling (DMM), is increasingly used in dealing with the complexity of the inflammatory response and organ dysfunction. The use of DMM often requires a broadening of research methods and a multidisciplinary team approach that includes bioscientists, mathematicians, engineers, and computer scientists. However, the development of these groups must overcome domain-specific barriers to communication and understanding. Methods We present four case studies of successful translational, interdisciplinary systems biology efforts, which differ by organizational level from an individual to an entire research community. Results Case 1 is a single investigator involved in DMM of the acute inflammatory response at Cook County Hospital, in which extensive translational progress was made using agent-based models of inflammation and organ damage. Case 2 is a community-level effort from the University of Witten-Herdecke in Cologne, whose efforts have led to the formation of the Society for Complexity in Acute Illness. Case 3 is an institution-based group, the Biosystems Group at the University of California, San Francisco, whose work has included a focus on a common lexicon for DMM. Case 4 is an institution-based, trans-disciplinary research group (the Center for Inflammation and Regenerative Modeling at the University of Pittsburgh, whose modeling work has led to internal education efforts, grant support, and commercialization. Conclusion A transdisciplinary approach, which involves team interaction in an iterative fashion to address ambiguity and is supported by educational initiatives, is likely to be necessary for DMM in acute illness. Community-wide organizations such as the Society of Complexity in Acute Illness (SCAI) must strive to facilitate the implementation of DMM in sepsis/trauma research into the research community as a whole. PMID:17548029

Transfusion-Related Acute Lung Injury (TRALI) and Transfusion-Associated Circulatory Overload (TACO) in Liver Transplantation: A Case Report and Focused Review.

PubMed

Smith, Natalie K; Kim, Sang; Hill, Bryan; Goldberg, Andrew; DeMaria, Samuel; Zerillo, Jeron

2018-06-01

Liver transplantation (LT) is a complex procedure in a patient with multi-organ system dysfunction and coagulation defects. The surgical procedure involves dissection, major vessel manipulation, and pathophysiologic effects of graft storage and reperfusion. As a result, LT frequently involves significant hemorrhage. Subsequent massive transfusion carries high risk of transfusion-associated complications. Transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) are the leading causes of transfusion associated mortality. In this case report and focused review, we present data that suggest that patients undergoing liver transplantation may be at higher risk for TRALI and TACO than the general population. Anesthesiologists can play a role in decreasing these risks by increasing recognition and reporting of TRALI and TACO, using point of care testing with thromboelastography to guide and decrease transfusion, and considering alternatives to traditional blood products like solvent/detergent plasma.

Mitochondrial Function in Sepsis

PubMed Central

Arulkumaran, Nishkantha; Deutschman, Clifford S.; Pinsky, Michael R.; Zuckerbraun, Brian; Schumacker, Paul T.; Gomez, Hernando; Gomez, Alonso; Murray, Patrick; Kellum, John A.

2015-01-01

Mitochondria are an essential part of the cellular infrastructure, being the primary site for high energy adenosine triphosphate (ATP) production through oxidative phosphorylation. Clearly, in severe systemic inflammatory states, like sepsis, cellular metabolism is usually altered and end organ dysfunction not only common but predictive of long term morbidity and mortality. Clearly, interest is mitochondrial function both as a target for intracellular injury and response to extrinsic stress have been a major focus of basic science and clinical research into the pathophysiology of acute illness. However, mitochondria have multiple metabolic and signaling functions that may be central in both the expression of sepsis and its ultimate outcome. In this review, the authors address five primary questions centered on the role of mitochondria in sepsis. This review should be used as both a summary source in placing mitochondrial physiology within the context of acute illness and as a focal point for addressing new research into diagnostic and treatment opportunities these insights provide. PMID:26871665

MITOCHONDRIAL FUNCTION IN SEPSIS.

PubMed

Arulkumaran, Nishkantha; Deutschman, Clifford S; Pinsky, Michael R; Zuckerbraun, Brian; Schumacker, Paul T; Gomez, Hernando; Gomez, Alonso; Murray, Patrick; Kellum, John A

2016-03-01

Mitochondria are an essential part of the cellular infrastructure, being the primary site for high-energy adenosine triphosphate production through oxidative phosphorylation. Clearly, in severe systemic inflammatory states, like sepsis, cellular metabolism is usually altered, and end organ dysfunction is not only common, but also predictive of long-term morbidity and mortality. Clearly, interest is mitochondrial function both as a target for intracellular injury and response to extrinsic stress have been a major focus of basic science and clinical research into the pathophysiology of acute illness. However, mitochondria have multiple metabolic and signaling functions that may be central in both the expression of sepsis and its ultimate outcome. In this review, the authors address five primary questions centered on the role of mitochondria in sepsis. This review should be used both as a summary source in placing mitochondrial physiology within the context of acute illness and as a focal point for addressing new research into diagnostic and treatment opportunities these insights provide.

Vascular impairment as a pathological mechanism underlying long-lasting cognitive dysfunction after pediatric traumatic brain injury.

PubMed

Ichkova, Aleksandra; Rodriguez-Grande, Beatriz; Bar, Claire; Villega, Frederic; Konsman, Jan Pieter; Badaut, Jerome

2017-12-01

Traumatic brain injury (TBI) is the leading cause of death and disability in children. Indeed, the acute mechanical injury often evolves to a chronic brain disorder with long-term cognitive, emotional and social dysfunction even in the case of mild TBI. Contrary to the commonly held idea that children show better recovery from injuries than adults, pediatric TBI patients actually have worse outcome than adults for the same injury severity. Acute trauma to the young brain likely interferes with the fine-tuned developmental processes and may give rise to long-lasting consequences on brain's function. This review will focus on cerebrovascular dysfunction as an important early event that may lead to long-term phenotypic changes in the brain after pediatric TBI. These, in turn may be associated with accelerated brain aging and cognitive dysfunction. Finally, since no effective treatments are currently available, understanding the unique pathophysiological mechanisms of pediatric TBI is crucial for the development of new therapeutic options. Copyright © 2017 Elsevier Ltd. All rights reserved.

Impaired Pituitary Axes Following Traumatic Brain Injury

PubMed Central

Scranton, Robert A.; Baskin, David S.

2015-01-01

Pituitary dysfunction following traumatic brain injury (TBI) is significant and rarely considered by clinicians. This topic has received much more attention in the last decade. The incidence of post TBI anterior pituitary dysfunction is around 30% acutely, and declines to around 20% by one year. Growth hormone and gonadotrophic hormones are the most common deficiencies seen after traumatic brain injury, but also the most likely to spontaneously recover. The majority of deficiencies present within the first year, but extreme delayed presentation has been reported. Information on posterior pituitary dysfunction is less reliable ranging from 3%–40% incidence but prospective data suggests a rate around 5%. The mechanism, risk factors, natural history, and long-term effect of treatment are poorly defined in the literature and limited by a lack of standardization. Post TBI pituitary dysfunction is an entity to recognize with significant clinical relevance. Secondary hypoadrenalism, hypothyroidism and central diabetes insipidus should be treated acutely while deficiencies in growth and gonadotrophic hormones should be initially observed. PMID:26239686

Compliance-guided versus FiO2-driven positive-end expiratory pressure in patients with moderate or severe acute respiratory distress syndrome according to the Berlin definition.

PubMed

Pintado, M-C; de Pablo, R; Trascasa, M; Milicua, J-M; Sánchez-García, M

To study the effect of setting positive end-expiratory pressure (PEEP) in an individualized manner (based on highest static compliance) compared to setting PEEP according to FiO 2 upon mortality at 28 and 90 days, in patients with different severity acute respiratory distress syndrome (ARDS). A Spanish medical-surgical ICU. A post hoc analysis of a randomized controlled pilot study. Patients with ARDS. Ventilation with low tidal volumes and pressure limitation at 30cmH 2 O, randomized in two groups according to the method used to set PEEP: FiO 2 -guided PEEP group according to FiO 2 applied and compliance-guided group according to the highest compliance. Demographic data, risk factors and severity of ARDS, APACHE II and SOFA scores, daily Lung Injury Score, ventilatory measurements, ICU and hospital stay, organ failure and mortality at day 28 and 90 after inclusion. A total of 159 patients with ARDS were evaluated, but just 70 patients were included. Severe ARDS patients showed more organ dysfunction-free days at 28 days (12.83±10.70 versus 3.09±7.23; p=0.04) and at 90 days (6.73±22.31 vs. 54.17±42.14, p=0.03), and a trend toward lower 90-days mortality (33.3% vs. 90.9%, p=0.02), when PEEP was applied according to the best static compliance. Patients with moderate ARDS did not show these effects. In patients with severe ARDS, individualized PEEP selection based on the best static compliance was associated to lower mortality at 90 days, with an increase in organ dysfunction-free days at 28 and 90 days. Copyright © 2016 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

Nutrition: A Primary Therapy in Pediatric Acute Respiratory Distress Syndrome

PubMed Central

Wilson, Bryan; Typpo, Katri

2016-01-01

Appropriate nutrition is an essential component of intensive care management of children with acute respiratory distress syndrome (ARDS) and is linked to patient outcomes. One out of every two children in the pediatric intensive care unit (PICU) will develop malnutrition or have worsening of baseline malnutrition and present with specific micronutrient deficiencies. Early and adequate enteral nutrition (EN) is associated with improved 60-day survival after pediatric critical illness, and, yet, despite early EN guidelines, critically ill children receive on average only 55% of goal calories by PICU day 10. Inadequate delivery of EN is due to perceived feeding intolerance, reluctance to enterally feed children with hemodynamic instability, and fluid restriction. Underlying each of these factors is large practice variation between providers and across institutions for initiation, advancement, and maintenance of EN. Strategies to improve early initiation and advancement and to maintain delivery of EN are needed to improve morbidity and mortality from pediatric ARDS. Both, over and underfeeding, prolong duration of mechanical ventilation in children and worsen other organ function such that precise calorie goals are needed. The gut is thought to act as a “motor” of organ dysfunction, and emerging data regarding the role of intestinal barrier functions and the intestinal microbiome on organ dysfunction and outcomes of critical illness present exciting opportunities to improve patient outcomes. Nutrition should be considered a primary rather than supportive therapy for pediatric ARDS. Precise nutritional therapies, which are titrated and targeted to preservation of intestinal barrier function, prevention of intestinal dysbiosis, preservation of lean body mass, and blunting of the systemic inflammatory response, offer great potential for improving outcomes of pediatric ARDS. In this review, we examine the current evidence regarding dose, route, and timing of nutrition, current recommendations for provision of nutrition to children with ARDS, and the current literature for immune-modulating diets for pediatric ARDS. We will examine emerging data regarding the role of the intestinal microbiome in modulating the response to critical illness. PMID:27790606

Irritant vocal cord dysfunction at first misdiagnosed as reactive airway dysfunction syndrome.

PubMed

Galdi, Eugenia; Perfetti, Luca; Pagella, Fabio; Bertino, Giulia; Ferrari, Massimo; Moscato, Gianna

2005-06-01

This report describes a case of vocal cord dysfunction at first misdiagnosed as reactive airway dysfunction syndrome (RADS). A woman developed recurrent episodes of cough, dyspnea, and wheezing unresponsive to asthma therapy after irritant exposure to glutaraldehyde. Direct laryngoscopy was performed immediately after the induction of symptoms. Laryngoscopy showed a paradoxical adduction of the vocal cord on inspiration. Vocal cord dysfunction was diagnosed. A case of vocal cord dysfunction occurred after exposure to glutaraldhyde in a person with a history highly suggestive of RADS. Vocal cord dysfunction should always be considered in the differential diagnosis of patients with acute respiratory symptoms after exposure to irritants and with asthma-like symptoms that fail to respond to conventional asthma therapy.

Myocardial oedema as the sole marker of acute injury in Takotsubo cardiomyopathy: a cardiovascular magnetic resonance (CMR) study.

PubMed

Iacucci, Ilaria; Carbone, Iacopo; Cannavale, Giuseppe; Conti, Bettina; Iampieri, Ilaria; Rosati, Riccardo; Sardella, Gennaro; Frustaci, Andrea; Fedele, Francesco; Catalano, Carlo; Francone, Marco

2013-12-01

The main hallmark of Takotsubo cardiomyopathy (TT-CMP) is transient ischaemia, with completely reversible regional contractile dysfunction, which involves the mid-apical segments and shows no angiographic signs of coronary artery disease (CAD). The acute and reversible myocardial injury suggests that tissue oedema may be an important marker of disease. Seventeen patients with a clinical and angiographic diagnosis of TT-CMP underwent cardiovascular magnetic resonance (CMR) imaging in the acute phase and at follow-up after 4 months. A standard acquisition protocol including turbo spin echo (TSE) T2-weighted short-tau inversion-recovery (T2 STIR), steady-state free-precession cine (SSFP cine) and lateenhancement (LE) imaging after gadolinium benzyloxypropionic tetraacetic acid (Gd-BOPTA) administration was performed. All images were analysed, and data on oedema and LE were correlated with regional dysfunction and histological findings from endomyocardial biopsy (EMB) where available. In all patients, T2 STIR images showed a diffuse homogeneous hyperintensity that extended to all mid-apical segments and perfectly matched the area of regional dysfunction, reflecting tissue oedema. In the five patients who underwent EMB, histology confirmed the massive interstitial oedema associated with typical contraction-band necrosis. No cases of LE were observed. At follow-up, complete regression of oedema was observed in all cases, with significant recovery of regional and global left ventricular (LV) function (ejection fraction from 48.7% to 59.8%). Myocardial oedema on CMR is a characteristic feature of acute TT-CMP, which reflects acute inflammation and acute myocardial injury. It could therefore be used as a specific marker of disease severity.

Prevalence of multiple organ dysfunction in the pediatric intensive care unit: Pediatric Risk of Mortality III versus Pediatric Logistic Organ Dysfunction scores for mortality prediction

PubMed Central

Hamshary, Azza Abd Elkader El; Sherbini, Seham Awad El; Elgebaly, HebatAllah Fadel; Amin, Samah Abdelkrim

2017-01-01

Objectives To assess the frequency of primary multiple organ failure and the role of sepsis as a causative agent in critically ill pediatric patients; and calculate and evaluate the accuracy of the Pediatric Risk of Mortality III (PRISM III) and Pediatric Logistic Organ Dysfunction (PELOD) scores to predict the outcomes of critically ill children. Methods Retrospective study, which evaluated data from patients admitted from January to December 2011 in the pediatric intensive care unit of the Children's Hospital of the University of Cairo. Results Out of 237 patients in the study, 72% had multiple organ dysfunctions, and 45% had sepsis with multiple organ dysfunctions. The mortality rate in patients with multiple organ dysfunction was 73%. Independent risk factors for death were mechanical ventilation and neurological failure [OR: 36 and 3.3, respectively]. The PRISM III score was more accurate than the PELOD score in predicting death, with a Hosmer-Lemeshow X2 (Chi-square value) of 7.3 (df = 8, p = 0.5). The area under the curve was 0.723 for PRISM III and 0.78 for PELOD. Conclusion A multiple organ dysfunctions was associated with high mortality. Sepsis was the major cause. Pneumonia, diarrhea and central nervous system infections were the major causes of sepsis. PRISM III had a better calibration than the PELOD for prognosis of the patients, despite the high frequency of the multiple organ dysfunction syndrome. PMID:28977260

Aphasia and unilateral spatial neglect due to acute thalamic hemorrhage: clinical correlations and outcomes.

PubMed

Osawa, Aiko; Maeshima, Shinichiro

2016-04-01

Thalamic hemorrhages are associated with a variety of cognitive dysfunctions, and it is well known that such cognitive changes constitute a limiting factor of recovery of the activities of daily living (ADL). The relationship between cognitive dysfunction and hematomas is unclear. In this study, we investigated the relationship between aphasia/neglect and hematoma volume, hematoma type, and the ADL. One hundred fifteen patients with thalamic hemorrhage (70 men and 45 women) were studied. Their mean age was 68.9 ± 10.3 years, and patients with both left and right lesions were included. We calculated hematoma volume and examined the presence or absence of aphasia/neglect and the relationships between these dysfunctions and hematoma volume, hematoma type, and the ADL. Fifty-nine patients were found to have aphasia and 35 were found to have neglect. Although there was no relationship between hematoma type and cognitive dysfunction, hematoma volume showed a correlation with the severity of cognitive dysfunction. The ADL score and ratio of patient discharge for patients with aphasia/neglect were lower than those for patients without aphasia/neglect. We observed a correlation between the hematoma volume in thalamic hemorrhage and cognitive dysfunction. Aphasia/neglect is found frequently in patients with acute thalamic hemorrhage and may influence the ADL.

Changing Definitions of Sepsis

PubMed Central

Gül, Fethi; Arslantaş, Mustafa Kemal; Cinel, İsmail; Kumar, Anand

2017-01-01

Sepsis is one of the main causes of morbidity and mortality in critically ill patients despite the use of modern antibiotics and resuscitation therapies. Outcomes in sepsis have improved overall, probably because of an enhanced focus on early diagnosis and other improvements in supportive care, but mortality rates still remain unacceptably high. The diagnosis and definition of sepsis is a critical problem due to the heterogeneity of this disease process. Although it is apparent that much more needs to be done to advance our understanding, sepsis and related terms remain difficult to define. A 1991 consensus conference developed initial definitions that systemic inflammatory response syndrome (SIRS) to infection would be called sepsis. Definitions of sepsis and septic shock were revised in 2001 to incorporate the threshold values for organ damage. In early 2016, the new definitions of sepsis and septic shock have changed dramatically. Sepsis is now defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. The consensus document describes organ dysfunction as an acute increase in total Sequential Organ Failure Assessment (SOFA) score two points consequently to the infection. A significant change in the new definitions is the elimination of any mention of SIRS. The Sepsis-3 Task Force also introduced a new bedside index, called the qSOFA, to identify outside of critical care units patients with suspected infection who are likely to develop sepsis. Recently updated the consensus definitions improved specificity compared with the previous descriptions. PMID:28752002

Source localization of intermittent rhythmic delta activity in a patient with acute confusional migraine: cross-spectral analysis using standardized low-resolution brain electromagnetic tomography (sLORETA).

PubMed

Kim, Dae-Eun; Shin, Jung-Hyun; Kim, Young-Hoon; Eom, Tae-Hoon; Kim, Sung-Hun; Kim, Jung-Min

2016-01-01

Acute confusional migraine (ACM) shows typical electroencephalography (EEG) patterns of diffuse delta slowing and frontal intermittent rhythmic delta activity (FIRDA). The pathophysiology of ACM is still unclear but these patterns suggest neuronal dysfunction in specific brain areas. We performed source localization analysis of IRDA (in the frequency band of 1-3.5 Hz) to better understand the ACM mechanism. Typical IRDA EEG patterns were recorded in a patient with ACM during the acute stage. A second EEG was obtained after recovery from ACM. To identify source localization of IRDA, statistical non-parametric mapping using standardized low-resolution brain electromagnetic tomography was performed for the delta frequency band comparisons between ACM attack and non-attack periods. A difference in the current density maximum was found in the dorsal anterior cingulated cortex (ACC). The significant differences were widely distributed over the frontal, parietal, temporal and limbic lobe, paracentral lobule and insula and were predominant in the left hemisphere. Dorsal ACC dysfunction was demonstrated for the first time in a patient with ACM in this source localization analysis of IRDA. The ACC plays an important role in the frontal attentional control system and acute confusion. This dysfunction of the dorsal ACC might represent an important ACM pathophysiology.

Acute hypopituitarism complicating Russell's viper envenomation: case series and systematic review.

PubMed

Rajagopala, S; Thabah, M M; Ariga, K K; Gopalakrishnan, M

2015-09-01

Chronic hypopituitarism following Russell viper envenomation (RVE) is a rare but well-recognized syndrome. The clinical features, associations, management and outcomes of RVE associated-acute hypopituitarism (AHP) are not well described. To describe the clinical features, intensive care unit (ICU) management and outcomes of a series of patients with RVE-AHP and identify the clinical associations of RVE-AHP. We describe a series of patients with prospectively identified AHP related to RVE and describe our findings comparing RVE with and without AHP and a systematic search of literature on AHP related to RVE. We identified nine cases of AHP related to RVE. Unexplained hypoglycemia (100%) and hypotension (66.7%) were the most common findings at presentation. AHP occurred after a median of 9 (range, 2-14) days after severe envenomation and was associated with multi-organ dysfunction, lower platelet counts, more bleeding and transfusions when compared to patients with RVE alone. The presence of clinically defined capillary leak syndrome, disseminated intravascular coagulation and mortality were not different from those without AHP. Our systematic search yielded 12 cases of AHP related to RVE; data on associated clinical manifestations, therapy and ASV administration were not available in most reports. AHP is a very rare complication of RVE. Unexplained hypoglycemia and hypotension should prompt evaluation for AHP in RVE. AHP is associated with severe RVE, multi-organ dysfunction, bleeding and need for transfusion. Prompt treatment with steroids may reduce mortality related to AHP in RVE. © The Author 2015. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Factors involved in the paradox of reverse epidemiology.

PubMed

Martín-Ponce, Esther; Santolaria, Francisco; Alemán-Valls, María-Remedios; González-Reimers, Emilio; Martínez-Riera, Antonio; Rodríguez-Gaspar, Melchor; Rodríguez-Rodríguez, Eva

2010-08-01

The hypothesis of reverse epidemiology holds that some cardiovascular risk factors, such as obesity, hypercholesterolemia and hypertension, in the elderly or in some chronic diseases are not harmful but permit better survival. However, this phenomenon is controversial and the underlying reasons are poorly understood. To search for factors simultaneously linked to reverse epidemiology and to short or long term survival. We included 400 patients, older than 60 years, hospitalized in a general internal medicine unit; 61 died in hospital and 338 were followed up by telephone. Obesity, higher blood pressure and serum cholesterol, besides being related to lower mortality both in hospital and after discharge, were associated with better nutrition and functional capacity, less intense acute phase reaction and organ dysfunction, and lower incidence of high-mortality diseases such as dementia, pneumonia, sepsis or cancer. These associations may explain why obesity and other reverse epidemiology data are inversely related to mortality. Weight loss was related to mortality independently of BMI. Patients with BMI under 30 kg/m(2) who died in hospital showed more weight loss than those who survived; the lower the BMI, the greater the weight loss. In contrast, patients with BMI over 30 kg/m(2) who died in hospital gained more weight than those who survived; the higher the BMI, the greater the weight gain. In patients over 60 years of age admitted to an internal medicine ward, obesity did not show independent survival value, being displaced by other nutritional parameters, functional capacity, acute phase reaction, organ dysfunction and diseases with poor prognosis. Copyright 2009 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

A Two-Biomarker Model Predicts Mortality in the Critically Ill with Sepsis.

PubMed

Mikacenic, Carmen; Price, Brenda L; Harju-Baker, Susanna; O'Mahony, D Shane; Robinson-Cohen, Cassianne; Radella, Frank; Hahn, William O; Katz, Ronit; Christiani, David C; Himmelfarb, Jonathan; Liles, W Conrad; Wurfel, Mark M

2017-10-15

Improving the prospective identification of patients with systemic inflammatory response syndrome (SIRS) and sepsis at low risk for organ dysfunction and death is a major clinical challenge. To develop and validate a multibiomarker-based prediction model for 28-day mortality in critically ill patients with SIRS and sepsis. A derivation cohort (n = 888) and internal test cohort (n = 278) were taken from a prospective study of critically ill intensive care unit (ICU) patients meeting two of four SIRS criteria at an academic medical center for whom plasma was obtained within 24 hours. The validation cohort (n = 759) was taken from a prospective cohort enrolled at another academic medical center ICU for whom plasma was obtained within 48 hours. We measured concentrations of angiopoietin-1, angiopoietin-2, IL-6, IL-8, soluble tumor necrosis factor receptor-1, soluble vascular cell adhesion molecule-1, granulocyte colony-stimulating factor, and soluble Fas. We identified a two-biomarker model in the derivation cohort that predicted mortality (area under the receiver operator characteristic curve [AUC], 0.79; 95% confidence interval [CI], 0.74-0.83). It performed well in the internal test cohort (AUC, 0.75; 95% CI, 0.65-0.85) and the external validation cohort (AUC, 0.77; 95% CI, 0.72-0.83). We determined a model score threshold demonstrating high negative predictive value (0.95) for death. In addition to a low risk of death, patients below this threshold had shorter ICU length of stay, lower incidence of acute kidney injury, acute respiratory distress syndrome, and need for vasopressors. We have developed a simple, robust biomarker-based model that identifies patients with SIRS/sepsis at low risk for death and organ dysfunction.

Concise Review: Mesenchymal Stem (Stromal) Cells: Biology and Preclinical Evidence for Therapeutic Potential for Organ Dysfunction Following Trauma or Sepsis.

PubMed

Matthay, Michael A; Pati, Shibani; Lee, Jae-Woo

2017-02-01

Several experimental studies have provided evidence that bone-marrow derived mesenchymal stem (stromal) cells (MSC) may be effective in treating critically ill surgical patients who develop traumatic brain injury, acute renal failure, or the acute respiratory distress syndrome. There is also preclinical evidence that MSC may be effective in treating sepsis-induced organ failure, including evidence that MSC have antimicrobial properties. This review considers preclinical studies with direct relevance to organ failure following trauma, sepsis or major infections that apply to critically ill patients. Progress has been made in understanding the mechanisms of benefit, including MSC release of paracrine factors, transfer of mitochondria, and elaboration of exosomes and microvesicles. Regardless of how well they are designed, preclinical studies have limitations in modeling the complexity of clinical syndromes, especially in patients who are critically ill. In order to facilitate translation of the preclinical studies of MSC to critically ill patients, there will need to be more standardization regarding MSC production with a focus on culture methods and cell characterization. Finally, well designed clinical trials will be needed in critically ill patient to assess safety and efficacy. Stem Cells 2017;35:316-324. © 2016 AlphaMed Press.

Acute hepatitis E in a renal transplantation recipient: a case report.

PubMed

Shindo, Mitsutoshi; Takemae, Hiroaki; Kubo, Takafumi; Soeno, Masatsugu; Ando, Tetsuo; Morishita, Yoshiyuki

2018-01-01

Hepatitis E is caused by infection with the hepatitis E virus (HEV). HEV is transmitted orally via HEV-contaminated food or drink. Hepatitis E usually shows mild symptoms and is self-limiting in the general population; however, it may progress to chronic hepatitis in immunosuppressed patients such as recipients of organ transplantation. However, a few cases of acute hepatitis E have been reported in organ transplantation recipients. We herein report a case of acute hepatitis E in a 31-year-old male renal transplant recipient. The patient underwent renal transplantation 2 years ago, and his postoperative course was uneventful without rejection. After complaining of general fatigue and low-grade fever for 1 week, he was referred to and admitted to our hospital. Careful interview revealed that he ate undercooked pork 10 weeks prior. Blood analysis revealed liver dysfunction but was serologically negative for hepatitis A, B and C virus, cytomegalovirus infection and collagen diseases. Immunoglobulin A antibody against hepatitis E virus (HEV-IgA) was also negative at that point. After 2 weeks of admission, HEV-IgA and HEV-RNA were measured again as hepatitis E could not be ruled out due to history of ingestion of undercooked meat that may have been contaminated with HEV. At that time, HEV-IgA and HEV-RNA (genotype 3) were positive. Thus, an acute hepatitis E was diagnosed. His liver function gradually improved to within the normal range, and HEV-IgA and HEV-RNA were negative at 11 weeks after admission. In conclusion, we describe here a case of acute hepatitis E in a renal transplant recipient. Careful interview regarding the possibility of ingestion of HEV-contaminated food and repeated measurements of HEV-IgA were helpful in finalizing a diagnosis.

An Evaluation of the Usefulness of Extracorporeal Liver Support Techniques in Patients Hospitalized in the ICU for Severe Liver Dysfunction Secondary to Alcoholic Liver Disease

PubMed Central

Piechota, Mariusz; Piechota, Anna

2016-01-01

Background The mortality rate in patients with severe liver dysfunction secondary to alcoholic liver disease (ALD) who do not respond to the standard treatment is exceptionally high. Objectives The main aim of this study was to evaluate the usefulness of applying extracorporeal liver support techniques to treat this group of patients. Patients and Methods The data from 23 hospital admissions of 21 patients with ALD who were admitted to the department of anesthesiology and intensive therapy (A&IT) at the Dr Wł. Biegański Regional Specialist Hospital in Łódź between March 2013 and July 2015 were retrospectively analyzed. Results A total of 111 liver dialysis procedures were performed during the 23 hospitalizations, including 13 dialyses using fractionated plasma separation and adsorption (FPSA) with the Prometheus® system, and 98 procedures using the single pass albumin dialysis (SPAD) system. Upon admission to the intensive care unit (ICU), the median (interquartile range [IQR]) Glasgow coma scale (GCS), sequential organ failure assessment (SOFA), acute physiology and chronic health evaluation (APACHE) II, and simplified acute physiology score (SAPS) II scores were 15 (14 - 15), 9 (7 - 13), 17 (14 - 24), and 32 (22 - 50), respectively. The ICU, 30-day, and three-month mortality rates were 43.48%, 39.13%, and 73.91%, respectively. As determined by the receiver operative characteristic (ROC) analysis for single-factor models, the significant predictors of death in the ICU included the patients’ SOFA, APACHE II, SAPS II, and model of end-stage liver disease modified by the united network for organ sharing (MELD UNOS Modification) scores; the duration of stay (in days) in the A&IT Department; and bile acid, creatinine and albumin levels upon ICU admission. The ROC analysis indicated the significant discriminating power of the SOFA, APACHE II, SAPS II, and MELD UNOS modification scores on the three-month mortality rate. Conclusions The application of extracorporeal liver support techniques in patients with severe liver dysfunction secondary to ALD appears justified in the subset of patients with MELD UNOS Modification scores of 18 - 30. PMID:27642344

Interventional Treatment of Abdominal Compartment Syndrome during Severe Acute Pancreatitis: Current Status and Historical Perspective.

PubMed

Radenkovic, Dejan V; Johnson, Colin D; Milic, Natasa; Gregoric, Pavle; Ivancevic, Nenad; Bezmarevic, Mihailo; Bilanovic, Dragoljub; Cijan, Vladimir; Antic, Andrija; Bajec, Djordje

2016-01-01

Abdominal compartment syndrome (ACS) in patients with severe acute pancreatitis (SAP) is a marker of severe disease. It occurs as combination of inflammation of retroperitoneum, visceral edema, ascites, acute peripancreatic fluid collections, paralytic ileus, and aggressive fluid resuscitation. The frequency of ACS in SAP may be rising due to more aggressive fluid resuscitation, a trend towards conservative treatment, and attempts to use a minimally invasive approach. There remains uncertainty about the most appropriate surgical technique for the treatment of ACS in SAP. Some unresolved questions remain including medical treatment, indications, timing, and interventional techniques. This review will focus on interventional treatment of this serious condition. First line therapy is conservative treatment aiming to decrease IAP and to restore organ dysfunction. If nonoperative measures are not effective, early abdominal decompression is mandatory. Midline laparostomy seems to be method of choice. Since it carries significant morbidity we need randomized studies to establish firm advantages over other described techniques. After ACS resolves efforts should be made to achieve early primary fascia closure. Additional data are necessary to resolve uncertainties regarding ideal timing and indication for operative treatment.

Determinants of 1-year survival in critically ill acute leukemia patients: a GRRR-OH study.

PubMed

Tavares, Márcio; Lemiale, Virginie; Mokart, Djamel; Pène, Frédéric; Lengliné, Etienne; Kouatchet, Achille; Mayaux, Julien; Vincent, François; Nyunga, Martine; Bruneel, Fabrice; Rabbat, Antoine; Lebert, Christine; Perez, Pierre; Meert, Anne-Pascale; Benoit, Dominique; Darmon, Michael; Azoulay, Elie

2018-06-01

Acute leukemia (AL) is the most common hematological malignancy requiring intensive care unit (ICU) management. Data on long-term survival are limited. This is a post hoc analysis of the prospective multicenter data from France and Belgium: A Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique [A Research Group on Acute Respiratory Failure in Onco-Hematological Patients (French)] Study, to identify determinants of 1-year survival in critically ill AL patients. A total of 278 patients were admitted in the 17 participating ICUs. Median age was 58 years and 70% had newly diagnosed leukemia. ICU mortality rate was 28.6 and 39.6% of the patients alive at 1 year. Admission for intensive monitoring was independently associated with better 1-year survival by multivariate analysis. Conversely, relapsed/refractory disease, secondary leukemia, mechanical ventilation and renal replacement therapy were independently associated with 1-year mortality. This study confirms the impact of organ dysfunction on long-term survival in ICU patients with AL. Follow-up studies to assess respiratory and renal recovery are warranted.

The impact of duration of organ dysfunction on the outcome of patients with severe sepsis and septic shock.

PubMed

Freitas, Flávio G R; Salomão, Reinaldo; Tereran, Nathalia; Mazza, Bruno Franco; Assunção, Murillo; Jackiu, Mirian; Fernandes, Haggeas; Machado, Flávia Ribeiro

2008-08-01

This study aimed to assess the impact of the duration of organ dysfunction on the outcome of patients with severe sepsis or septic shock. Clinical data were collected from hospital charts of patients with severe sepsis and septic shock admitted to a mixed intensive care unit from November 2003 to February 2004. The duration of organ dysfunction prior to diagnosis was correlated with mortality. Results were considered significant if p<0.05. Fifty-six patients were enrolled. Mean age was 55.6+/-20.7 years, mean APACHE II score was 20.6+/-6.9, and mean SOFA score was 7.9+/-3.7. Thirty-six patients (64.3%) had septic shock. The mean duration of organ dysfunction was 1.9+/-1.9 days. Within the univariate analysis, the variables correlated with hospital mortality were: age (p=0.015), APACHE II (p=0.008), onset outside the intensive care unit (p=0.05), blood glucose control (p=0.05) and duration of organ dysfunction (p=0.0004). In the multivariate analysis, only a duration of organ dysfunction persisting longer than 48 hours correlated with mortality (p=0.004, OR: 8.73 (2.37-32.14)), whereas the APACHE II score remained only a slightly significant factor (p=0.049, OR: 1.11 (1.00-1.23)). Patients who received therapeutic interventions within the first 48 hours after the onset of organ dysfunction exhibited lower mortality (32.1% vs. 82.1%, p=0.0001). These findings suggest that the diagnosis of organ dysfunction is not being made in a timely manner. The time elapsed between the onset of organ dysfunction and initiation of therapeutic intervention can be quite long, and this represents an important determinant of survival in cases of severe sepsis and septic shock.

Endothelium-derived contracting factors mediate the Ang II-induced endothelial dysfunction in the rat aorta: preventive effect of red wine polyphenols.

PubMed

Kane, Modou O; Etienne-Selloum, Nelly; Madeira, Soccoro V F; Sarr, Mamadou; Walter, Allison; Dal-Ros, Stéphanie; Schott, Christa; Chataigneau, Thierry; Schini-Kerth, Valérie B

2010-04-01

Angiotensin II (Ang II)-induced hypertension is associated with vascular oxidative stress and an endothelial dysfunction. This study examined the role of reactive oxygen species (ROS) and endothelium-derived contracting factors in Ang II-induced endothelial dysfunction and whether these effects are prevented by red wine polyphenols (RWPs), a rich source of natural antioxidants. Rats were infused with Ang II for 14 days. RWPs were administered in the drinking water 1 week before and during the Ang II infusion. Arterial pressure was measured in conscious rats. Vascular reactivity was assessed in organ chambers and cyclooxygenase-1 (COX-1) and COX-2 expression by Western blot and immunofluorescence analyses. Ang II-induced hypertension was associated with blunted endothelium-dependent relaxations and induction of endothelium-dependent contractions in the presence of nitro-L-arginine in response to acetylcholine (Ach). These effects were not affected by the combination of membrane permeant analogs of superoxide dismutase and catalase but were abolished by the thromboxane A(2) (TP) receptor antagonist GR32191B and the COX-2 inhibitor NS-398. The COX-1 inhibitor SC-560 also prevented contractile responses to Ach. Ang II increased the expression of COX-1 and COX-2 in the aortic wall. RWPs prevented Ang II-induced hypertension, endothelial dysfunction, and upregulation of COX-1 and COX-2. Thus, Ang II-induced endothelial dysfunction cannot be explained by an acute formation of ROS reducing the bioavailability of nitric oxide but rather by COX-dependent formation of contracting factors acting on TP receptors. RWPs are able to prevent the Ang II-induced endothelial dysfunction mostly due to their antioxidant properties.

Prospective investigation of pituitary functions in patients with acute infectious meningitis: is acute meningitis induced pituitary dysfunction associated with autoimmunity?

PubMed

Tanriverdi, F; De Bellis, A; Teksahin, H; Alp, E; Bizzarro, A; Sinisi, A A; Bellastella, G; Paglionico, V A; Bellastella, A; Unluhizarci, K; Doganay, M; Kelestimur, F

2012-12-01

Previous case reports and retrospective studies suggest that pituitary dysfunction may occur after acute bacterial or viral meningitis. In this prospective study we assessed the pituitary functions, lipid profile and anthropometric measures in adults with acute bacterial or viral meningitis. Moreover, in order to investigate whether autoimmune mechanisms could play a role in the pathogenesis of acute meningitis-induced hypopituitarism we also investigated the anti-pituitary antibodies (APA) and anti-hypothalamus antibodies (AHA) prospectively. Sixteen patients (10 males, 6 females; mean ± SD age 40.9 ± 15.9) with acute infectious meningitis were included and the patients were evaluated in the acute phase, and at 6 and 12 months after the acute meningitis. In the acute phase 18.7% of the patients had GH deficiency, 12.5% had ACTH and FSH/LH deficiencies. At 12 months after acute meningitis 6 of 14 patients (42.8%) had GH deficiency, 1 of 14 patients (7.1%) had ACTH and FSH/LH deficiencies. Two of 14 patients (14.3%) had combined hormone deficiencies and four patients (28.6%) had isolated hormone deficiencies at 12 months. Four of 9 (44.4%) hormone deficiencies at 6 months were recovered at 12 months, and 3 of 8 (37.5%) hormone deficiencies at 12 months were new-onset hormone deficiencies. At 12 months there were significant negative correlations between IGF-I level vs. LDL-C, and IGF-I level vs. total cholesterol. The frequency of AHA and APA positivity was substantially high, ranging from 35 to 50% of the patients throughout the 12 months period. However there were no significant correlations between AHA or APA positivity and hypopituitarism. The risk of hypopituitarism, GH deficiency in particular, is substantially high in the acute phase, after 6 and 12 months of the acute infectious meningitis. Moreover we found that 6th month after meningitis is too early to make a decision for pituitary dysfunction and these patients should be screened for at least 12 months. In addition, the occurrence of AHA and APA positivity due to acute infectious meningitis was demonstrated for the first time. Further longer-term prospective investigations need to be carried out on a larger cohort of patients to understand the role of autoimmunity in the pathogenesis of late hypopituitarism after acute infectious meningitis.

Kynurenine–3–monooxygenase inhibition prevents multiple organ failure in rodent models of acute pancreatitis

PubMed Central

Mole, Damian J; Webster, Scott P; Uings, Iain; Zheng, Xiaozhong; Binnie, Margaret; Wilson, Kris; Hutchinson, Jonathan P; Mirguet, Olivier; Walker, Ann; Beaufils, Benjamin; Ancellin, Nicolas; Trottet, Lionel; Bénéton, Véronique; Mowat, Christopher G; Wilkinson, Martin; Rowland, Paul; Haslam, Carl; McBride, Andrew; Homer, Natalie ZM; Baily, James E; Sharp, Matthew GF; Garden, O James; Hughes, Jeremy; Howie, Sarah EM; Holmes, Duncan S; Liddle, John; Iredale, John P

2015-01-01

Acute pancreatitis (AP) is a common and devastating inflammatory condition of the pancreas that is considered to be a paradigm of sterile inflammation leading to systemic multiple organ dysfunction syndrome (MODS) and death1,2 Acute mortality from AP-MODS exceeds 20%3 and for those who survive the initial episode, their lifespan is typically shorter than the general population4. There are no specific therapies available that protect individuals against AP-MODS. Here, we show that kynurenine-3-monooxygenase (KMO), a key enzyme of tryptophan metabolism5, is central to the pathogenesis of AP-MODS. We created a mouse strain deficient for Kmo with a robust biochemical phenotype that protected against extrapancreatic tissue injury to lung, kidney and liver in experimental AP-MODS. A medicinal chemistry strategy based on modifications of the kynurenine substrate led to the discovery of GSK180 as a potent and specific inhibitor of KMO. The binding mode of the inhibitor in the active site was confirmed by X-ray co-crystallography at 3.2 Å resolution. Treatment with GSK180 resulted in rapid changes in levels of kynurenine pathway metabolites in vivo and afforded therapeutic protection against AP-MODS in a rat model of AP. Our findings establish KMO inhibition as a novel therapeutic strategy in the treatment of AP-MODS and open up a new area for drug discovery in critical illness. PMID:26752518

Acute-on-chronic liver failure: Pathogenesis, prognostic factors and management

PubMed Central

Blasco-Algora, Sara; Masegosa-Ataz, José; Gutiérrez-García, María Luisa; Alonso-López, Sonia; Fernández-Rodríguez, Conrado M

2015-01-01

Acute-on-chronic liver failure (ACLF) is increasingly recognized as a complex syndrome that is reversible in many cases. It is characterized by an acute deterioration of liver function in the background of a pre-existing chronic liver disease often associated with a high short-term mortality rate. Organ failure (OF) is always associated, and plays a key role in determining the course, and the outcome of the disease. The definition of ACLF remains controversial due to its overall ambiguity, with several disparate criteria among various associations dedicated to the study of liver diseases. Although the precise pathogenesis needs to be clarified, it appears that an altered host response to injury might be a contributing factor caused by immune dysfunction, ultimately leading to a pro-inflammatory status, and eventually to OF. The PIRO concept (Predisposition, Insult, Response and Organ Failure) has been proposed to better approach the underlying mechanisms. It is accepted that ACLF is a different and specific form of liver failure, where a precipitating event is always involved, even though it cannot always be ascertained. According to several studies, infections and active alcoholism often trigger ACLF. Viral hepatitis, gastrointestinal haemorrhage, or drug induced liver injury, which can also provoke the syndrome. This review mainly focuses on the physiopathology and prognostic aspects. We believe these features are essential to further understanding and providing the rationale for improveddisease management strategies. PMID:26576097

Evaluation and Management of Right-Sided Heart Failure: A Scientific Statement From the American Heart Association.

PubMed

Konstam, Marvin A; Kiernan, Michael S; Bernstein, Daniel; Bozkurt, Biykem; Jacob, Miriam; Kapur, Navin K; Kociol, Robb D; Lewis, Eldrin F; Mehra, Mandeep R; Pagani, Francis D; Raval, Amish N; Ward, Carey

2018-05-15

The diverse causes of right-sided heart failure (RHF) include, among others, primary cardiomyopathies with right ventricular (RV) involvement, RV ischemia and infarction, volume loading caused by cardiac lesions associated with congenital heart disease and valvular pathologies, and pressure loading resulting from pulmonic stenosis or pulmonary hypertension from a variety of causes, including left-sided heart disease. Progressive RV dysfunction in these disease states is associated with increased morbidity and mortality. The purpose of this scientific statement is to provide guidance on the assessment and management of RHF. The writing group used systematic literature reviews, published translational and clinical studies, clinical practice guidelines, and expert opinion/statements to summarize existing evidence and to identify areas of inadequacy requiring future research. The panel reviewed the most relevant adult medical literature excluding routine laboratory tests using MEDLINE, EMBASE, and Web of Science through September 2017. The document is organized and classified according to the American Heart Association to provide specific suggestions, considerations, or reference to contemporary clinical practice recommendations. Chronic RHF is associated with decreased exercise tolerance, poor functional capacity, decreased cardiac output and progressive end-organ damage (caused by a combination of end-organ venous congestion and underperfusion), and cachexia resulting from poor absorption of nutrients, as well as a systemic proinflammatory state. It is the principal cause of death in patients with pulmonary arterial hypertension. Similarly, acute RHF is associated with hemodynamic instability and is the primary cause of death in patients presenting with massive pulmonary embolism, RV myocardial infarction, and postcardiotomy shock associated with cardiac surgery. Functional assessment of the right side of the heart can be hindered by its complex geometry. Multiple hemodynamic and biochemical markers are associated with worsening RHF and can serve to guide clinical assessment and therapeutic decision making. Pharmacological and mechanical interventions targeting isolated acute and chronic RHF have not been well investigated. Specific therapies promoting stabilization and recovery of RV function are lacking. RHF is a complex syndrome including diverse causes, pathways, and pathological processes. In this scientific statement, we review the causes and epidemiology of RV dysfunction and the pathophysiology of acute and chronic RHF and provide guidance for the management of the associated conditions leading to and caused by RHF. © 2018 American Heart Association, Inc.

Recurrence of clinically significant hepatitis A following liver transplantation for fulminant hepatitis A.

PubMed

Eisenbach, Christoph; Longerich, Thomas; Fickenscher, Helmut; Schalasta, Gunnar; Stremmel, Wolfgang; Encke, Jens

2006-01-01

We report hepatitis A virus (HAV) infection of a liver allograft following transplantation for fulminant liver failure due to HAV infection. This rare condition has been described in only three patients to date. After liver transplantation allograft function was good, but starting 80 days after transplantation, episodes of acute graft dysfunction were observed. To elucidate the reason for acute hepatic dysfunction a large number of differential diagnoses were tested. HAV RNA was undetectable for more than 80 days after transplantation. Detection of genomic HAV RNA by RT-PCR in serum and stool at the time of graft dysfunction led to the diagnosis of recurrent HAV infection. We suggest that the risk of HAV reinfection after liver transplantation may be far higher than expected as results may be misinterpreted as rejection episodes.

[Acute left ventricular systolic dysfunction after pericardial effusion drainage].

PubMed

Brauner, F B; Nunes, C E; Fabra, R; Riesgo, A; Thomé, L G

1997-12-01

A patient with a thymoma and initially normal ventricular systolic function developed cardiac tamponade, which was relieved by pericardiocentesis. After four days, the tumor was removed and, one week after the relief of tamponade, she developed severe left ventricular systolic dysfunction, that recovered in three days with venous therapy.

The Effect of Intermittent Noise Stress on Ozone-Induced Cardiovascular Dysfunction in Wistar-Kyoto Rats

EPA Science Inventory

Previous studies have established that acute exposure to air pollution increases the risk of cardiovascular dysfunction. Intrinsic factors are likely the most important determinants of how the body responds to an exposure. But data also suggests that non-environmental stressors l...

Risk Factors for Multiple Organ Dysfunction Syndrome in Severe Stroke Patients

PubMed Central

Yang, Shuna; Li, Yue; Yuan, Junliang; Yang, Lei; Li, Shujuan; Hu, Wenli

2016-01-01

Background Severe stroke patients have poor clinical outcome which may be associated with development of multiple organ dysfunction syndrome (MODS). Therefore, the aim of our study was to investigate independent risk factors for development of MODS in severe stroke patients. Methods Ninety seven severe stroke patients were prospective recruited from Jan 2011 to Jun 2015. The development of MODS was identified by Sequential Organ Failure Assessment (SOFA) score (score ≥ 3, at least two organs), which was assessed on day 1, 4, 7, 10 and 14 after admission. Baseline characteristics, Acute Physiology and Chronic Health Evaluation (APACHE) II score, Glasgow coma score (GCS) and cerebral imaging parameters were collected at admission. Cox regression was performed to determine predictors for the development of MODS. Medical complications after admission and in-hospital mortality were also investigated. Results 33 (34%) patients were in MODS group and 64 (66%) were in non-MODS group within 14 days after admission. Patients in MODS group had more smoker (51.5% vs 28.1%, p = 0.023), higher NIHSS score (23.48 ± 6.12 vs 19.81 ± 4.83, p = 0.004), higher APACHE II score (18.70 ± 5.18 vs 15.64 ± 4.36, p = 0.003) and lower GCS score (6.33 ± 2.48 vs 8.14 ± 2.73, p = 0.002). They also had higher rate of infarction in multi vascular territories (36.4% vs 10.9%, p = 0.003). The most common complication in all patients was pulmonary infection, while complication scores were comparable between two groups. Patients with MODS had higher in-hospital mortality (69.7% vs 9.4%, p = 0.000). In Cox regression, NIHSS score (RR = 1.084, 95% CI 1.019–1.153) and infarction in multi vascular territories (RR = 2.345 95% CI 1.105–4.978) were independent risk factors for development of MODS. Conclusions In acute phase of stroke, NIHSS score and infarction in multi vascular territories predicted MODS in severe stroke patients. Moreover, patients with MODS had higher in-hospital mortality, suggesting that early identification of MODS is critical important. PMID:27893797

Hypoglycaemia and hypoxic-ischaemic encephalopathy.

PubMed

Boardman, James P; Hawdon, Jane M

2015-04-01

The transition from fetal to neonatal life requires metabolic adaptation to ensure that energy supply to vital organs and systems is maintained after separation from the placental circulation. Under normal conditions, this is achieved through the mobilization and use of alternative cerebral fuels (fatty acids, ketone bodies, and lactate) when blood glucose concentration falls. Severe hypoxia-ischaemia is associated with impaired metabolic adaptation, and animal and human data suggest that levels of hypoglycaemia that are tolerated under normal conditions can be harmful in association with hypoxia-ischaemia. The optimal target blood glucose level for ensuring adequate energy provision in hypoxic-ischaemic encephalopathy (HIE) remains unknown. However, recent data support guidance to maintain a blood glucose concentration of 2.5 mmol/L or more in neonates with signs of acute neurological dysfunction, which includes those with HIE, and this is higher than the accepted threshold of 2 mmol/L in infants without signs of neurological dysfunction or hyperinsulinism. © The Authors. Journal compilation © 2015 Mac Keith Press.

Septic Pulmonary Embolism Requiring Critical Care: Clinicoradiological Spectrum, Causative Pathogens and Outcomes

PubMed Central

Chou, Deng-Wei; Wu, Shu-Ling; Chung, Kuo-Mou; Han, Shu-Chen; Cheung, Bruno Man-Hon

2016-01-01

OBJECTIVES: Septic pulmonary embolism is an uncommon but life-threatening disorder. However, data on patients with septic pulmonary embolism who require critical care have not been well reported. This study elucidated the clinicoradiological spectrum, causative pathogens and outcomes of septic pulmonary embolism in patients requiring critical care. METHODS: The electronic medical records of 20 patients with septic pulmonary embolism who required intensive care unit admission between January 2005 and December 2013 were reviewed. RESULTS: Multiple organ dysfunction syndrome developed in 85% of the patients, and acute respiratory failure was the most common organ failure (75%). The most common computed tomographic findings included a feeding vessel sign (90%), peripheral nodules without cavities (80%) or with cavities (65%), and peripheral wedge-shaped opacities (75%). The most common primary source of infection was liver abscess (40%), followed by pneumonia (25%). The two most frequent causative pathogens were Klebsiella pneumoniae (50%) and Staphylococcus aureus (35%). Compared with survivors, nonsurvivors had significantly higher serum creatinine, arterial partial pressure of carbon dioxide, and Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores, and they were significantly more likely to have acute kidney injury, disseminated intravascular coagulation and lung abscesses. The in-hospital mortality rate was 30%. Pneumonia was the most common cause of death, followed by liver abscess. CONCLUSIONS: Patients with septic pulmonary embolism who require critical care, especially those with pneumonia and liver abscess, are associated with high mortality. Early diagnosis, appropriate antibiotic therapy, surgical intervention and respiratory support are essential. PMID:27759843

[Clinical effect of compound monoammonium glycyrrhizinate combined with dandelion in treatment of acute paraquat poisoning].

PubMed

Zhao, Y; Jian, X D

2016-07-20

Objective: To investigate the clinical effect of compound monoammonium glycyrrhizinate combined with dandelion in the treatment of acute paraquat poisoning. Methods: A total of 80 patients with acute paraquat poisoning who were admitted to our hospital were enrolled as study subjects and randomly divided into routine treatment group (38 patients) and traditional Chinese medicine (TCM) group (42 patients) . The patients in the TCM group were given compound monoammonium glycyrrhizinate and dandelion in addition to the treatment in the control group. Serum alanine aminotransferase (ALT) , total bilirubin (TBil) , blood urea nitrogen (BUN) , creatinine (Cr) , and arterial blood lactate (Lac) and partial pressure of oxygen (PaO 2 ) during different time periods on day 3, 7, and 9 of treatment were observed in both groups, and ulceration of oral mucosa, pulmonary fibrosis, multiple organ dysfunction syndrome (MODS) , and mortality were compared between the two groups. Results: On days 3, 7, and 9 of treatment, the routine treatment group had significantly higher serum ALT, TBil, BUN, Cr, and arterial blood Lac than the TCM group. The routine treatment group had significantly lower arterial blood PaO 2 than the TCM group, while the TCM group had significantly lower incidence rates of ulceration of oral mucosa, pulmonary fibrosis, and MODS and a significantly lower mortality rate than the routine treatment group ( P <0.05) . Conclusion: In the treatment of patients with acute paraquat poisoning, compound monoammonium glycyrrhizinate combined with dandelion can effectively improve organ function, reduce the incidence of pulmonary fibrosis and MODS, improve the healing rate of oral ulcer, improve prognosis, and reduce mortality rate.

Abnormal permeability of inner and outer mitochondrial membranes contributes independently to mitochondrial dysfunction in the liver during acute endotoxemia.

PubMed

Crouser, Elliott D; Julian, Mark W; Huff, Jennifer E; Joshi, Mandar S; Bauer, John A; Gadd, Martha E; Wewers, Mark D; Pfeiffer, Douglas R

2004-02-01

This study was designed to determine the role played by the mitochondrial permeability transition in the pathogenesis of mitochondrial damage and dysfunction in a representative systemic organ during the acute phase of endotoxemia. A well-established, normotensive feline model was employed to determine whether pretreatment with cyclosporine A, a potent inhibitor of the mitochondrial permeability transition, normalizes mitochondrial ultrastructural injury and dysfunction in the liver during acute endotoxemia. The Ohio State University Medical Center research laboratory. Random source, adult, male conditioned cats. Hemodynamic resuscitation and maintenance of acid-base balance and tissue oxygen availability were provided, as needed, to minimize the potentially confounding effects of tissue hypoxia and/or acidosis on the experimental results. Treatment groups received isotonic saline vehicle (control; n = 6), lipopolysaccharide (3.0 mg/kg, intravenously; n = 8), or cyclosporine A (6.0 mg/kg, intravenously; n = 6) or tacrolimus (FK506, 0.1 mg/kg, intravenously; n = 4) followed in 30 mins by lipopolysaccharide (3.0 mg/kg, intravenously). Liver samples were obtained 4 hrs posttreatment, and mitochondrial ultrastructure, function, and cytochrome c, Bax, and ceramide contents were assessed. As expected, significant mitochondrial injury was apparent in the liver 4 hrs after lipopolysaccharide treatment, despite maintenance of regional tissue oxygen availability. Namely, mitochondria demonstrated high-amplitude swelling and exhibited altered respiratory function. Cyclosporine A pretreatment attenuated lipopolysaccharide-induced mitochondrial ultrastructural abnormalities and normalized mitochondrial respiratory control, reflecting protection against inner mitochondrial membrane damage. However, an abnormal permeability of outer mitochondrial membranes to cytochrome c was observed in all lipopolysaccharide-treated groups and was associated with increased mitochondrial concentrations of Bax and ceramide. These studies confirm that liver mitochondria are early targets of injury during endotoxemia and that inner and outer mitochondrial membrane damage occurs through different mechanisms. Inner mitochondrial membrane damage appears to relate to the mitochondrial permeability transition, whereas outer mitochondrial membrane damage can occur independent of the mitochondrial permeability transition. Preliminary evidence suggests that Bax may participate in lipopolysaccharide-induced outer mitochondrial membrane damage, but further investigations are needed to confirm this.

Diagnosis and management of sepsis

NASA Astrophysics Data System (ADS)

Arifin

2018-03-01

Sepsis is the life-threatening condition with organ dysfunction caused by dysregulated host response to the infection. Septic shock is part of sepsis where circulatory abnormalities and cellular metabolism occur. Sepsis and septic shock are still a problem in the world, where one in four people with sepsis will die. As well as any trauma case, acute myocardial infarction, or stroke, early identification and appropriate treatment of sepsis immediately after sepsis will improve the prognosis of the patient. Comprehensive management of septic patients is required, ranging from infection controls that include antibiotic administration and infection source control as well as hemodynamic stabilization that included fluid resuscitation and vasoactive drug delivery.

Clinical prevalence and outcome impact of pituitary dysfunction after aneurysmal subarachnoid hemorrhage: a systematic review with meta-analysis.

PubMed

Robba, Chiara; Bacigaluppi, Susanna; Bragazzi, Nicola; Lavinio, Andrea; Gurnell, Mark; Bilotta, Federico; Menon, David K

2016-10-01

Pituitary dysfunction is reported to be a common complication following aneurysmal subarachnoid hemorrhage (aSAH). The aim of this meta-analysis is to analyze the literature on clinical prevalence, risk factors and outcome impact of pituitary dysfunction after aSAH, and to assess the possible need for pituitary screening in aSAH patients. We performed a systematic review with meta-analysis based on a comprehensive search of four databases (PubMed/MEDLINE, ISI/Web of Science, Scopus and Google Scholar). A total of 20 papers met criteria for inclusion. The prevalence of pituitary dysfunction in the acute phase (within the first 6 months after aSAH) was 49.30 % (95 % CI 41.6-56.9), decreasing in the chronic phase (after 6 months from aSAH) to 25.6 % (95 % CI 18.0-35.1). Abnormalities in basal hormonal levels were more frequent when compared to induction tests, and the prevalence of a single pituitary hormone dysregulation was more frequent than multiple pituitary hormone dysregulation. Increasing age was associated with a lower prevalence of endocrine dysfunction in the acute phase, and surgical treatment of the aneurysm (clipping) was related to a higher prevalence of single hormone dysfunction. The prevalence of pituitary dysfunction did not correlate with the outcome of the patient. Neuroendocrine dysfunction is common after aSAH, but these abnormalities have not been shown to consistently impact outcome in the data available. There is a need for well-designed prospective studies to more precisely assess the incidence, clinical course, and outcome impact of pituitary dysfunction after aSAH.

Scrub Typhus in a Tertiary Care Hospital in North India.

PubMed

Sharma, Navneet; Biswal, Manisha; Kumar, Abhay; Zaman, Kamran; Jain, Sanjay; Bhalla, Ashish

2016-08-03

Scrub typhus, a zoonotic disease caused by the bacterium Orientia tsutsugamushi, has become endemic in many parts of India. We studied the clinical profile of this infection in 228 patients that reported to this tertiary care center from July 2013 to December 2014. The median age of patients was 35 years (interquartile range = 24.5-48.5 years), and 111 were males and 117 females. A high-grade fever occurred in 85%, breathlessness in 42%, jaundice in 32%, abdominal pain in 28%, renal failure in 11%, diarrhea in 10%, rashes in 9%, and seizures in 7%. Common laboratory abnormalities at presentation were a deranged hepatic function in 61%, anemia in 54%, leukopenia in 15%, and thrombocytopenia in 90% of our patients. Acute kidney injury (32%), acute respiratory distress syndrome (ARDS) (25%), and disseminated intravascular coagulation (DIC) (16%) were the commonest complications. A hepatorenal syndrome was seen in 38% and multiple organ dysfunction syndrome (MODS) in 20% patients. The overall case fatality rate was 13.6%. In univariate analysis, ARDS requiring mechanical ventilation, acute kidney injury requiring hemodialysis, hypotension requiring inotropic support, central nervous system dysfunction at presentation, and MODS were inversely associated with survival. Survival was significantly higher in patients that presented with a duration of fever < 10 days compared with those that presented ≥ 12 days (P < 0.05) after onset. In conclusion, scrub typhus has become a leading infectious disease in north India and an important cause of infectious fever. An increasing awareness of this disease coupled with prompt management will go a long way in reducing both morbidity and mortality from this disease. © The American Society of Tropical Medicine and Hygiene.

Persistent cerebrovascular effects of MDMA and acute responses to the drug.

PubMed

Ferrington, Linda; Kirilly, Eszter; McBean, Douglas E; Olverman, Henry J; Bagdy, György; Kelly, Paul A T

2006-07-01

Acutely, 3,4,-methylenedioxymethamphetamine (MDMA) induces cerebrovascular dysfunction [Quate et al., (2004)Psychopharmacol., 173, 287-295]. In the longer term the same single dose results in depletion of 5-hydroxytrptamine (5-HT) nerve terminals. In this study we examined the cerebrovascular consequences of this persistent neurodegeneration, and the acute effects of subsequent MDMA exposure, upon the relationship that normally exists between local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCMRglu). Dark agouti (DA) rats were pre-treated with 15 mg/kg i.p. MDMA or saline. Three weeks later, rats from each pre-treatment group were treated with an acute dose of MDMA (15 mg/kg i.p.) or saline. Quantitative autoradiographic imaging was used to measure LCBF or LCMRglu with [(14)C]-iodoantipyrine and [(14)C]-2-deoxyglucose, respectively. Serotonergic terminal depletion was assessed using radioligand binding with [(3)H]-paroxetine and immunohistochemistry. Three weeks after MDMA pre-treatment there were significant reductions in densities of 5-HT transporter (SERT)-positive fibres (-46%) and [(3)H]-paroxetine binding (-47%). In animals pre-treated with MDMA there were widespread significant decreases in LCMRglu, but no change in LCBF indicating a persistent loss of cerebrovascular constrictor tone. In both pre-treatment groups, acute MDMA produced significant increases in LCMRglu, while LCBF was significantly decreased. In 50% of MDMA-pre-treated rats, random areas of focal hyperaemia indicated a loss of autoregulatory capacity in response to MDMA-induced hypertension. These results suggest that cerebrovascular regulatory dysfunction resulting from acute exposure to MDMA is not diminished by previous exposure, despite a significant depletion in 5-HT terminals. However, there may be a sub-population, or individual circumstances, in which this dysfunction develops into a condition that might predispose to stroke.

Reversal of anemia with allogenic RBC transfusion prevents post-cardiopulmonary bypass acute kidney injury in swine

PubMed Central

Patel, Nishith N.; Lin, Hua; Toth, Tibor; Welsh, Gavin I.; Jones, Ceri; Ray, Paramita; Satchell, Simon C.; Sleeman, Philippa; Angelini, Gianni D.

2011-01-01

Anemia during cardiopulmonary bypass (CPB) is strongly associated with acute kidney injury in clinical studies; however, reversal of anemia with red blood cell (RBC) transfusions is associated with further renal injury. To understand this paradox, we evaluated the effects of reversal of anemia during CPB with allogenic RBC transfusion in a novel large-animal model of post-cardiac surgery acute kidney injury with significant homology to that observed in cardiac surgery patients. Adult pigs undergoing general anesthesia were allocated to a Sham procedure, CPB alone, Sham+RBC transfusion, or CPB+RBC transfusion, with recovery and reassessment at 24 h. CPB was associated with dilutional anemia and caused acute kidney injury in swine characterized by renal endothelial dysfunction, loss of nitric oxide (NO) bioavailability, vasoconstriction, medullary hypoxia, cortical ATP depletion, glomerular sequestration of activated platelets and inflammatory cells, and proximal tubule epithelial cell stress. RBC transfusion in the absence of CPB also resulted in renal injury. This was characterized by endothelial injury, microvascular endothelial dysfunction, platelet activation, and equivalent cortical tubular epithelial phenotypic changes to those observed in CPB pigs, but occurred in the absence of severe intrarenal vasoconstriction, ATP depletion, or reductions in creatinine clearance. In contrast, reversal of anemia during CPB with RBC transfusion prevented the reductions in creatinine clearance, loss of NO bioavailability, platelet activation, inflammation, and epithelial cell injury attributable to CPB although it did not prevent the development of significant intrarenal vasoconstriction and endothelial dysfunction. In conclusion, contrary to the findings of observational studies in cardiac surgery, RBC transfusion during CPB protects pigs against acute kidney injury. Our study underlines the need for translational research into indications for transfusion and prevention strategies for acute kidney injury. PMID:21653630

Bladder, bowel, and sexual dysfunction in Parkinson's disease.

PubMed

Sakakibara, Ryuji; Kishi, Masahiko; Ogawa, Emina; Tateno, Fuyuki; Uchiyama, Tomoyuki; Yamamoto, Tatsuya; Yamanishi, Tomonori

2011-01-01

Bladder dysfunction (urinary urgency/frequency), bowel dysfunction (constipation), and sexual dysfunction (erectile dysfunction) (also called "pelvic organ" dysfunctions) are common nonmotor disorders in Parkinson's disease (PD). In contrast to motor disorders, pelvic organ autonomic dysfunctions are often nonresponsive to levodopa treatment. The brain pathology causing the bladder dysfunction (appearance of overactivity) involves an altered dopamine-basal ganglia circuit, which normally suppresses the micturition reflex. By contrast, peripheral myenteric pathology causing slowed colonic transit (loss of rectal contractions) and central pathology causing weak strain and paradoxical anal sphincter contraction on defecation (PSD, also called as anismus) are responsible for the bowel dysfunction. In addition, hypothalamic dysfunction is mostly responsible for the sexual dysfunction (decrease in libido and erection) in PD, via altered dopamine-oxytocin pathways, which normally promote libido and erection. The pathophysiology of the pelvic organ dysfunction in PD differs from that in multiple system atrophy; therefore, it might aid in differential diagnosis. Anticholinergic agents are used to treat bladder dysfunction in PD, although these drugs should be used with caution particularly in elderly patients who have cognitive decline. Dietary fibers, laxatives, and "prokinetic" drugs such as serotonergic agonists are used to treat bowel dysfunction in PD. Phosphodiesterase inhibitors are used to treat sexual dysfunction in PD. These treatments might be beneficial in maximizing the patients' quality of life.

Establishment of a canine model of acute pulmonary embolism with definite right ventricular dysfunction through introduced autologous blood clots.

PubMed

Zhao, Lin-Bo; Jia, Zhen-Yu; Lu, Guang-Dong; Zhu, Yin-Su; Jing, Lei; Shi, Hai-Bin

2015-04-01

To establish a canine model of acute pulmonary embolism (PE) with right ventricular (RV) dysfunction using autologous blood clots and evaluate by echocardiography and contrast-enhanced Computed Tomography (CT). Autologous blood clots formed in vitro were introduced sequentially into the pulmonary arteries of eight healthy mixed-breed dogs while monitoring pulmonary and systemic hemodynamic function. Blood clots were injected until the mean pulmonary artery pressure (MPAP) reached two-three times the baseline pressure, which was maintained up to 1 hour. The RV function was assessed by echocardiography and ECG-gated dual-source contrast CT. All animals survived the imaging procedure. The post-injection pulmonary angiograms showed extensive PE, and MPAP increased from 16.50±2.45 mmHg to 43.13±4.91 mmHg (P<0.001). On echocardiography, the RV fractional area change decreased from 42.06±3.36 to 27.96±3.54 (P<0.001), and the RV myocardial performance increased from 0.20±0.05 to 0.63±0.16 (P<0.001). On CT, the RV end-systolic volume increased from 11.11±1.81 ml to 24.71±4.60 ml (P<0.001), RV end-diastolic volume from 20.73±2.83 ml to 34.63±5.76 ml (P<0.001), and the four-chamber RV/left ventricular diameter ratio from 0.38±0.07 to 0.81±0.14 (P<0.001). Acute PE with RV dysfunction was established in a large animal model through controlled injection of autologous blood clots, which may be useful for developing and evaluating new therapeutic approaches for acute PE with RV dysfunction. Copyright © 2015 Elsevier Ltd. All rights reserved.

Sensitivity of the Balance Error Scoring System and the Sensory Organization Test in the Combat Environment.

PubMed

Haran, F Jay; Slaboda, Jill C; King, Laurie A; Wright, W Geoff; Houlihan, Daniel; Norris, Jacob N

2016-04-01

This study evaluated the utility of the Balance Error Scoring System (BESS) and the Sensory Organization Test (SOT) as tools for the screening and monitoring of Service members (SMs) with mild traumatic brain injury (mTBI) in a deployed setting during the acute and subacute phases of recovery. Patient records (N = 699) were reviewed for a cohort of SMs who sustained a blast-related mTBI while deployed to Afghanistan and were treated at the Concussion Restoration Care Center (CRCC) at Camp Leatherneck. On initial intake into the CRCC, participants completed two assessments of postural control, the BESS, and SOT. SMs with mTBI performed significantly worse on the BESS and SOT when compared with comparative samples. When the SOT data were further examined using sensory ratios, the results indicated that postural instability was primarily a result of vestibular and visual integration dysfunction (r > 0.62). The main finding of this study was that the sensitivity of the SOT composite score (50-58%) during the acute phase was higher than previous sensitivities found in the sports medicine literature for impact-related trauma.

Lung Transplant Outcomes in Systemic Sclerosis with Significant Esophageal Dysfunction. A Comprehensive Single-Center Experience

PubMed Central

Schwab, Kristin; Saggar, Rajeev; Duffy, Erin; Elashoff, David; Tseng, Chi-Hong; Weigt, Sam; Charan, Deepshikha; Abtin, Fereidoun; Johannes, Jimmy; Derhovanessian, Ariss; Conklin, Jeffrey; Ghassemi, Kevin; Khanna, Dinesh; Siddiqui, Osama; Ardehali, Abbas; Hunter, Curtis; Kwon, Murray; Biniwale, Reshma; Lo, Michelle; Volkmann, Elizabeth; Torres Barba, David; Belperio, John A.; Mahrer, Thomas; Furst, Daniel E.; Kafaja, Suzanne; Clements, Philip; Shino, Michael; Gregson, Aric; Kubak, Bernard; Lynch, Joseph P.; Ross, David

2016-01-01

Rationale: Consideration of lung transplantation in patients with systemic sclerosis (SSc) remains guarded, often due to the concern for esophageal dysfunction and the associated potential for allograft injury and suboptimal post–lung transplantation outcomes. Objectives: The purpose of this study was to systematically report our single-center experience regarding lung transplantation in the setting of SSc, with a particular focus on esophageal dysfunction. Methods: We retrospectively reviewed all lung transplants at our center from January 1, 2000 through August 31, 2012 (n = 562), comparing the SSc group (n = 35) to the following lung transplant diagnostic subsets: all non-SSc (n = 527), non-SSc diffuse fibrotic lung disease (n = 264), and a non-SSc matched group (n = 109). We evaluated post–lung transplant outcomes, including survival, primary graft dysfunction, acute rejection, bronchiolitis obliterans syndrome, and microbiology of respiratory isolates. In addition, we defined severe esophageal dysfunction using esophageal manometry and esophageal morphometry criteria on the basis of chest computed tomography images. For patients with SSc referred for lung transplant but subsequently denied (n = 36), we queried the reason(s) for denial with respect to the concern for esophageal dysfunction. Measurements and Main Results: The 1-, 3-, and 5-year post–lung transplant survival for SSc was 94, 77, and 70%, respectively, and similar to the other groups. The remaining post–lung transplant outcomes evaluated were also similar between SSc and the other groups. Approximately 60% of the SSc group had severe esophageal dysfunction. Pre–lung transplant chest computed tomography imaging demonstrated significantly abnormal esophageal morphometry for SSc when compared with the matched group. Importantly, esophageal dysfunction was the sole reason for lung transplant denial in a single case. Conclusions: Relative to other lung transplant indications, our SSc group experienced comparable survival, primary graft dysfunction, acute rejection, bronchiolitis obliterans syndrome, and microbiology of respiratory isolates, despite the high prevalence of severe esophageal dysfunction. Esophageal dysfunction rarely precluded active listing for lung transplantation. PMID:27078625

[Sacroiliac joint dysfunction presented with acute low back pain: three case reports].

PubMed

Hamauchi, Shuji; Morimoto, Daijiro; Isu, Toyohiko; Sugawara, Atsushi; Kim, Kyongsong; Shimoda, Yusuke; Motegi, Hiroaki; Matsumoto, Ryoji; Isobe, Masanori

2010-07-01

Sacroiliac joint (SIJ) can cause low back pain when its joint capsule and ligamentous tissue are damaged. We report our experience in treating three SIJ dysfunction patients presenting with acute low back pain (a 38 year-old male, a 24 year-old male, and a 32 year-old female). SIJ dysfunction was diagnosed using the one-finger test, the modified Newton test, and SIJ injection. In all three patients, lumbar MRI demonstrated slightly degenerated lumbar lesions (lumbar canal stenosis, lumbar disc hernia). Two patients had paresthesia or pain in the leg and all three patients showed iliac muscle tenderness in the groin, which was thought to be a referred symptom because of improvement after SIJ injection. The two male patients returned to work and the problems have not recurred. Although our female patient resumed daily life as a housewife, her condition recurred at intervals of 2-3 months and she required regular SIJ injections. The prevalence of SIJ dysfunction of low back pain is about 10%, so it should be considered as a differential diagnosis when treating low back pain and designing treatment for lumbar spinal disorders.

Association between in-hospital mortality and renal dysfunction in 186,219 patients hospitalized for acute stroke in the Emilia-Romagna region of Italy.

PubMed

Fabbian, Fabio; Gallerani, Massimo; Pala, Marco; De Giorgi, Alfredo; Salmi, Raffaella; Dentali, Francesco; Ageno, Walter; Manfredini, Roberto

2014-11-01

Using a regional Italian database, we evaluated the relationship between renal dysfunction and in-hospital mortality (IHM) in patients with acute stroke (ischemic/hemorrhagic). Patients were classified on the basis of renal damage: without renal dysfunction, with chronic kidney disease (CKD), and with end-stage renal disease (ESRD). Of a total of 186,219 patients with a first episode of stroke, 1626 (0.9%) had CKD and 819 (0.4%) had ESRD. Stroke-related IHM (total cases) was independently associated with CKD, ESRD, atrial fibrillation (AF), age, and Charlson comorbidity index (CCI). In patients with ischemic stroke (n=154,026), IHM remained independently associated with CKD, ESRD, AF, and CCI. In patients with hemorrhagic stroke (n=32,189), variables that were independently associated with IHM were CKD, ESRD, and AF. Renal dysfunction is associated with IHM related to stroke, both ischemic and hemorrhagic, with even higher odds ratios than those of other established risk factors, such as age, comorbidities, and AF. © The Author(s) 2013.

Herpes zoster-associated voiding dysfunction in hematopoietic malignancy patients.

PubMed

Imafuku, Shinichi; Takahara, Masakazu; Uenotsuchi, Takeshi; Iwato, Koji; Furue, Masutaka

2008-01-01

Voiding dysfunction is a rare but important complication of lumbo-sacral herpes zoster. Although the symptoms are transient, the clinical impact on immunocompromised patients cannot be overlooked. To clarify the time course of voiding dysfunction in herpes zoster, 13 herpes zoster patients with voiding dysfunction were retrospectively analyzed. Of 13 patients, 12 had background disease, and six of these were hematopoietic malignancies; four of these patients were hematopoietic stem cell transplant (HSCT) recipients. Ten patients had sacral lesions, two had lumbar, and one had thoracic lesions. Interestingly, patients with severe rash, or with hematopoietic malignancy had later onset of urinary retention than did patients with mild skin symptoms (Mann-Whitney U analysis, P = 0.053) or with other background disease (P = 0.0082). Patients with severe skin rash also had longer durations (P = 0.035). In one case, acute urinary retention occurred as late as 19 days after the onset of skin rash. In immune compromised subjects, attention should be paid to patients with herpes zoster in the lumbo-sacral area for late onset of acute urinary retention even after the resolution of skin symptoms.

Management of chronic spinal cord dysfunction.

PubMed

Abrams, Gary M; Ganguly, Karunesh

2015-02-01

Both acute and chronic spinal cord disorders present multisystem management problems to the clinician. This article highlights key issues associated with chronic spinal cord dysfunction. Advances in symptomatic management for chronic spinal cord dysfunction include use of botulinum toxin to manage detrusor hyperreflexia, pregabalin for management of neuropathic pain, and intensive locomotor training for improved walking ability in incomplete spinal cord injuries. The care of spinal cord dysfunction has advanced significantly over the past 2 decades. Management and treatment of neurologic and non-neurologic complications of chronic myelopathies ensure that each patient will be able to maximize their functional independence and quality of life.

[Oliguria and acute renal dysfunction in a six-month-old infant].

PubMed

Cui, Ya-Jie; Song, Chun-Lan; Cheng, Yi-Bing

2017-02-01

The infant (a girl aged 6 months) was admitted to the hospital because of oliguria and acute renal dysfunction. The laboratory examination results showed serious metabolic acidosis and increased blood urea nitrogen and serum creatinine levels. The patient continued to be anuric after 10 days of treatment with continuous renal replacement therapy (CRRT). she died a day later. The family history showed that the patient's sister died of acute renal failure 6 months after birth. The genomic sequencing results showed AGXT mutation in the patient and confirmed the diagnosis of primary hyperoxaluria type 1 (PH1). Her parents were heterozygous carriers. PH1 should be considered when the children have abnormal renal function or recurrent renal calculi or have a family history of these symptoms. AGXT gene analysis is an important method for PH1 diagnosis.

Dysfunctional Attitudes Scale Perfectionism: A Predictor and Partial Mediator of Acute Treatment Outcome among Clinically Depressed Adolescents

PubMed Central

Jacobs, Rachel H.; Silva, Susan G.; Reinecke, Mark A.; Curry, John F.; Ginsburg, Golda S.; Kratochvil, Christopher J.; March, John S.

2009-01-01

The effect of perfectionism on acute treatment outcomes was explored in a randomized controlled trial of 439 clinically depressed adolescents (12–17 years of age) enrolled in the Treatment for Adolescents with Depression Study (TADS) who received cognitive behavior therapy (CBT), fluoxetine, a combination of CBT and FLX, or pill placebo. Measures included the Children’s Depression Rating Scale–Revised, the Suicidal Ideation Questionnaire–Grades 7–9, and the perfectionism subscale from the Dysfunctional Attitudes Scale (DAS). Predictor results indicate that adolescents with higher versus lower DAS perfectionism scores at baseline, regardless of treatment, continued to demonstrate elevated depression scores across the acute treatment period. In the case of suicidality, DAS perfectionism impeded improvement. Treatment outcomes were partially mediated by the change in DAS perfectionism across the 12-week period. PMID:20183664

 Rapid identification system of frontal dysfunction in subclinical hepatic encephalopathy.

PubMed

Moretti, Rita; Gazzin, Silvia; Crocè, Lory Saveria; Baso, Beatrice; Masutti, Flora; Bedogni, Giorgio; Tiribelli, Claudio

2016-01-01

 Introduction and aim. Liver disease is associated with cognitive dysfunction also at early stages, and minimal hepatic encephalopathy, affecting 20-70% of patients, is frequently under-recognized. The main purpose of this work was to demonstrate that a substantial number of patients, enrolled due to an acute confusional state in absence of a diagnosis of liver disease, suffers of hepatic encephalopathy. Before a diagnosis of a well-compensated liver diseases was performed, 410 patients with an acute confusional state were enrolled in this study. Even in the presence of minimal alterations of hepatic function, the psychometric tests applied demonstrated early signs of cerebral frontal alteration. The alteration was associated with the severity of liver disease, paralleling the progression of the patient to minimal hepatic failure or chronic liver disease. These psychometric tests are essential to detect early and subclinical frontal failure. Frontal dysfunction may be a useful tool in the follow-up of these patients.

Adolescent TBI-induced hypopituitarism causes sexual dysfunction in adult male rats.

PubMed

Greco, Tiffany; Hovda, David A; Prins, Mayumi L

2015-02-01

Adolescents are at greatest risk for traumatic brain injury (TBI) and repeat TBI (RTBI). TBI-induced hypopituitarism has been documented in both adults and juveniles and despite the necessity of pituitary function for normal physical and brain development, it is still unrecognized and untreated in adolescents following TBI. TBI induced hormonal dysfunction during a critical developmental window has the potential to cause long-term cognitive and behavioral deficits and the topic currently remains unaddressed. The purpose of this study was to determine if four mild TBIs delivered to adolescent male rats disrupts testosterone production and adult behavioral outcomes. Plasma testosterone was quantified from 72 hrs preinjury to 3 months postinjury and pubertal onset, reproductive organ growth, erectile function and reproductive behaviors were assessed at 1 and 2 months postinjury. RTBI resulted in both acute and chronic decreases in testosterone production and delayed onset of puberty. Significant deficits were observed in reproductive organ growth, erectile function and reproductive behaviors in adult rats at both 1 and 2 months postinjury. These data suggest adolescent RTBI-induced hypopituitarism underlies abnormal behavioral changes observed during adulthood. The impact of undiagnosed hypopituitarism following RTBI in adolescence has significance not only for growth and puberty, but also for brain development and neurobehavioral function as adults. © 2014 Wiley Periodicals, Inc.

Peptidylarginine deiminase 4 promotes age-related organ fibrosis

PubMed Central

Erpenbeck, Luise; Savchenko, Alexander; Hayashi, Hideki; Cherpokova, Deya; Gallant, Maureen; Mauler, Maximilian; Cifuni, Stephen M.

2017-01-01

Aging promotes inflammation, a process contributing to fibrosis and decline in organ function. The release of neutrophil extracellular traps (NETs [NETosis]), orchestrated by peptidylarginine deiminase 4 (PAD4), damages organs in acute inflammatory models. We determined that NETosis is more prevalent in aged mice and investigated the role of PAD4/NETs in age-related organ fibrosis. Reduction in fibrosis was seen in the hearts and lungs of aged PAD4−/− mice compared with wild-type (WT) mice. An increase in left ventricular interstitial collagen deposition and a decline in systolic and diastolic function were present only in WT mice, and not in PAD4−/− mice. In an experimental model of cardiac fibrosis, cardiac pressure overload induced NETosis and significant platelet recruitment in WT but not PAD4−/− myocardium. DNase 1 was given to assess the effects of extracellular chromatin. PAD4 deficiency or DNase 1 similarly protected hearts from fibrosis. We propose a role for NETs in cardiac fibrosis and conclude that PAD4 regulates age-related organ fibrosis and dysfunction. PMID:28031479

Chronic kidney disease and worsening renal function in acute heart failure: different phenotypes with similar prognostic impact?

PubMed

Palazzuoli, Alberto; Lombardi, Carlo; Ruocco, Gaetano; Padeletti, Margherita; Nuti, Ranuccio; Metra, Marco; Ronco, Claudio

2016-12-01

Nearly a third of patients with acute heart failure experience concomitant renal dysfunction. This condition is often associated with increased costs of care, length of hospitalisation and high mortality. Although the clinical impact of chronic kidney disease (CKD) has been well established, the exact clinical significance of worsening renal function (WRF) during the acute and post-hospitalisation phases is not completely understood. Therefore, it is still unclear which of the common laboratory markers are able to identify WRF at an early stage. Recent studies comparing CKD with WRF showed contradictory results; this could depend on a different WRF definition, clinical characteristics, haemodynamic disorders and the presence of prior renal dysfunction in the population enrolled. The current definition of acute cardiorenal syndrome focuses on both the heart and kidney but it lacks precise laboratory marker cut-offs and a specific diagnostic approach. WRF and CKD could represent different pathophysiological mechanisms in the setting of acute heart failure; the traditional view includes reduced cardiac output with systemic and renal vasoconstriction. Nevertheless, it has become a mixed model that encompasses both forward and backward haemodynamic dysfunction. Increased central venous pressure, renal congestion with tubular obliteration, tubulo-glomerular feedback and increased abdominal pressure are all potential additional contributors. The impact of WRF on patients who experience preserved renal function and individuals affected with CKD is currently unknown. Therefore it is extremely important to understand the origins, the clinical significance and the prognostic impact of WRF on CKD. © The European Society of Cardiology 2015.

Detrimental effects of acute hyperglycaemia on the rat heart.

PubMed

Mapanga, R F; Joseph, D; Symington, B; Garson, K-L; Kimar, C; Kelly-Laubscher, R; Essop, M Faadiel

2014-03-01

Hyperglycaemia is an important risk factor for acute myocardial infarction. It can lead to increased induction of non-oxidative glucose pathways (NOGPs) - polyol and hexosamine biosynthetic pathways, advanced glycation end products and protein kinase C - that may contribute to cardiovascular diseases onset. However, the precise underlying mechanisms remain poorly understood. Here we hypothesized that acute hyperglycaemia increases myocardial oxidative stress and NOGP activation resulting in cardiac dysfunction during ischaemia-reperfusion and that inhibition of, and/or shunting flux away from NOGPs [by benfotiamine (BFT) treatment], leads to cardioprotection. We employed several experimental systems: (i) Isolated rat hearts were perfused ex vivo with Krebs-Henseleit buffer containing 33 mm glucose vs. controls (11 mm glucose) ± global ischaemia and reperfusion ± BFT (first 20 min of reperfusion); (ii) Infarct size determination as per the ischaemic protocol, but with regional ischaemia and reperfusion ± BFT treatment; in separate experiments, NOGP inhibitors were also employed for (i) and (ii); and (iii) In vivo coronary ligations performed on streptozotocin-treated rats ± BFT treatment (early reperfusion). Acute hyperglycaemia generated myocardial oxidative stress, NOGP activation and apoptosis, but caused no impairment of cardiac function during pre-ischaemia, thereby priming hearts for later damage. Following ischaemia-reperfusion (under hyperglycaemic conditions), such effects were exacerbated together with cardiac contractile dysfunction. Moreover, inhibition of respective NOGPs and shunting away by BFT treatment (in part) improved cardiac function during ischaemia-reperfusion. Coordinate NOGP activation in response to acute hyperglycaemia results in contractile dysfunction during ischaemia-reperfusion, allowing for the development of novel cardioprotective agents. © 2013 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Diagnostic yield of lumbosacral magnetic resonance imaging requested by paediatric urology consultations.

PubMed

Fernández-Ibieta, M; Rojas Ticona, J; Villamil, V; Guirao Piñera, M J; López García, A; Zambudio Carmona, G

2017-11-01

In the historical series, the diagnostic yield of lumbosacral magnetic resonance imaging to rule out occult spinal dysraphism (or occult myelodysplasia), requested by paediatric urology, ranged from 2% to 15%. The aim of this study was to define our cost-effectiveness in children with urinary symptoms and to define endpoints that increase the possibility of finding occult spinal dysraphism. A screening was conducted on patients with urinary dysfunction for whom an magnetic resonance imaging was requested by the paediatric urology clinic, for persistent symptoms after treatment, voiding dysfunction or other clinical or urodynamic findings. We analysed clinical (UTI, daytime leaks, enuresis, voiding dysfunction, urgency, renal ultrasonography, lumbosacral radiography, history of acute urine retention, skin stigma and myalgia) and urodynamic endpoints (hyperactivity or areflexia, voiding dysfunction, interrupted pattern, accommodation value and maximum flow). A univariate analysis was conducted with SPSS 20.0. We analysed 21 patients during the period 2011-2015. The median age was 6 years (3-10). Three patients (14.3%) had occult spinal dysraphism: one spinal lipoma, one filum lipomatosus and one caudal regression syndrome with channel stenosis. The endpoints with statistically significant differences were the myalgias and the history of acute urine retention (66.7% vs. 5.6%, P=.04; OR= 34; 95%CI: 1.5-781 for both endpoints). The diagnostic yield of magnetic resonance imaging requested for children with urinary dysfunctions without skin stigma or neuro-orthopaedic abnormalities is low, although nonnegligible. In this group, the patients with a history of acute urine retention and muscle pain (pain, «cramps») can experience a greater diagnostic yield or positive predictive value. Copyright © 2017 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Vascular dysfunctions following spinal cord injury

PubMed Central

Popa, F; Grigorean, VT; Onose, G; Sandu, AM; Popescu, M; Burnei, G; Strambu, V; Sinescu, C

2010-01-01

The aim of this article is to analyze the vascular dysfunctions occurring after spinal cord injury (SCI). Vascular dysfunctions are common complications of SCI. Cardiovascular disturbances are the leading causes of morbidity and mortality in both acute and chronic stages of SCI. Neuroanatomy and physiology of autonomic nervous system, sympathetic and parasympathetic, is reviewed. SCI implies disruption of descendent pathways from central centers to spinal sympathetic neurons, originating in intermediolateral nuclei of T1–L2 cord segments. Loss of supraspinal control over sympathetic nervous system results in reduced overall sympathetic activity below the level of injury and unopposed parasympathetic outflow through intact vagal nerve. SCI associates significant vascular dysfunction. Spinal shock occurs during the acute phase following SCI and it is a transitory suspension of function and reflexes below the level of the injury. Neurogenic shock, part of spinal shock, consists of severe arterial hypotension and bradycardia. Autonomic dysreflexia appears during the chronic phase, after spinal shock resolution, and it is a life–threatening syndrome of massive imbalanced reflex sympathetic discharge occurring in patients with SCI above the splanchnic sympathetic outflow (T5–T6). Arterial hypotension with orthostatic hypotension occurs in both acute and chronic phases. The etiology is multifactorial. We described a few factors influencing the orthostatic hypotension occurrence in SCI: sympathetic nervous system dysfunction, low plasma catecholamine levels, rennin–angiotensin–aldosterone activity, peripheral alpha–adrenoceptor hyperresponsiveness, impaired function of baroreceptors, hyponatremia and low plasmatic volume, cardiovascular deconditioning, morphologic changes in sympathetic neurons, plasticity within spinal circuits, and motor deficit leading to loss of skeletal muscle pumping activity. Additional associated cardiovascular concerns in SCI, such as deep vein thrombosis and long–term risk for coronary heart disease and systemic atherosclerosis are also described. Proper prophylaxis, including non–pharmacologic and pharmacological strategies, diminishes the occurrence of the vascular dysfunction following SCI. Each vascular disturbance requires a specific treatment. PMID:20945818

Effects of statin therapy on clinical outcomes after acute myocardial infarction in patients with advanced renal dysfunction: A propensity score-matched analysis.

PubMed

Kim, Jin Sug; Kim, Weon; Park, Ji Yoon; Woo, Jong Shin; Lee, Tae Won; Ihm, Chun Gyoo; Kim, Yang Gyun; Moon, Ju-Young; Lee, Sang Ho; Jeong, Myung Ho; Jeong, Kyung Hwan

2017-01-01

Lipid lowering therapy is widely used for the prevention of cardiovascular complications after acute myocardial infarction (AMI). However, some studies show that this benefit is uncertain in patients with renal dysfunction, and the role of statins is based on the severity of renal dysfunction. In this study, we investigated the impact of statin therapy on major adverse cardiac events (MACEs) and all-cause mortality in patients with advanced renal dysfunction undergoing percutaneous coronary intervention (PCI) after AMI. This study was based on the Korea Acute Myocardial Infarction Registry database. We included 861 patients with advanced renal dysfunction from among 33,205 patients who underwent PCI after AMI between November 2005 and July 2012. Patients were divided into two groups: a statin group (n = 537) and a no-statin group (n = 324). We investigated the 12-month MACEs (cardiac death, myocardial infarction, repeated PCI or coronary artery bypass grafting) and all-cause mortality of each group. Subsequently, a propensity score-matched analysis was performed. In the total population studied, no significant differences were observed between the two groups with respect to the rate of recurrent MI, repeated PCI, coronary artery bypass grafting (CABG), or all-cause mortality. However, the cardiac death rate was significantly lower in the statin group (p = 0.009). Propensity score-matched analysis yielded 274 pairs demonstrating, results similar to those obtained from the total population. However, there was no significant difference in the cardiac death rate in the propensity score-matched population (p = 0.103). Cox-regression analysis revealed only left ventricular ejection fraction to be an independent predictor of 12-month MACEs (Hazard ratio [HR] of 0.979, 95% confidence interval [CI], 0962-0.996, p = 0.018). Statin therapy was not significantly associated with a reduction in the 12-month MACEs or all-cause mortality in patients with advanced renal dysfunction undergoing PCI after AMI.

Acute Traumatic Coagulopathy

DTIC Science & Technology

2014-12-01

therapeutic approaches are discussed, including viscoelastic coagulation monitoring and the role of tranexamic acid and blood products. Summary...and tranexamic acid in addition to red cell units in order to reduce bleeding and improve clinical outcomes. Keywords acute traumatic coagulopathy...endothelial activation, fibrinolysis, hemostatic resuscitation, hypoperfusion, microparticles, platelet dysfunction, tranexamic acid , viscoelastic

Dietary ω-3 fatty acids protect against vasculopathy in a transgenic mouse model of sickle cell disease.

PubMed

Kalish, Brian T; Matte, Alessandro; Andolfo, Immacolata; Iolascon, Achille; Weinberg, Olga; Ghigo, Alessandra; Cimino, James; Siciliano, Angela; Hirsch, Emilio; Federti, Enrica; Puder, Mark; Brugnara, Carlo; De Franceschi, Lucia

2015-07-01

The anemia of sickle cell disease is associated with a severe inflammatory vasculopathy and endothelial dysfunction, which leads to painful and life-threatening clinical complications. Growing evidence supports the anti-inflammatory properties of ω-3 fatty acids in clinical models of endothelial dysfunction. Promising but limited studies show potential therapeutic effects of ω-3 fatty acid supplementation in sickle cell disease. Here, we treated humanized healthy and sickle cell mice for 6 weeks with ω-3 fatty acid diet (fish-oil diet). We found that a ω-3 fatty acid diet: (i) normalizes red cell membrane ω-6/ω-3 ratio; (ii) reduces neutrophil count; (iii) decreases endothelial activation by targeting endothelin-1 and (iv) improves left ventricular outflow tract dimensions. In a hypoxia-reoxygenation model of acute vaso-occlusive crisis, a ω-3 fatty acid diet reduced systemic and local inflammation and protected against sickle cell-related end-organ injury. Using isolated aortas from sickle cell mice exposed to hypoxia-reoxygenation, we demonstrated a direct impact of a ω-3 fatty acid diet on vascular activation, inflammation, and anti-oxidant systems. Our data provide the rationale for ω-3 dietary supplementation as a therapeutic intervention to reduce vascular dysfunction in sickle cell disease. Copyright© Ferrata Storti Foundation.

Early Allograft Dysfunction After Liver Transplantation Is Associated With Short- and Long-Term Kidney Function Impairment.

PubMed

Wadei, H M; Lee, D D; Croome, K P; Mai, M L; Golan, E; Brotman, R; Keaveny, A P; Taner, C B

2016-03-01

Early allograft dysfunction (EAD) after liver transplantation (LT) is related to ischemia-reperfusion injury and may lead to a systemic inflammatory response and extrahepatic organ dysfunction. We evaluated the effect of EAD on new-onset acute kidney injury (AKI) requiring renal replacement therapy within the first month and end-stage renal disease (ESRD) within the first year post-LT in 1325 primary LT recipients. EAD developed in 358 (27%) of recipients. Seventy-one (5.6%) recipients developed AKI and 38 (2.9%) developed ESRD. Compared with those without EAD, recipients with EAD had a higher risk of AKI and ESRD (4% vs. 9% and 2% vs. 6%, respectively, p < 0.001 for both). Multivariate logistic regression analysis showed an independent relationship between EAD and AKI as well as ESRD (odds ratio 3.5, 95% confidence interval 1.9-6.4, and odds ratio 3.1, 95% confidence interval 11.9-91.2, respectively). Patients who experienced both EAD and AKI had inferior 1-, 3-, 5-, and 10-year patient and graft survival compared with those with either EAD or AKI alone, while those who had neither AKI nor EAD had the best outcomes (p < 0.001). Post-LT EAD is a risk factor for both AKI and ESRD and should be considered a target for future intervention to reduce post-LT short- and long-term renal dysfunction. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Investigation of pituitary functions in patients with acute meningitis: a pilot study.

PubMed

Tanriverdi, F; Alp, E; Demiraslan, H; Dokmetas, H S; Unluhizarci, K; Doganay, M; Casanueva, F F; Kelestimur, F

2008-06-01

Although long-term pituitary consequences of tuberculous meningitis are well documented in the literature, there have been few case reports of pituitary dysfunction after acute bacterial or viral meningitis. In this preliminary study, we have assessed the pituitary functions in adult patients who had acute bacterial or viral meningitis. Fourteen patients (8 men, 6 women; mean age 35.3+/-13.3) were included in the study. The diagnosis of bacterial and viral meningitis was proven by clinical findings, cerebrospinal fluid (CSF) examination, gram staining, and blood and CSF cultures. Pituitary functions were evaluated ranging from 6 to 48 months (mean 20 months) after acute meningitis. GH deficiency was investigated by the GHRH+arginine stimulation test. Four of 14 patients (28.6%) had isolated GH deficiency. In GH-deficient patients, the earliest duration was 6 months and the latest duration was 48 months after the diagnosis of acute meningitis. Three of the GH-deficient patients had acute bacterial meningitis and 1 patient had acute viral meningitis. Pituitary magnetic resonance imaging revealed normal pituitary gland in the patients with GH deficiency. This is the first systematic study evaluating the anterior pituitary function long term after the diagnosis of acute meningitis. Based on the present study, it is tempting to speculate that pituitary dysfunction is a more common sequel of acute bacterial or viral meningitis than hitherto reported. Studies with high numbers of patients are warranted to ascertain the prevalence of meningitis-induced hypopituitarism.

FC-99 ameliorates sepsis-induced liver dysfunction by modulating monocyte/macrophage differentiation via Let-7a related monocytes apoptosis

PubMed Central

Zhao, Yarong; Zhu, Haiyan; Wang, Haining; Ding, Liang; Xu, Lizhi; Chen, Dai; Shen, Sunan; Hou, Yayi; Dou, Huan

2018-01-01

Background The liver is a vital target for sepsis-related injury, leading to inflammatory pathogenesis, multiple organ dysfunction and high mortality rates. Monocyte-derived macrophage transformations are key events in hepatic inflammation. N1-[(4-methoxy)methyl]-4-methyl-1,2-benzenediamine (FC-99) previously displayed therapeutic potential on experimental sepsis. However, the underlying mechanism of this protective effect is still not clear. Results FC-99 treatment attenuated the liver dysfunction in septic mice that was accompanied with reduced numbers of pro-inflammatory Ly6Chi monocytes in the peripheral blood and CD11b+F4/80lo monocyte-derived macrophages in the liver. These effects were attributed to the FC-99-induced apoptosis of CD11b+ cells. In PMA-differentiated THP-1 cells, FC-99 repressed the expression of CD11b, CD14 and caspase3 and resulted in a high proportion of Annexin V+ cells. Moreover, let-7a-5p expression was abrogated upon CLP stimulation in vivo, whereas it was restored by FC-99 treatment. TargetScan analysis and luciferase assays indicated that the anti-apoptotic protein BCL-XL was targeted by let-7a-5p. BCL-XL was inhibited by FC-99 in order to induce monocyte apoptosis, leading to the impaired monocyte-to-macrophage differentiation. Materials and Methods Murine acute liver failure was generated by caecal ligation puncture surgery after FC-99 administration; Blood samples and liver tissues were collected to determine the monocyte/macrophage subsets and the induction of apoptosis. Human acute monocytic leukemia cell line (THP-1) cells were pretreated with FC-99 followed by phorbol-12-myristate-13-acetate (PMA) stimulation, in order to induce monocyte-to-macrophage differentiation. The target of FC-99 and the mechanistic analyses were conducted by microarrays, qRT-PCR validation, TargetScan algorithms and a luciferase report assay. Conclusions FC-99 exhibits potential therapeutic effects on CLP-induced liver dysfunction by restoring let-7a-5p levels. PMID:29599918

The relationship of physical trauma and surgical stress to menstrual dysfunction.

PubMed

To, W W; Wong, M W

2000-02-01

To evaluate the incidence and pattern of menstrual dysfunction in reproductive age group women suffering acute musculoskeletal trauma, 198 women between 15 and 50 years of age admitted consecutively into an acute orthopaedic unit were recruited over a 6-month period. The patients were then followed up for 6 months with menstrual diaries to compare their menstrual pattern with their preadmission status. Excluding those with significant menstrual problems before admission, the menstrual pattern remained normal in 135 (68%) (EM), while 12 (6%) developed polymenorrhoea (PM), and 51 (25%) had oligomenorrhoea or amenorrhoea (OAM) within the 6-month observation. The three groups did not differ in their mean age, body mass index, parity or age of menarche, but previous cycle lengths were shortest in the PM group (25.4 days, SD 7.64) (p<0.05) and history of amenorrhoea in the previous one year was most common in the OAM group (p<0.025). Univariate analysis showed the incidence of moderate to major trauma,operative treatment, longer operative time, general anaesthesia, blood transfusion and immobilisation were significantly higher in the PM and OAM groups compared to the unchanged group (p<0.05). A logistic regression model showed that general anaesthesia and longer surgical operations remained significantly related to the development of menstrual dysfunction. We conclude that the pattern of menstrual dysfunction after acute orthopaedic trauma appeared to be dictated by the woman's pre-existing menstrual characteristics and the stress of surgical treatment.

STAT3 in the Systemic Inflammation of Cancer Cachexia

PubMed Central

Zimmers, Teresa A.; Fishel, Melissa L.; Bonetto, Andrea

2016-01-01

Weight loss is diagnostic of cachexia, a debilitating syndrome contributing mightily to morbidity and mortality in cancer. Most research has probed mechanisms leading to muscle atrophy and adipose wasting in cachexia; however cachexia is a truly systemic phenomenon. Presence of the tumor elicits an inflammatory response and profound metabolic derangements involving not only muscle and fat, but also the hypothalamus, liver, heart, blood, spleen and likely other organs. This global response is orchestrated in part through circulating cytokines that rise in conditions of cachexia. Exogenous Interleukin-6 (IL6) and related cytokines can induce most cachexia symptomatology, including muscle and fat wasting, the acute phase response and anemia, while IL-6 inhibition reduces muscle loss in cancer. Although mechanistic studies are ongoing, certain of these cachexia phenotypes have been causally linked to the cytokine-activated transcription factor, STAT3, including skeletal muscle wasting, cardiac dysfunction and hypothalamic inflammation. Correlative studies implicate STAT3 in fat wasting and the acute phase response in cancer cachexia. Parallel data in non-cancer models and disease states suggest both contributory and protective functions for STAT3 in other organs during cachexia. Finally, STAT3 contributes to cancer cachexia through enhancing tumorigenesis, metastasis and immune suppression, particularly in tumors associated with high prevalence of cachexia. This review examines the evidence linking STAT3 to multi-organ manifestations of cachexia in cancer and evidence for targeting STAT3 for anti-cachexia therapies. PMID:26860754

Lung Matrix Metalloproteinase Activation following Partial Hepatic Ischemia/Reperfusion Injury in Rats

PubMed Central

Ferrigno, Andrea; Rizzo, Vittoria; Tarantola, Eleonora

2014-01-01

Purpose. Warm hepatic ischemia-reperfusion (I/R) injury can lead to multiorgan dysfunction. The aim of the present study was to investigate whether acute liver I/R does affect the function and/or structure of remote organs such as lung, kidney, and heart via modulation of extracellular matrix remodelling. Methods. Male Sprague-Dawley rats were subjected to 30 min partial hepatic ischemia by clamping the hepatic artery and the portal vein. After a 60 min reperfusion, liver, lung, kidney, and heart biopsies and blood samples were collected. Serum hepatic enzymes, creatinine, urea, Troponin I and TNF-alpha, and tissue matrix metalloproteinases (MMP-2, MMP-9), myeloperoxidase (MPO), malondialdehyde (MDA), and morphology were monitored. Results. Serum levels of hepatic enzymes and TNF-alpha were concomitantly increased during hepatic I/R. An increase in hepatic MMP-2 and MMP-9 activities was substantiated by tissue morphology alterations. Notably, acute hepatic I/R affect the lung inasmuch as MMP-9 activity and MPO levels were increased. No difference in MMPs and MPO was observed in kidney and heart. Conclusions. Although the underlying mechanism needs further investigation, this is the first study in which the MMP activation in a distant organ is reported; this event is probably TNF-alpha-mediated and the lung appears as the first remote organ to be involved in hepatic I/R injury. PMID:24592193

Acute cerebellar ataxia and infectious mononucleosis.

PubMed Central

Wadhwa, N. K.; Ghose, R. R.

1983-01-01

A 28-year-old man, who presented with acute cerebellar ataxia, was found to have haematological features of infectious mononucleosis. There was serological evidence of recent infection with Epstein-Barr virus. It is speculated that cerebellar dysfunction results from virus-induced inflammatory changes within the central nervous system. PMID:6312442

Takotsubo cardiomyopathy in a patient with Addison disease: is apical ballooning always reversible?

PubMed

Barcin, Cem; Kursaklioglu, Hurkan; Kose, Sedat; Amasyali, Basri; Isik, Ersoy

2010-01-07

Takotsubo cardiomyopathy is characterized by acute ventricular dysfunction in the absence of coronary obstruction. Complete improvement of ventricular function is seen in the vast majority of the patients. We describe a 40-year-old woman with Addison disease who experienced Takotsubo cardiomyopathy but with persistent apical dysfunction during 5-month-follow up.

Review article: scoring systems for assessing prognosis in critically ill adult cirrhotics.

PubMed

Cholongitas, E; Senzolo, M; Patch, D; Shaw, S; Hui, C; Burroughs, A K

2006-08-01

Cirrhotic patients admitted to intensive care units (ICU) still have poor outcomes. Some current ICU prognostic models [Acute Physiology and Chronic Health Evaluation (APACHE), Organ System Failure (OSF) and Sequential Organ Failure Assessment (SOFA)] were used to stratify cirrhotics into risk categories, but few cirrhotics were included in the original model development. Liver-specific scores [Child-Turcotte-Pugh (CTP) and model for end-stage liver disease (MELD)] could be useful in this setting. To evaluate whether ICU prognostic models perform better compared with liver-disease specific ones in cirrhotics admitted to ICU. We performed a structured literature review identifying clinical studies focusing on prognosis and risk factors for mortality in adult cirrhotics admitted to ICU. We found 21 studies (five solely dealing with gastrointestinal bleeding) published during the last 20 years (54-420 patients in each). APACHE II and III, SOFA and OSF had better discrimination for correctly predicting death compared with the CTP score. The MELD score was evaluated only in one study and had good predictive accuracy [receiver operator characteristic (ROC) curve: 0.81). Organ dysfunction models (OSF, SOFA) were superior compared with APACHE II and III (ROC curve: range 0.83-0.94 vs. 0.66-0.88 respectively). Cardiovascular, liver and renal system dysfunction were more frequently independently associated with mortality. General-ICU models had better performance in cirrhotic populations compared with CTP score; OSF and SOFA had the best predictive ability. Further prospective and validation studies are needed.

Anaesthetic management of patients with severe sepsis.

PubMed

Eissa, D; Carton, E G; Buggy, D J

2010-12-01

Severe sepsis, a syndrome characterized by systemic inflammation and acute organ dysfunction in response to infection, is a major healthcare problem affecting all age groups throughout the world. Anaesthetists play a central role in the multidisciplinary management of patients with severe sepsis from their initial deterioration at ward level, transfer to the diagnostic imaging suite, and intraoperative management for emergency surgery. The timely administration of appropriate i.v. antimicrobial therapy is a crucial step in the care of patients with severe sepsis who may require surgery to control the source of sepsis. Preoperative resuscitation, aimed at optimizing major organ perfusion, is based on judicious use of fluids, vasopressors, and inotropes. Intraoperative anaesthesia management requires careful induction and maintenance of anaesthesia, optimizing intravascular volume status, avoidance of lung injury during mechanical ventilation, and ongoing monitoring of arterial blood gases, lactate concentration, haematological and renal indices, and electrolyte levels. Postoperative care overlaps with ongoing management of the severe sepsis syndrome patient in the intensive care unit. These patients are by definition, high risk, already requiring multiple supports, and require experienced and skilful decision-making to optimize their chances of a favourable outcome. Similar to acute myocardial infarction, stroke, or acute trauma, the initial hours (golden hours) of clinical management of severe sepsis represent an important opportunity to reduce morbidity and mortality. Rapid clinical assessment, resuscitation and surgical management by a focused multidisciplinary team, and early effective antimicrobial therapy are the key components to improved patient outcome.

Kynurenine-3-monooxygenase inhibition prevents multiple organ failure in rodent models of acute pancreatitis.

PubMed

Mole, Damian J; Webster, Scott P; Uings, Iain; Zheng, Xiaozhong; Binnie, Margaret; Wilson, Kris; Hutchinson, Jonathan P; Mirguet, Olivier; Walker, Ann; Beaufils, Benjamin; Ancellin, Nicolas; Trottet, Lionel; Bénéton, Véronique; Mowat, Christopher G; Wilkinson, Martin; Rowland, Paul; Haslam, Carl; McBride, Andrew; Homer, Natalie Z M; Baily, James E; Sharp, Matthew G F; Garden, O James; Hughes, Jeremy; Howie, Sarah E M; Holmes, Duncan S; Liddle, John; Iredale, John P

2016-02-01

Acute pancreatitis (AP) is a common and devastating inflammatory condition of the pancreas that is considered to be a paradigm of sterile inflammation leading to systemic multiple organ dysfunction syndrome (MODS) and death. Acute mortality from AP-MODS exceeds 20% (ref. 3), and the lifespans of those who survive the initial episode are typically shorter than those of the general population. There are no specific therapies available to protect individuals from AP-MODS. Here we show that kynurenine-3-monooxygenase (KMO), a key enzyme of tryptophan metabolism, is central to the pathogenesis of AP-MODS. We created a mouse strain that is deficient for Kmo (encoding KMO) and that has a robust biochemical phenotype that protects against extrapancreatic tissue injury to the lung, kidney and liver in experimental AP-MODS. A medicinal chemistry strategy based on modifications of the kynurenine substrate led to the discovery of the oxazolidinone GSK180 as a potent and specific inhibitor of KMO. The binding mode of the inhibitor in the active site was confirmed by X-ray co-crystallography at 3.2 Å resolution. Treatment with GSK180 resulted in rapid changes in the levels of kynurenine pathway metabolites in vivo, and it afforded therapeutic protection against MODS in a rat model of AP. Our findings establish KMO inhibition as a novel therapeutic strategy in the treatment of AP-MODS, and they open up a new area for drug discovery in critical illness.

Mental health screening in women with severe pelvic organ prolapse, chronic fourth-degree obstetric tear and genital tract fistula in western Uganda.

PubMed

Krause, Hannah G; Hall, Barbara A; Ng, Shu-Kay; Natukunda, Harriet; Singasi, Isaac; Goh, Judith T W

2017-06-01

High levels of mental health dysfunction have been identified in women with genital tract fistula. The aim of this study was to use the General Health Questionnaire-28 (GHQ-28) to screen women in western Uganda with severe pelvic organ prolapse, chronic fourth-degree obstetric tear and genital tract fistula for risk of mental health dysfunction. Women undergoing surgery for severe pelvic organ prolapse, chronic fourth-degree obstetric tear, and genital tract fistula were interviewed using the GHQ-28 to screen for the risk of mental health dysfunction. A total of 125 women completed the GHQ-28, including 22 with pelvic organ prolapse, 47 with fourth-degree obstetric tear, 21 with genital tract fistula, and 35 controls. Nearly all women with these serious gynaecological conditions were positive for the risk of mental health dysfunction. In the domain assessing symptoms of severe depression, women with fourth-degree obstetric tear and genital tract fistula scored higher than women with pelvic organ prolapse. A significant risk of mental health dysfunction was identified in women with severe pelvic organ prolapse and chronic fourth-degree obstetric tear. These rates are similar to the high rates of mental health dysfunction in women with genital tract fistula. Identification and management of mental health dysfunction in women with these conditions should be a priority.

Neuroanatomy and Physiology of Brain Dysfunction in Sepsis.

PubMed

Mazeraud, Aurelien; Pascal, Quentin; Verdonk, Franck; Heming, Nicholas; Chrétien, Fabrice; Sharshar, Tarek

2016-06-01

Sepsis-associated encephalopathy (SAE), a complication of sepsis, is often complicated by acute and long-term brain dysfunction. SAE is associated with electroencephalogram pattern changes and abnormal neuroimaging findings. The major processes involved are neuroinflammation, circulatory dysfunction, and excitotoxicity. Neuroinflammation and microcirculatory alterations are diffuse, whereas excitotoxicity might occur in more specific structures involved in the response to stress and the control of vital functions. A dysfunction of the brainstem, amygdala, and hippocampus might account for the increased mortality, psychological disorders, and cognitive impairment. This review summarizes clinical and paraclinical features of SAE and describes its mechanisms at cellular and structural levels. Copyright © 2016 Elsevier Inc. All rights reserved.

Intermittent, noncyclic dysfunction of a mechanical aortic prosthesis by pannus formation.

PubMed

Giroux, Sylvie K; Labinaz, Marino X; Grisoli, Dominique; Klug, Andrew P; Veinot, John P; Burwash, Ian G

2010-01-01

Mechanical aortic prosthesis dysfunction can result from thrombosis or pannus formation. Pannus formation usually restricts systolic excursion of the occluding disk, resulting in progressive stenosis of the aortic prosthesis. Intermittent dysfunction of a mechanical aortic prosthesis is usually ascribed to thrombus formation. We describe an unusual case of intermittent, noncyclic dysfunction of a mechanical aortic prosthesis due to pannus formation in the absence of systolic restriction of disk excursion that presented with intermittent massive aortic regurgitation, severe ischemia, and shock. Pannus formation should be considered as a potential cause of acute intermittent severe aortic regurgitation in a patient with a mechanical aortic prosthesis.

Macrophages: contributors to allograft dysfunction, repair, or innocent bystanders?

PubMed

Mannon, Roslyn B

2012-02-01

Macrophages are members of the innate immune response. However, their role in the adaptive immune response is not known. The purpose of this review is to highlight our current understanding of macrophage structure and function and how they may participate in allograft injury. Studies in acute kidney injury models identify macrophages as key mediators of inflammatory injury, while more recent studies indicate that they may play a reparative role, depending on phenotype - M1 or M2 type macrophages. Mregs, generated in vitro, appear to have immune suppressive abilities and a unique phenotype. In solid-organ transplant, the emphasis of studies has been on acute or chronic injury. These data are derived from animal models using depletion of macrophages or antagonizing their activation and inflammatory responses. The relative contribution of macrophage phenotype in transplantation has not been explored. These studies suggest that macrophages play an injurious role in acute cellular allograft rejection, as well as in chronic injury. Infiltration of an allograft with macrophages is also associated with worse graft function and poor prognosis. Further studies are needed to understand the mechanisms of macrophage-mediated injury, explore their potential reparative role, and determine if they or their functional products are biomarkers of poor graft outcomes.

Ritonavir and disulfiram may be synergistic in lowering active interleukin-18 levels in acute pancreatitis, and thereby hasten recovery.

PubMed

Kast, Richard Eric

2008-05-08

Interleukin-18 (IL-18) is one of the mediators of both pancreas damage and systemic complications like hypotension and multi-organ dysfunction during acute pancreatitis. IL-18 is generated intracellularly from pro-IL-18 by caspase-1 mediated proteolysis. Active caspase-1 itself is generated intracellularly by the action of the inflammasome, autocatalysis and other stimuli. The anti-retroviral drug ritonavir inhibits conversion of inactive pro-caspase-1 to active caspase-1. Since ritonavir is well tolerated in short-term use it may therefore prove useful in treating acute pancreatitis by lowering caspase-1 mediated IL-18 formation and the many inflammatory mediators downstream from that. The alcoholism treatment drug disulfiram has been in continuous use since the 1950s. It likewise has a low risk profile. Disulfiram inhibits several human proteases, among them caspase-1. Given the current morbidity and mortality of pancreatitis, research should be directed to ritonavir and disulfiram as treatment options for illnesses like pancreatitis where excessive IL-18 contributes to pathology. The first clinically used angiotensin converting enzyme inhibitor, captopril, has shown potent caspase-1 inhibiting activity as well and should be investigated in rodent models of human pancreatitis.

Structural and mechanistic basis of differentiated inhibitors of the acute pancreatitis target kynurenine-3-monooxygenase

NASA Astrophysics Data System (ADS)

Hutchinson, Jonathan P.; Rowland, Paul; Taylor, Mark R. D.; Christodoulou, Erica M.; Haslam, Carl; Hobbs, Clare I.; Holmes, Duncan S.; Homes, Paul; Liddle, John; Mole, Damian J.; Uings, Iain; Walker, Ann L.; Webster, Scott P.; Mowat, Christopher G.; Chung, Chun-Wa

2017-06-01

Kynurenine-3-monooxygenase (KMO) is a key FAD-dependent enzyme of tryptophan metabolism. In animal models, KMO inhibition has shown benefit in neurodegenerative diseases such as Huntington's and Alzheimer's. Most recently it has been identified as a target for acute pancreatitis multiple organ dysfunction syndrome (AP-MODS); a devastating inflammatory condition with a mortality rate in excess of 20%. Here we report and dissect the molecular mechanism of action of three classes of KMO inhibitors with differentiated binding modes and kinetics. Two novel inhibitor classes trap the catalytic flavin in a previously unobserved tilting conformation. This correlates with picomolar affinities, increased residence times and an absence of the peroxide production seen with previous substrate site inhibitors. These structural and mechanistic insights culminated in GSK065(C1) and GSK366(C2), molecules suitable for preclinical evaluation. Moreover, revising the repertoire of flavin dynamics in this enzyme class offers exciting new opportunities for inhibitor design.

Role of NMDA Receptor-Mediated Glutamatergic Signaling in Chronic and Acute Neuropathologies

PubMed Central

2016-01-01

N-Methyl-D-aspartate receptors (NMDARs) have two opposing roles in the brain. On the one hand, NMDARs control critical events in the formation and development of synaptic organization and synaptic plasticity. On the other hand, the overactivation of NMDARs can promote neuronal death in neuropathological conditions. Ca2+ influx acts as a primary modulator after NMDAR channel activation. An imbalance in Ca2+ homeostasis is associated with several neurological diseases including schizophrenia, Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. These chronic conditions have a lengthy progression depending on internal and external factors. External factors such as acute episodes of brain damage are associated with an earlier onset of several of these chronic mental conditions. Here, we will review some of the current evidence of how traumatic brain injury can hasten the onset of several neurological conditions, focusing on the role of NMDAR distribution and the functional consequences in calcium homeostasis associated with synaptic dysfunction and neuronal death present in this group of chronic diseases. PMID:27630777

Structural and mechanistic basis of differentiated inhibitors of the acute pancreatitis target kynurenine-3-monooxygenase.

PubMed

Hutchinson, Jonathan P; Rowland, Paul; Taylor, Mark R D; Christodoulou, Erica M; Haslam, Carl; Hobbs, Clare I; Holmes, Duncan S; Homes, Paul; Liddle, John; Mole, Damian J; Uings, Iain; Walker, Ann L; Webster, Scott P; Mowat, Christopher G; Chung, Chun-Wa

2017-06-12

Kynurenine-3-monooxygenase (KMO) is a key FAD-dependent enzyme of tryptophan metabolism. In animal models, KMO inhibition has shown benefit in neurodegenerative diseases such as Huntington's and Alzheimer's. Most recently it has been identified as a target for acute pancreatitis multiple organ dysfunction syndrome (AP-MODS); a devastating inflammatory condition with a mortality rate in excess of 20%. Here we report and dissect the molecular mechanism of action of three classes of KMO inhibitors with differentiated binding modes and kinetics. Two novel inhibitor classes trap the catalytic flavin in a previously unobserved tilting conformation. This correlates with picomolar affinities, increased residence times and an absence of the peroxide production seen with previous substrate site inhibitors. These structural and mechanistic insights culminated in GSK065(C1) and GSK366(C2), molecules suitable for preclinical evaluation. Moreover, revising the repertoire of flavin dynamics in this enzyme class offers exciting new opportunities for inhibitor design.

Structural and mechanistic basis of differentiated inhibitors of the acute pancreatitis target kynurenine-3-monooxygenase

PubMed Central

Hutchinson, Jonathan P.; Rowland, Paul; Taylor, Mark R. D.; Christodoulou, Erica M.; Haslam, Carl; Hobbs, Clare I.; Holmes, Duncan S.; Homes, Paul; Liddle, John; Mole, Damian J.; Uings, Iain; Walker, Ann L.; Webster, Scott P.; Mowat, Christopher G.; Chung, Chun-wa

2017-01-01

Kynurenine-3-monooxygenase (KMO) is a key FAD-dependent enzyme of tryptophan metabolism. In animal models, KMO inhibition has shown benefit in neurodegenerative diseases such as Huntington's and Alzheimer's. Most recently it has been identified as a target for acute pancreatitis multiple organ dysfunction syndrome (AP-MODS); a devastating inflammatory condition with a mortality rate in excess of 20%. Here we report and dissect the molecular mechanism of action of three classes of KMO inhibitors with differentiated binding modes and kinetics. Two novel inhibitor classes trap the catalytic flavin in a previously unobserved tilting conformation. This correlates with picomolar affinities, increased residence times and an absence of the peroxide production seen with previous substrate site inhibitors. These structural and mechanistic insights culminated in GSK065(C1) and GSK366(C2), molecules suitable for preclinical evaluation. Moreover, revising the repertoire of flavin dynamics in this enzyme class offers exciting new opportunities for inhibitor design. PMID:28604669

Assessment and clinical implications of cognitive impairment in acutely ill geriatric patients using a revised simplified short-term memory recall test (STMT-R).

PubMed

Yamamoto, Hiroshi; Ogawa, Kenichi; Huaman Battifora, Henry; Yamamuro, Kaori; Ishitake, Tatsuya

2018-05-24

Cognitive dysfunction due to delirium or dementia is a common finding in acutely ill geriatric patients, but often remains undetected. A brief and sensitive clinical identification method could prevent errors or complications while evaluating the mental status of elderly patients. To evaluate the usefulness and clinical implications of the revised simplified short-term memory recall test (STMT-R) in geriatric patients admitted in the emergency department; with age, gender, dementia history, serum albumin, underlying diseases and clinical outcome used as comparative factors. Mini-mental state examination and STMT-R scores were initially compared and a positive correlation was observed (r = 0.66, p < 0.001). Subsequently, 885 inpatients aged over 50 years underwent STMT-R evaluation between October 2014 and September 2015. We considered as cognitive dysfunction STMT-R scores ≤ 4 of a maximum score of 8. Among enrolled patients, 52.2% were female and the mean age was 78.9 years. There were 159 patients who were unable to complete the test (incomplete testing group). We observed cognitive dysfunction in 460 patients, while 266 did not have cognitive dysfunction. There were significant differences between those with and without cognitive dysfunction in terms of age, dementia history, underlying respiratory diseases, and hospital outcome. Cognitive dysfunction at admission can have a negative effect on the hospital outcomes of elderly patients. Age, a history of dementia and underlying respiratory diseases may also influence cognitive functional decline.

Pituitary and/or hypothalamic dysfunction following moderate to severe traumatic brain injury: Current perspectives

PubMed Central

Javed, Zeeshan; Qamar, Unaiza; Sathyapalan, Thozhukat

2015-01-01

There is an increasing deliberation regarding hypopituitarism following traumatic brain injury (TBI) and recent data have suggested that pituitary dysfunction is very common among survivors of patients having moderate-severe TBI which may evolve or resolve over time. Due to high prevalence of pituitary dysfunction after moderate-severe TBI and its association with increased morbidity and poor recovery and the fact that it can be easily treated with hormone replacement, it has been suggested that early detection and treatment is necessary to prevent long-term neurological consequences. The cause of pituitary dysfunction after TBI is still not well understood, but evidence suggests few possible primary and secondary causes. Results of recent studies focusing on the incidence of hypopituitarism in the acute and chronic phases after TBI are varied in terms of severity and time of occurrence. Although the literature available does not show consistent values and there is difference in study parameters and diagnostic tests used, it is clear that pituitary dysfunction is very common after moderate to severe TBI and patients should be carefully monitored. The exact timing of development cannot be predicted but has suggested regular assessment of pituitary function up to 1 year after TBI. In this narrative review, we aim to explore the current evidence available regarding the incidence of pituitary dysfunction in acute and chronic phase post-TBI and recommendations for screening and follow-up in these patients. We will also focus light over areas in this field worthy of further investigation. PMID:26693424

Outcome and prognostic factors of malaria-associated acute kidney injury requiring hemodialysis: A single center experience

PubMed Central

Kute, V. B.; Shah, P. R.; Munjappa, B. C.; Gumber, M. R.; Patel, H. V.; Jain, S. H.; Engineer, D. P.; Naresh, V. V. Sai; Vanikar, A. V.; Trivedi, H. L.

2012-01-01

Acute kidney injury (AKI) is one of the most dreaded complications of severe malaria. We carried out prospective study in 2010, to describe clinical characteristics, laboratory parameters, prognostic factors, and outcome in 59 (44 males, 15 females) smear-positive malaria patients with AKI. The severity of illness was assessed using Acute Physiology and Chronic Health Evaluation (APACHE) II, Sequential Organ Failure Assessment (SOFA) score, Multiple Organ Dysfunction Score (MODS), and Glasgow Coma Scale (GCS) scores. All patients received artesunate and hemodialysis (HD). Mean age of patients was 33.63 ± 14 years. Plasmodium falciparum malaria was seen in 76.3% (n = 45), Plasmodium vivax in 16.9% (n = 10), and mixed infection in 6.8% (n = 4) patients. Presenting clinical features were fever (100%), nausea-vomiting (85%), oliguria (61%), abdominal pain/tenderness (50.8%), and jaundice (74.5%). Mean APACHE II, SOFA, MODS, and GCS scores were 18.1 ± 3, 10.16 ± 3.09, 9.71 ± 2.69, and 14.15 ± 1.67, respectively, all were higher among patients who died than among those who survived. APACHE II ≥20, SOFA and MODS scores ≥12 were associated with higher mortality (P < 0.05). 34% patients received blood component transfusion and exchange transfusion was done in 15%. Mean number of HD sessions required was 4.59 ± 3.03. Renal biopsies were performed in five patients (three with patchy cortical necrosis and two with acute tubular necrosis). 81.3% of patients had complete renal recovery and 11.8% succumbed to malaria. Prompt diagnosis, timely HD, and supportive therapy were associated with improved survival and recovery of kidney functions in malarial with AKI. Mortality was associated with higher APACHE II, SOFA, MODS, GCS scores, requirement of inotrope, and ventilator support. PMID:22279340

Perirenal space blocking restores gastrointestinal function in patients with severe acute pancreatitis

PubMed Central

Sun, Jun-Jun; Chu, Zhi-Jie; Liu, Wei-Feng; Qi, Shi-Fang; Yang, Yan-Hui; Ge, Peng-Lei; Zhang, Xiao-Hui; Li, Wen-Sheng; Yang, Cheng; Zhang, Yu-Ming

2013-01-01

AIM: To investigate effects of perirenal space blocking (PSB) on gastrointestinal function in patients with severe acute pancreatitis (SAP). METHODS: Forty patients with SAP were randomly allocated to receive PSB or no PSB (NPSB). All the SAP patients received specialized medical therapy (SMT). Patients in the PSB group received PSB + SMT when hospitalized and after diagnosis, whereas patients in the NPSB group only received SMT. A modified gastrointestinal failure (GIF) scoring system was used to assess the gastrointestinal function in SAP patients after admission. Pain severity (visual analog scale, 0 to 100) was monitored every 24 h for 72 h. RESULTS: Modified GIF score decreased in both groups during the 10-d study period. The median score decrease was initially significantly greater in the PSB group than in the NPSB group after PSB was performed. During the 72-h study period, pain intensity decreased in both groups. The median pain decrease was significantly greater in the PSB group than in the NPSB group at single time points. Patients in the PSB group had significantly lower incidences of hospital mortality, multiple organ dysfunction syndrome, systemic inflammatory response syndrome, and pancreatic infection, and stayed in the intensive care unit for a shorter duration. However, no difference in terms of operation incidence was found between the two groups. CONCLUSION: PSB could ameliorate gastrointestinal dysfunction or failure during the early stage of SAP. Moreover, PSB administration could improve prognosis and decrease the mortality of SAP patients. PMID:24379596

Circulating intestinal fatty acid-binding protein (I-FABP) levels in acute decompensated heart failure.

PubMed

Kitai, Takeshi; Kim, Yong-Hyun; Kiefer, Kathryn; Morales, Rommel; Borowski, Allen G; Grodin, Justin L; Tang, W H Wilson

2017-06-01

Venous congestion has become increasingly recognized as a potential contributor to end-organ dysfunction in heart failure. Elevated I-FABP, which is excreted specifically from damaged intestinal epithelial cells, has been found in patients with abdominal hypertension and intestinal ischemia. We hypothesize that elevated intestinal fatty acid-binding protein (I-FABP) levels would identify patients with more advanced heart failure who have venous and intestinal congestion. Baseline serum I-FABP levels were measured in 69 acute decompensated heart failure (ADHF) patients admitted to the intensive care unit for invasive hemodynamic monitoring and tailored medical therapy. Comprehensive echocardiography examinations were performed in all study patients, and clinical outcomes (death, cardiac transplant or left ventricular assist device placement) were assessed. The median circulating I-FABP level was 853pg/ml (interquartile range: 533 to 1448pg/ml). Age, gender, race, and baseline comorbidities were comparable between patients with low and high I-FABP levels. Although there were no significant correlations between I-FABP levels and invasively-measured hemodynamic parameters nor echocardiographic parameters, patients with higher I-FABP levels (≥853g/ml) had significantly worse clinical outcomes compared to those with lower I-FABP levels (<853pg/ml, P=0.025). Circulating I-FABP levels had no association with invasively-measured hemodynamic parameters, but were associated with adverse clinical outcomes in patients with ADHF with systolic dysfunction. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Primary tuberculosis of the eustachian tube causing otitis media with effusion.

PubMed

Oh, Se-Joon; Yi, Keun-Ik; Lee, Chang-Hoon; Cho, Kyu-Sup

2015-01-01

Eustachian tube (ET) dysfunction may cause pathological changes in the middle ear, including recurrent acute otitis media and otitis media with effusion (OME). Mechanical obstruction of the ET may be caused by primary tumor-like lesions arising from ET or secondary ET infiltration due to nasopharyngeal and parapharyngeal space tumor. Tuberculosis is known to affect almost every organ in the body, and it should be a concern of each and every medical practitioner. However, tuberculosis of the ET has not been reported in the literature previously. This article reports primary tuberculosis arising in the ET that presented as aural fullness and hearing disturbance in a patient with OME. Copyright © 2015 Elsevier Inc. All rights reserved.

Tenofovir Disoproxil Fumarate Fails to Prevent HIV Acquisition or the Establishment of a Viral Reservoir: Two Case Reports.

PubMed

Fox, Julie; Brady, Michael; Alexander, Hannah; Davies, Olubanke; Robinson, Nicola; Pace, Mathew; Else, Laura; Cason, John; Khoo, Saye; Back, David; Fidler, Sarah; Frater, John

2016-03-01

The use of antiretrovirals as pre-exposure prophylaxis (PrEP) is highly efficacious in HIV prevention. The World Health Organization recently recommended Truvada(®) (Gilead Sciences, Inc.) or tenofovir disoproxil fumarate (TDF) for high-risk individuals, with limited data for single-agent TDF PrEP in men who have sex with men (MSM). We report two cases of TDF PrEP failure in MSM who had received long-term TDF for hepatitis B infection and had therapeutic levels of drug immediately after HIV acquisition. Rapid antiretroviral intensification at diagnosis of acute HIV infection failed to limit immune dysfunction or prevent the establishment of a viral reservoir.

Neonatal circulatory failure due to acute hypertensive crisis: clinical and echocardiographic clues.

PubMed

Louw, Jacoba; Brown, Stephen; Thewissen, Liesbeth; Smits, Anne; Eyskens, Benedicte; Heying, Ruth; Cools, Bjorn; Levtchenko, Elena; Allegaert, Karel; Gewillig, Marc

2013-04-01

Circulatory failure due to acute arterial hypertension in the neonatal period is rare. This study was undertaken to assess the clinical and echocardiographic manifestations of circulatory failure resulting from acute neonatal hypertensive crisis. Neonatal and cardiology databases from 2007 to 2010 were reviewed. An established diagnosis of circulatory failure due to neonatal hypertension before the age of 14 days was required for inclusion. Six patients were identified. Five patients presented with circulatory failure due to an acute hypertensive crisis. The median age at presentation was 8.5 days (range: 6.0-11.0) with a median body weight of 3.58 kg (range: 0.86-4.70). Echocardiography demonstrated mild left ventricular dysfunction [median shortening fraction (SF) 25%, range 10-30] and mild aortic regurgitation in 83% (5/6) of patients. One patient with left ventricular dysfunction (SF = 17%) had a large apical thrombus. Two patients were hypotensive, and hypertension only became evident after restoration of cardiac output. Administration of intravenous milrinone was successful, with rapid improvement of the clinical condition. Left ventricular function normalised in all survivors. Early neonatal circulatory collapse due to arterial hypertension is a rare but potentially life-threatening condition. At presentation, hypotension, especially in the presence of a dysfunctional left ventricle, does not exclude a hypertensive crisis being the cause of circulatory failure. The echocardiographic presence of mild aortic regurgitation combined with left ventricular hypocontractility in a structurally normal heart should alert the physician to the presence of underlying hypertension.

A mathematical model of aging-related and cortisol induced hippocampal dysfunction

PubMed Central

McAuley, Mark T; Kenny, Rose Anne; Kirkwood, Thomas BL; Wilkinson, Darren J; Jones, Janette JL; Miller, Veronica M

2009-01-01

Background The hippocampus is essential for declarative memory synthesis and is a core pathological substrate for Alzheimer's disease (AD), the most common aging-related dementing disease. Acute increases in plasma cortisol are associated with transient hippocampal inhibition and retrograde amnesia, while chronic cortisol elevation is associated with hippocampal atrophy. Thus, cortisol levels could be monitored and managed in older people, to decrease their risk of AD type hippocampal dysfunction. We generated an in silicomodel of the chronic effects of elevated plasma cortisol on hippocampal activity and atrophy, using the systems biology mark-up language (SBML). We further challenged the model with biologically based interventions to ascertain if cortisol associated hippocampal dysfunction could be abrogated. Results The in silicoSBML model reflected the in vivoaging of the hippocampus and increased plasma cortisol and negative feedback to the hypothalamic pituitary axis. Aging induced a 12% decrease in hippocampus activity (HA), increased to 30% by acute and 40% by chronic elevations in cortisol. The biological intervention attenuated the cortisol associated decrease in HA by 2% in the acute cortisol simulation and by 8% in the chronic simulation. Conclusion Both acute and chronic elevations in cortisol secretion increased aging-associated hippocampal atrophy and a loss of HA in the model. We suggest that this first SMBL model, in tandem with in vitroand in vivostudies, may provide a backbone to further frame computational cortisol and brain aging models, which may help predict aging-related brain changes in vulnerable older people. PMID:19320982

Can the Pediatric Logistic Organ Dysfunction-2 Score on Day 1 Be Used in Clinical Criteria for Sepsis in Children?

PubMed

Leclerc, Francis; Duhamel, Alain; Deken, Valérie; Grandbastien, Bruno; Leteurtre, Stéphane

2017-08-01

A recent task force has proposed the use of Sequential Organ Failure Assessment in clinical criteria for sepsis in adults. We sought to evaluate the predictive validity for PICU mortality of the Pediatric Logistic Organ Dysfunction-2 and of the "quick" Pediatric Logistic Organ Dysfunction-2 scores on day 1 in children with suspected infection. Secondary analysis of the database used for the development and validation of the Pediatric Logistic Organ Dysfunction-2. Nine university-affiliated PICUs in Europe. Only children with hypotension-low systolic blood pressure or low mean blood pressure using age-adapted cutoffs-and lactatemia greater than 2 mmol/L were considered in shock. We developed the quick Pediatric Logistic Organ Dysfunction-2 score on day 1 including tachycardia, hypotension, and altered mentation (Glasgow < 11): one point for each variable (range, 0-3). Outcome was mortality at PICU discharge. Discrimination (Area under receiver operating characteristic curve-95% CI) and calibration (goodness of fit test) of the scores were studied. This study included 862 children with suspected infection (median age: 12.3 mo; mortality: n = 60 [7.0%]). Area under the curve of the Pediatric Logistic Organ Dysfunction-2 score on day 1 was 0.91 (0.86-0.96) in children with suspected infection, 0.88 (0.79-0.96) in those with low systolic blood pressure and hyperlactatemia, and 0.91 (0.85-0.97) in those with low mean blood pressure and hyperlactatemia; calibration p value was 0.03, 0.36, and 0.49, respectively. A Pediatric Logistic Organ Dysfunction-2 score on day 1 greater than or equal to 8 reflected an overall risk of mortality greater than or equal to 9.3% in children with suspected infection. Area under the curve of the quick Pediatric Logistic Organ Dysfunction-2 score on day 1 was 0.82 (0.76-0.87) with systolic blood pressure or mean blood pressure; calibration p value was 0.89 and 0.72, respectively. A score greater than or equal to 2 reflected a mortality risk greater than or equal to 19.8% with systolic blood pressure and greater than or equal to 15.9% with mean blood pressure. Among children admitted to PICU with suspected infection, Pediatric Logistic Organ Dysfunction-2 score on day 1 was highly predictive of PICU mortality suggesting its use to standardize definitions and diagnostic criteria of pediatric sepsis. Further studies are needed to determine the usefulness of the quick Pediatric Logistic Organ Dysfunction-2 score on day 1 outside of the PICU.

Endotoxin Tolerance Variation over 24 h during Porcine Endotoxemia: Association with Changes in Circulation and Organ Dysfunction

PubMed Central

Castegren, Markus; Skorup, Paul; Lipcsey, Miklós; Larsson, Anders; Sjölin, Jan

2013-01-01

Endotoxin tolerance (ET), defined as reduced inflammatory responsiveness to endotoxin challenge following a first encounter with endotoxin, is an extensively studied phenomenon. Although reduced mortality and morbidity in the presence of ET has been demonstrated in animal studies, little is known about the temporal development of ET. Further, in acute respiratory distress syndrome ET correlates to the severity of the disease, suggesting a complicated relation between ET and organ dysfunction. Eighteen pigs were subjected to intensive care and a continuous endotoxin infusion for 24 h with the aim to study the time course of early ET and to relate ET to outcome in organ dysfunction. Three animals served as non-endotoxemic controls. Blood samples for cytokine analyses were taken and physiological variables registered every third hour. Production of TNF-α, IL-6, and IL-10 before and after endotoxin stimulation ex vivo was measured. The difference between cytokine values after and before ex vivo LPS stimulation (Δ-values) was calculated for all time points. ΔTNF-α was employed as the principal marker of ET and lower ΔTNF-α values were interpreted as higher levels of ET. During endotoxin infusion, there was suppression of ex vivo productions of TNF-α and IL-6 but not of IL-10 in comparison with that at 0 h. The ex vivo TNF-α values followed another time concentration curve than those in vivo. ΔTNF-α was at the lowest already at 6 h, followed by an increase during the ensuing hours. ΔTNF-α at 6 h correlated positively to blood pressure and systemic vascular resistance and negatively to cardiac index at 24 h. In this study a temporal variation of ET was demonstrated that did not follow changes in plasma TNF-α concentrations. Maximal ET occurred early in the course and the higher the ET, the more hyperdynamic the circulation 18 h later. PMID:23326400

Clinical diagnosis of sepsis and the combined use of biomarkers and culture- and non-culture-based assays.

PubMed

Bloos, Frank

2015-01-01

Sepsis is among the most common causes of death in hospitalized patients, and early recognition followed by immediate initiation of therapy is an important concept to improve survival in these patients. According to the definition of sepsis, diagnosis of sepsis requires the recognition of the systemic inflammatory response syndrome (SIRS) caused by infection as well as recognition of possible infection-related organ dysfunctions for diagnosis of severe sepsis or septic shock. Both SIRS and organ dysfunctions may occur frequently in hospitalized patients for various reasons. However, the fast recognition of acute infection as a cause of SIRS and newly developed organ dysfunction may be a demanding task since culture-based results of microbiological samples will be available only days after onset of symptoms. Biomarkers and PCR-based pathogen detection may help the physician in differentiating SIRS from sepsis. Procalcitonin (PCT) is the best investigated biomarker for this purpose. Furthermore, the current data support the usage of PCT for guidance of antimicrobial therapy. C-reactive protein (CRP) may be used to monitor the course of infection but has only limited discriminative capabilities. Interleukin-6 is widely used for its fast response to the infectious stimulus, but conclusive data for the application of this biomarker are missing. None of the available biomarkers can by itself reliably differentiate SIRS from sepsis but can aid and shorten the decision process. PCR-based pathogen detection can theoretically shorten the recognition of the underlying pathogen to about 8 h. However, this technique is expensive and requires additional staff in the laboratory; controlled prospective studies are missing. Although current studies suggest that PCR-based pathogen detection may be useful to shorten time to adequate antimicrobial therapy and diagnose invasive Candida infections, no general recommendations about the application of PCR for the diagnosis of sepsis can be given.

Diagnostic value of plasma and bronchoalveolar lavage samples in acute lung allograft rejection: differential cytology.

PubMed

Speck, Nicole E; Schuurmans, Macé M; Murer, Christian; Benden, Christian; Huber, Lars C

2016-06-21

Diagnosis of acute lung allograft rejection is currently based on transbronchial lung biopsies. Additional methods to detect acute allograft dysfunction derived from plasma and bronchoalveolar lavage samples might facilitate diagnosis and ultimately improve allograft survival. This review article gives an overview of the cell profiles of bronchoalveolar lavage and plasma samples during acute lung allograft rejection. The value of these cells and changes within the pattern of differential cytology to support the diagnosis of acute lung allograft rejection is discussed. Current findings on the topic are highlighted and trends for future research are identified.

Right Hemispatial Neglect: Frequency and Characterization Following Acute Left Hemisphere Stroke

ERIC Educational Resources Information Center

Kleinman, Jonathan T.; Newhart, Melissa; Davis, Cameron; Heidler-Gary, Jennifer; Gottesman, Rebecca F.; Hillis, Argye E.

2007-01-01

The frequency of various types of unilateral spatial neglect and associated areas of neural dysfunction after left hemisphere stroke are not well characterized. Unilateral spatial neglect (USN) in distinct spatial reference frames have been identified after acute right, but not left hemisphere stroke. We studied 47 consecutive right handed…

Investigating Metacognition, Cognition, and Behavioral Deficits of College Students with Acute Traumatic Brain Injuries

ERIC Educational Resources Information Center

Martinez, Sarah; Davalos, Deana

2016-01-01

Objective: Executive dysfunction in college students who have had an acute traumatic brain injury (TBI) was investigated. The cognitive, behavioral, and metacognitive effects on college students who endorsed experiencing a brain injury were specifically explored. Participants: Participants were 121 college students who endorsed a mild TBI, and 121…

Opening the Door: The Experience of Chronic Critical Illness in a Long-Term Acute Care Hospital.

PubMed

Lamas, Daniela J; Owens, Robert L; Nace, R Nicholas; Massaro, Anthony F; Pertsch, Nathan J; Gass, Jonathon; Bernacki, Rachelle E; Block, Susan D

2017-04-01

Chronically critically ill patients have recurrent infections, organ dysfunction, and at least half die within 1 year. They are frequently cared for in long-term acute care hospitals, yet little is known about their experience in this setting. Our objective was to explore the understanding and expectations and goals of these patients and surrogates. We conducted semi-structured interviews with chronically critically ill long-term acute care hospital patients or surrogates. Conversations were recorded, transcribed, and analyzed. One long-term acute care hospital. Chronically critically ill patients, defined by tracheotomy for prolonged mechanical ventilation, or surrogates. Semi-structured conversation about quality of life, expectations, and planning for setbacks. A total of 50 subjects (30 patients and 20 surrogates) were enrolled. Thematic analyses demonstrated: 1) poor quality of life for patients; 2) surrogate stress and anxiety; 3) optimistic health expectations; 4) poor planning for medical setbacks; and 5) disruptive care transitions. Nearly 80% of patient and their surrogate decision makers identified going home as a goal; 38% were at home at 1 year. Our study describes the experience of chronically critically ill patients and surrogates in an long-term acute care hospital and the feasibility of patient-focused research in this setting. Our findings indicate overly optimistic expectations about return home and unmet palliative care needs, suggesting the need for integration of palliative care within the long-term acute care hospital. Further research is also needed to more fully understand the challenges of this growing population of ICU survivors.

[EFFICIENCY OF SEROTONIN ADIPINATE IN INTESTINAL DYSFUNCTION IN PATIENTS AFTER COLORECTAL OPERATIONS].

PubMed

Stakanov, A V; Musaeva, T S

2015-01-01

We performed a retrospective analysis of case histories of acute colonic obstruction due to colon cancer A total of 291 patients were divided on two groups: 1--a control group (patients presenting risk of developing intestinal dysfunction with 'basic' therapy, n = 123); 2--the comparison group (n = 57) represented patients who were taken to optimize the post-operative period with the inclusion in the scheme of the basic treatment of serotonin adipinate. The use of serotonin adipinatein treatment of intestinal dysfunction allows fully restore bowel motility to 3rd day.

Heparin-Binding Protein Measurement Improves the Prediction of Severe Infection With Organ Dysfunction in the Emergency Department

PubMed Central

Arnold, Ryan; Boyd, John H.; Zindovic, Marko; Zindovic, Igor; Lange, Anna; Paulsson, Magnus; Nyberg, Patrik; Russell, James A.; Pritchard, David; Christensson, Bertil; Åkesson, Per

2015-01-01

Objectives: Early identification of patients with infection and at risk of developing severe disease with organ dysfunction remains a difficult challenge. We aimed to evaluate and validate the heparin-binding protein, a neutrophil-derived mediator of vascular leakage, as a prognostic biomarker for risk of progression to severe sepsis with circulatory failure in a multicenter setting. Design: A prospective international multicenter cohort study. Setting: Seven different emergency departments in Sweden, Canada, and the United States. Patients: Adult patients with a suspected infection and at least one of three clinical systemic inflammatory response syndrome criteria (excluding leukocyte count). Intervention: None. Measurements and Main Results: Plasma levels of heparin-binding protein, procalcitonin, C-reactive protein, lactate, and leukocyte count were determined at admission and 12–24 hours after admission in 759 emergency department patients with suspected infection. Patients were defined depending on the presence of infection and organ dysfunction. Plasma samples from 104 emergency department patients with suspected sepsis collected at an independent center were used to validate the results. Of the 674 patients diagnosed with an infection, 487 did not have organ dysfunction at enrollment. Of these 487 patients, 141 (29%) developed organ dysfunction within the 72-hour study period; 78.0% of the latter patients had an elevated plasma heparin-binding protein level (> 30 ng/mL) prior to development of organ dysfunction (median, 10.5 hr). Compared with other biomarkers, heparin-binding protein was the best predictor of progression to organ dysfunction (area under the receiver operating characteristic curve = 0.80). The performance of heparin-binding protein was confirmed in the validation cohort. Conclusion: In patients presenting at the emergency department, heparin-binding protein is an early indicator of infection-related organ dysfunction and a strong predictor of disease progression to severe sepsis within 72 hours. PMID:26468696

Hypothalamic-pituitary dysfunction following traumatic brain injury affects functional improvement during acute inpatient rehabilitation.

PubMed

Rosario, Emily R; Aqeel, Rubina; Brown, Meghan A; Sanchez, Gabriel; Moore, Colleen; Patterson, David

2013-01-01

To evaluate the occurrence of hypothalamic-pituitary dysfunction following a traumatic brain injury (TBI) and to determine its effect on functional improvement in acute inpatient rehabilitation. A retrospective chart review identified male patients with a primary diagnosis of TBI with or without a skull fracture, an onset date within 6 months prior to admission, and were 16 years of age or older. The percentage of individuals in this population with abnormal hormone levels was determined on the basis of the established normal reference range for each hormone assay. The functional independence measure, which assesses functional outcomes in acute inpatient rehabilitation, was used to examine the relationship between hormone levels and functional improvement. Hypothalamic-pituitary dysfunction was identified in nearly 70% of men following TBI. Hypogonadism, or low testosterone levels, was observed in 66% of the patients, followed by low levels of free T4 in 46% and low levels of insulin growth factor-1 in 26% of patients. Hypopituitarism associated with impaired functional recovery. Specifically, the functional independence measure change per day was significantly lower in patients with low levels of testosterone and insulin growth factor-1. These findings suggest the importance of testosterone and insulin growth factor-1 activity in the early stages of physical and cognitive rehabilitation.

Therapeutic effect of Tripterygium wilfordii Hook F multiglycosides on gut barrier dysfunction in rats with acute necrotizing pancreatitis.

PubMed

Wang, Jie; Wu, Gang; Ma, Baojin; Wu, Jianhua; Cai, Duan

2013-02-01

The aim of the current study was to investigate the therapeutic effect of Tripterygium wilfordii Hook F multiglycosides (TWG) on gut barrier dysfunction in rats with acute necrotizing pancreatitis (ANP). ANP was induced in rats using 3.5% sodium taurocholate. The rats were divided into 3 groups: the sham operation (SO), ANP and ANP+TWG groups. Biochemical and pathological change of pancreatic tissue and ileal mucosa, bacterial cultures and the survival rate were measured following surgery and treatment. TWG treatment significantly decreased amylase and lipase activities and plasma endotoxin and D-lactate levels. Edema and inflammation in the pancreas and ileal mucosa were alleviated. Positive bacterial cultures were significantly reduced. The survival rate of the rats in the ANP+TWG group was higher than that of the rats in the ANP group. TWG treatment showed beneficial effects by protecting the pancreas from bacterial infection caused by gut barrier dysfunction and improving the outcomes of the rats with ANP.

Protective role of testosterone in ischemia-reperfusion-induced acute kidney injury

PubMed Central

Soljancic, Andrea; Ruiz, Arnaldo Lopez; Chandrashekar, Kiran; Maranon, Rodrigo; Liu, Ruisheng; Juncos, Luis A.

2013-01-01

Men are at greater risk for renal injury and dysfunction after acute ischemia-reperfusion (I/R) than are women. Studies in animals suggest that the reason for the sex difference in renal injury and dysfunction after I/R is the protective effect of estrogens in females. However, a reduction in testosterone in men is thought to play an important role in mediating cardiovascular and renal disease, in general. In the present study, we tested the hypothesis that I/R of the kidney reduces serum testosterone, and that contributes to renal dysfunction and injury. Male rats that were subjected to renal ischemia of 40 min followed by reperfusion had a 90% reduction in serum testosterone by 3 h after reperfusion that remained at 24 h. Acute infusion of testosterone 3 h after reperfusion attenuated the increase in plasma creatinine and urinary kidney injury molecule-1 (KIM-1) at 24 h, prevented the reduction in outer medullary blood flow, and attenuated the increase in intrarenal TNF-α and the decrease in intrarenal VEGF at 48 h. Castration of males caused greater increases in plasma creatinine and KIM-1 at 24 h than in intact males with renal I/R, and treatment with anastrozole, an aromatase inhibitor, plus testosterone almost normalized plasma creatinine and KIM-1 in rats with renal I/R. These data show that renal I/R is associated with sustained reductions in testosterone, that testosterone repletion protects the kidney, whereas castration promotes renal dysfunction and injury, and that the testosterone-mediated protection is not conferred by conversion to estradiol. PMID:23552495

Acute Kidney Injury Enhances Outcome Prediction Ability of Sequential Organ Failure Assessment Score in Critically Ill Patients

PubMed Central

Chang, Chih-Hsiang; Fan, Pei-Chun; Chang, Ming-Yang; Tian, Ya-Chung; Hung, Cheng-Chieh; Fang, Ji-Tseng; Yang, Chih-Wei; Chen, Yung-Chang

2014-01-01

Introduction Acute kidney injury (AKI) is a common and serious complication in intensive care unit (ICU) patients and also often part of a multiple organ failure syndrome. The sequential organ failure assessment (SOFA) score is an excellent tool for assessing the extent of organ dysfunction in critically ill patients. This study aimed to evaluate the outcome prediction ability of SOFA and Acute Physiology and Chronic Health Evaluation (APACHE) III score in ICU patients with AKI. Methods A total of 543 critically ill patients were admitted to the medical ICU of a tertiary-care hospital from July 2007 to June 2008. Demographic, clinical and laboratory variables were prospectively recorded for post hoc analysis as predictors of survival on the first day of ICU admission. Results One hundred and eighty-seven (34.4%) patients presented with AKI on the first day of ICU admission based on the risk of renal failure, injury to kidney, failure of kidney function, loss of kidney function, and end-stage renal failure (RIFLE) classification. Major causes of the ICU admissions involved respiratory failure (58%). Overall in-ICU mortality was 37.9% and the hospital mortality was 44.7%. The predictive accuracy for ICU mortality of SOFA (areas under the receiver operating characteristic curves: 0.815±0.032) was as good as APACHE III in the AKI group. However, cumulative survival rates at 6-month follow-up following hospital discharge differed significantly (p<0.001) for SOFA score ≤10 vs. ≥11 in these ICU patients with AKI. Conclusions For patients coexisting with AKI admitted to ICU, this work recommends application of SOFA by physicians to assess ICU mortality because of its practicality and low cost. A SOFA score of ≥ “11” on ICU day 1 should be considered an indicator of negative short-term outcome. PMID:25279844

Perioperative renal outcome in cardiac surgical patients with preoperative renal dysfunction: aprotinin versus epsilon aminocaproic acid.

PubMed

Maslow, Andrew D; Chaudrey, Alyas; Bert, Arthur; Schwartz, Carl; Singh, Arun

2008-02-01

The administration of aprotinin to patients with pre-existing renal dysfunction who are undergoing cardiac surgery is controversial. Therefore, the authors present their experience with the use of aprotinin for patients with preoperative renal dysfunction who underwent elective cardiac surgery requiring cardiopulmonary bypass (CPB). Retrospective analysis. University hospital. Consecutive cardiac surgical patients with preoperative serum creatinine (SCr) > or =1.8 mg/dL undergoing nonemergent cardiac surgery requiring CPB. None. One hundred twenty-three patients either received epsilon aminocaproic acid (EACA, n = 82) or aprotinin (n = 41) as decided by the attending anesthesiologist and surgeon. Data were collected from the Society of Thoracic Surgeons database and from automated intraoperative anesthesia records. Renal function was assessed from measured serum creatinine (SCr) and calculated creatinine clearances (CrCls). Acute perioperative renal dysfunction was defined as a worsening of perioperative renal function by > or =25% and/or the need for hemodialysis (HD). Data were recorded as mean and standard deviation or percentage of population depending on whether the data were continuous or not. Data were compared by using an analysis of variance, chi-square analysis, Student paired and unpaired t tests, Fisher exact test, Wilcoxon rank sum test, and Mann-Whitney U test. A p value <0.05 was considered significant. Overall, 32% and 41% of patients had acute perioperative renal dysfunction measured by CrCl and SCr, respectively. Seven patients required HD (5.7%). Six of these 7 had complicated postoperative courses. Of all the variables measured, only the duration of the aortic crossclamp (AoXCl) and CPB were significantly associated with acute perioperative renal dysfunction. Acute perioperative renal dysfunction was associated with increased intensive care unit and hospital stays, postoperative blood transfusion, dialysis, and major infection. Aprotinin patients were significantly older (75.2 v 70.2 years, p < 0.05), had lower left ventricular ejection fraction (44.4% v 49.2%, p < 0.05), a greater preoperative history of congestive heart failure (63 v 44%, p < 0.05), a greater renal risk score (5.8 v 4.9, p < 0.05), and underwent more nonisolated coronary artery bypass graft surgeries (77% v 29%, p < 0.0001). CPB time (126.0 v 96.5 minutes, p < 0.001) and AoXCl duration (100.9 v 78.0 minutes, p < 0.005) were longer in the aprotinin group. Diabetes (60.5% v 41.5%, p < 0.05) and hypertension (90.1% v 73.2%, p < 0.05) were more prevalent in the EACA group. Baseline renal function and renal outcomes were not significantly different between the aprotinin and EACA groups. Six of the 7 patients who required HD received EACA (p = 0.1). The earliest SCr recorded > or =3 months after surgery was significantly lower in the aprotinin group compared with the EACA group (1.8 v 2.2 mg/dL, p < 0.05). Acute perioperative renal dysfunction was associated with worse patient outcome and longer CPB and AoXCl times. Demographic and surgical variables indicated that the sicker patients undergoing more complex surgeries were more likely to be treated with aprotinin. Although aprotinin patients had a higher renal risk score, the administration of aprotinin did not negatively impact renal outcome.

Acute Inactivation of the VHL gene Contributes to Protective Effects of Ischemic Preconditioning in the Mouse Kidney

PubMed Central

Iguchi, Mitsuko; Kakinuma, Yoshihiko; Kurabayashi, Atsushi; Sato, Takayuki; Shuin, Taro; Hong, Seung-Beom; Schmidt, Laura S.; Furihata, Mutsuo

2009-01-01

Background/Aims The von Hippel-Lindau (pVHL) protein functions as an E3 ubiquitin ligase, controlling the stability of hypoxia inducible factor (HIF). Pre-induction of HIF-1α before pathological insult activates a self-defense mechanism and suppresses further aggravation of organ or cellular injury by ischemia. We investigated whether acute inactivation of the VHL gene might play a role in the response of mice to ischemic renal injury. Methods We generated tamoxifen-inducible conditional VHL knockout (VHL-KO) mice to inactivate the VHL gene in an acute manner during renal ischemia-reperfusion injury (IRI) induced by bilateral clamping of kidney arteries. Renal IRI is characterized by renal dysfunction and tubular damage. Results After the procedure of IRI, blood urea nitrogen (BUN) and creatinine (CRN) levels in control mice were significantly higher (BUN, 138.10±13.03 mg/dL; CRN, 0.72±0.16 mg/dL) than in VHL-KO mice (BUN, 52.12±6.61 mg/dL; CRN, 0.24±0.04 mg/dL; BUN: p<0.05; CRN: p<0.05). Histologically, tubular injury scores were higher in control mice than in VHL-KO mice (p<0.05). Conclusion We suggest that the acute inactivation of the VHL gene contributes to protective effects of ischemic preconditioning in renal tubules of the mouse. PMID:18957870

Pelvic organ prolapse (POP) surgery: the evidence for the repairs.

PubMed

Gomelsky, Alex; Penson, David F; Dmochowski, Roger R

2011-06-01

What is known on the subject? and What does the study add? Substantial experience of the outcomes has been gathered regarding the acute and sub-acute experience with various types of corrective procedures for POP. These include long-term POP correction as well as more recent recognition of improvement in functional disorders associated with POP such as UI, colorectal dysfunction, and sexual dysfunction. Long-term follow-up is available for some of the older types of interventions and current multicentre trials are being accrued with longer term follow-up for new interventions including mesh-type repairs. The study adds a condensed and summarized version of the current literature regarding the various interventions for POP and also provides an overview of the current controversies and areas where knowledge is incomplete and in need of further elaboration for definitive answers regarding optimization of surgical care for POP. Our aim is to summarise the available data on the transvaginal placement of synthetic mesh for pelvic organ prolapse (POP) repair, with a focus on the outcomes and complications of commercial POP-repair kits. As the stability and durability of autologous tissues may be questionable, nonabsorbable, synthetic materials are an attractive alternative for providing additional support during POP surgery. These materials are not novel, and most have been used for many years in surgical applications, e.g. hernia repairs. While theoretically appealing, the implantation of synthetic mesh in the pelvis may be associated with inherent adverse consequences, such as erosion, extrusion, and infection. Additionally, the routine use of these materials may carry potential long-term complications, such as dyspareunia, chronic pelvic pain, and vaginal distortion. The success and failure of mesh-augmented POP repair is related not only to the synthetic material itself, but also to patient- and surgeon-related factors. Recent warnings by the USA Food and Drug Administration and other groups regarding adverse events further complicate the decision to use synthetic mesh. © 2011 THE AUTHORS; BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.

Acute kidney injury in critically ill child.

PubMed

Al-Jboor, Wejdan; Almardini, Reham; Al Bderat, Jwaher; Frehat, Mahdi; Al Masri, Hazem; Alajloni, Mohammad Saleh

2016-01-01

Acute kidney injury (AKI) is a common and serious complication in patients in the Pediatric Intensive Care Unit (PICU). We conducted this study to estimate the incidence and the mortality rate of AKI in critically ill children as well as to describe some other related factors. A retrospective study was conducted at PICU of Queen Rania Abdulla Children Hospital, Amman, Jordan for the period extending from May 2011 to June 2013. The medical records of all patients admitted during this period, and their demographic data were reviewed. Patients with AKI were identified, and management and outcomes were reviewed and analyzed. AKI was evaluated according to modified RIFLE criteria. Of the 372 patients admitted to PICU, 64 (17.2%) patients developed AKI. Of these 64 patients who had AKI, 28 (43.7%) patients reached RIFLE max of risk, 21 (32.8%) patients reached injury, and 15 (23.4%) reached failure. Mean Pediatric Risk of Mortality II score at admission was significantly higher in patients with AKI than those without P <0.001. The age ranged between one month and 14 years with the median age as 5.4 year. Thirty-five (54.7%) were males. Sepsis was the most common cause of AKI. The mortality rate in critically ill children without AKI was 58.7%, whereas increased in children with AKI to 73.4%. The mortality rate in patients who received renal replacement therapy was 71.4% and was higher (81.5%) in patients who received mechanical ventilation (95%, [confidence interval (CI)] 79.3-83.4%) and was significantly higher in patients with multi-organ system dysfunction 90.3% (95%, [CI] 88.7-92.5%). The incidence of AKI in critically ill children is high and increased their mortality rate and higher mortality seen in the younger age group, especially those below one year. High mortality rate was associated with multi-organ system dysfunction and the need for mechanical ventilation.

Hypoventilation improvement in an adult non-invasively ventilated patient with Rapid-onset Obesity with Hypothalamic Dysfunction Hypoventilation and Autonomic Dysregulation (ROHHAD).

PubMed

Graziani, Alessandro; Casalini, Pierpaolo; Mirici-Cappa, Federica; Pezzi, Giuseppe; Giuseppe Stefanini, Francesco

2016-01-01

Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) is a rare disease of unknown etiology, characterized by rapid-onset obesity in young children, hypoventilation, hypothalamic and autonomic dysfunction. Patients between the ages of 2 and 4 present with hyperphagia and weight gain, followed by neuro-hormonal dysfunction and central hypoventilation months or years later. Cardiac arrest may represent the fatal complication of alveolar hypoventilation and early mechanical ventilation is essential for the patient's life. In this paper, we describe a 22-year-old patient with ROHHAD syndrome who had an acute respiratory failure during nocturnal non-invasive ventilation (NIV).

Diastolic dysfunction in the critically ill patient.

PubMed

Suárez, J C; López, P; Mancebo, J; Zapata, L

2016-11-01

Left ventricular diastolic dysfunction is a common finding in critically ill patients. It is characterized by a progressive deterioration of the relaxation and the compliance of the left ventricle. Two-dimensional and Doppler echocardiography is a cornerstone in its diagnosis. Acute pulmonary edema associated with hypertensive crisis is the most frequent presentation of diastolic dysfunction critically ill patients. Myocardial ischemia, sepsis and weaning failure from mechanical ventilation also may be associated with diastolic dysfunction. The treatment is based on the reduction of pulmonary congestion and left ventricular filling pressures. Some studies have found a prognostic role of diastolic dysfunction in some diseases such as sepsis. The present review aims to analyze thoroughly the echocardiographic diagnosis and the most frequent scenarios in critically ill patients in whom diastolic dysfunction plays a key role. Copyright © 2016 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

Stroke patients who regain urinary continence in the first week after acute first-ever stroke have better prognosis than patients with persistent lower urinary tract dysfunction.

PubMed

Rotar, Melita; Blagus, Rok; Jeromel, Miran; Skrbec, Miha; Tršinar, Bojan; Vodušek, David B

2011-09-01

Urinary incontinence (UI) is a predictor of greater mortality and poor functional recovery; however published studies failed to evaluate lower urinary tract (LUT) function immediately after stroke. The aim of our study was to evaluate the course of LUT function in the first week after stroke, and its impact on prognosis. We included 100 consecutively admitted patients suffering first-ever stroke and evaluated them within 72 hours after stroke, after 7 days, 6 months, and 12 months. For LUT function assessment we used ultrasound measurement. The patients were divided into three groups: (i) patients who remained continent after stroke, (ii) patients who had LUT dysfunction in the acute phase but regained continence in the first week, and (iii) patients who did not regain normal LUT control in the first week. We assessed the influence of variables on death using the multiple logistic regression model. Immediately after stroke 58 patients had LUT dysfunction. The odds of dying in group with LUT dysfunction were significantly larger than odds in group without LUT dysfunction. Odds for death for patients who regained LUT function in 1 week after stroke were comparable to patients without LUT dysfunction. We confirmed that post-stroke UI is a predictor of greater mortality at 1 week, 6 months and 12 months after stroke. However, patients who regain normal bladder control in the first week have a comparable prognosis as the patients who do not have micturition disturbances following stroke. Copyright © 2011 Wiley-Liss, Inc.

Dietary choline requirements of women: effects of estrogen and genetic variation123

PubMed Central

Fischer, Leslie M; da Costa, Kerry-Ann; Kwock, Lester; Galanko, Joseph

2010-01-01

Background: Choline is obtained from the diet and from the biosynthesis of phosphatidylcholine. Phosphatidylcholine is catalyzed by the enzyme phosphatidylethanolamine-N-methyltransferase (PEMT), which is induced by estrogen. Because they have lower estrogen concentrations, postmenopausal women are more susceptible to the risk of organ dysfunction in response to a low-choline diet. A common genetic polymorphism (rs12325817) in the PEMT gene can also increase this risk. Objective: The objective was to determine whether the risk of low choline–related organ dysfunction increases with the number of alleles of rs12325817 in premenopausal women and whether postmenopausal women (with or without rs12325817) treated with estrogen are more resistant to developing such symptoms. Design: Premenopausal women (n = 27) consumed a choline-sufficient diet followed by a very-low-choline diet until they developed organ dysfunction (or for 42 d), which was followed by a high-choline diet. Postmenopausal women (n = 22) were placed on the same diets but were first randomly assigned to receive estrogen or a placebo. The women were monitored for organ dysfunction and plasma choline metabolites and were genotyped for rs12325817. Results: A dose-response effect of rs12325817 on the risk of choline-related organ dysfunction was observed in premenopausal women: 80%, 43%, and 13% of women with 2, 1, or 0 alleles, respectively, developed organ dysfunction. Among postmenopausal women, 73% who received placebo but only 18% who received estrogen developed organ dysfunction during the low-choline diet. Conclusions: Because of their lower estrogen concentrations, postmenopausal women have a higher dietary requirement for choline than do premenopausal women. Choline requirements for both groups of women are further increased by rs12325817. This trial was registered at clinicaltrials.gov as NCT00065546. PMID:20861172

Dietary choline requirements of women: effects of estrogen and genetic variation.

PubMed

Fischer, Leslie M; da Costa, Kerry-Ann; Kwock, Lester; Galanko, Joseph; Zeisel, Steven H

2010-11-01

Choline is obtained from the diet and from the biosynthesis of phosphatidylcholine. Phosphatidylcholine is catalyzed by the enzyme phosphatidylethanolamine-N-methyltransferase (PEMT), which is induced by estrogen. Because they have lower estrogen concentrations, postmenopausal women are more susceptible to the risk of organ dysfunction in response to a low-choline diet. A common genetic polymorphism (rs12325817) in the PEMT gene can also increase this risk. The objective was to determine whether the risk of low choline-related organ dysfunction increases with the number of alleles of rs12325817 in premenopausal women and whether postmenopausal women (with or without rs12325817) treated with estrogen are more resistant to developing such symptoms. Premenopausal women (n = 27) consumed a choline-sufficient diet followed by a very-low-choline diet until they developed organ dysfunction (or for 42 d), which was followed by a high-choline diet. Postmenopausal women (n = 22) were placed on the same diets but were first randomly assigned to receive estrogen or a placebo. The women were monitored for organ dysfunction and plasma choline metabolites and were genotyped for rs12325817. A dose-response effect of rs12325817 on the risk of choline-related organ dysfunction was observed in premenopausal women: 80%, 43%, and 13% of women with 2, 1, or 0 alleles, respectively, developed organ dysfunction. Among postmenopausal women, 73% who received placebo but only 18% who received estrogen developed organ dysfunction during the low-choline diet. Because of their lower estrogen concentrations, postmenopausal women have a higher dietary requirement for choline than do premenopausal women. Choline requirements for both groups of women are further increased by rs12325817. This trial was registered at clinicaltrials.gov as NCT00065546.

A Review: Radiographic Iodinated Contrast Media-Induced Thyroid Dysfunction

PubMed Central

Leung, Angela M.; Braverman, Lewis E.; Brent, Gregory A.; Pearce, Elizabeth N.

2015-01-01

Context: Thyroid hormone production is dependent on adequate iodine intake. Excess iodine is generally well-tolerated, but thyroid dysfunction can occur in susceptible individuals after excess iodine exposure. Radiological iodinated contrast media represent an increasingly common source of excess iodine. Objective: This review will discuss the thyroidal response after acute exposure to excess iodine; contrast iodine-induced thyroid dysfunction; risks of iodine-induced thyroid dysfunction in vulnerable populations, such as the fetus, neonate, and patients with impaired renal function; and recommendations for the assessment and treatment of contrast iodine-induced thyroid dysfunction. Methods: Data for this review were identified by searching PubMed, Google Scholar, and references from relevant articles from 1948 to 2014. Conclusions: With the increase in the use of computed tomography scans in the United States, there is increasing risk of contrast-induced thyroid dysfunction. Patients at risk of developing iodine-induced thyroid dysfunction should be closely monitored after receiving iodinated contrast media and should be treated as needed. PMID:25375985

Mesenchymal stem cells correct haemodynamic dysfunction associated with liver injury after extended resection in a pig model.

PubMed

Tautenhahn, Hans-Michael; Brückner, Sandra; Uder, Christiane; Erler, Silvio; Hempel, Madlen; von Bergen, Martin; Brach, Janine; Winkler, Sandra; Pankow, Franziska; Gittel, Claudia; Baunack, Manja; Lange, Undine; Broschewitz, Johannes; Dollinger, Matthias; Bartels, Michael; Pietsch, Uta; Amann, Kerstin; Christ, Bruno

2017-06-01

In patients, acute kidney injury (AKI) is often due to haemodynamic impairment associated with hepatic decompensation following extended liver surgery. Mesenchymal stem cells (MSCs) supported tissue protection in a variety of acute and chronic diseases, and might hence ameliorate AKI induced by extended liver resection. Here, 70% liver resection was performed in male pigs. MSCs were infused through a central venous catheter and haemodynamic parameters as well as markers of acute kidney damage were monitored under intensive care conditions for 24 h post-surgery. Cytokine profiles were established to anticipate the MSCs' potential mode of action. After extended liver resection, hyperdynamic circulation, associated with hyponatraemia, hyperkalaemia, an increase in serum aldosterone and low urine production developed. These signs of hepatorenal dysfunction and haemodynamic impairment were corrected by MSC treatment. MSCs elevated PDGF levels in the serum, possibly contributing to circulatory homeostasis. Another 14 cytokines were increased in the kidney, most of which are known to support tissue regeneration. In conclusion, MSCs supported kidney and liver function after extended liver resection. They probably acted through paracrine mechanisms improving haemodynamics and tissue homeostasis. They might thus provide a promising strategy to prevent acute kidney injury in the context of post-surgery acute liver failure.

Impaired left ventricular diastolic function is related to the formation of left ventricular apical thrombus in patients with acute anterior myocardial infarction.

PubMed

Choi, Ung Lim; Park, Jae-Hyeong; Sun, Byung Joo; Oh, Jin Kyung; Seong, Seok Woo; Lee, Jae-Hwan; Choi, Si Wan; Jeong, Jin-Ok; Kwon, In Sun; Seong, In-Whan

2018-05-01

Left ventricular (LV) apical thrombus is a clinically important complication which can cause systemic embolization in patients with anterior acute myocardial infarction (AMI). Systolic dysfunction has been a risk factor for developing LV apical thrombus in AMI patients. However, the role of diastolic dysfunction in the development of LV apical thrombus in these patients is still unknown. We performed this study to evaluate whether diastolic dysfunction can influence the development of LV apical thrombus in anterior AMI patients. We retrospectively analyzed all consecutive anterior AMI patients with available echocardiographic images within 1 month from January 2005 to April 2016. After gathering clinical characteristics from their medical records, systolic and diastolic functions were analyzed from digitally stored echocardiographic images. We included a total of 1045 patients (748 males, mean age 64 ± 12 years) with anterior AMI, and 494 (47%) were diagnosed as STEMI. The incidence of LV apical thrombus was 3.3% (34/1045). The LV apical thrombus group had larger LV diastolic dimension, larger LV diastolic and systolic volumes, and lower LVEF than the no LV thrombus group. The LV apical thrombus group showed higher mitral E velocity over mitral annular E' velocity ratio, an indicator of LV end-diastolic pressure (P < 0.001). In the LV apical thrombus group, the incidence of grade 2 diastolic dysfunction (32 vs 12%, P = 0.001) and grade 3 diastolic dysfunction (26 vs 2%, P < 0.001) were significantly higher than in the no LV apical thrombus group. The presence of more than grade 2 diastolic dysfunction, LVEF and presence of LV apical aneurysm were statistically significant factors associated with LV apical thrombus after the multivariate analysis. In conclusion, along with LV systolic dysfunction and LV apical aneurysm, LV diastolic dysfunction was also related with the presence of LV apical thrombus in patients with anterior AMI.

STAT3 in the systemic inflammation of cancer cachexia.

PubMed

Zimmers, Teresa A; Fishel, Melissa L; Bonetto, Andrea

2016-06-01

Weight loss is diagnostic of cachexia, a debilitating syndrome contributing mightily to morbidity and mortality in cancer. Most research has probed mechanisms leading to muscle atrophy and adipose wasting in cachexia; however cachexia is a truly systemic phenomenon. Presence of the tumor elicits an inflammatory response and profound metabolic derangements involving not only muscle and fat, but also the hypothalamus, liver, heart, blood, spleen and likely other organs. This global response is orchestrated in part through circulating cytokines that rise in conditions of cachexia. Exogenous Interleukin-6 (IL6) and related cytokines can induce most cachexia symptomatology, including muscle and fat wasting, the acute phase response and anemia, while IL-6 inhibition reduces muscle loss in cancer. Although mechanistic studies are ongoing, certain of these cachexia phenotypes have been causally linked to the cytokine-activated transcription factor, STAT3, including skeletal muscle wasting, cardiac dysfunction and hypothalamic inflammation. Correlative studies implicate STAT3 in fat wasting and the acute phase response in cancer cachexia. Parallel data in non-cancer models and disease states suggest both pathological and protective functions for STAT3 in other organs during cachexia. STAT3 also contributes to cancer cachexia through enhancing tumorigenesis, metastasis and immune suppression, particularly in tumors associated with high prevalence of cachexia. This review examines the evidence linking STAT3 to multi-organ manifestations of cachexia and the potential and perils for targeting STAT3 to reduce cachexia and prolong survival in cancer patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Liver Cirrhosis is Independently Associated With 90-Day Mortality in ARDS Patients.

PubMed

Gacouin, Arnaud; Locufier, Maxime; Uhel, Fabrice; Letheulle, Julien; Bouju, Pierre; Fillatre, Pierre; Le Tulzo, Yves; Tadié, Jean Marc

2016-01-01

In a few studies, cirrhosis has been associated with increased mortality in patients with acute respiratory distress syndrome (ARDS). These studies were, however, conducted mostly before 2000. Over the last 15 years, the prognosis of cirrhotic patients admitted to the intensive care unit (ICU) seems to have improved and major changes in the management of mechanical ventilation (MV) of ARDS have appeared. The aim of this study was to determine whether cirrhosis remains a factor for poor prognosis despite improvements in MV techniques and supportive therapies for ARDS. Retrospective analysis of data recorded from 232 patients (42 with cirrhosis and 290 without cirrhosis) who received lung-protective ventilation for ARDS defined according to American-European Consensus Conference criteria and admitted from 2006 to 2013. Alcohol was the most common aetiology of the cirrhosis. The end point was mortality at day-90 from the diagnosis of ARDS, survival was calculated using the Kaplan-Meier method, and we used a Cox-proportional hazard model to determine whether cirrhosis remained independently associated with mortality after adjustment for other prognostic variables for ARDS described previously. Organ dysfunctions were assessed based on the Sequential Organ Failure Assessment (SOFA) criteria, pulmonary and nonpulmonary dysfunctions were distinguished and compared between cirrhotic and non-cirrhotic patients on the first 3 days of VM. Comparison of survival curves showed that cirrhotic patients had a poorer 90-day prognosis than non-cirrhotic patients (P = 0.03 by the log-rank test). After adjusted analysis, cirrhosis remained independently associated with mortality at day 90 (adjusted hazard ratio 2.09, 95% CI, 1.27-3.45, P = 0.004). Non-pulmonary SOFA scores were significantly higher in cirrhotic patients than in non-cirrhotic patients on day 1 (P < 0.001), day 2 (P = 0.003), and day 3 (P = 0.002) of MV for ARDS whereas pulmonary SOFA scores did not differ significantly. Despite improvements in the management of cirrhotic patients admitted to the ICU and in the management of MV for the treatment of ARDS, cirrhosis remained associated with a poorer prognosis in ARDS patients. The prognosis of cirrhotic patients with ARDS appears related to extrapulmonary organ dysfunctions rather than pulmonary dysfunction.

Dysfunctional uterine bleeding (DUB)

MedlinePlus

... and Gynecologists website. ACOG committee opinion no. 557: Management of acute abnormal uterine bleeding in nonpregnant reproductive-aged women. Reaffirmed 2015. www.acog.org/Resources-And-Publications/Committee-Opinions/ ...

An update of clinical management of acute intermittent porphyria

PubMed Central

Pischik, Elena; Kauppinen, Raili

2015-01-01

Acute intermittent porphyria (AIP) is due to a deficiency of the third enzyme, the hydroxymethylbilane synthase, in heme biosynthesis. It manifests with occasional neuropsychiatric crises associated with overproduction of porphyrin precursors, aminolevulinic acid and porphobilinogen. The clinical criteria of an acute attack include the paroxysmal nature and various combinations of symptoms, such as abdominal pain, autonomic dysfunction, hyponatremia, muscle weakness, or mental symptoms, in the absence of other obvious causes. Intensive abdominal pain without peritoneal signs, acute peripheral neuropathy, and encephalopathy usually with seizures or psychosis are the key symptoms indicating possible acute porphyria. More than fivefold elevation of urinary porphobilinogen excretion together with typical symptoms of an acute attack is sufficient to start a treatment. Currently, the prognosis of the patients with AIP is good, but physicians should be aware of a potentially fatal outcome of the disease. Mutation screening and identification of type of acute porphyria can be done at the quiescent phase of the disease. The management of patients with AIP include following strategies: A, during an acute attack: 1) treatment with heme preparations, if an acute attack is severe or moderate; 2) symptomatic treatment of autonomic dysfunctions, polyneuropathy and encephalopathy; 3) exclusion of precipitating factors; and 4) adequate nutrition and fluid therapy. B, during remission: 1) exclusion of precipitating factors (education of patients and family doctors), 2) information about on-line drug lists, and 3) mutation screening for family members and education about precipitating factors in mutation-positive family members. C, management of patients with recurrent attacks: 1) evaluation of the lifestyle, 2) evaluation of hormonal therapy in women, 3) prophylactic heme therapy, and 4) liver transplantation in patients with severe recurrent attacks. D, follow-up of the AIP patients for long-term complications: chronic hypertension, chronic kidney insufficiency, chronic pain syndrome, and hepatocellular carcinoma. PMID:26366103

Acute kidney injury by radiographic contrast media: pathogenesis and prevention.

PubMed

Andreucci, Michele; Faga, Teresa; Pisani, Antonio; Sabbatini, Massimo; Michael, Ashour

2014-01-01

It is well known that iodinated radiographic contrast media may cause kidney dysfunction, particularly in patients with preexisting renal impairment associated with diabetes. This dysfunction, when severe, will cause acute renal failure (ARF). We may define contrast-induced Acute Kidney Injury (AKI) as ARF occurring within 24-72 hrs after the intravascular injection of iodinated radiographic contrast media that cannot be attributed to other causes. The mechanisms underlying contrast media nephrotoxicity have not been fully elucidated and may be due to several factors, including renal ischaemia, particularly in the renal medulla, the formation of reactive oxygen species (ROS), reduction of nitric oxide (NO) production, and tubular epithelial and vascular endothelial injury. However, contrast-induced AKI can be prevented, but in order to do so, we need to know the risk factors. We have reviewed the risk factors for contrast-induced AKI and measures for its prevention, providing a long list of references enabling readers to deeply evaluate them both.

Acute Kidney Injury by Radiographic Contrast Media: Pathogenesis and Prevention

PubMed Central

Faga, Teresa; Pisani, Antonio; Michael, Ashour

2014-01-01

It is well known that iodinated radiographic contrast media may cause kidney dysfunction, particularly in patients with preexisting renal impairment associated with diabetes. This dysfunction, when severe, will cause acute renal failure (ARF). We may define contrast-induced Acute Kidney Injury (AKI) as ARF occurring within 24–72 hrs after the intravascular injection of iodinated radiographic contrast media that cannot be attributed to other causes. The mechanisms underlying contrast media nephrotoxicity have not been fully elucidated and may be due to several factors, including renal ischaemia, particularly in the renal medulla, the formation of reactive oxygen species (ROS), reduction of nitric oxide (NO) production, and tubular epithelial and vascular endothelial injury. However, contrast-induced AKI can be prevented, but in order to do so, we need to know the risk factors. We have reviewed the risk factors for contrast-induced AKI and measures for its prevention, providing a long list of references enabling readers to deeply evaluate them both. PMID:25197639

Risk of Erectile Dysfunction in Transfusion-naive Thalassemia Men

PubMed Central

Chen, Yu-Guang; Lin, Te-Yu; Lin, Cheng-Li; Dai, Ming-Shen; Ho, Ching-Liang; Kao, Chia-Hung

2015-01-01

Abstract Based on the mechanism of pathophysiology, thalassemia major or transfusion-dependent thalassemia patients may have an increased risk of developing organic erectile dysfunction resulting from hypogonadism. However, there have been few studies investigating the association between erectile dysfunction and transfusion-naive thalassemia populations. We constructed a population-based cohort study to elucidate the association between transfusion-naive thalassemia populations and organic erectile dysfunction This nationwide population-based cohort study involved analyzing data from 1998 to 2010 obtained from the Taiwanese National Health Insurance Research Database, with a follow-up period extending to the end of 2011. We identified men with transfusion-naive thalassemia and selected a comparison cohort that was frequency-matched with these according to age, and year of diagnosis thalassemia at a ratio of 1 thalassemia man to 4 control men. We analyzed the risks for transfusion-naive thalassemia men and organic erectile dysfunction by using Cox proportional hazards regression models. In this study, 588 transfusion-naive thalassemia men and 2337 controls were included. Total 12 patients were identified within the thalassaemia group and 10 within the control group. The overall risks for developing organic erectile dysfunction were 4.56-fold in patients with transfusion-naive thalassemia men compared with the comparison cohort after we adjusted for age and comorbidities. Our long-term cohort study results showed that in transfusion-naive thalassemia men, there was a higher risk for the development of organic erectile dysfunction, particularly in those patients with comorbidities. PMID:25837766

Risk of erectile dysfunction in transfusion-naive thalassemia men: a nationwide population-based retrospective cohort study.

PubMed

Chen, Yu-Guang; Lin, Te-Yu; Lin, Cheng-Li; Dai, Ming-Shen; Ho, Ching-Liang; Kao, Chia-Hung

2015-04-01

Based on the mechanism of pathophysiology, thalassemia major or transfusion-dependent thalassemia patients may have an increased risk of developing organic erectile dysfunction resulting from hypogonadism. However, there have been few studies investigating the association between erectile dysfunction and transfusion-naive thalassemia populations. We constructed a population-based cohort study to elucidate the association between transfusion-naive thalassemia populations and organic erectile dysfunction. This nationwide population-based cohort study involved analyzing data from 1998 to 2010 obtained from the Taiwanese National Health Insurance Research Database, with a follow-up period extending to the end of 2011. We identified men with transfusion-naive thalassemia and selected a comparison cohort that was frequency-matched with these according to age, and year of diagnosis thalassemia at a ratio of 1 thalassemia man to 4 control men. We analyzed the risks for transfusion-naive thalassemia men and organic erectile dysfunction by using Cox proportional hazards regression models. In this study, 588 transfusion-naive thalassemia men and 2337 controls were included. Total 12 patients were identified within the thalassaemia group and 10 within the control group. The overall risks for developing organic erectile dysfunction were 4.56-fold in patients with transfusion-naive thalassemia men compared with the comparison cohort after we adjusted for age and comorbidities. Our long-term cohort study results showed that in transfusion-naive thalassemia men, there was a higher risk for the development of organic erectile dysfunction, particularly in those patients with comorbidities.

A stochastic model for the normal tissue complication probability (NTCP) and applicationss.

PubMed

Stocks, Theresa; Hillen, Thomas; Gong, Jiafen; Burger, Martin

2017-12-11

The normal tissue complication probability (NTCP) is a measure for the estimated side effects of a given radiation treatment schedule. Here we use a stochastic logistic birth-death process to define an organ-specific and patient-specific NTCP. We emphasize an asymptotic simplification which relates the NTCP to the solution of a logistic differential equation. This framework is based on simple modelling assumptions and it prepares a framework for the use of the NTCP model in clinical practice. As example, we consider side effects of prostate cancer brachytherapy such as increase in urinal frequency, urinal retention and acute rectal dysfunction. © The authors 2016. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved.

Clinical review: Extracorporeal blood purification in severe sepsis

PubMed Central

Venkataraman, Ramesh; Subramanian, Sanjay; Kellum, John A

2003-01-01

Sepsis and septic shock are the leading causes of acute renal failure, multiple organ system dysfunction, and death in the intensive care unit. The pathogenesis of sepsis is complex and comprises a mosaic of interconnected pathways. Several attempts to improve patient outcomes by targeting specific components of this network have been unsuccessful. For these reasons, the ideal immunomodulating strategy would be one that restores immunologic stability rather than blindly inhibiting or stimulating one or another component of this complex network. Hence, the recent focus of immunomodulatory therapy in sepsis has shifted to nonspecific methods of influencing the entire inflammatory response without suppressing it. Here, we discuss the various modalities of extracorporeal blood purification, the existing evidence, and future prospects. PMID:12720560

Disruption of Glucagon-Like Peptide 1 Signaling in Sim1 Neurons Reduces Physiological and Behavioral Reactivity to Acute and Chronic Stress.

PubMed

Ghosal, Sriparna; Packard, Amy E B; Mahbod, Parinaz; McKlveen, Jessica M; Seeley, Randy J; Myers, Brent; Ulrich-Lai, Yvonne; Smith, Eric P; D'Alessio, David A; Herman, James P

2017-01-04

Organismal stress initiates a tightly orchestrated set of responses involving complex physiological and neurocognitive systems. Here, we present evidence for glucagon-like peptide 1 (GLP-1)-mediated paraventricular hypothalamic circuit coordinating the global stress response. The GLP-1 receptor (Glp1r) in mice was knocked down in neurons expressing single-minded 1, a transcription factor abundantly expressed in the paraventricular nucleus (PVN) of the hypothalamus. Mice with single-minded 1-mediated Glp1r knockdown had reduced hypothalamic-pituitary-adrenal axis responses to both acute and chronic stress and were protected against weight loss associated with chronic stress. In addition, regional Glp1r knockdown attenuated stress-induced cardiovascular responses accompanied by decreased sympathetic drive to the heart. Finally, Glp1r knockdown reduced anxiety-like behavior, implicating PVN GLP-1 signaling in behavioral stress reactivity. Collectively, these findings support a circuit whereby brainstem GLP-1 activates PVN signaling to mount an appropriate whole-organism response to stress. These results raise the possibility that dysfunction of this system may contribute to stress-related pathologies, and thereby provide a novel target for intervention. Dysfunctional stress responses are linked to a number of somatic and psychiatric diseases, emphasizing the importance of precise neuronal control of effector pathways. Pharmacological evidence suggests a role for glucagon-like peptide-1 (GLP-1) in modulating stress responses. Using a targeted knockdown of the GLP-1 receptor in the single-minded 1 neurons, we show dependence of paraventricular nucleus GLP-1 signaling in the coordination of neuroendocrine, autonomic, and behavioral responses to acute and chronic stress. To our knowledge, this is the first direct demonstration of an obligate brainstem-to-hypothalamus circuit orchestrating general stress excitation across multiple effector systems. These findings provide novel information regarding signaling pathways coordinating central control of whole-body stress reactivity. Copyright © 2017 the authors 0270-6474/17/370184-10$15.00/0.

DYSFUNCTION OF VARIOUS ORGAN SYSTEMS INDUCED BY SEPSIS WITH UNDERLYING SEVERE MYELOMIC DISEASES AND PROSTATE CANCER (CASE REPORT).

PubMed

Ratiani, L; Intskirveli, N; Goliadze, L; Chkhikvadze, T; Koptonashvili, L; Khuchua, E

2018-02-01

A 65-year-old male patient, unconscious, was admitted into the clinic by the Ambulance. From the patient's medical history it was revealed that several hours before the admission in the clinic the following symptoms were present: shortness of breath, fever, hypotonia, consciousness inhibition, because of which emergency brigade was called and was brought by the Emergency Brigade. The history is loaded by chronic pathologies: myeloma disease, prostate cancer, ciliary arrhythmia, heart failure; received several courses of polichemotherapy, last ten days has been treated for pneumonia with antibiotics of ceftriaxone group in outpatient setting. It is also noteworthy that for the last three months dysfunction of musculoskeletal system with muscle weakness, restricted motion has been present. Clinically there was present dysfunction syndrome of several organs: disorder of function of several organs that required emergency intervention, recovery chance was very low, correlation with morbidity in PIRO was high. By investigation it is known, that as SIRS aggravates, and turns into septic shock, lethal index increases, especially when the underlying severe diseases are present. On basis of certain data we can conclude that the severity of the disease may have some compatibility with results, although it is alteration of further clinical status of initial stage that has the closest compatibility with results. Sepsis toward MODS experiences progress with lethal results. Mortality rate in the patients with acute respiratory deficiency increases from 50% to 80%. In most patients with sepsis syndrome, who have 3 or more organs damaged, lethality is more than 90%. In this certain case organ systems that are mostly involved in the process during the sepsis, are respiratory, blood, renal and cardiovascular systems, were all involved , in the mentioned case a reasonable symptomatic and pathognomic treatment and the appropriate measures led to the recovery of the above mentioned patient. Sepsis syndrome is developed when the balance between the substances that contribute to the inflammation and anti-inflammatory substances is violated. By the mentioned case there is sepsis - induced polyorganic insufficiency with underlying severe somatic pathological condition, with violation of hemodynamics. Clinically the insufficiency of all the organic systems developed at the background of cardio-respiratory-cerebral insufficiency, with functional insufficiency of all the organ systems and violation of buffer system. With reasonable pathognomic and symptomatic treatment eradication of vicious circle was possible. The patient was discharged from the clinic with positive clinic-laboratory recovery. The condition is stable. Neurological status -contact, adequate, with high capacity to work, and with an achievement of 2 year remission.

[Dysfunctional workplace organization and mobbing. 4 representative cases].

PubMed

Albini, Elisa; Benedetti, Laura; Giordano, S; Punzi, Silvia; Cassitto, Maria Grazia

2003-01-01

Stress and psychological harassment at work are increasing worldwide, according to International Agencies (European Community, NIOSH) and to most authors. To describe typical working situations responsible for distress and mobbing, with the aim of early diagnosis and effectiveness of therapy and rehabilitation. Four cases are reported as representative of dysfunctional organization producing distress and pathology or inducing mobbing behavior or mobbing without clear organization responsibilities. In all cases dysfunctional organization appeared to have played a significant role even though not always a direct one. Also, common characteristics were highlighted in the three cases where mobbing was recognized.

[Aspirative pneumonia associated to swallowing dysfunction: case report].

PubMed

Toufen Junior, Carlos; Camargo, Fernanda Pereira de; Carvalho, Carlos Roberto Ribeiro

2007-03-01

Critically ill patients represent a population with multiple risk factors for aspiration. Features such as decreased level of consciousness, mechanical ventilation, and comorbities as stroke, correlate with this increased threat in intensive care unit (ICU) patients. Recognition of deglutition dysfunction may identify patients at high risk of aspiration, and thereby help to avoid pulmonary complications such as recurrent pneumonia. The goal of our report is show a severe case of recurrent aspirative pneumonia after acute stroke and intubation, alerting to appropriate diagnosis and treatment of this condition. A male patient, 57 year old, was admitted to the hospital because of acute stroke. Ten days later, the patient began to have fever and severe shortness of breath. He was admitted to the ICU necessitating of intratracheal intubation. Four days after intubation he was extubated, however, he had a new aspirative pneumonia in ICU, newly treated. An evaluation of swallowing demonstrated a severe deglutition dysfunction with a high risk of aspiration. The patient was transferred, but aspirative pneumonia was diagnosed eight days after his ICU discharge and he was readmitted, stayed for a long time in ICU and presenting severe morbidity. ICU patients who are at risk for swallowing dysfunction and aspiration should be identified to prevent their associated morbidity and mortality.

Case Studies in Cardiac Dysfunction After Acute Aneurysmal Subarachnoid Hemorrhage

PubMed Central

Hamilton, Jason C.; Korn-Naveh, Lauren; Crago, Elizabeth A.

2015-01-01

Patients with acute aneurysmal subarachnoid hemorrhage (SAH) often present with more than just neurological compromise. A wide spectrum of complicating cardiopulmonary abnormalities have been documented in patients with acute SAH, presenting additional challenges to the healthcare providers who attempt to treat and stabilize these patients. The patients described in this article presented with both acute aneurysmal SAH and cardiopulmonary compromise. Education and further research on this connection is needed to provide optimal care and outcomes for this vulnerable population. Nurses play a key role in balancing the critical and diverse needs of patients presenting with these symptoms. PMID:18856247

Bladder, Bowel, and Sexual Dysfunction in Parkinson's Disease

PubMed Central

Sakakibara, Ryuji; Kishi, Masahiko; Ogawa, Emina; Tateno, Fuyuki; Uchiyama, Tomoyuki; Yamamoto, Tatsuya; Yamanishi, Tomonori

2011-01-01

Bladder dysfunction (urinary urgency/frequency), bowel dysfunction (constipation), and sexual dysfunction (erectile dysfunction) (also called “pelvic organ” dysfunctions) are common nonmotor disorders in Parkinson's disease (PD). In contrast to motor disorders, pelvic organ autonomic dysfunctions are often nonresponsive to levodopa treatment. The brain pathology causing the bladder dysfunction (appearance of overactivity) involves an altered dopamine-basal ganglia circuit, which normally suppresses the micturition reflex. By contrast, peripheral myenteric pathology causing slowed colonic transit (loss of rectal contractions) and central pathology causing weak strain and paradoxical anal sphincter contraction on defecation (PSD, also called as anismus) are responsible for the bowel dysfunction. In addition, hypothalamic dysfunction is mostly responsible for the sexual dysfunction (decrease in libido and erection) in PD, via altered dopamine-oxytocin pathways, which normally promote libido and erection. The pathophysiology of the pelvic organ dysfunction in PD differs from that in multiple system atrophy; therefore, it might aid in differential diagnosis. Anticholinergic agents are used to treat bladder dysfunction in PD, although these drugs should be used with caution particularly in elderly patients who have cognitive decline. Dietary fibers, laxatives, and “prokinetic” drugs such as serotonergic agonists are used to treat bowel dysfunction in PD. Phosphodiesterase inhibitors are used to treat sexual dysfunction in PD. These treatments might be beneficial in maximizing the patients' quality of life. PMID:21918729

Differential diagnosis of acute rejection and chronic cyclosporine nephropathy after rat renal transplantation by detection of endothelial microparticles (EMP).

PubMed

Cui, Jiewei; Yang, Jing; Cao, Weike; Sun, Yi

2010-12-01

Endothelial microparticles (EMP) are small vesicles smaller than 1.0μm, released from endothelial cells (EC) during their activation and (or) apoptosis. The assay of the level of elevated EMP is a new approach to evaluate the dysfunction of endothelial cell. EMP can be classified into several types according to their membrane molecular, and the levels of various types of EMP may be different. As the most cost-effective immunodepressant, cyclosporine A (CsA) has been used widely in organ transplantation. But its dose is hard to control, under-medication may cause the acute rejection (AR) and overdose may cause chronic cyclosporine nephropathy (CCN). The cyclosporine A (CsA) caused CCN and the AR caused renal injury after renal transplantation are both vascular diseases related with endothelial dysfunction, and up to now, there is still no effective method to distinguish the two kinds of diseases. Owing to distinct pathogenesis of the two kinds of vascular diseases, the level of each type of EMP originated from vascular endothelial cells may be different. We hypothesize that maybe we can distinguish them by detecting the different levels of some types of EMP which is also related with vascular disease, and we propose to prove our hypothesis through animal experiment. If our hypothesis is proved, it will be more helpful for clinicians to adjust the dose of CsA promptly according to the differential diagnosis of the two kinds of diseases. Copyright © 2010 Elsevier Ltd. All rights reserved.

Zero-order metoprolol pharmacokinetics after therapeutic doses: severe toxicity and cardiogenic shock.

PubMed

Isbister, Geoffrey K; Ang, Karyn; Gorman, Kieron; Cooper, Joyce; Mostafa, Ahmed; Roberts, Michael S

2016-11-01

Acute beta-blocker overdose can cause severe cardiac dysfunction. Chronic toxicity is rare but potentially severe. We report therapeutic dosing of metoprolol resulting in unusual pharmacokinetics and toxicity, given high-dose insulin therapy for treatment. A 90-year-old female presented with hypotension, tachycardia and severe cardiac dysfunction after commencing a rapidly increasing metoprolol dose of 250 mg split daily. She was admitted to intensive care and given high-dose insulin therapy (10 U/kg/h), noradrenaline, adrenaline and dobutamine for severe cardiac dysfunction (cardiac index, 0.76 L/min/m 2 ). She developed acute renal failure, ischaemic hepatitis and disseminated intravascular coagulopathy. Inotropes and high-dose insulin were weaned over four days with complete recovery. Metoprolol was quantified with liquid chromatography-tandem mass spectrometry and concentration-time data were analysed using MONOLIX ® vs 4.3 ( www.lixoft.com ). Admission metoprolol concentration was 2.39 μg/mL (therapeutic reference range: 0.035-0.5 μg/mL). Data best fitted a one compartmental model with Michaelis-Menten kinetics and zero order elimination at high concentrations. Final parameter estimates were V, 63.4 L, maximum rate [V m ], 9.57 mg h -1 , Michaelis constant [K m ], 1.97 mg L -1 . Predicted elimination half-life decreased from 20 h over time until there was first order elimination with a half-life 9 h. The time course of cardiac dysfunction was longer than acute overdose but consistent with prolonged zero order elimination of metoprolol, suggesting the patient was a poor CYP2D6 metaboliser. High-dose insulin euglycaemia appeared to be effective in combination with vasoconstrictors/inotropes.

High urinary albumin/creatinine ratio at admission predicts poor functional outcome in patients with acute ischaemic stroke.

PubMed

Watanabe, Yoko; Suda, Satoshi; Kanamaru, Takuya; Katsumata, Toshiya; Okubo, Seiji; Kaneko, Tomohiro; Mii, Akiko; Sakai, Yukinao; Katayama, Yasuo; Kimura, Kazumi; Tsuruoka, Shuichi

2017-03-01

Albuminuria and a low estimated glomerular filtration rate (eGFR) are widely recognized indices of kidney dysfunction and have been linked to cardiovascular events, including stroke. We evaluated albuminuria, measured using the urinary albumin/creatinine ratio (UACR), and the eGFR in the acute phase of ischaemic stroke, and investigated the clinical characteristics of ischaemic stroke patients with and those without kidney dysfunction. The study included 422 consecutive patients admitted between June 2010 and May 2012. General blood and urine examinations were performed at admission. Kidney dysfunction was defined as a low eGFR (<60 mL/min per 1.73 m 2 ), high albuminuria (≥30 mg/g creatinine), or both. Neurological severity was evaluated using the National Institutes of Health Stroke Scale (NIHSS) at admission and the modified Rankin scale (mRS) at discharge. A poor outcome was defined as a mRS score of 3-5 or death. The impacts of the eGFR and UACR on outcomes at discharge were evaluated using multiple logistic regression analysis. Kidney dysfunction was diagnosed in 278 of the 422 patients (65.9%). The eGFR was significantly lower and UACR was significantly higher in patients with a poor outcome than in those with a good outcome. In multivariate analyses performed after adjusting for confounding factors, UACR >31.2 mg/g creatinine (OR, 2.58; 95% CI, 1.52-4.43; P = 0.0005) was independently associated with a poor outcome, while a low eGFR was not associated. A high UACR at admission may predict a poor outcome at discharge in patients with acute ischaemic stroke. © 2016 Asian Pacific Society of Nephrology.

Dysfunctional Attitudes Scale Perfectionism: A Predictor and Partial Mediator of Acute Treatment Outcome among Clinically Depressed Adolescents

ERIC Educational Resources Information Center

Jacobs, Rachel H.; Silva, Susan G.; Reinecke, Mark A.; Curry, John F.; Ginsburg, Golda S.; Kratochvil, Christopher J.; March, John S.

2009-01-01

The effect of perfectionism on acute treatment outcomes was explored in a randomized controlled trial of 439 clinically depressed adolescents (12-17 years of age) enrolled in the Treatment for Adolescents with Depression Study (TADS) who received cognitive behavior therapy (CBT), fluoxetine, a combination of CBT and FLX, or pill placebo. Measures…

Gravity-dependent nystagmus and inner-ear dysfunction suggest anterior and posterior inferior cerebellar artery infarct.

PubMed

Shaikh, Aasef G; Miller, Benjamin R; Sundararajan, Sophia; Katirji, Bashar

2014-04-01

Cerebellar lesions may present with gravity-dependent nystagmus, where the direction and velocity of the drifts change with alterations in head position. Two patients had acute onset of hearing loss, vertigo, oscillopsia, nausea, and vomiting. Examination revealed gravity-dependent nystagmus, unilateral hypoactive vestibulo-ocular reflex (VOR), and hearing loss ipsilateral to the VOR hypofunction. Traditionally, the hypoactive VOR and hearing loss suggest inner-ear dysfunction. Vertigo, nausea, vomiting, and nystagmus may suggest peripheral or central vestibulopathy. The gravity-dependent modulation of nystagmus, however, localizes to the posterior cerebellar vermis. Magnetic resonance imaging in our patients revealed acute cerebellar infarct affecting posterior cerebellar vermis, in the vascular distribution of the posterior inferior cerebellar artery (PICA). This lesion explains the gravity-dependent nystagmus, nausea, and vomiting. Acute onset of unilateral hearing loss and VOR hypofunction could be the manifestation of inner-ear ischemic injury secondary to the anterior inferior cerebellar artery (AICA) compromise. In cases of combined AICA and PICA infarction, the symptoms of peripheral vestibulopathy might masquerade the central vestibular syndrome and harbor a cerebellar stroke. However, the gravity-dependent nystagmus allows prompt identification of acute cerebellar infarct. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Acute Unilateral Vestibular Failure Does Not Cause Spatial Hemineglect.

PubMed

Conrad, Julian; Habs, Maximilian; Brandt, Thomas; Dieterich, Marianne

2015-01-01

Visuo-spatial neglect and vestibular disorders have common clinical findings and involve the same cortical areas. We questioned (1) whether visuo-spatial hemineglect is not only a disorder of spatial attention but may also reflect a disorder of higher cortical vestibular function and (2) whether a vestibular tone imbalance due to an acute peripheral dysfunction can also cause symptoms of neglect or extinction. Therefore, patients with an acute unilateral peripheral vestibular failure (VF) were tested for symptoms of hemineglect. Twenty-eight patients with acute VF were assessed for signs of vestibular deficits and spatial neglect using clinical measures and various common standardized paper-pencil tests. Neglect severity was evaluated further with the Center of Cancellation method. Pathological neglect test scores were correlated with the degree of vestibular dysfunction determined by the subjective visual vertical and caloric testing. Three patients showed isolated pathological scores in one or the other neglect test, either ipsilesionally or contralesionally to the VF. None of the patients fulfilled the diagnostic criteria of spatial hemineglect or extinction. A vestibular tone imbalance due to unilateral failure of the vestibular endorgan does not cause spatial hemineglect, but evidence indicates it causes mild attentional deficits in both visual hemifields.

Acute Unilateral Vestibular Failure Does Not Cause Spatial Hemineglect

PubMed Central

Conrad, Julian; Habs, Maximilian; Brandt, Thomas; Dieterich, Marianne

2015-01-01

Objectives Visuo-spatial neglect and vestibular disorders have common clinical findings and involve the same cortical areas. We questioned (1) whether visuo-spatial hemineglect is not only a disorder of spatial attention but may also reflect a disorder of higher cortical vestibular function and (2) whether a vestibular tone imbalance due to an acute peripheral dysfunction can also cause symptoms of neglect or extinction. Therefore, patients with an acute unilateral peripheral vestibular failure (VF) were tested for symptoms of hemineglect. Methods Twenty-eight patients with acute VF were assessed for signs of vestibular deficits and spatial neglect using clinical measures and various common standardized paper-pencil tests. Neglect severity was evaluated further with the Center of Cancellation method. Pathological neglect test scores were correlated with the degree of vestibular dysfunction determined by the subjective visual vertical and caloric testing. Results Three patients showed isolated pathological scores in one or the other neglect test, either ipsilesionally or contralesionally to the VF. None of the patients fulfilled the diagnostic criteria of spatial hemineglect or extinction. Conclusions A vestibular tone imbalance due to unilateral failure of the vestibular endorgan does not cause spatial hemineglect, but evidence indicates it causes mild attentional deficits in both visual hemifields. PMID:26247469

Alda-1 Protects Against Acrolein-Induced Acute Lung Injury and Endothelial Barrier Dysfunction.

PubMed

Lu, Qing; Mundy, Miles; Chambers, Eboni; Lange, Thilo; Newton, Julie; Borgas, Diana; Yao, Hongwei; Choudhary, Gaurav; Basak, Rajshekhar; Oldham, Mahogany; Rounds, Sharon

2017-12-01

Inhalation of acrolein, a highly reactive aldehyde, causes lung edema. The underlying mechanism is poorly understood and there is no effective treatment. In this study, we demonstrated that acrolein not only dose-dependently induced lung edema but also promoted LPS-induced acute lung injury. Importantly, acrolein-induced lung injury was prevented and rescued by Alda-1, an activator of mitochondrial aldehyde dehydrogenase 2. Acrolein also dose-dependently increased monolayer permeability, disrupted adherens junctions and focal adhesion complexes, and caused intercellular gap formation in primary cultured lung microvascular endothelial cells (LMVECs). These effects were attenuated by Alda-1 and the antioxidant N-acetylcysteine, but not by the NADPH inhibitor apocynin. Furthermore, acrolein inhibited AMP-activated protein kinase (AMPK) and increased mitochondrial reactive oxygen species levels in LMVECs-effects that were associated with impaired mitochondrial respiration. AMPK total protein levels were also reduced in lung tissue of mice and LMVECs exposed to acrolein. Activation of AMPK with 5-aminoimidazole-4-carboxamide-1-β-4-ribofuranoside blunted an acrolein-induced increase in endothelial monolayer permeability, but not mitochondrial oxidative stress or inhibition of mitochondrial respiration. Our results suggest that acrolein-induced mitochondrial dysfunction may not contribute to endothelial barrier dysfunction. We speculate that detoxification of acrolein by Alda-1 and activation of AMPK may be novel approaches to prevent and treat acrolein-associated acute lung injury, which may occur after smoke inhalation.

Low-dose dopamine or low-dose nesiritide in acute heart failure with renal dysfunction: the ROSE acute heart failure randomized trial.

PubMed

Chen, Horng H; Anstrom, Kevin J; Givertz, Michael M; Stevenson, Lynne W; Semigran, Marc J; Goldsmith, Steven R; Bart, Bradley A; Bull, David A; Stehlik, Josef; LeWinter, Martin M; Konstam, Marvin A; Huggins, Gordon S; Rouleau, Jean L; O'Meara, Eileen; Tang, W H Wilson; Starling, Randall C; Butler, Javed; Deswal, Anita; Felker, G Michael; O'Connor, Christopher M; Bonita, Raphael E; Margulies, Kenneth B; Cappola, Thomas P; Ofili, Elizabeth O; Mann, Douglas L; Dávila-Román, Víctor G; McNulty, Steven E; Borlaug, Barry A; Velazquez, Eric J; Lee, Kerry L; Shah, Monica R; Hernandez, Adrian F; Braunwald, Eugene; Redfield, Margaret M

2013-12-18

Small studies suggest that low-dose dopamine or low-dose nesiritide may enhance decongestion and preserve renal function in patients with acute heart failure and renal dysfunction; however, neither strategy has been rigorously tested. To test the 2 independent hypotheses that, compared with placebo, addition of low-dose dopamine (2 μg/kg/min) or low-dose nesiritide (0.005 μg/kg/min without bolus) to diuretic therapy will enhance decongestion and preserve renal function in patients with acute heart failure and renal dysfunction. Multicenter, double-blind, placebo-controlled clinical trial (Renal Optimization Strategies Evaluation [ROSE]) of 360 hospitalized patients with acute heart failure and renal dysfunction (estimated glomerular filtration rate of 15-60 mL/min/1.73 m2), randomized within 24 hours of admission. Enrollment occurred from September 2010 to March 2013 across 26 sites in North America. Participants were randomized in an open, 1:1 allocation ratio to the dopamine or nesiritide strategy. Within each strategy, participants were randomized in a double-blind, 2:1 ratio to active treatment or placebo. The dopamine (n = 122) and nesiritide (n = 119) groups were independently compared with the pooled placebo group (n = 119). Coprimary end points included 72-hour cumulative urine volume (decongestion end point) and the change in serum cystatin C from enrollment to 72 hours (renal function end point). Compared with placebo, low-dose dopamine had no significant effect on 72-hour cumulative urine volume (dopamine, 8524 mL; 95% CI, 7917-9131 vs placebo, 8296 mL; 95% CI, 7762-8830 ; difference, 229 mL; 95% CI, -714 to 1171 mL; P = .59) or on the change in cystatin C level (dopamine, 0.12 mg/L; 95% CI, 0.06-0.18 vs placebo, 0.11 mg/L; 95% CI, 0.06-0.16; difference, 0.01; 95% CI, -0.08 to 0.10; P = .72). Similarly, low-dose nesiritide had no significant effect on 72-hour cumulative urine volume (nesiritide, 8574 mL; 95% CI, 8014-9134 vs placebo, 8296 mL; 95% CI, 7762-8830; difference, 279 mL; 95% CI, -618 to 1176 mL; P = .49) or on the change in cystatin C level (nesiritide, 0.07 mg/L; 95% CI, 0.01-0.13 vs placebo, 0.11 mg/L; 95% CI, 0.06-0.16; difference, -0.04; 95% CI, -0.13 to 0.05; P = .36). Compared with placebo, there was no effect of low-dose dopamine or nesiritide on secondary end points reflective of decongestion, renal function, or clinical outcomes. In participants with acute heart failure and renal dysfunction, neither low-dose dopamine nor low-dose nesiritide enhanced decongestion or improved renal function when added to diuretic therapy. clinicaltrials.gov Identifier: NCT01132846.

ARFI-based tissue elasticity quantification and kidney graft dysfunction: first clinical experiences.

PubMed

Stock, K F; Klein, B S; Cong, M T Vo; Regenbogen, C; Kemmner, S; Büttner, M; Wagenpfeil, S; Matevossian, E; Renders, L; Heemann, U; Küchle, C

2011-01-01

Beyond the medical history, the clinical exam and lab findings, non-invasive ultrasound parameters such as kidney size and Doppler values (e.g. the resistive index) are important tools assisting clinical decision making in the monitoring of renal allografts. The gold standard for the diagnosis of renal allograft dysfunction remains the renal biopsy; while an invasive procedure, the justifiable necessity for this derives from its definitive nature a requirement beyond the synopses of all non-invasive tools. "Acoustic Radiation Force Impulse Imaging"(ARFI)-quantification is a novel ultrasound-based technology measuring tissue elasticity properties. So far experience related to this new method has not been reported in renal transplant follow-up. The purpose of this study was to evaluate changes in ARFI-measurements between clinically stable renal allografts and biopsy-proven transplant dysfunction. We employed "Virtual Touch™ tissue quantification" (Siemens Acuson, S2000) for the quantitative measurement of tissue stiffness in the cortex of transplant kidneys. We performed initial baseline and later disease-evaluative ultrasound examinations in 8 renal transplant patients in a prospective study design. Patients were first examined during stable allograft function with a routine post-transplant renal ultrasound protocol. A second follow-up examination was carried out on subsequent presentation with transplant dysfunction prior to allograft biopsy and histological evaluation. All patiens were examined using ARFI-quantification (15 measurements/kidney). Resistive indices (RI) were calculated using pulsed-wave Doppler ultrasound, and transplant kidney size was measured on B-mode ultrasound images. All biopsies were evaluated histologically by a reference nephropathologist unaware of the results of the ultrasound studies. Histopathological diagnoses were based on biopsy results, taking clinical and laboratory findings into account. Finally we calculated the relative changes in ARFI-quantification, resistive indices and the absolute change of kidney size on a percentage basis at these defined assessment times and compared the results with the final pathologic diagnosis. Histological results enumerated five cases of acute T-cell-mediated rejection, one case of calcineurin inhibitor toxicity and two cases of acute tubular necrosis. Calcineurin inhibitor toxicity and acute tubular necrosis were subsumed as "other pathologies". Mean ARFI-values showed an average increase of more than 15% percent in transplants with histologically proven acute rejection whereas no increase was seen in transplants with other pathologies. Mean RI-values showed no increase either in the diagnostic group of acute rejection, nor in the group with other pathologies. Kidney size showed a mean absolute increase of 0.5 centimetres in allografts with acute rejection, whereas a mean decrease of 0.17 centimetres was seen in the group with other pathologies. As shown before in other studies, RI values and kidney size are of doubtful utility in the evaluation of kidney allograft dysfunction. ARFI-based elasticity measurement shows promise as a complementary non-invasive parameter in follow-on diagnosis of renal allograft rejection.

Macrophages: Contributors to Allograft Dysfunction, Repair or Innocent Bystanders?

PubMed Central

Mannon, Roslyn B.

2012-01-01

Purpose of this review Macrophages are members of the innate immune response. However, their role in the adaptive immune response is not known. The purpose of this review is to highlight our current understanding of macrophage structure and function and how they may participate in allograft injury. Recent Findings Studies in acute kidney injury models identify macrophages as key mediators of inflammatory injury while more recent studies indicate that they may play a reparative role, depending on phenotype—M1 or M2 type macrophages. Mregs, generated in vitro, appear to have immune suppressive abilities and a unique phenotype. In solid organ transplant, the emphasis of studies has been on acute or chronic injury. These data are derived from animal models using depletion of macrophages or antagonizing their activation and inflammatory responses. The relative contribution of macrophage phenotype in transplantation has not been explored. Summary These studies suggest that macrophages play an injurious role in acute cellular allograft rejection, as well as in chronic injury. Infiltration of an allograft with macrophages is also associated with worse graft function and poor prognosis. Further studies are needed to understand the mechanisms of macrophage mediated injury, explore their potential reparative role and determine if they or their functional products are biomarkers of poor graft outcomes. PMID:22157320

Mortality indicators and risk factors for intra-abdominal hypertension in severe acute pancreatitis.

PubMed

Zhao, J G; Liao, Q; Zhao, Y P; Hu, Y

2014-01-01

This study assessed the risk factors associated with mortality and the development of intra-abdominal hypertension (IAH) in patients with severe acute pancreatitis (SAP). To identify significant risk factors, we assessed the following variables in 102 patients with SAP: age, gender, etiology, serum amylase level, white blood cell (WBC) count, serum calcium level, Acute Physiology and Chronic Health Evaluation II (APACHE-II) score, computed tomography severity index (CTSI) score, pancreatic necrosis, surgical interventions, and multiple organ dysfunction syndrome (MODS). Statistically significant differences were identified using the Student t test and the χ (2) test. Independent risk factors for survival were analyzed by Cox proportional hazards regression. The following variables were significantly related to both mortality and IAH: WBC count, serum calcium level, serum amylase level, APACHE-II score, CTSI score, pancreatic necrosis, pancreatic necrosis >50%, and MODS. However, it was found that surgical intervention had no significant association with mortality. MODS and pancreatic necrosis >50% were found to be independent risk factors for survival in patients with SAP. Mortality and IAH from SAP were significantly related to WBC count, serum calcium level, serum amylase level, APACHE-II score, CTSI score, pancreatic necrosis, and MODS. However, Surgical intervention did not result in higher mortality. Moreover, MODS and pancreatic necrosis >50% predicted a worse prognosis in SAP patients.

Pediatric Multiple Organ Dysfunction Syndrome: Promising Therapies.

PubMed

Doctor, Allan; Zimmerman, Jerry; Agus, Michael; Rajasekaran, Surender; Bubeck Wardenburg, Juliane; Fortenberry, James; Zajicek, Anne; Mairson, Emma; Typpo, Katri

2017-03-01

To describe the state of the science, identify knowledge gaps, and offer potential future research questions regarding promising therapies for children with multiple organ dysfunction syndrome presented during the Eunice Kennedy Shriver National Institute of Child Health and Human Development Workshop on Pediatric Multiple Organ Dysfunction Syndrome (March 26-27, 2015). Literature review, research data, and expert opinion. Not applicable. Moderated by an expert from the field, issues relevant to the association of multiple organ dysfunction syndrome with a variety of conditions were presented, discussed, and debated with a focus on identifying knowledge gaps and research priorities. Summary of presentations and discussion supported and supplemented by relevant literature. Among critically ill children, multiple organ dysfunction syndrome is relatively common and associated with significant morbidity and mortality. For outcomes to improve, effective therapies aimed at preventing and treating this condition must be discovered and rigorously evaluated. In this article, a number of potential opportunities to enhance current care are highlighted including the need for a better understanding of the pharmacokinetics and pharmacodynamics of medications, the effect of early and optimized nutrition, and the impact of effective glucose control in the setting of multiple organ dysfunction syndrome. Additionally, a handful of the promising therapies either currently being implemented or developed are described. These include extracorporeal therapies, anticytokine therapies, antitoxin treatments, antioxidant approaches, and multiple forms of exogenous steroids. For the field to advance, promising therapies and other therapies must be assessed in rigorous manner and implemented accordingly.

Acute kidney injury: not just acute renal failure anymore?

PubMed

Dirkes, Susan

2011-02-01

Until recently, no uniform standard existed for diagnosing and classifying acute renal failure. To clarify diagnosis, the Acute Dialysis Quality Initiative group stated its consensus on the need for a clear definition and classification system of renal dysfunction with measurable criteria. Today the term acute kidney injury has replaced the term acute renal failure, with an understanding that such injury is a common clinical problem in critically ill patients and typically is predictive of an increase in morbidity and mortality. A classification system, known as RIFLE (risk of injury, injury, failure, loss of function, and end-stage renal failure), includes specific goals for preventing acute kidney injury: adequate hydration, maintenance of renal perfusion, limiting exposure to nephrotoxins, drug protective strategies, and the use of renal replacement therapies that reduce renal injury.

Aging and sleep deprivation induce the unfolded protein response in the pancreas: implications for metabolism

PubMed Central

Naidoo, Nirinjini; Davis, James G; Zhu, Jingxu; Yabumoto, Maya; Singletary, Kristan; Brown, Marishka; Galante, Raymond; Agarwal, Beamon; Baur, Joseph A

2014-01-01

Sleep disruption has detrimental effects on glucose metabolism through pathways that remain poorly defined. Although numerous studies have examined the consequences of sleep deprivation (SD) in the brain, few have directly tested its effects on peripheral organs. We examined several tissues in mice for induction of the unfolded protein response (UPR) following acute SD. In young animals, we found a robust induction of BiP in the pancreas, indicating an active UPR. At baseline, pancreata from aged animals exhibited a marked increase in a pro-apoptotic transcription factor, CHOP, that was amplified by SD, whereas BiP induction was not observed, suggesting a maladaptive response to cellular stress with age. Acute SD increased plasma glucose levels in both young and old animals. However, this change was not overtly related to stress in the pancreatic beta cells, as plasma insulin levels were not lower following acute SD. Accordingly, animals subjected to acute SD remained tolerant to a glucose challenge. In a chronic SD experiment, young mice were found to be sensitized to insulin and have improved glycemic control, whereas aged animals became hyperglycemic and failed to maintain appropriate plasma insulin concentrations. Our results show that both age and SD cooperate to induce the UPR in pancreatic tissue. While changes in insulin secretion are unlikely to play a major role in the acute effects of SD, CHOP induction in pancreatic tissues suggests that chronic SD may contribute to the loss or dysfunction of endocrine cells and that these effects may be exacerbated by normal aging. PMID:24102714

Evaluation of effect of hybrid bioartificial liver using end-stage liver disease model

PubMed Central

Liu, Qing; Duan, Zhong-Ping; Huang, Chun; Zhao, Chun-Hui

2004-01-01

AIM: To study the role of hybrid bioartificial liver (HBL) in clearing proinflammatory cytokines and endotoxin in patients with acute and sub-acute liver failure and the effects of HBL on systemic inflammatory syndrome (SIRS) and multiple organ dysfunction syndrome (MODS). METHODS: Five cases with severe liver failure (3 acute and 2 subacute) were treated with HBL. The clinical signs and symptoms, total bilirubin (TBIL), serum ammonia, endotoxin TNF-α, IL-6 and prothrombin activity (PTA), cholinesterase (CHE) were recorded before, during and after treatment. The end-stage liver disease (MELD) was used for the study. RESULTS: Two patients were bridged for spontaneous recovery and 1 patient was bridged for OLT successfully. Another 2 patients died on d 8 and d 21. The spontaneous recovery rate was 30.0%. PTA and CHE in all patients were significantly increased (P < 0.01), while the serum TBIL, endotoxin,TNF-α, IL-6 were decreased. MELD score (mean 43.6) predicted 100% deaths within 3 mo before treatment with HBL. After treatment with HBL, four out of 5 patients had decreased MELD scores (mean 36.6). The MELD score predicted 66% mortalities. CONCLUSION: The proinflammatory cytokines (TNFα, IL-6 and endotoxin)can be significantly removed by hybrid bioartificial liver and HBL appears to be effective in blocking SIRS and MODS in patients with acute and sub-acute liver failure. MELD is a reliable measure for predicting short-term mortality risk in patients with end-stage liver disease. The prognostic result also corresponds to clinical outcome. PMID:15112365

Prevention of cardiorenal syndromes.

PubMed

McCullough, Peter A

2010-01-01

The cardiorenal syndromes (CRS) are composed of five recently defined syndromes which represent common clinical scenarios in which both the heart and the kidney are involved in a bidirectional injury process leading to dysfunction of both organs. Common to each subtype are multiple complex pathogenic factors, a precipitous decline in function and a progressive course. Most pathways that lead to CRS involve acute injury to organs which manifest evidence of chronic disease, suggesting reduced ability to sustain damage, maintain vital functions, and facilitate recovery. Prevention of CRS is an ideal clinical goal, because once initiated, CRS cannot be readily aborted, are not completely reversible, and are associated with serious consequences including hospitalization, complicated procedures, need for renal replacement therapy, and death. Principles of prevention include identification and amelioration of precipitating factors, optimal management of both chronic heart and kidney diseases, and future use of multimodality therapies for end-organ protection at the time of systemic injury. This paper will review the core concepts of prevention of CRS with practical applications to be considered in today's practice. 2010 S. Karger AG, Basel.

Glutamatergic dysfunction in catatonia? Successful treatment of three acute akinetic catatonic patients with the NMDA antagonist amantadine.

PubMed Central

Northoff, G; Eckert, J; Fritze, J

1997-01-01

Therapeutic efficiacy of the NMDA antagonist amantadine is reported in three acute neuroleptic free akinetic catatonic patients. Intravenous infusion of amantadine led to the resolution of catatonic symptoms and considerable reductions of scores in various motor scales (Simpson Angus scale for extrapyramidal side effects (SEPS), the abnormal involuntary movement scale (AIMS), Rogers catatonia and schizophrenia scales). The therapeutic effect of amantadine showed a characteristic temporal pattern with most pronounced effects four to six hours after administration and recurrence of catatonic symptoms by 24 hours later, at least partially. Such a temporal pattern of therapeutic efficacy and decreasing efficacy occurred in all three patients on all days. The results suggest the central importance of glutamatergic dysfunction in catatonic syndrome. PMID:9120462

Galectin 3 complements BNP in risk stratification in acute heart failure.

PubMed

Fermann, Gregory J; Lindsell, Christopher J; Storrow, Alan B; Hart, Kimberly; Sperling, Matthew; Roll, Susan; Weintraub, Neal L; Miller, Karen F; Maron, David J; Naftilan, Allen J; McPherson, John A; Sawyer, Douglas B; Christenson, Robert; Collins, Sean P

2012-12-01

Galectin 3 (G3) is a mediator of fibrosis and remodeling in heart failure. Patients diagnosed with and treated for Acute Heart Failure Syndromes were prospectively enrolled in the Decision Making in Acute Decompensated Heart Failure multicenter trial. Patients with a higher G3 had a history of renal disease, a lower heart rate and acute kidney injury. They also tended to have a history of HF and 30-day adverse events compared with B-type natriuretic peptide. In Acute Heart Failure Syndromes, G3 levels do not provide prognostic value, but when used complementary to B-type natriuretic peptide, G3 is associated with renal dysfunction and may predict 30-day events.

Chronic hypopituitarism is uncommon in survivors of aneurysmal subarachnoid haemorrhage.

PubMed

Hannon, M J; Behan, L A; O'Brien, M M; Tormey, W; Javadpour, M; Sherlock, M; Thompson, C J

2015-01-01

The incidence of hypopituitarism after aneurysmal subarachnoid haemorrhage (SAH) is unclear from the conflicting reports in the literature. As routine neuroendocrine screening for hypopituitarism for all patients would be costly and logistically difficult, there is a need for precise data on the frequency of hypopituitarism and on factors which might predict the later development of pituitary dysfunction. We aimed to: (i) Establish the incidence of long-term hypopituitarism in patients with aneurysmal SAH. (ii) Determine whether data from patients' acute admission with SAH could predict the occurrence of long-term hypopituitarism. One hundred patients were studied prospectively from the time of presentation with acute SAH. Plasma cortisol, plasma sodium and a variety of clinical and haemodynamic parameters were sequentially measured for the first 12 days of their acute admission. Forty-one patients then underwent dynamic pituitary testing at median 15 months following SAH (range 7-30 months), with insulin tolerance test (ITT) or, if contraindicated, a glucagon stimulation test (GST) plus short synacthen test (SST). If symptoms of cranial diabetes insipidus (CDI) were present, a water deprivation test was also performed. Forty-one patients attended for follow-up dynamic pituitary testing. Although 14 of 100 had acute glucocorticoid deficiency immediately following SAH, only two of 41 had long-term adrenocorticotrophic hormone (ACTH) deficiency and four of 41 had growth hormone (GH) deficiency. None were hypothyroid or gonadotrophin deficient. None had chronic CDI or hyponatraemia. There was no association between acute glucocorticoid deficiency, acute CDI or acute hyponatraemia and long-term pituitary dysfunction. Both anterior and posterior hypopituitarism are very uncommon following SAH and are not predicted by acute clinical, haemodynamic or endocrinological parameters. Routine neuroendocrine screening is not justified in SAH patients. © 2014 John Wiley & Sons Ltd.

The anti-caspase inhibitor Q-VD-OPH prevents AIDS disease progression in SIV-infected rhesus macaques.

PubMed

Laforge, Mireille; Silvestre, Ricardo; Rodrigues, Vasco; Garibal, Julie; Campillo-Gimenez, Laure; Mouhamad, Shahul; Monceaux, Valérie; Cumont, Marie-Christine; Rabezanahary, Henintsoa; Pruvost, Alain; Cordeiro-da-Silva, Anabela; Hurtrel, Bruno; Silvestri, Guido; Senik, Anna; Estaquier, Jérôme

2018-04-02

Apoptosis has been proposed as a key mechanism responsible for CD4+ T cell depletion and immune dysfunction during HIV infection. We demonstrated that Q-VD-OPH, a caspase inhibitor, inhibits spontaneous and activation-induced death of T cells from SIV-infected rhesus macaques (RMs). When administered during the acute phase of infection, Q-VD-OPH was associated with (a) reduced levels of T cell death, (b) preservation of CD4+/CD8+ T cell ratio in lymphoid organs and in the gut, (c) maintenance of memory CD4+ T cells, and (d) increased specific CD4+ T cell response associated with the expression of cytotoxic molecules. Although therapy was limited to the acute phase of infection, Q-VD-OPH-treated RMs showed lower levels of both viral load and cell-associated SIV DNA as compared with control SIV-infected RMs throughout the chronic phase of infection, and prevented the development of AIDS. Overall, our data demonstrate that Q-VD-OPH injection in SIV-infected RMs may represent an adjunctive therapeutic agent to control HIV infection and delaying disease progression to AIDS.

The Deakin/Graeff hypothesis: focus on serotonergic inhibition of panic

PubMed Central

Paul, Evan D.; Johnson, Philip L.; Shekhar, Anantha; Lowry, Christopher A.

2014-01-01

The Deakin/Graeff hypothesis proposes that different subpopulations of serotonergic neurons through topographically organized projections to forebrain and brainstem structures modulate the response to acute and chronic stressors, and that dysfunction of these neurons increases vulnerability to affective and anxiety disorders, including Panic Disorder. We outline evidence supporting the existence of a serotonergic system originally discussed by Deakin/Graeff that is implicated in the inhibition of panic-like behavioral and physiological responses. Evidence supporting this panic inhibition system comes from the following observations: 1) serotonergic neurons located in the ‘ventrolateral dorsal raphe nucleus (DRVL) as well as the ventrolateral periaqueductal gray (VLPAG) inhibit dorsal periaqueductal gray-elicited panic-like responses; 2) chronic, but not acute, antidepressant treatment potentiates serotonin’s panicolytic effect; 3) contextual fear activates a central nucleus of the amygdala-DRVL/VLPAG circuit implicated in mediating freezing and inhibiting panic-like escape behaviors; 4) DRVL/VLPAG serotonergic neurons are central chemoreceptors and modulate the behavioral and cardiorespiratory response to panicogenic agents such as sodium lactate and CO2. Implications of the panic inhibition system are discussed. PMID:24661986

The Deakin/Graeff hypothesis: focus on serotonergic inhibition of panic.

PubMed

Paul, Evan D; Johnson, Philip L; Shekhar, Anantha; Lowry, Christopher A

2014-10-01

The Deakin/Graeff hypothesis proposes that different subpopulations of serotonergic neurons through topographically organized projections to forebrain and brainstem structures modulate the response to acute and chronic stressors, and that dysfunction of these neurons increases vulnerability to affective and anxiety disorders, including panic disorder. We outline evidence supporting the existence of a serotonergic system originally discussed by Deakin/Graeff that is implicated in the inhibition of panic-like behavioral and physiological responses. Evidence supporting this panic inhibition system comes from the following observations: (1) serotonergic neurons located in the 'ventrolateral dorsal raphe nucleus' (DRVL) as well as the ventrolateral periaqueductal gray (VLPAG) inhibit dorsal periaqueductal gray-elicited panic-like responses; (2) chronic, but not acute, antidepressant treatment potentiates serotonin's panicolytic effect; (3) contextual fear activates a central nucleus of the amygdala-DRVL/VLPAG circuit implicated in mediating freezing and inhibiting panic-like escape behaviors; (4) DRVL/VLPAG serotonergic neurons are central chemoreceptors and modulate the behavioral and cardiorespiratory response to panicogenic agents such as sodium lactate and CO2. Implications of the panic inhibition system are discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Pathophysiological Approaches of Acute Respiratory Distress syndrome: Novel Bases for Study of Lung Injury

PubMed Central

Castillo, R.L; Carrasco Loza, R; Romero-Dapueto, C

2015-01-01

Experimental approaches have been implemented to research the lung damage related-mechanism. These models show in animals pathophysiological events for acute respiratory distress syndrome (ARDS), such as neutrophil activation, reactive oxygen species burst, pulmonary vascular hypertension, exudative edema, and other events associated with organ dysfunction. Moreover, these approaches have not reproduced the clinical features of lung damage. Lung inflammation is a relevant event in the develop of ARDS as component of the host immune response to various stimuli, such as cytokines, antigens and endotoxins. In patients surviving at the local inflammatory states, transition from injury to resolution is an active mechanism regulated by the immuno-inflammatory signaling pathways. Indeed, inflammatory process is regulated by the dynamics of cell populations that migrate to the lung, such as neutrophils and on the other hand, the role of the modulation of transcription factors and reactive oxygen species (ROS) sources, such as nuclear factor kappaB and NADPH oxidase. These experimental animal models reproduce key components of the injury and resolution phases of human ALI/ARDS and provide a methodology to explore mechanisms and potential new therapies. PMID:26312099

The effects of acute oral antioxidants on diving-induced alterations in human cardiovascular function

PubMed Central

Obad, Ante; Palada, Ivan; Valic, Zoran; Ivančev, Vladimir; Baković, Darija; Wisløff, Ulrik; Brubakk, Alf O; Dujić, Željko

2007-01-01

Diving-induced acute alterations in cardiovascular function such as arterial endothelial dysfunction, increased pulmonary artery pressure (PAP) and reduced heart function have been recently reported. We tested the effects of acute antioxidants on arterial endothelial function, PAP and heart function before and after a field dive. Vitamins C (2 g) and E (400 IU) were given to subjects 2 h before a second dive (protocol 1) and in a placebo-controlled crossover study design (protocol 2). Seven experienced divers performed open sea dives to 30 msw with standard decompression in a non-randomized protocol, and six of them participated in a randomized trial. Before and after the dives ventricular volumes and function and pulmonary and brachial artery function were assessed by ultrasound. The control dive resulted in a significant reduction in flow-mediated dilatation (FMD) and heart function with increased mean PAP. Twenty-four hours after the control dive FMD was still reduced 37% below baseline (8.1 versus 5.1%, P = 0.005), while right ventricle ejection fraction (RV-EF), left ventricle EF and endocardial fractional shortening were reduced much less (∼2–3%). At the same time RV end-systolic volume was increased by 9% and mean PAP by 5%. Acute antioxidants significantly attenuated only the reduction in FMD post-dive (P < 0.001), while changes in pulmonary artery and heart function were unaffected by antioxidant ingestion. These findings were confirmed by repeating the experiments in a randomized study design. FMD returned to baseline values 72 h after the dive with pre-dive placebo, whereas for most cardiovascular parameters this occurred earlier (24–48 h). Right ventricular dysfunction and increased PAP lasted longer. Acute antioxidants attenuated arterial endothelial dysfunction after diving, while reduction in heart and pulmonary artery function were unchanged. Cardiovascular changes after diving are not fully reversed up to 3 days after a dive, suggesting longer lasting negative effects. PMID:17110413

Spaceflight Sensorimotor Analogs: Simulating Acute and Adaptive Effects

NASA Technical Reports Server (NTRS)

Taylor, Laura C.; Harm, Deborah L.; Kozlovskaya, Inessa; Reschke, Millard F.; Wood, Scott J.

2009-01-01

Adaptive changes in sensorimotor function during spaceflight are reflected by spatial disorientation, motion sickness, gaze destabilization and decrements in balance, locomotion and eye-hand coordination that occur during and following transitions between different gravitational states. The purpose of this study was to conduct a meta-synthesis of data from spaceflight analogs to evaluate their effectiveness in simulating adaptive changes in sensorimotor function. METHODS. The analogs under review were categorized as either acute analogs used to simulate performance decrements accompanied with transient changes, or adaptive analogs used to drive sensorimotor learning to altered sensory feedback. The effectiveness of each analog was evaluated in terms of mechanisms of action, magnitude and time course of observed deficits compared to spaceflight data, and the effects of amplitude and exposure duration. RESULTS. Parabolic flight has been used extensively to examine effects of acute variation in gravitational loads, ranging from hypergravity to microgravity. More recently, galvanic vestibular stimulation has been used to elicit acute postural, locomotor and gaze dysfunction by disrupting vestibular afferents. Patient populations, e.g., with bilateral vestibular loss or cerebellar dysfunction, have been proposed to model acute sensorimotor dysfunction. Early research sponsored by NASA involved living onboard rotating rooms, which appeared to approximate the time course of adaptation and post-exposure recovery observed in astronauts following spaceflight. Exposure to different bed-rest paradigms (6 deg head down, dry immersion) result in similar motor deficits to that observed following spaceflight. Shorter adaptive analogs have incorporated virtual reality environments, visual distortion paradigms, exposure to conflicting tilt-translation cues, and exposure to 3Gx centrifugation. As with spaceflight, there is considerable variability in responses to most of the analogs reviewed. DISCUSSION. A true ground-based flight analog for sensorimotor function is not feasible. A combination of flight analogs; however, can be used to selectively mimic different aspects of the spaceflight-induced sensorimotor performance decrements.

The effects of acute oral antioxidants on diving-induced alterations in human cardiovascular function.

PubMed

Obad, Ante; Palada, Ivan; Valic, Zoran; Ivancev, Vladimir; Baković, Darija; Wisløff, Ulrik; Brubakk, Alf O; Dujić, Zeljko

2007-02-01

Diving-induced acute alterations in cardiovascular function such as arterial endothelial dysfunction, increased pulmonary artery pressure (PAP) and reduced heart function have been recently reported. We tested the effects of acute antioxidants on arterial endothelial function, PAP and heart function before and after a field dive. Vitamins C (2 g) and E (400 IU) were given to subjects 2 h before a second dive (protocol 1) and in a placebo-controlled crossover study design (protocol 2). Seven experienced divers performed open sea dives to 30 msw with standard decompression in a non-randomized protocol, and six of them participated in a randomized trial. Before and after the dives ventricular volumes and function and pulmonary and brachial artery function were assessed by ultrasound. The control dive resulted in a significant reduction in flow-mediated dilatation (FMD) and heart function with increased mean PAP. Twenty-four hours after the control dive FMD was still reduced 37% below baseline (8.1 versus 5.1%, P = 0.005), while right ventricle ejection fraction (RV-EF), left ventricle EF and endocardial fractional shortening were reduced much less (approximately 2-3%). At the same time RV end-systolic volume was increased by 9% and mean PAP by 5%. Acute antioxidants significantly attenuated only the reduction in FMD post-dive (P < 0.001), while changes in pulmonary artery and heart function were unaffected by antioxidant ingestion. These findings were confirmed by repeating the experiments in a randomized study design. FMD returned to baseline values 72 h after the dive with pre-dive placebo, whereas for most cardiovascular parameters this occurred earlier (24-48 h). Right ventricular dysfunction and increased PAP lasted longer. Acute antioxidants attenuated arterial endothelial dysfunction after diving, while reduction in heart and pulmonary artery function were unchanged. Cardiovascular changes after diving are not fully reversed up to 3 days after a dive, suggesting longer lasting negative effects.

Assessing the effect of preoperative levosimendan on renal function in patients with right ventricular dysfunction.

PubMed

Guerrero Orriach, Jose L; Galán Ortega, M; Ramírez Fernandez, A; Ariza Villanueva, D; Florez Vela, A; Moreno Cortés, I; Rubio Navarro, M; Cruz Mañas, J

2017-02-01

The Acute Kidney Injury Network (AKIN) classification considers SCr values, urea and urine output in order to improve timely diagnose ARF and improve patient prognosis by early treatment. Preoperative levosimendan is a new way for cardiac and kidney protection, we try to evaluate this drug in fifteen patients comparing values of AKIN scale parameters pre and post cardiac surgery in patients with right ventricle dysfunction.

Renal function changes after fenestrated endovascular aneurysm repair.

PubMed

Tran, Kenneth; Fajardo, Andres; Ullery, Brant W; Goltz, Christopher; Lee, Jason T

2016-08-01

Limited data exist regarding the effect of fenestrated endovascular aneurysm repair (fEVAR) on renal function. We performed a comprehensive analysis of acute and chronic renal function changes in patients after fEVAR. This study included patients undergoing fEVAR at two institutions between September 2012 and March 2015. Glomerular filtration rate was estimated using the Modification of Diet in Renal Disease formula with serum creatinine levels obtained during the study period. Acute and chronic renal dysfunction was assessed using the RIFLE (Risk, Injury, Failure, Loss, End-stage renal disease) criteria and the chronic kidney disease (CKD) staging system, respectively. fEVAR was performed in 110 patients for juxtarenal or paravisceral aortic aneurysms, with a mean follow-up of 11.7 months. A total of 206 renal stents were placed, with a mean aneurysm size of 62.9 mm (range, 45-105 mm) and a mean neck length of 4.1 mm. Primary renal stent patency was 97.1% at the latest follow-up. Moderate kidney disease (CKD stage ≥ 3) was present in 51% of patients at baseline, with a mean preoperative glomerular filtration rate of 60.0 ± 19.6 mL/min/1.73 m 2 . Acute kidney injury occurred in 25 patients (22.7%), although 15 of these (60%) were classified as having mild dysfunction. During follow-up, 59 patients (73.7%) were found to have no change or improved renal disease by CKD staging, and 19 (23.7%) had a CKD increase of one stage. Two patients were noted to have end-stage renal failure requiring hemodialysis. Clinically significant renal dysfunction was noted in 21 patients (26.2%) at the latest follow-up. Freedom from renal decline at 1 year was 76.1% (95% confidence interval, 63.2%-85.0%). Surrogate markers for higher operative complexity, including operating time (P = .001), fluoroscopy time (P < .001), contrast volume (P = .017), and blood loss (P = .002), served as dependent risk factors for acute kidney injury, although though no independent predictors were identified. Age (P = .008) was an independent risk factor for long-term decline, whereas paradoxically, baseline kidney disease (P = .032) and longer operative times (P = .014) were protective of future renal dysfunction. Acute and chronic renal dysfunction both occur in approximately one-quarter of patients after fEVAR; however, most of these cases are classified as mild according to consensus definitions of renal injury. The presence of mild or moderate baseline kidney disease should not preclude endovascular repair in the juxtarenal population. Routine biochemical analysis and branch vessel surveillance remain important aspects of clinical follow-up for patients undergoing fEVAR. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Cardiac, renal, and neurological benefits of preoperative levosimendan administration in patients with right ventricular dysfunction and pulmonary hypertension undergoing cardiac surgery: evaluation with two biomarkers neutrophil gelatinase-associated lipocalin and neuronal enolase.

PubMed

Guerrero-Orriach, José Luis; Ariza-Villanueva, Daniel; Florez-Vela, Ana; Garrido-Sánchez, Lourdes; Moreno-Cortés, María Isabel; Galán-Ortega, Manuel; Ramírez-Fernández, Alicia; Alcaide Torres, Juan; Fernandez, Concepción Santiago; Navarro Arce, Isabel; Melero-Tejedor, José María; Rubio-Navarro, Manuel; Cruz-Mañas, José

2016-01-01

To evaluate if the preoperative administration of levosimendan in patients with right ventricular (RV) dysfunction, pulmonary hypertension, and high perioperative risk would improve cardiac function and would also have a protective effect on renal and neurological functions, assessed using two biomarkers neutrophil gelatinase-associated lipocalin (N-GAL) and neuronal enolase. This is an observational study. Twenty-seven high-risk cardiac patients with RV dysfunction and pulmonary hypertension, scheduled for cardiac valve surgery, were prospectively followed after preoperative administration of levosimendan. Levosimendan was administered preoperatively on the day before surgery. All patients were considered high risk of cardiac and perioperative renal complications. Cardiac function was assessed by echocardiography, renal function by urinary N-GAL levels, and the acute kidney injury scale. Neuronal damage was assessed by neuron-specific enolase levels. After surgery, no significant variations were found in mean and SE levels of N-GAL (14.31 [28.34] ng/mL vs 13.41 [38.24] ng/mL), neuron-specific enolase (5.40 [0.41] ng/mL vs 4.32 [0.61] ng/mL), or mean ± SD creatinine (1.06±0.24 mg/dL vs 1.25±0.37 mg/dL at 48 hours). RV dilatation decreased from 4.23±0.7 mm to 3.45±0.6 mm and pulmonary artery pressure from 58±18 mmHg to 42±19 mmHg at 48 hours. Preoperative administration of levosimendan has shown a protective role against cardiac, renal, and neurological damage in patients with a high risk of multiple organ dysfunctions undergoing cardiac surgery.

Acute Gonadotroph and Somatotroph Hormonal Suppression after Traumatic Brain Injury

PubMed Central

Wagner, Justin; Dusick, Joshua R.; McArthur, David L.; Cohan, Pejman; Wang, Christina; Swerdloff, Ronald; Boscardin, W. John

2010-01-01

Abstract Hormonal dysfunction is a known consequence of moderate and severe traumatic brain injury (TBI). In this study we determined the incidence, time course, and clinical correlates of acute post-TBI gonadotroph and somatotroph dysfunction. Patients had daily measurement of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, estradiol, growth hormone, and insulin-like growth factor-1 (IGF-1) for up to 10 days post-injury. Values below the fifth percentile of a healthy cohort were considered abnormal, as were non-measurable growth hormone (GH) values. Outcome measures were frequency and time course of hormonal suppression, injury characteristics, and Glasgow Outcome Scale (GOS) score. The cohort consisted of 101 patients (82% males; mean age 35 years; Glasgow Coma Scale [GCS] score ≤8 in 87%). In men, 100% had at least one low testosterone value, and 93% of all values were low; in premenopausal women, 43% had at least one low estradiol value, and 39% of all values were low. Non-measurable GH levels occurred in 38% of patients, while low IGF-1 levels were observed in 77% of patients, but tended to normalize within 10 days. Multivariate analysis revealed associations of younger age with low FSH and low IGF-1, acute anemia with low IGF-1, and older age and higher body mass index (BMI) with low GH. Hormonal suppression was not predictive of GOS score. These results indicate that within 10 days of complicated mild, moderate, and severe TBI, testosterone suppression occurs in all men and estrogen suppression occurs in over 40% of women. Transient somatotroph suppression occurs in over 75% of patients. Although this acute neuroendocrine dysfunction may not be TBI-specific, low gonadal steroids, IGF-1, and GH may be important given their putative neuroprotective functions. PMID:20214417

Cardiac Auscultation for Noncardiologists: Application in Cardiac Rehabilitation Programs: PART I: PATIENTS AFTER ACUTE CORONARY SYNDROMES AND HEART FAILURE.

PubMed

Compostella, Leonida; Compostella, Caterina; Russo, Nicola; Setzu, Tiziana; Iliceto, Sabino; Bellotto, Fabio

2017-09-01

During outpatient cardiac rehabilitation after an acute coronary syndrome or after an episode of congestive heart failure, a careful, periodic evaluation of patients' clinical and hemodynamic status is essential. Simple and traditional cardiac auscultation could play a role in providing useful prognostic information.Reduced intensity of the first heart sound (S1), especially when associated with prolonged apical impulse and the appearance of added sounds, may help identify left ventricular (LV) dysfunction or conduction disturbances, sometimes associated with transient myocardial ischemia. If both S1 and second heart sound (S2) are reduced in intensity, a pericardial effusion may be suspected, whereas an increased intensity of S2 may indicate increased pulmonary artery pressure. The persistence of a protodiastolic sound (S3) after an acute coronary syndrome is an indicator of severe LV dysfunction and a poor prognosis. In patients with congestive heart failure, the association of an S3 and elevated heart rate may indicate impending decompensation. A presystolic sound (S4) is often associated with S3 in patients with LV failure, although it could also be present in hypertensive patients and in patients with an LV aneurysm. Careful evaluation of apical systolic murmurs could help identifying possible LV dysfunction or mitral valve pathology, and differentiate them from a ruptured papillary muscle or ventricular septal rupture. Friction rubs after an acute myocardial infarction, due to reactive pericarditis or Dressler syndrome, are often associated with a complicated clinical course.During cardiac rehabilitation, periodic cardiac auscultation may provide useful information about the clinical-hemodynamic status of patients and allow timely detection of signs, heralding possible complications in an efficient and low-cost manner.

Diverse autonomic regulation of pupillary function and the cardiovascular system during alcohol withdrawal.

PubMed

Jochum, Thomas; Hoyme, Johannes; Schulz, Steffen; Weißenfels, Markus; Voss, Andreas; Bär, Karl-Jürgen

2016-02-01

Previous research indicated the complexity of autonomic dysfunction during acute alcohol withdrawal. This study aimed to investigate the pupillary light reflex as an indicator of midbrain and brainstem regulatory systems in relation to cardiovascular autonomic function. Thirty male patients were included in the study. They were investigated during acute alcohol withdrawal syndrome and 24h later during clomethiazole treatment and compared to healthy controls. Parameters of pupillary light reflex of both eyes as well as heart rate variability, blood pressure variability and baroreflex sensitivity (BRS) were studied. We observed significantly reduced sympathetic (small diameter, e.g., left eye: 5.00 in patients vs. 5.91 mm in controls) and vagal modulation (e.g., prolonged latencies, left eye: 0.28 vs. 0.26 ms) regarding both pupils during acute alcohol withdrawal syndrome. Cardiovascular parameters showed reduced vagal modulation (e.g., b-slope of BRS: 7. 57 vs. 13.59 ms/mm Hg) and mixed results for sympathetic influence. After 24h, autonomic dysfunction improved significantly, both for the pupils (e.g., left diameter: 5.38 mm) and the heart (e.g., b-slope of BRS: 9.34 ms/mm Hg). While parameters obtained from the pupil correlated with cardiac autonomic function (e.g, BRS and left diameter: r=0.564) in healthy controls, no such pattern was observed in patients. Results obtained from the pupil during acute alcohol withdrawal do not simply mirror autonomic dysfunction regarding the heart. Pupillary and cardiovascular changes after 24h indicate state dependencies of the results. The findings are discussed with respect to autonomic mechanisms and potentially involved brain regions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Clinical and Electrographic Correlates of Bilateral Independent Periodic Discharges.

PubMed

Freund, Brin; Gugger, James J; Reynolds, Alexandra; Tatum, William O; Claassen, Jan; Kaplan, Peter W

2018-05-01

Periodic discharges (PDs) are EEG patterns denoting brain dysfunction and ictal tendency. Their exact meaning regarding etiology and outcomes is not well known. In particular, bilateral independent PDs (BIPDs) are poorly described. We performed a retrospective, multicenter study evaluating neuroimaging, epileptic, clinical, and EEG correlates of BIPDs. Twenty-five patients studied with a mean Glasgow Coma Scale 6.5 and modified Rankin scale 3.9 who underwent EEG monitoring, mean duration 287 hours (range 0.75-3,216). Most common causes of BIPDs were cardiac arrest, Central Nervous System infections, and acute/chronic ischemic/hemorrhagic stroke. Most had subcortical and cortical injuries on neuroimaging. Most of the PDs ranged from 0.5 to 2 Hz in frequency, were of multiple phase types, and localized to the frontal head regions. Eighteen of 25 patients had clinical or electrographic seizures. There was a trend toward seizures in those with BIPDs with a history of epilepsy (P = 0.08) and acute metabolic dysfunction (P = 0.08), particularly with coincident acute structural lesions (P = 0.05). Seizures were predicted by bilaterally symmetric frequencies (P = 0.02) and trended toward higher likelihood with PD frequency <2 Hz (P = 0.08). Two of 25 patients survived past discharge with modified Rankin scale <3. Cardiac arrest was associated with withdrawal of life-sustaining therapy (P < 0.001). BIPDs arise from acute and chronic neurologic injuries, often associated with metabolic dysfunction. Outcomes are poor in this population. Seizures are common, particularly in patients with PDs that are of a lower frequency or are symmetric in frequency. Further study is warranted to evaluate the association between BIPDs and seizures, as well as functional and longer term outcomes.

Developing Interventions for Cancer-Related Cognitive Dysfunction in Childhood Cancer Survivors

PubMed Central

Ullrich, Nicole J.; Whelen, Megan J.; Lange, Beverly J.

2014-01-01

Survivors of childhood cancer frequently experience cancer-related cognitive dysfunction, commonly months to years after treatment for pediatric brain tumors, acute lymphoblastic leukemia (ALL), or tumors involving the head and neck. Risk factors for cancer-related cognitive dysfunction include young age at diagnosis, treatment with cranial irradiation, use of parenteral or intrathecal methotrexate, female sex, and pre-existing comorbidities. Limiting use and reducing doses and volume of cranial irradiation while intensifying chemotherapy have improved survival and reduced the severity of cognitive dysfunction, especially in leukemia. Nonetheless, problems in core functional domains of attention, processing speed, working memory and visual-motor integration continue to compromise quality of life and performance. We review the epidemiology, pathophysiology and assessment of cancer-related cognitive dysfunction, the impact of treatment changes for prevention, and the broad strategies for educational and pharmacological interventions to remediate established cognitive dysfunction following childhood cancer. The increased years of life saved after childhood cancer warrants continued study toward the prevention and remediation of cancer-related cognitive dysfunction, using uniform assessments anchored in functional outcomes. PMID:25080574

Prophylactic antibiotics in acute pancreatitis: endless debate.

PubMed

Mourad, M M; Evans, Rpt; Kalidindi, V; Navaratnam, R; Dvorkin, L; Bramhall, S R

2017-02-01

INTRODUCTION The development of pancreatic infection is associated with the development of a deteriorating disease with subsequent high morbidity and mortality. There is agreement that in mild pancreatitis there is no need to use antibiotics; in severe pancreatitis it would appear to be a logical choice to use antibiotics to prevent secondary pancreatic infection and decrease associated mortality. MATERIALS AND METHODS A non-systematic review of current evidence, meta-analyses and randomized controlled trials was conducted to assess the role of prophylactic antibiotics in acute pancreatitis and whether it might improve morbidity and mortality in pancreatitis. RESULTS Mixed evidence was found to support and refute the role of prophylactic antibiotics in acute pancreatitis. Most studies have failed to demonstrate much benefit from its routine use. Data from our unit suggested little benefit of their routine use, and showed that the mortality of those treated with antibiotics was significantly higher compared with those not treated with antibiotics (9% vs 0%, respectively, P = 0.043). In addition, the antibiotic group had significantly higher morbidity (36% vs 5%, respectively, P = 0.002). CONCLUSIONS Antibiotics should be used in patients who develop sepsis, infected necrosis-related systemic inflammatory response syndrome, multiple organ dysfunction syndrome or pancreatic and extra-pancreatic infection. Despite the many other factors that should be considered, prompt antibiotic therapy is recommended once inflammatory markers are raised, to prevent secondary pancreatic infection. Unfortunately, there remain many unanswered questions regarding the indications for antibiotic administration and the patients who benefit from antibiotic treatment in acute pancreatitis.

Acute right ventricular dysfunction: real-time management with echocardiography.

PubMed

Krishnan, Sundar; Schmidt, Gregory A

2015-03-01

In critically ill patients, the right ventricle is susceptible to dysfunction due to increased afterload, decreased contractility, or alterations in preload. With the increased use of point-of-care ultrasonography and a decline in the use of pulmonary artery catheters, echocardiography can be the ideal tool for evaluation and to guide hemodynamic and respiratory therapy. We review the epidemiology of right ventricular failure in critically ill patients; echocardiographic parameters for evaluating the right ventricle; and the impact of mechanical ventilation, fluid therapy, and vasoactive infusions on the right ventricle. Finally, we summarize the principles of management in the context of right ventricular dysfunction and provide recommendations for echocardiography-guided management.

5-Fluorouracil cardiotoxicity: reversible left ventricular systolic dysfunction with early detection.

PubMed

Iskandar, Muhammad Zaid; Quasem, Wahid; El-Omar, Magdi

2015-05-02

A 33-year-old man presented to hospital with acute shortness of breath and evolving ST segment changes on ECG 3 days following a cycle of 5-fluorouracil (5-FU) for colon cancer. Despite no cardiac history, subsequent echocardiogram showed severe left ventricular systolic dysfunction. The patient was initially treated with heart failure medications and his coronary angiogram was normal. Chemotherapy was stopped and he was started on nitrates and calcium channel blockers. A repeat echocardiogram and cardiac MRI a week later showed complete resolution of his left ventricular dysfunction and he was discharged home. This case report summarises 5-FU cardiotoxicity, and emphasises the importance of early recognition and correct treatment, as left ventricular systolic dysfunction in this context is potentially reversible. 2015 BMJ Publishing Group Ltd.

5-Fluorouracil cardiotoxicity: reversible left ventricular systolic dysfunction with early detection

PubMed Central

Iskandar, Muhammad Zaid; Quasem, Wahid; El-Omar, Magdi

2015-01-01

A 33-year-old man presented to hospital with acute shortness of breath and evolving ST segment changes on ECG 3 days following a cycle of 5-fluorouracil (5-FU) for colon cancer. Despite no cardiac history, subsequent echocardiogram showed severe left ventricular systolic dysfunction. The patient was initially treated with heart failure medications and his coronary angiogram was normal. Chemotherapy was stopped and he was started on nitrates and calcium channel blockers. A repeat echocardiogram and cardiac MRI a week later showed complete resolution of his left ventricular dysfunction and he was discharged home. This case report summarises 5-FU cardiotoxicity, and emphasises the importance of early recognition and correct treatment, as left ventricular systolic dysfunction in this context is potentially reversible. PMID:25935919

Flavanol-rich cocoa ameliorates lipemia-induced endothelial dysfunction.

PubMed

Westphal, Sabine; Luley, Claus

2011-09-01

Consumption of flavanols improves chronic endothelial dysfunction. We investigated whether it can also improve acute lipemia-induced endothelial dysfunction. In this randomized, placebo-controlled, double-blind, crossover trial, 18 healthy subjects received a fatty meal with cocoa either rich in flavanols (918 mg) or flavanol-poor. Flow-mediated dilation (FMD), triglycerides, and free fatty acids were then determined over 6 h. After the flavanol-poor fat loading, the FMD deteriorated over 4 h. The consumption of flavanol-rich cocoa, in contrast, improved this deterioration in hours 2, 3, and 4 without abolishing it completely. Flavanols did not have any influence on triglycerides or on free fatty acids. Flavanol-rich cocoa can alleviate the lipemia-induced endothelial dysfunction, probably through an improvement in endothelial NO synthase.

Acute oxygen sensing by the carotid body: from mitochondria to plasma membrane.

PubMed

Chang, Andy J

2017-11-01

Maintaining oxygen homeostasis is crucial to the survival of animals. Mammals respond acutely to changes in blood oxygen levels by modulating cardiopulmonary function. The major sensor of blood oxygen that regulates breathing is the carotid body (CB), a small chemosensory organ located at the carotid bifurcation. When arterial blood oxygen levels drop in hypoxia, neuroendocrine cells in the CB called glomus cells are activated to signal to afferent nerves that project to the brain stem. The mechanism by which hypoxia stimulates CB sensory activity has been the subject of many studies over the past 90 years. Two discrete models emerged that argue for the seat of oxygen sensing to lie either in the plasma membrane or mitochondria of CB cells. Recent studies are bridging the gap between these models by identifying hypoxic signals generated by changes in mitochondrial function in the CB that can be sensed by plasma membrane proteins on glomus cells. The CB is important for physiological adaptation to hypoxia, and its dysfunction contributes to sympathetic hyperactivity in common conditions such as sleep-disordered breathing, chronic heart failure, and insulin resistance. Understanding the basic mechanism of oxygen sensing in the CB could allow us to develop strategies to target this organ for therapy. In this short review, I will describe two historical models of CB oxygen sensing and new findings that are integrating these models. Copyright © 2017 the American Physiological Society.

Early Immune Function and Duration of Organ Dysfunction in Critically Ill Septic Children.

PubMed

Muszynski, Jennifer A; Nofziger, Ryan; Moore-Clingenpeel, Melissa; Greathouse, Kristin; Anglim, Larissa; Steele, Lisa; Hensley, Josey; Hanson-Huber, Lisa; Nateri, Jyotsna; Ramilo, Octavio; Hall, Mark W

2018-02-22

Late immune suppression is associated with nosocomial infection and mortality in septic adults and children. Relationships between early immune suppression and outcomes in septic children remain unclear. Prospective observational study to test the hypothesis that early innate and adaptive immune suppression are associated with longer duration of organ dysfunction in children with severe sepsis/septic shock. Methods, Measurements and Main Results: Children aged < 18 years meeting consensus criteria for severe sepsis or septic shock were sampled within 48 hours of sepsis onset. Healthy controls were sampled once. Innate immune function was quantified by whole blood ex vivo lipopolysaccharide-induced TNFα production capacity. Adaptive immune function was quantified by ex vivo phytohemagglutinin-induced IFNγ production capacity. 102 septic children and 35 healthy children were enrolled. Compared to healthy children, septic children demonstrated lower LPS-induced TNFα production (p < 0.0001) and lower PHA-induced IFNγ production (p<0.0001). Among septic children, early innate and adaptive immune suppression were associated with greater number of days with multiple organ dysfunction (MODS) and greater number of days with any organ dysfunction. On multivariable analyses, early innate immune suppression remained independently associated with increased MODS days [aRR 1.2 (1.03, 1.5)] and organ dysfunction days [aRR 1.2 (1.1, 1.3)]. Critically ill children with severe sepsis or septic shock demonstrate early innate and adaptive immune suppression. Early suppression of both innate and adaptive immunity are associated with longer duration of organ dysfunction and may be useful markers to guide investigations of immunomodulatory therapies in septic children.

Protocolized Treatment Is Associated With Decreased Organ Dysfunction in Pediatric Severe Sepsis.

PubMed

Balamuth, Fran; Weiss, Scott L; Fitzgerald, Julie C; Hayes, Katie; Centkowski, Sierra; Chilutti, Marianne; Grundmeier, Robert W; Lavelle, Jane; Alpern, Elizabeth R

2016-09-01

To determine whether treatment with a protocolized sepsis guideline in the emergency department was associated with a lower burden of organ dysfunction by hospital day 2 compared to nonprotocolized usual care in pediatric patients with severe sepsis. Retrospective cohort study. Tertiary care children's hospital from January 1, 2012, to March 31, 2014. Patients older than 56 days old and younger than 18 years old with international consensus defined severe sepsis and who required PICU admission within 24 hours of emergency department arrival were included. The exposure was the use of a protocolized emergency department sepsis guideline. The primary outcome was complete resolution of organ dysfunction by hospital day 2. One hundred eighty nine subjects were identified during the study period. Of these, 121 (64%) were treated with the protocolized emergency department guideline and 68 were not. There were no significant differences between the groups in age, sex, race, number of comorbid conditions, emergency department triage level, or organ dysfunction on arrival to the emergency department. Patients treated with protocolized emergency department care were more likely to be free of organ dysfunction on hospital day 2 after controlling for sex, comorbid condition, indwelling central venous catheter, Pediatric Index of Mortality-2 score, and timing of antibiotics and IV fluids (adjusted odds ratio, 4.2; 95% CI, 1.7-10.4). Use of a protocolized emergency department sepsis guideline was independently associated with resolution of organ dysfunction by hospital day 2 compared to nonprotocolized usual care. These data indicate that morbidity outcomes in children can be improved with the use of protocolized care.

Smoking and atherosclerosis: mechanisms of disease and new therapeutic approaches.

PubMed

Siasos, Gerasimos; Tsigkou, Vasiliki; Kokkou, Eleni; Oikonomou, Evangelos; Vavuranakis, Manolis; Vlachopoulos, Charalambos; Verveniotis, Alexis; Limperi, Maria; Genimata, Vasiliki; Papavassiliou, Athanasios G; Stefanadis, Christodoulos; Tousoulis, Dimitris

2014-01-01

It has been clear that at least 1 billion adults worldwide are smokers and at least 700 million children are passive smokers at home. Smoking exerts a detrimental effect to many organ systems and is responsible for illnesses such as lung cancer, pneumonia, chronic obstructive pulmonary disease, cancer of head and neck, cancer of the urinary and gastrointestinal tract, periodontal disease, cataract and arthritis. Additionally, smoking is an important modifiable risk factor for the development of cardiovascular disease such as coronary artery disease, stable angina, acute coronary syndromes, sudden death, stroke, peripheral vascular disease, congestive heart failure, erectile dysfunction and aortic aneurysms via initiation and progression of atherosclerosis. A variety of studies has proved that cigarette smoking induces oxidative stress, vascular inflammation, platelet coagulation, vascular dysfunction and impairs serum lipid pro-file in both current and chronic smokers, active and passive smokers and results in detrimental effects on the cardiovascular system. The aim of this review is to depict the physical and biochemical properties of cigarette smoke and, furthermore, elucidate the main pathophysiological mechanisms of cigarette-induced atherosclerosis and overview the new therapeutic approaches for smoking cessation and augmentation of cardiovascular health.

Traumatic Brain Injury: At the Crossroads of Neuropathology and Common Metabolic Endocrinopathies

PubMed Central

Li, Melanie

2018-01-01

Building on the seminal work by Geoffrey Harris in the 1970s, the neuroendocrinology field, having undergone spectacular growth, has endeavored to understand the mechanisms of hormonal connectivity between the brain and the rest of the body. Given the fundamental role of the brain in the orchestration of endocrine processes through interactions among neurohormones, it is thus not surprising that the structural and/or functional alterations following traumatic brain injury (TBI) can lead to endocrine changes affecting the whole organism. Taking into account that systemic hormones also act on the brain, modifying its structure and biochemistry, and can acutely and chronically affect several neurophysiological endpoints, the question is to what extent preexisting endocrine dysfunction may set the stage for an adverse outcome after TBI. In this review, we provide an overview of some aspects of three common metabolic endocrinopathies, e.g., diabetes mellitus, obesity, and thyroid dysfunction, and how these could be triggered by TBI. In addition, we discuss how the complex endocrine networks are woven into the responses to sudden changes after TBI, as well as some of the potential mechanisms that, separately or synergistically, can influence outcomes after TBI. PMID:29538298

Models of Lung Transplant Research: a consensus statement from the National Heart, Lung, and Blood Institute workshop.

PubMed

Lama, Vibha N; Belperio, John A; Christie, Jason D; El-Chemaly, Souheil; Fishbein, Michael C; Gelman, Andrew E; Hancock, Wayne W; Keshavjee, Shaf; Kreisel, Daniel; Laubach, Victor E; Looney, Mark R; McDyer, John F; Mohanakumar, Thalachallour; Shilling, Rebecca A; Panoskaltsis-Mortari, Angela; Wilkes, David S; Eu, Jerry P; Nicolls, Mark R

2017-05-04

Lung transplantation, a cure for a number of end-stage lung diseases, continues to have the worst long-term outcomes when compared with other solid organ transplants. Preclinical modeling of the most common and serious lung transplantation complications are essential to better understand and mitigate the pathophysiological processes that lead to these complications. Various animal and in vitro models of lung transplant complications now exist and each of these models has unique strengths. However, significant issues, such as the required technical expertise as well as the robustness and clinical usefulness of these models, remain to be overcome or clarified. The National Heart, Lung, and Blood Institute (NHLBI) convened a workshop in March 2016 to review the state of preclinical science addressing the three most important complications of lung transplantation: primary graft dysfunction (PGD), acute rejection (AR), and chronic lung allograft dysfunction (CLAD). In addition, the participants of the workshop were tasked to make consensus recommendations on the best use of these complimentary models to close our knowledge gaps in PGD, AR, and CLAD. Their reviews and recommendations are summarized in this report. Furthermore, the participants outlined opportunities to collaborate and directions to accelerate research using these preclinical models.

Contemporary management of Bell palsy.

PubMed

Jowett, Nate; Hadlock, Tessa A

2015-04-01

Bell palsy (BP) is the most common diagnosis in acute and chronic facial palsy. Although most patients fully recover, more than one-quarter will have residual dysfunction. Of these, nearly half will demonstrate severe limitations in facial expression. Though significant attention has been paid to acute management and prognosis, a paucity of literature exists addressing management of the long-term sequelae of BP. This article describes contemporary use of physical therapy, injectables, and static and dynamic surgical procedures in facial reanimation of acute and chronic BP. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Nitrite therapy after cardiac arrest reduces ROS generation, improves cardiac and neurological function and enhances survival via reversible inhibition of mitochondrial complex I

PubMed Central

Dezfulian, Cameron; Shiva, Sruti; Alekseyenko, Aleksey; Pendyal, Akshay; Beiser, DG; Munasinghe, Jeeva P.; Anderson, Stasia A.; Chesley, Christopher F.; Hoek, TL Vanden; Gladwin, Mark T.

2009-01-01

Background Three-fourths of cardiac arrest survivors die prior to hospital discharge or suffer significant neurological injury. Excepting therapeutic hypothermia and revascularization, no novel therapies have been developed that improve survival or cardiac and neurological function after resuscitation. Nitrite (NO2−) increases cellular resilience to focal ischemia-reperfusion injury in multiple organs. We hypothesized that nitrite therapy may improve outcomes after the unique global ischemia-reperfusion insult of cardiopulmonary arrest. Methods and Results We developed a mouse model of cardiac arrest characterized by 12-minutes of normothermic asystole and a high cardiopulmonary resuscitation (CPR) rate. In this model, global ischemia and CPR was associated with blood and organ nitrite depletion, reversible myocardial dysfunction, impaired alveolar gas exchange, neurological injury and an approximate 50% mortality. A single low dose of intravenous nitrite (50 nmol=1.85 μmol/kg=0.13 mg/kg) compared to blinded saline placebo given at CPR initiation with epinephrine improved cardiac function, survival and neurological outcomes. From a mechanistic standpoint, nitrite treatment restored intracardiac nitrite and increased S-nitrosothiol levels, decreased pathological cardiac mitochondrial oxygen consumption due to reactive oxygen species formation and prevented oxidative enzymatic injury via reversible specific inhibition of respiratory chain complex I. Conclusion Nitrite therapy after resuscitation from 12-minutes of asystole rapidly and reversibly modulated mitochondrial reactive oxygen species generation during early reperfusion, limiting acute cardiac dysfunction and death, as well as neurological impairment in survivors. PMID:19704094

Static cardiomyoplasty with synthetic elastic net suppresses ventricular dilatation and dysfunction after myocardial infarction in the rat: a chronic study.

PubMed

Kato, Nobusuke; Kawaguchi, Akira T; Kishida, Akio; Yamaoka, Tetsuji

2013-07-01

Although static cardiomyoplasty prevents the left ventricle (LV) from dilatation, it may interfere with diastolic relaxation, or cause restriction. We developed a synthetic net with dual elasticity and tested its effect late after myocardial infarction in the rat. LV pressure-volume relationships (PVR) were successively analyzed before, after intravenous volume load, and 10 minutes after occlusion of the left anterior descending artery. Rats were then randomized into groups receiving synthetic net wrapping around the heart (NET+, n = 8) and only partially behind LV (NET-, n = 9), and they underwent the same PVR studies 6 weeks later. End-diastolic and end-systolic PVR were defined, and LV size and function were compared under standardized loading conditions. Although there was no difference in Day 0, increase in LV end-diastolic and end-systolic volumes were significantly attenuated in NET+ rats 6 weeks later when there was a significant correlation between LV volumes by PVR estimation and actual measurements, with significant differences in both measures between the groups: NET+ < NET-. The presence or absence of net did not show restrictive hemodynamics under acute volume load. Static cardiomyoplasty using a synthetic elastic net significantly attenuated LV dilatation and dysfunction without restriction late after myocardial infarction in the rat. © 2013, Copyright the Authors. Artificial Organs © 2013, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Heme Oxygenase-1 Counteracts Contrast Media-Induced Endothelial Cell Dysfunction

PubMed Central

Chang, Chao-Fu; Liu, Xiao-Ming; Peyton, Kelly J.; Durante, William

2013-01-01

Endothelial cell (EC) dysfunction is involved in the pathogenesis of contrast-induced acute kidney injury, which is a major adverse event following coronary angiography. In this study, we evaluated the effect of contrast media (CM) on human EC proliferation, migration, and inflammation, and determined if heme oxygenase-1 (HO-1) influences the biological actions of CM. We found that three distinct CM, including high-osmolar (diatrizoate), low-osmolar (iopamidol), and iso-osmolar (iodixanol), stimulated the expression of HO-1 protein and mRNA. The induction of HO-1 was associated with an increase in NF-E2-related factor-2 (Nrf2) activity and reactive oxygen species (ROS). CM also stimulated HO-1 promoter activity and this was prevented by mutating the antioxidant responsive element or by overexpressing dominant-negative Nrf2. In addition, the CM-mediated induction of HO-1 and activation of Nrf2 was abolished by acetylcysteine. Finally, CM inhibited the proliferation and migration of ECs and stimulated the expression of intercellular adhesion molecule-1 and the adhesion of monocytes on ECs. Inhibition or silencing of HO-1 exacerbated the anti-proliferative and inflammatory actions of CM but had no effect on the anti-migratory effect. Thus, induction of HO-1 via the ROS-Nrf2 pathway counteracts the anti-proliferative and inflammatory actions of CM. Therapeutic approaches targeting HO-1 may provide a novel approach in preventing CM-induced endothelial and organ dysfunction. PMID:24239896

Exacerbation of acute kidney injury by bone marrow stromal cells from rats with persistent renin-angiotensin system activation.

PubMed

Kankuri, Esko; Mervaala, Elina E; Storvik, Markus; Ahola, Aija M J; Levijoki, Jouko; Müller, Dominik N; Finckenberg, Piet; Mervaala, Eero M

2015-06-01

Hypertension and persistent activation of the renin-angiotensin system (RAS) are predisposing factors for the development of acute kidney injury (AKI). Although bone-marrow-derived stromal cells (BMSCs) have shown therapeutic promise in treatment of AKI, the impact of pathological RAS on BMSC functionality has remained unresolved. RAS and its local components in the bone marrow are involved in several key steps of cell maturation processes. This may also render the BMSC population vulnerable to alterations even in the early phases of RAS pathology. We isolated transgenic BMSCs (TG-BMSCs) from young end-organ-disease-free rats with increased RAS activation [human angiotensinogen/renin double transgenic rats (dTGRs)] that eventually develop hypertension and die of end-organ damage and kidney failure at 8 weeks of age. Control cells (SD-BMSCs) were isolated from wild-type Sprague-Dawley rats. Cell phenotype, mitochondrial reactive oxygen species (ROS) production and respiration were assessed, and gene expression profiling was carried out using microarrays. Cells' therapeutic efficacy was evaluated in a rat model of acute ischaemia/reperfusion-induced AKI. Serum urea and creatinine were measured at 24 h and 48 h. Acute tubular damage was scored and immunohistochemistry was used for evaluation for markers of inflammation [monocyte chemoattractant protein (MCP-1), ED-1], and kidney injury [kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL)]. TG-BMSCs showed distinct mitochondrial morphology, decreased cell respiration and increased production of ROS. Gene expression profiling revealed a pronounced pro-inflammatory phenotype. In contrast with the therapeutic effect of SD-BMSCs, administration of TG-BMSCs in the AKI model resulted in exacerbation of kidney injury and high mortality. Our results demonstrate that early persistent RAS activation can dramatically compromise therapeutic potential of BMSCs by causing a shift into a pro-inflammatory phenotype with mitochondrial dysfunction.

High glucose, glucose fluctuation and carbonyl stress enhance brain microvascular endothelial barrier dysfunction: Implications for diabetic cerebral microvasculature.

PubMed

Li, Wei; Maloney, Ronald E; Aw, Tak Yee

2015-08-01

We previously demonstrated that in normal glucose (5mM), methylglyoxal (MG, a model of carbonyl stress) induced brain microvascular endothelial cell (IHEC) dysfunction that was associated with occludin glycation and prevented by N-acetylcysteine (NAC). Herein, we investigated the impact of high glucose and low GSH, conditions that mimicked the diabetic state, on MG-induced IHEC dysfunction. MG-induced loss of transendothelial electrical resistance (TEER) was potentiated in IHECs cultured for 7 or 12 days in 25 mM glucose (hyperglycemia); moreover, barrier function remained disrupted 6h after cell transfer to normal glucose media (acute glycemic fluctuation). Notably, basal occludin glycation was elevated under these glycemic states. TEER loss was exaggerated by inhibition of glutathione (GSH) synthesis and abrogated by NAC, which corresponded to GSH decreases and increases, respectively. Significantly, glyoxalase II activity was attenuated in hyperglycemic cells. Moreover, hyperglycemia and GSH inhibition increased MG accumulation, consistent with a compromised capacity for MG elimination. α-Oxoaldehydes (MG plus glyoxal) levels were elevated in streptozotocin-induced diabetic rat plasma. Immunohistochemistry revealed a prevalence of MG-positive, but fewer occludin-positive microvessels in the diabetic brain in vivo, and Western analysis confirmed an increase in MG-occludin adducts. These results provide the first evidence that hyperglycemia and acute glucose fluctuation promote MG-occludin formation and exacerbate brain microvascular endothelial dysfunction. Low occludin expression and high glycated-occludin contents in diabetic brain in vivo are factors that would contribute to the dysfunction of the cerebral microvasculature during diabetes. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Alcohol dehydrogenase accentuates ethanol-induced myocardial dysfunction and mitochondrial damage in mice: role of mitochondrial death pathway.

PubMed

Guo, Rui; Ren, Jun

2010-01-18

Binge drinking and alcohol toxicity are often associated with myocardial dysfunction possibly due to accumulation of the ethanol metabolite acetaldehyde although the underlying mechanism is unknown. This study was designed to examine the impact of accelerated ethanol metabolism on myocardial contractility, mitochondrial function and apoptosis using a murine model of cardiac-specific overexpression of alcohol dehydrogenase (ADH). ADH and wild-type FVB mice were acutely challenged with ethanol (3 g/kg/d, i.p.) for 3 days. Myocardial contractility, mitochondrial damage and apoptosis (death receptor and mitochondrial pathways) were examined. Ethanol led to reduced cardiac contractility, enlarged cardiomyocyte, mitochondrial damage and apoptosis, the effects of which were exaggerated by ADH transgene. In particular, ADH exacerbated mitochondrial dysfunction manifested as decreased mitochondrial membrane potential and accumulation of mitochondrial O(2) (*-). Myocardium from ethanol-treated mice displayed enhanced Bax, Caspase-3 and decreased Bcl-2 expression, the effect of which with the exception of Caspase-3 was augmented by ADH. ADH accentuated ethanol-induced increase in the mitochondrial death domain components pro-caspase-9 and cytochrome C in the cytoplasm. Neither ethanol nor ADH affected the expression of ANP, total pro-caspase-9, cytosolic and total pro-caspase-8, TNF-alpha, Fas receptor, Fas L and cytosolic AIF. Taken together, these data suggest that enhanced acetaldehyde production through ADH overexpression following acute ethanol exposure exacerbated ethanol-induced myocardial contractile dysfunction, cardiomyocyte enlargement, mitochondrial damage and apoptosis, indicating a pivotal role of ADH in ethanol-induced cardiac dysfunction possibly through mitochondrial death pathway of apoptosis.

High glucose, glucose fluctuation and carbonyl stress enhance brain microvascular endothelial barrier dysfunction: Implications for diabetic cerebral microvasculature

PubMed Central

Li, Wei; Maloney, Ronald E.; Aw, Tak Yee

2015-01-01

We previously demonstrated that in normal glucose (5 mM), methylglyoxal (MG, a model of carbonyl stress) induced brain microvascular endothelial cell (IHEC) dysfunction that was associated with occludin glycation and prevented by N-acetylcysteine (NAC). Herein, we investigated the impact of high glucose and low GSH, conditions that mimicked the diabetic state, on MG-induced IHEC dysfunction. MG-induced loss of transendothelial electrical resistance (TEER) was potentiated in IHECs cultured for 7 or 12 days in 25 mM glucose (hyperglycemia); moreover, barrier function remained disrupted 6 h after cell transfer to normal glucose media (acute glycemic fluctuation). Notably, basal occludin glycation was elevated under these glycemic states. TEER loss was exaggerated by inhibition of glutathione (GSH) synthesis and abrogated by NAC, which corresponded to GSH decreases and increases, respectively. Significantly, glyoxalase II activity was attenuated in hyperglycemic cells. Moreover, hyperglycemia and GSH inhibition increased MG accumulation, consistent with a compromised capacity for MG elimination. α-Oxoaldehydes (MG plus glyoxal) levels were elevated in streptozotocin-induced diabetic rat plasma. Immunohistochemistry revealed a prevalence of MG-positive, but fewer occludin-positive microvessels in the diabetic brain in vivo, and Western analysis confirmed an increase in MG–occludin adducts. These results provide the first evidence that hyperglycemia and acute glucose fluctuation promote MG–occludin formation and exacerbate brain microvascular endothelial dysfunction. Low occludin expression and high glycated-occludin contents in diabetic brain in vivo are factors that would contribute to the dysfunction of the cerebral microvasculature during diabetes. PMID:25867911

Do subjects with acute/subacute temporomandibular disorder have associated cervical impairments: A cross-sectional study.

PubMed

von Piekartz, Harry; Pudelko, Ani; Danzeisen, Mira; Hall, Toby; Ballenberger, Nikolaus

2016-12-01

There is preliminary evidence of cervical musculoskeletal impairment in some temporomandibular disorder (TMD) pain states. To determine whether people with TMD, classified as either mild or moderate/severe TMD, have more cervical signs of dysfunction than healthy subjects. Cross-sectional survey. Based on the Conti Amnestic Questionnaire and examination of the temporomandibular joint (Axis I classification of the Research Diagnostic Criteria for TMD), of 144 people examined 59 were classified to a mild TMD group, 40 to a moderate/severe TMD group and 45 to an asymptomatic control group without TMD. Subjects were evaluated for signs of cervical musculoskeletal impairment and disability including the Neck Disability Index, active cervical range of motion, the Flexion-Rotation Test, mechanical pain threshold of the upper trapezius and obliquus capitis inferior muscles, Cranio-Cervical Flexion test and passive accessory movements of the upper 3 cervical vertebrae. According to cervical musculoskeletal dysfunction, the control group without TMD were consistently the least impaired and the group with moderate/severe TMD were the most impaired. These results suggest, that the more dysfunction and pain is identified in the temporomandibular region, the greater levels of dysfunction is observable on a number of cervical musculoskeletal function tests. The pattern of cervical musculoskeletal dysfunction is distinct to other cervical referred pain phenomenon such as cervicogenic headache. These findings provide evidence that TMD in an acute/subacute pain state is strongly related with certain cervical spine musculoskeletal impairments which suggests the cervical spine should be examined in patients with TMD as a potential contributing factor. Copyright © 2016 Elsevier Ltd. All rights reserved.

Outcomes in critically ill cancer patients with septic shock of pulmonary origin.

PubMed

de Montmollin, Etienne; Tandjaoui-Lambiotte, Yacine; Legrand, Mattieu; Lambert, Jérôme; Mokart, Djamel; Kouatchet, Achille; Lemiale, Virginie; Pène, Frédéric; Bruneel, Fabrice; Vincent, François; Mayaux, Julien; Chevret, Sylvie; Azoulay, Elie

2013-03-01

Increased therapeutic intensity has translated into better survival at a price of infectious and toxic life-threatening complications, chiefly affecting the lungs. Yet, no study specifically evaluated outcomes in cancer patients admitted to the intensive care unit (ICU) for septic shock of pulmonary origin. This is a multicenter cohort study of cancer patients admitted to the ICU for septic shock and pneumonia between 1998 and 2008. Independent determinants of hospital mortality were assessed using a multivariate logistic regression model. Prognostic impact of persistence or acquisition of organ failures was evaluated by survival conditional probabilities. During the 10-year study period, 218 patients were included. Hematologic malignancy (mostly non-Hodgkin lymphoma and acute leukemia) affected 84%, and solid tumors (mostly lung cancer) affected 16% of patients. Chemotherapy was recently administered in 89% of patients, and 24.5% of patients were recipients of hematopoietic stem cell transplantation (35 autologous, 18 allogeneic). At the time of ICU admission, 60% of patients were in partial or complete remission. All patients received vasopressors; invasive mechanical ventilation (MV) was needed in 78.4% and dialysis in 30% of patients. Intensive care unit and hospital mortality rates were 56.4% and 62.4%, respectively. Independent risk factors for hospital mortality were age older than 60 years, time between first symptoms and ICU admission, use of invasive MV, need for invasive MV after use of noninvasive ventilation, and coma. Analysis of survival probability showed that there was no temporal threshold after which persistence or gain of organ dysfunction indicated no hope for survival. Survival in cancer patients with septic shock from pulmonary origin is substantial, even when organ dysfunctions are not rapidly reversible. Delayed ICU management is an independent predictor of death. Studies assessing survival benefits from early ICU management are warranted.

The diagnosis and management of progressive dysfunction of health care organizations.

PubMed

Chervenak, Frank A; McCullough, Laurence B

2005-04-01

This paper presents an ethically justified approach to the diagnosis and management of progressive dysfunction of health care organizational cultures. We explain the concept of professional integrity in terms of the ethical concept of the cofiduciary responsibility of physicians and health care organizations. We identify the ethical features of a healthy health care organization and the spectrum of progressive dysfunction of organizational cultures from cynical through wonderland and Kafkaesque to postmodern. Physicians should respond to cynical health care organizations by creating moral enclaves of professional integrity for the main purpose of confrontation and reform, to wonderland organizations by strengthening moral enclaves for the main purpose of resisting self-deception, to Kafkaesque organizations by strengthening moral enclaves still further for the main purpose of defending professional integrity (adopting a Machiavellian appearance of virtue as necessary), and to postmodern organizations by creating moral fortresses and, should these fail, quitting.

Ambulatory blood pressure monitoring in solid organ transplantation.

PubMed

Ramesh Prasad, G V

2012-01-01

Solid organ transplant recipients are at an increased risk for hypertension and cardiovascular disease. To assist in their management, 24-h ambulatory blood pressure monitoring (ABPM) has become increasingly used in both clinical research settings and practice. ABPM has been used to better define post-transplant hypertension incidence and prevalence in different solid organ transplantation populations. ABPM provides additional information on cardiovascular risk beyond that obtained by clinic-based readings, based on its ability to assess 24-h blood pressure (BP) load, detect nocturnal non-dipping, and predict target organ damage. It has provided some assurance about the safety of living kidney donation. Information from ABPM can be used to guide living kidney donor selection, and because ABPM-related data has been correlated with clinically important kidney and heart transplant recipient outcomes, it may be a valuable adjunct in their management. Despite these advantages, barriers to wider use of ABPM include expense, clinical inertia in hypertension management, lack of prospective clinical trial data, and clinical problems that compete with hypertension for attention such as acute or chronic allograft dysfunction. The increasing amount of research and clinical use for ABPM may allow for closer assessment and intervention to help address the increased cardiovascular risk faced by many solid organ transplant recipients. © 2011 John Wiley & Sons A/S.

Bioactivation of organic nitrates and the mechanism of nitrate tolerance.

PubMed

Klemenska, Emila; Beresewicz, Andrzej

2009-01-01

Organic nitrates, such as nitroglycerin, are commonly used in the therapy of cardiovascular disease. Long-term therapy with these drugs, however, results in the rapid development of nitrate tolerance, limiting their hemodynamic and anti-ischemic efficacy. In addition, nitrate tolerance is associated with the expression of potentially deleterious modifications such as increased oxidative stress, endothelial dysfunction, and sympathetic activation. In this review we discuss current concepts regarding the mechanisms of organic nitrate bioactivation, nitrate tolerance, and nitrate-mediated oxidative stress and endothelial dysfunction. We also examine how hydralazine may prevent nitrate tolerance and related endothelial dysfunction.

Herpes zoster induced neuropathic bladder--a case report.

PubMed

Tsai, Hsiu-Nan; Wu, Wen-Jeng; Huang, Shu-Pin; Su, Chin-Ming; Chen, Chung-Chin; Wang, Chii-Jye; Chou, Yii-Her; Huang, Chun-Hsiung

2002-01-01

Herpes zoster infection involving the sacral dermatomes has been associated with bladder dysfunction and, although rarely, with acute urinary retention. Less than 150 cases have been reported in the literature. After reviewing our institute's chart records covering a period of time dating from 1991 to 2001, we found that three of our patients had developed acute urinary retention following herpes zoster skin lesions of the S2-4 dermatomes. Herein we report our findings. These three patients had previously been found to have normal voiding status. However, at the time of complaint urodynamic studies revealed detrusor areflexia or detrusor hyporeflexia with decreased sensation of bladder filling. After micturation recovery, repeat urodynamic studies revealed detrusor pressure and bladder sensation recovery. After one to six weeks of treatment, all three patients could void spontaneously without catheterization. We found that, when treated with antiviral medication, supportive analgesics, and temporary urinary drainage, which included urethral catheterization and suprapubic cystostomy, acute urinary retention associated with herpes zoster has a generally favorable prognosis. In other words, we found that in spite of its rarity, herpes zoster induced neuropathic bladder dysfunction is reversible when treated appropriately.

Serum Uric Acid, Kidney Function and Acute Ischemic Stroke Outcomes in Elderly Patients: A Single-Cohort, Perspective Study

PubMed Central

Falsetti, Lorenzo; Capeci, William; Tarquinio, Nicola; Viticchi, Giovanna; Silvestrini, Mauro; Catozzo, Vania; Fioranelli, Agnese; Buratti, Laura; Pellegrini, Francesco

2017-01-01

Chronic kidney disease and hyperuricemia have been associated to an increased risk and a worse prognosis in acute ischemic stroke. Several mechanisms, including platelet dysfunction, coagulation disorders, endothelial dysfunction, inflammation, and an increased risk of atrial fibrillation could be implicated. The role of serum uric acid in this setting is still object of debate. We enrolled all the consecutive patients admitted to our department for acute ischemic stroke. Cox regression analysis was used to evaluate the risk of in-hospital death considering serum uric acid levels and all the comorbidities. In the overall sample, hyperuricemia was independently associated to an increased risk of in-hospital mortality. This effect was stronger in patients with chronic kidney disease while, in the group of patients with normal renal function, the relationship between hyperuricemia and increased stroke mortality was not confirmed. Hyperuricemia could be associated to higher in-hospital mortality for ischemic stroke among elderly patients when affected by kidney disease. Survival does not seem to be affected by hyperuricemia in patients with normal kidney function. PMID:28461885

Galectin 3 complements BNP in risk stratification in acute heart failure

PubMed Central

Fermann, Gregory J.; Lindsell, Christopher J.; Storrow, Alan B.; Hart, Kimberly; Sperling, Matthew; Roll, Susan; Weintraub, Neal L.; Miller, Karen F.; Maron, David J.; Naftilan, Allen J.; Mcpherson, John A.; Sawyer, Douglas B.; Christenson, Robert; Collins, Sean P.

2013-01-01

Background Galectin 3 (G3) is a mediator of fibrosis and remodeling in heart failure. Methods Patients diagnosed with and treated for Acute Heart Failure Syndromes were prospectively enrolled in the Decision Making in Acute Decompensated Heart Failure multicenter trial. Results Patients with a higher G3 had a history of renal disease, a lower heart rate and acute kidney injury. They also tended to have a history of HF and 30-day adverse events compared with B-type natriuretic peptide. Conclusion In Acute Heart Failure Syndromes, G3 levels do not provide prognostic value, but when used complementary to B-type natriuretic peptide, G3 is associated with renal dysfunction and may predict 30-day events. PMID:22998064

Laser-assisted tympanostomy (LAT) in adult individuals

NASA Astrophysics Data System (ADS)

Prokopakis, E. P.; Lachanas, V. A.; Helidonis, Emmanuel S.; Velegrakis, G.

2004-06-01

Objectives: To assess outcome, in adult individuals undergone Laser Assisted Tympanostomy (LAT) without ventilation tube placement. Method: LAT was performed on a total of 95 ears (72 individuals). Indications included serous otitis media with effusion (44 ears/31 patients), eustachian tube dysfunction (32 ears/24 patients), acute otitis media (13 ears/11 patients), and endoscopic visualization of the middle ear (6 ears/6 patients). Results: Middle ear disease was resolved after the closure of tympanostomy in 48% of patients with serous otitis media with effusion. In 78% of patients with Eustachian tube dysfunction symptoms were diminished. All patients with acute otitis media had a satisfactory outcome. LAT was found quite effective in patients undergoing middle ear endoscopy. Conclusion: LAT without ventilation tubes provides a safe alternative surgical option in adult patients in certain cases. The selection criteria for this procedure are addressed in detail.

The central role of renal microcirculatory dysfunction in the pathogenesis of acute kidney injury.

PubMed

Ince, Can

2014-01-01

Acute kidney injury (AKI) is a rapidly developing condition often associated with critical illness, with a high degree of morbidity and mortality, whose pathophysiology is ill understood. Recent investigations have identified the dysfunction of the renal microcirculation and its cellular and subcellular constituents as being central to the etiology of AKI. Injury is caused by inflammatory activation involving endothelial leucocyte interactions in combination with dysregulation of the homeostatis between oxygen, nitric oxide, and reactive oxygen species. Effective therapies expected to resolve AKI will have to control inflammation and restore this homeostasis. In order to apply and guide these therapies effectively, diagnostic tools aimed at physiological biomarkers of AKI for monitoring renal microcirculatory function in advance of changes in pharmacological biomarkers associated with structural damage of the kidney will need to be developed. 2014 S. Karger AG, Basel.

A porcine model for acute ischaemic right ventricular dysfunction.

PubMed

Haraldsen, Pernille; Lindstedt, Sandra; Metzsch, Carsten; Algotsson, Lars; Ingemansson, Richard

2014-01-01

To establish an experimental model for acute ischaemic isolated right ventricular dysfunction and the subsequent haemodynamic changes. An open-chest porcine model with ischaemic dysfunction of the right ventricle induced by ligation of the three main branches supporting the right ventricular free wall. Invasive monitoring of mean arterial blood pressure (MAP), central venous pressure (CVP), left atrial pressure (LAP) and right ventricular pressure (RVP); ultrasonic measurement of cardiac output (CO) and calculation of haemodynamic parameters such as stroke volume (SV), systemic vascular resistance (SVR), pulmonary vascular resistance (PVR) and right ventricular stroke work (RVSW) using standard formulae. The ischaemic challenge to the right ventricle resulted in a significant (≥30%) reduction in RVSW associated with an increase (6-25%) in CVP and reduction (8-18%) in pulmonary artery pressure (PAP) despite unchanged PVR, all reflecting the failing right ventricle. There was also a significant drop in CO (14-22%) despite unchanged LAP indicating lessened transpulmonary delivery of left ventricular preload due to the failing right ventricle causing the haemodynamic compromise rather than left ventricular failure. Supraventricular and ventricular arrhythmias occurred in three and two out of seven pigs, respectively-all of which except one were successfully resuscitated with cardioversion and/or defibrillation. This novel open-chest porcine model of induced ischaemia of the right ventricular free wall resulted in significant haemodynamic compromise confirmed using standard haemodynamic measurements making it useful for further research on acute, ischaemic isolated right ventricular failure.

Postoperative Takotsubo cardiomyopathy triggered by intraoperative fluid overload and acute hypertensive crisis.

PubMed

Varutti, Rosanna; Setti, Tommaso; Ezri, Tiberiu; Nicolosi, Gianluigi; Rellini, Gianluigi; Cassin, Matteo; Leykin, Yigal

2015-04-01

The Takotsubo cardiomyopathy is a rare haemodynamic dysfunction, only recently reported perioperatively. While the diagnostic criteria have been established and the outcome is known as favorable, the pathophysiological mechanisms are not entirely understood. Here we present the case of a patient scheduled for laparoscopic hysterectomy and adnexectomy, who early postoperatively developed a Takotsubo cardiomyopathy supposedly triggered by an acute hypertensive crisis due to intraoperative fluid overload.

Surfactant Dysfunction in ARDS and Bronchiolitis is Repaired with Cyclodextrins.

PubMed

Al-Saiedy, Mustafa; Gunasekara, Lasantha; Green, Francis; Pratt, Ryan; Chiu, Andrea; Yang, Ailian; Dennis, John; Pieron, Cora; Bjornson, Candice; Winston, Brent; Amrein, Matthias

2018-03-01

Acute respiratory distress syndrome (ARDS) is caused by many factors including inhalation of toxicants, acute barotrauma, acid aspiration, and burns. Surfactant function is impaired in ARDS and acute airway injury resulting in high surface tension with alveolar and small airway collapse, edema, hypoxemia, and death. In this study, we explore the mechanisms whereby surfactant becomes dysfunctional in ARDS and bronchiolitis and its repair with a cyclodextrin drug that sequesters cholesterol. We used in vitro model systems, a mouse model of ARDS, and samples from patients with acute bronchiolitis. Surface tension was measured by captive bubble surfactometry. Patient samples showed severe surfactant inhibition even in the absence of elevated cholesterol levels. Surfactant was also impaired in ARDS mice where the cholesterol to phospholipid ratio (W/W%) was increased. Methyl-β-cyclodextrin (MβCD) restored surfactant function to normal in both human and animal samples. Model studies showed that the inhibition of surfactant was due to both elevated cholesterol and an interaction between cholesterol and oxidized phospholipids. MβCD was also shown to have anti-inflammatory effects. Inhaled cyclodextrins have potential for the treatment of ARDS. They could be delivered in a portable device carried in combat and used following exposure to toxic gases and fumes or shock secondary to hemorrhage and burns.

Heart Rate Variability in Patients with Acute Ischemic Stroke at Different Stages of Renal Dysfunction: A Cross-sectional Observational Study.

PubMed

Wei, Lin; Zhao, Wen-Bo; Ye, Huan-Wen; Chen, Yan-Hua; Zhang, Xiao-Pei; Huang, Yan; Cai, Ye-Feng; Chen, Quan-Fu; Pan, Su-Yue

2017-03-20

Renal function is associated with mortality and functional disabilities in stroke patients, and impaired autonomic function is common in stroke, but little is known regarding its effects on stroke patients with renal dysfunction. This study sought to evaluate the association between autonomic function and stroke in patients with renal dysfunction. This study comprised 232 patients with acute ischemic stroke consecutively enrolled from February 2013 to November 2014 at Guangdong Provincial Hospital of Chinese Medicine in China. All patients recruited underwent laboratory evaluation and 24 h Holter electrocardiography (ECG). Autonomic function was measured based on the heart rate variability (HRV) using 24 h Holter ECG. Renal damage was assessed through the estimated glomerular filtration rate (eGFR), and stroke severity was rated according to the National Institutes of Health Stroke Scale (NIHSS). The Barthel index and modified Rankin score were also determined following admission. All the clinical covariates that could potentially affect autonomic outcome variables were adjusted with linear regression. In the patients with a mild or moderate decreased eGFR, the values for the standard deviation of the averaged normal-to-normal RR interval (SDANN) index (P = 0.022), very low frequency (VLF) (P = 0.043), low frequency (LF) (P = 0.023), and ratio of low-to-high frequency power (LF/HF) (P = 0.001) were significantly lower than those in the patients with a normal eGFR. A multinomial linear regression indicated that eGFR (t = 2.47, P = 0.014), gender (t = -3.60, P < 0.001), and a history of hypertension (t = -2.65, P = 0.008) were the risk factors of LF/HF; the NIHSS score (SDANN index: t = -3.83, P < 0.001; VLF: t = -3.07, P = 0.002; LF: t = -2.79, P = 0.006) and a history of diabetes (SDANN index: t = -3.58, P < 0.001; VLF: t = -2.54, P = 0.012; LF: t = -2.87, P = 0.004) were independent factors for the SDANN index, VLF, and LF; the Oxfordshire Community Stroke Project (t = -2.38, P = 0.018) was related to the SDANN index. Autonomic dysfunction is aggravated with the progression of eGFR stage in patients with acute ischemic stroke; the eGFR is an independent factor of LF/HF in the adjusted models. Stroke severity and a history of diabetes are more significantly associated with HRV in patients with acute ischemic stroke at different stages of renal dysfunction.

Right ventricular dysfunction as an echocardiographic prognostic factor in hemodynamically stable patients with acute pulmonary embolism: a meta-analysis.

PubMed

Cho, Jae Hyung; Kutti Sridharan, Gurusaravanan; Kim, Seon Ha; Kaw, Roop; Abburi, Triveni; Irfan, Affan; Kocheril, Abraham G

2014-05-06

We investigated whether right ventricular dysfunction (RVD) as assessed by echocardiogram can be used as a prognostic factor in hemodynamically stable patients with acute pulmonary embolism (PE). Short-term mortality has been investigated only in small studies and the results have been controversial. A PubMed search was conducted using two keywords, "pulmonary embolism" and "echocardiogram", for articles published between January 1st 1998 and December 31st 2011. Out of 991 articles, after careful review, we found 12 articles that investigated the implications of RVD as assessed by echocardiogram in predicting short-term mortality for hemodynamically stable patients with acute PE. We conducted a meta-analysis of these data to identify whether the presence of RVD increased short-term mortality. Among 3283 hemodynamically stable patients with acute PE, 1223 patients (37.3%) had RVD, as assessed by echocardiogram, while 2060 patients (62.7%) had normal right ventricular function. Short-term mortality was reported in 167 (13.7%) out of 1223 patients with RVD and in 134 (6.5%) out of 2060 patients without RVD. Hemodynamically stable patients with acute PE who had RVD as assessed by echocardiogram had a 2.29-fold increase in short-term mortality (odds ratio 2.29, 95% confidence interval 1.61-3.26) compared with patients without RVD. In hemodynamically stable patients with acute PE, RVD as assessed by echocardiogram increases short-term mortality by 2.29 times. Consideration should be given to obtaining echocardiogram to identify high-risk patients even if they are hemodynamically stable.

Right ventricular myocardial infarction: presentation and acute outcomes.

PubMed

Chockalingam, Anand; Gnanavelu, G; Subramaniam, T; Dorairajan, Smrita; Chockalingam, V

2005-01-01

Acute inferior wall myocardial infarction can be complicated by right ventricular myocardial infarction (RVMI), and the excess mortality cannot be fully explained by mechanical reasons. The authors try to systematically assess the incidence, clinical presentation and early outcomes of right ventricular infarction in a tertiary-care setup. Their study was a prospective observational series of consecutive patients with RVMI. All patients with acute inferior myocardial infarction (n=135) were enlisted. RVMI was diagnosed by > or = 1 mm ST elevation in lead V(4R) in a right-sided electrocardiogram. Right ventricular (RV) infarction occurred in 37% (n=50) of patients with acute inferior infarctions. Patients with isolated inferior infarction served as controls (n=85). Echocardiography was performed within 24 hours of admission. From both groups, 66% qualified for thrombolysis. The incidence of hypotension-bradycardia and heart blocks requiring pacing support was much higher in right ventricular infarction (n=21) than in inferior infarction (n=13). Clinically manifest RV dysfunction (raised jugular venous pulse [JVP], hypotension, tricuspid regurgitation) and right ventricular dilation detected by echocardiography were seen in only 13 patients. The in-hospital mortality rate was significantly higher (n=8, 16%) in right ventricular infarction group than in inferior infarction group (n=3, 3.5%). Right ventricular infarction was seen in a third of inferior myocardial infarctions (IMIs), but hemodynamically evident right ventricular dysfunction occurred in only a tenth of acute IMIs. Nevertheless, the acute in-hospital mortality rate of patients with right ventricular infarction was much higher than in those with inferior infarction owing to arrhythmic and mechanical complications.

Ammonia-induced brain swelling and neurotoxicity in an organotypic slice model

PubMed Central

Back, Adam; Tupper, Kelsey Y.; Bai, Tao; Chiranand, Paulpoj; Goldenberg, Fernando D.; Frank, Jeffrey I.; Brorson, James R.

2013-01-01

Objectives Acute liver failure produces cerebral dysfunction and edema, mediated in part by elevated ammonia concentrations, often leading to coma and death. The pathophysiology of cerebral edema in acute liver failure is incompletely understood. In vitro models of the cerebral effects of acute liver failure have predominately consisted of dissociated astrocyte cultures or acute brain slices. We describe a stable long-term culture model incorporating both neural and glial elements in a three-dimensional tissue structure offering significant advantages to the study of astrocytic-neuronal interactions in the pathophysiology of cerebral edema and dysfunction in acute liver failure. Methods We utilized chronic organotypic slice cultures from mouse forebrain, applying ammonium acetate in iso-osmolar fashion for 72 hours. Imaging of slice thickness to assess for tissue swelling was accomplished in living slices with optical coherence tomography, and confocal microscopy of fluorescence immunochemical and histochemical staining served to assess astrocyte and neuronal numbers, morphology, and volume in the fixed brain slices. Results Ammonia exposure at 1–10 mM produced swelling of immunochemically-identified astrocytes, and at 10 mM resulted in macroscopic tissue swelling, with slice thickness increasing by about 30%. Astrocytes were unchanged in number. In contrast, 10 mM ammonia treatment severely disrupted neuronal morphology and reduced neuronal survival at 72 hours by one-half. Discussion Elevated ammonia produces astrocytic swelling, tissue swelling, and neuronal toxicity in cerebral tissues. Ammonia-treated organotypic brain slice cultures provide an in vitro model of cerebral effects of conditions relevant to acute liver failure, applicable to pathophysiological investigations. PMID:22196764

APCAP--activated protein C in acute pancreatitis: a double-blind randomized human pilot trial.

PubMed

Pettilä, Ville; Kyhälä, Lea; Kylänpää, Marja-Leena; Leppäniemi, Ari; Tallgren, Minna; Markkola, Antti; Puolakkainen, Pauli; Repo, Heikki; Kemppainen, Esko

2010-01-01

Previous human studies have shown low activity of protein C (APC) in severe acute pancreatitis (SAP). This, together with the findings in animal models, suggests that activated protein C (APC) may protect against pancreatic injury and ameliorate the disease. We, therefore, evaluated its effect on multiple organ dysfunction (MOD) measured by the SOFA (Sequential Organ Failure Assessment) and on organ-failure-free days, and the safety of APC in SAP. A prospective double blind randomized pilot study was use. The study occurred in one university hospital tertiary intensive care unit (ICU) with eight beds. The patients were chosen according to the following inclusion criteria: 1) Those admitted to the hospital < 96 h from the onset of pain, 2) Those who had a three-fold increase in serum amylase over normal upper range or/and in whom computed tomography (CT) verification of SAP was noted, 3) Those who had one or more organ dysfunction (OD), and 4) Those in whom less than 48 hours had passed since their first OD. Of a total of 215 adult patients with SAP screened between June 2003 and August 2007, 158 fulfilled the study inclusion criteria. After exclusions 32 patients were randomized to the study. The intervention consisted of APC (N = 16) administered intravenously for 96 hours with a dose of 24 μg/kg/hour or placebo (N = 16) with a similar infusion rate. The sample size for the study was calculated according to the primary end-point: the change in SOFA during study drug infusion (Days 0 and 5). Comparisons between the study groups were performed using patient-related changes and calculation of difference in means (DIM, 95% CIs) and regarding categorical variables with Fisher's exact test. For all comparisons P < 0.05 was considered significant. No serious bleeding was detected clinically or by CT scans in either group. No significant difference in SOFA score change between the APC and placebo groups was found (difference in means (DIM) +2.3, 95% CI -0.7 to +5.3). Treatment with APC was associated with an increase in serum levels of both total and conjugated bilirubin. No differences in ventilator-free days, in renal replacement therapy-free days, in vasopressor-free days, or in days alive outside the hospital were detected. No serious bleeding or differences in the evolution of MOD were detected between APC and the placebo. Instead we found an increase in serum bilirubin in the APC group compared to the placebo group in patients with SAP. ClinicalTrials.gov NCT01017107.

Ecstasy (MDMA) Alters Cardiac Gene Expression and DNA Methylation: Implications for Circadian Rhythm Dysfunction in the Heart

PubMed Central

Koczor, Christopher A.; Ludlow, Ivan; Hight, Robert S.; Jiao, Zhe; Fields, Earl; Ludaway, Tomika; Russ, Rodney; Torres, Rebecca A.; Lewis, William

2015-01-01

MDMA (ecstasy) is an illicit drug that stimulates monoamine neurotransmitter release and inhibits reuptake. MDMA’s acute cardiotoxicity includes tachycardia and arrhythmia which are associated with cardiomyopathy. MDMA acute cardiotoxicity has been explored, but neither long-term MDMA cardiac pathological changes nor epigenetic changes have been evaluated. Microarray analyses were employed to identify cardiac gene expression changes and epigenetic DNA methylation changes. To identify permanent MDMA-induced pathogenetic changes, mice received daily 10- or 35-day MDMA, or daily 10-day MDMA followed by 25-day saline washout (10 + 25 days). MDMA treatment caused differential gene expression (p < .05, fold change >1.5) in 752 genes following 10 days, 558 genes following 35 days, and 113 genes following 10-day MDMA + 25-day saline washout. Changes in MAPK and circadian rhythm gene expression were identified as early as 10 days. After 35 days, circadian rhythm genes (Per3, CLOCK, ARNTL, and NPAS2) persisted to be differentially expressed. MDMA caused DNA hypermethylation and hypomethylation that was independent of gene expression; hypermethylation of genes was found to be 71% at 10 days, 68% at 35 days, and 91% at 10 + 25 days washout. Differential gene expression paralleled DNA methylation in 22% of genes at 10-day treatment, 17% at 35 days, and 48% at 10 + 25 days washout. We show here that MDMA induced cardiac epigenetic changes in DNA methylation where hypermethylation predominated. Moreover, MDMA induced gene expression of key elements of circadian rhythm regulatory genes. This suggests a fundamental organism-level event to explain some of the etiologies of MDMA dysfunction in the heart. PMID:26251327

Ecstasy (MDMA) Alters Cardiac Gene Expression and DNA Methylation: Implications for Circadian Rhythm Dysfunction in the Heart.

PubMed

Koczor, Christopher A; Ludlow, Ivan; Hight, Robert S; Jiao, Zhe; Fields, Earl; Ludaway, Tomika; Russ, Rodney; Torres, Rebecca A; Lewis, William

2015-11-01

MDMA (ecstasy) is an illicit drug that stimulates monoamine neurotransmitter release and inhibits reuptake. MDMA's acute cardiotoxicity includes tachycardia and arrhythmia which are associated with cardiomyopathy. MDMA acute cardiotoxicity has been explored, but neither long-term MDMA cardiac pathological changes nor epigenetic changes have been evaluated. Microarray analyses were employed to identify cardiac gene expression changes and epigenetic DNA methylation changes. To identify permanent MDMA-induced pathogenetic changes, mice received daily 10- or 35-day MDMA, or daily 10-day MDMA followed by 25-day saline washout (10 + 25 days). MDMA treatment caused differential gene expression (p < .05, fold change >1.5) in 752 genes following 10 days, 558 genes following 35 days, and 113 genes following 10-day MDMA + 25-day saline washout. Changes in MAPK and circadian rhythm gene expression were identified as early as 10 days. After 35 days, circadian rhythm genes (Per3, CLOCK, ARNTL, and NPAS2) persisted to be differentially expressed. MDMA caused DNA hypermethylation and hypomethylation that was independent of gene expression; hypermethylation of genes was found to be 71% at 10 days, 68% at 35 days, and 91% at 10 + 25 days washout. Differential gene expression paralleled DNA methylation in 22% of genes at 10-day treatment, 17% at 35 days, and 48% at 10 + 25 days washout. We show here that MDMA induced cardiac epigenetic changes in DNA methylation where hypermethylation predominated. Moreover, MDMA induced gene expression of key elements of circadian rhythm regulatory genes. This suggests a fundamental organism-level event to explain some of the etiologies of MDMA dysfunction in the heart. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Leptospirosis Renal Disease: Emerging Culprit of Chronic Kidney Disease Unknown Etiology.

PubMed

Yang, Chih-Wei

2018-01-01

Leptospirosis is the most prevalent zoonosis affecting more than 1 million populations worldwide. Interestingly, leptospirosis endemic regions coincide with chronic kidney disease (CKD) hotspots largely due to flooding and agricultural overlaps. Acute leptospirosis induces multiple organ dysfunction including acute kidney injury and may predispose to CKD and end-stage renal disease, if not treated timely. Asymptomatic infection may carry the bacteria in the kidney and CKD progresses insidiously. Histologic finding of leptospirosis renal disease includes tubulointerstitial nephritis, interstitial fibrosis, and tubular atrophy. Proximal tubule dysfunction and hypokalemia are observed in adult male workers with leptospirosis, a characteristic similarity to CKD unknown etiology (CKDu). CKDu is a form of CKD that is not attributable to traditional risk factors clustering in agricultural communities affecting young male farmers. Kidney pathology shows a chronic tubulointerstitial disease. CKDu is being reported as an endemic nephropathy across the globe. Recent surveys suggest that asymptomatic leptospira renal colonization is an overlooked risk for renal fibrosis and CKDu. Population with anti-leptospira seropositivity is associated with lower estimated glomerular filtration rate in endemic regions and carrier may progress to CKD. Leptospirosis has been considered as a risk factor for CKDu in Sri Lanka and in Mesoamerican area. Sugarcane workers in Nicaragua showed increased anti-leptospira seropositivity and higher urinary biomarkers for kidney injury. Emerging evidence with signs of infection were reported in these endemic population, indicating that leptospira exposure could play a role in CKDu as a cause of primary kidney disease or a susceptible factor when secondary injury such as heat stress or dehydration aggravates kidney disease. Therefore, leptospirosis as an emerging culprit of CKDu deserves further in-depth investigation. © 2017 S. Karger AG, Basel.

CXCR3 ligands are associated with the continuum of diffuse alveolar damage to chronic lung allograft dysfunction.

PubMed

Shino, Michael Y; Weigt, S Samuel; Li, Ning; Palchevskiy, Vyacheslav; Derhovanessian, Ariss; Saggar, Rajan; Sayah, David M; Gregson, Aric L; Fishbein, Michael C; Ardehali, Abbas; Ross, David J; Lynch, Joseph P; Elashoff, Robert M; Belperio, John A

2013-11-01

After lung transplantation, insults to the allograft generally result in one of four histopathologic patterns of injury: (1) acute rejection, (2) lymphocytic bronchiolitis, (3) organizing pneumonia, and (4) diffuse alveolar damage (DAD). We hypothesized that DAD, the most severe form of acute lung injury, would lead to the highest risk of chronic lung allograft dysfunction (CLAD) and that a type I immune response would mediate this process. Determine whether DAD is associated with CLAD and explore the potential role of CXCR3/ligand biology. Transbronchial biopsies from all lung transplant recipients were reviewed. The association between the four injury patterns and subsequent outcomes were evaluated using proportional hazards models with time-dependent covariates. Bronchoalveolar lavage (BAL) concentrations of the CXCR3 ligands (CXCL9/MIG, CXCL10/IP10, and CXCL11/ITAC) were compared between allograft injury patterns and "healthy" biopsies using linear mixed-effects models. The effect of these chemokine alterations on CLAD risk was assessed using Cox models with serial BAL measurements as time-dependent covariates. There were 1,585 biopsies from 441 recipients with 62 episodes of DAD. An episode of DAD was associated with increased risk of CLAD (hazard ratio, 3.0; 95% confidence interval, 1.9-4.7) and death (hazard ratio, 2.3; 95% confidence interval, 1.7-3.0). There were marked elevations in BAL CXCR3 ligand concentrations during DAD. Furthermore, prolonged elevation of these chemokines in serial BAL fluid measurements predicted the development of CLAD. DAD is associated with marked increases in the risk of CLAD and death after lung transplantation. This association may be mediated in part by an aberrant type I immune response involving CXCR3/ligands.

Severe imported malaria in an intensive care unit: a review of 59 cases

PubMed Central

2012-01-01

Background In view of the close relationship of Portugal with African countries, particularly former Portuguese colonies, the diagnosis of malaria is not a rare thing. When a traveller returns ill from endemic areas, malaria should be the number one suspect. World Health Organization treatment guidelines recommend that adults with severe malaria should be admitted to an intensive care unit (ICU). Methods Severe cases of malaria in patients admitted to an ICU were reviewed retrospectively (1990-2011) and identification of variables associated with in-ICU mortality performed. Malaria prediction score (MPS), malaria score for adults (MSA), simplified acute physiology score (SAPSII) and a score based on WHO's malaria severe criteria were applied. Statistical analysis was performed using StataV12. Results Fifty nine patients were included in the study, all but three were adults; 47 (79,6%) were male; parasitaemia on admission, quantified in 48/59 (81.3%) patients, was equal or greater than 2% in 47 of them (97.9%); the most common complications were thrombocytopaenia in 54 (91.5%) patients, associated with disseminated intravascular coagulation (DIC) in seven (11.8%), renal failure in 31 (52.5%) patients, 18 of which (30.5%) oliguric, shock in 29 (49.1%) patients, liver dysfunction in 27 (45.7%) patients, acidaemia in 23 (38.9%) patients, cerebral dysfunction in 22 (37.2%) patients, 11 of whom with unrousable coma, pulmonary oedema/ARDS in 22 (37.2%) patients, hypoglycaemia in 18 (30.5%) patients; 29 (49.1%) patients presented five or more dysfunctions. The case fatality rate was 15.2%. Comparing the four scores, the SAPS II and the WHO score were the most sensitive to death prediction. In the univariate analysis, death was associated with the SAPS II score, cerebral malaria, acute renal and respiratory failure, DIC, spontaneous bleeding, acidosis and hypoglycaemia. Age, partial immunity to malaria, delay in malaria diagnosis and the level of parasitaemia were not associated with death in this cohort. Conclusion Severe malaria cases should be continued monitored in the ICUs. SAPS II and the WHO score are good predictors of mortality in malaria patients, but other specific scores deserve to be studied prospectively. PMID:22458840

Effectiveness of physical exam signs for early detection of critical illness in pediatric systemic inflammatory response syndrome.

PubMed

Scott, Halden F; Donoghue, Aaron J; Gaieski, David F; Marchese, Ronald F; Mistry, Rakesh D

2014-11-19

Early detection of compensated pediatric septic shock requires diagnostic tests that are sensitive and specific. Four physical exam signs are recommended for detecting pediatric septic shock prior to hypotension (cold extremities, mental status, capillary refill, peripheral pulse quality); this study tested their ability to detect patients who develop organ dysfunction among a cohort of undifferentiated pediatric systemic inflammatory response syndrome patients. A prospective cohort of 239 pediatric emergency department patients <19 years with fever and tachycardia and undergoing phlebotomy were enrolled. Physicians recorded initial physical exams on a standardized form. Abstraction of the medical record determined outcomes including organ dysfunction, intensive care unit stay, serious bacterial infection, and therapies. Organ dysfunction occurred in 13/239 (5.4%) patients. Presence of at least one sign was significantly associated with organ dysfunction (Relative Risk: 2.71, 95% CI: 1.05-6.99), and presence of at least two signs had a Relative Risk = 4.98 (95% CI: 1.82-13.58). The sensitivity of exam findings ranged from 8-54%, specificity from 84-98%. Signs were associated with increased risk of intensive care and fluid bolus, but not with serious bacterial infection, intravenous antibiotics or admission. Altered mental status and peripheral pulse quality were significantly associated with organ dysfunction, while abnormal capillary refill time and presence of cold, mottled extremities were not. Certain recommended physical exam signs were associated with increased risk of organ dysfunction, a rare outcome in this undifferentiated pediatric population with fever and tachycardia. Sensitivity was low, while specificity was high. Additional research into optimally sensitive and specific diagnostic strategies is needed.

A comparison of three organ dysfunction scores: MODS, SOFA and LOD for predicting ICU mortality in critically ill patients.

PubMed

Khwannimit, Bodin

2007-06-01

To compare the validity of the Multiple Organ Dysfunction Score (MODS), Sequential Organ Failure Assessment (SOFA), and Logistic Organ Dysfunction Score (LOD) for predicting ICU mortality of Thai critically ill patients. A retrospective study was made of prospective data collected between the 1st July 2004 and 31st March 2006 at Songklanagarind Hospital. One thousand seven hundred and eighty two patients were enrolled in the present study. Two hundred and ninety three (16.4%) deaths were recorded in the ICU. The areas under the Receiver Operating Curves (A UC) for the prediction of ICU mortality the results were 0.861 for MODS, 0.879 for SOFA and 0.880 for LOD. The AUC of SOFA and LOD showed a statistical significance higher than the MODS score (p = 0.014 and p = 0.042, respectively). Of all the models, the neurological failure score showed the best correlation with ICU mortality. All three organ dysfunction scores satisfactorily predicted ICU mortality. The LOD and neurological failure had the best correlation with ICU outcome.

Vaginal Heparan Sulfate Linked to Neutrophil Dysfunction in the Acute Inflammatory Response Associated with Experimental Vulvovaginal Candidiasis.

PubMed

Yano, Junko; Noverr, Mairi C; Fidel, Paul L

2017-03-14

Despite acute inflammation by polymorphonuclear neutrophils (PMNs) during vulvovaginal candidiasis (VVC), clearance of Candida fails to occur. The purpose of this study was to uncover the mechanism of vaginal PMN dysfunction. Designs included assessing PMN migration, proinflammatory mediators, and tissue damage (by analysis of the activity of lactate dehydrogenase [LDH]) in mice susceptible (C3H/HeN-C57BL/6) or resistant (CD-1) to chronic VVC (CVVC-S or CVVC-R) and testing morphology-specific Candida albicans strains under conditions of preinduced PMN migration (CVVC-S mice) or PMN depletion (CVVC-R mice). In vitro designs included evaluation of C. albicans killing by elicited vaginal or peritoneal PMNs in standard or vaginal conditioned medium (VCM). Results showed that despite significant migration of PMNs and high levels of vaginal beta interleukin-1 (IL-1β) and alarmin S100A8, CVVC-S mice failed to reduce vaginal fungal burden irrespective of morphology or whether PMNs were present pre- or postinoculation, and had high LDH levels. In contrast, CVVC-R mice had reduced fungal burden and low LDH levels following PMN recruitment and IL-1β/S100A8 production, but maintained colonization in the absence of PMNs. Elicited vaginal and peritoneal PMNs showed substantial killing activity in standard media or VCM from CVVC-R mice but not in VCM from CVVC-S mice. The inhibitory effect of VCM from CVVC-S mice was unaffected by endogenous or exogenous estrogen and was ablated following depletion/neutralization of Mac-1 ligands using Mac-1 +/+ PMNs or recombinant Mac-1. Heparan sulfate (HS) was identified as the putative inhibitor as evidenced by the rescue of PMN killing following heparanase treatment of VCM, as well as by inhibition of killing by purified HS. These results suggest that vaginal HS is linked to PMN dysfunction in CVVC-S mice as a competitive ligand for Mac-1. IMPORTANCE Vaginal candidiasis, caused by Candida albicans , affects a significant number of women worldwide. Despite an acute inflammatory response by neutrophils during infection, the response fails to reduce the organism. Instead, the response is considered a key process underlying the symptoms of vaginitis. Therefore, it is important to determine the mechanism(s) associated with the lack of vaginal neutrophil antifungal activity. The established mouse model of Candida vaginitis was used to uncover the mechanism of neutrophil dysfunction. Results revealed that heparan sulfate present in the vagina of mice susceptible to chronic vaginitis served as a competitive ligand for the receptor (Mac-1) necessary for fungal recognition and neutrophil-mediated killing. This inhibitory function of heparan sulfate, confirmed through several approaches, provides the first evidence to explain the lack of antifungal immune reactivity during vaginal candidiasis. This finding paves the way for design of therapeutic strategies to reduce/eliminate symptomatic vaginal candidiasis and restore quality of life to those affected. Copyright © 2017 Yano et al.

Quality in Acute Stroke Care (QASC): process evaluation of an intervention to improve the management of fever, hyperglycemia, and swallowing dysfunction following acute stroke.

PubMed

Drury, Peta; Levi, Christopher; D'Este, Catherine; McElduff, Patrick; McInnes, Elizabeth; Hardy, Jennifer; Dale, Simeon; Cheung, N Wah; Grimshaw, Jeremy M; Quinn, Clare; Ward, Jeanette; Evans, Malcolm; Cadilhac, Dominique; Griffiths, Rhonda; Middleton, Sandy

2014-08-01

Our randomized controlled trial of a multifaceted evidence-based intervention for improving the inpatient management of fever, hyperglycemia, and swallowing dysfunction in the first three-days following stroke improved outcomes at 90 days by 15%. We designed a quantitative process evaluation to further explain and illuminate this finding. Blinded retrospective medical record audits were undertaken for patients from 19 stroke units prior to and following the implementation of three multidisciplinary evidence-based protocols (supported by team-building workshops, and site-based education and support) for the management of fever (temperature ≥37·5°C), hyperglycemia (glucose >11 mmol/l), and swallowing dysfunction in intervention stroke units. Data from 1804 patients (718 preintervention; 1086 postintervention) showed that significantly more patients admitted to hospitals allocated to the intervention group received care according to the fever (n = 186 of 603, 31% vs. n = 74 of 483, 15%, P < 0·001), hyperglycemia (n = 22 of 603, 3·7% vs. n = 3 of 483, 0·6%, P = 0·01), and swallowing dysfunction protocols (n = 241 of 603, 40% vs. n = 19 of 483, 4·0%, P ≤ 0·001). Significantly more patients in these intervention stroke units received four-hourly temperature monitoring (n = 222 of 603, 37% vs. n = 90 of 483, 19%, P < 0·001) and six-hourly glucose monitoring (194 of 603, 32% vs. 46 of 483, 9·5%, P < 0·001) within 72 hours of admission to a stroke unit, and a swallowing screen (242 of 522, 46% vs. 24 of 350, 6·8%, P ≤ 0·0001) within the first 24 hours of admission to hospital. There was no difference between the groups in the treatment of patients with fever with paracetamol (22 of 105, 21% vs. 38 of 131, 29%, P = 0·78) or their hyperglycemia with insulin (40 of 100, 40% vs. 17 of 57, 30%, P = 0·49). Our intervention resulted in better protocol adherence in intervention stroke units, which explains our main trial findings of improved patient 90-day outcomes. Although monitoring practices significantly improved, there was no difference between the groups in the treatment of fever and hyperglycemia following acute stroke. A significant link between improved treatment practices and improved outcomes would have explained further the success of our intervention, and we are still unable to explain definitively the large improvements in death and dependency found in the main trial results. One potential explanation is that improved monitoring may have led to better overall surveillance of deteriorating patients and faster initiation of treatments not measured as part of the main trial. © 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.

Early Detection of Junctional Adhesion Molecule-1 (JAM-1) in the Circulation after Experimental and Clinical Polytrauma

PubMed Central

Denk, Stephanie; Wiegner, Rebecca; Hönes, Felix M.; Messerer, David A. C.; Radermacher, Peter; Kalbitz, Miriam; Braumüller, Sonja; McCook, Oscar; Gebhard, Florian; Weckbach, Sebastian; Huber-Lang, Markus

2015-01-01

Severe tissue trauma-induced systemic inflammation is often accompanied by evident or occult blood-organ barrier dysfunctions, frequently leading to multiple organ dysfunction. However, it is unknown whether specific barrier molecules are shed into the circulation early after trauma as potential indicators of an initial barrier dysfunction. The release of the barrier molecule junctional adhesion molecule-1 (JAM-1) was investigated in plasma of C57BL/6 mice 2 h after experimental mono- and polytrauma as well as in polytrauma patients (ISS ≥ 18) during a 10-day period. Correlation analyses were performed to indicate a linkage between JAM-1 plasma concentrations and organ failure. JAM-1 was systemically detected after experimental trauma in mice with blunt chest trauma as a driving force. Accordingly, JAM-1 was reduced in lung tissue after pulmonary contusion and JAM-1 plasma levels significantly correlated with increased protein levels in the bronchoalveolar lavage as a sign for alveolocapillary barrier dysfunction. Furthermore, JAM-1 was markedly released into the plasma of polytrauma patients as early as 4 h after the trauma insult and significantly correlated with severity of disease and organ dysfunction (APACHE II and SOFA score). The data support an early injury- and time-dependent appearance of the barrier molecule JAM-1 in the circulation indicative of a commencing trauma-induced barrier dysfunction. PMID:26556956

Functional Turnover: An Empirical Assessment.

DTIC Science & Technology

1981-08-01

assumption that turnover is invariably dysfunctional to the organization (Dalton & Todor , 1979; Dalton & Todor , in press (a), (b); Jeswald, 1974; Muchinsky...34voluntary" turnover (Dalton, Todor & Krackhardt, in press). Dysfunctional (cell C) - The individual wants to leave the organization but the organization...criticized (Dalton & Todor , 1979; Dalton & Todor . in press (a), (b); Muchinsky & Tuttle, 1979; Muchinsky & Morrow, in press; Staw, in press; Staw

The role of imaging in diagnosing diseases of the distal radioulnar joint, triangular fibrocartilage complex, and distal ulna.

PubMed

Squires, Judy H; England, Eric; Mehta, Kaushal; Wissman, Robert D

2014-07-01

The purpose of this article is to review the anatomy, biomechanics, and multimodality imaging findings of common and uncommon distal radioulnar joint (DRUJ), triangular fibrocartilage complex, and distal ulna abnormalities. The DRUJ is a common site for acute and chronic injuries and is frequently imaged to evaluate chronic wrist pain, forearm dysfunction, and traumatic forearm injury. Given the complex anatomy of the wrist, the radiologist plays a vital role in the diagnosis of wrist pain and dysfunction.

Cognitive outcome of cerebral fat embolism.

PubMed

Manousakis, Georgios; Han, Dong Y; Backonja, Miroslav

2012-11-01

Cerebral fat embolism is an uncommon but serious complication of long-bone fracture. We report a young adult patient who sustained fat embolism after a femoral fracture. He developed stupor and coma within 24 hours from his injury. His acute recovery was characterized by marked frontal dysfunction. A comprehensive neuropsychological evaluation 4 months later revealed overall normal cognitive function, except for mild residual frontal dysfunction and weakness of verbal memory. Copyright © 2012 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Scleroderma Renal Crisis: A Reversible Cause of Left Ventricular Dysfunction.

PubMed

Martínez-Milla, Juan; Gaebelt, Hans Paul; Sánchez-Pernaute, Olga; Kallmeyer, Andrea; Romero, José; Farré, Jerónimo

2018-05-02

We report a case of acute left ventricular dysfunction due to myocarditis, in the setting of a scleroderma renal crisis. The case is particularly intriguing for the favorable outcome of both symptoms and heart function following immunosuppressive therapy. We also highlight the changes observed over time with image techniques as well as in electrocardiograms. Copyright © 2018 Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. Publicado por Elsevier España, S.L.U. All rights reserved.

Inflammatory response and extracorporeal circulation.

PubMed

Kraft, Florian; Schmidt, Christoph; Van Aken, Hugo; Zarbock, Alexander

2015-06-01

Patients undergoing cardiac surgery with extracorporeal circulation (EC) frequently develop a systemic inflammatory response syndrome. Surgical trauma, ischaemia-reperfusion injury, endotoxaemia and blood contact to nonendothelial circuit compounds promote the activation of coagulation pathways, complement factors and a cellular immune response. This review discusses the multiple pathways leading to endothelial cell activation, neutrophil recruitment and production of reactive oxygen species and nitric oxide. All these factors may induce cellular damage and subsequent organ injury. Multiple organ dysfunction after cardiac surgery with EC is associated with an increased morbidity and mortality. In addition to the pathogenesis of organ dysfunction after EC, this review deals with different therapeutic interventions aiming to alleviate the inflammatory response and consequently multiple organ dysfunction after cardiac surgery. Copyright © 2015 Elsevier Ltd. All rights reserved.

B-type natriuretic peptide testing for detection of heart failure.

PubMed

Saul, Lauren; Shatzer, Melanie

2003-01-01

The incidence of heart failure (HF) is on the increase with the aging population. Heart failure can manifest as either systolic or diastolic dysfunction. Systolic dysfunction causes impaired ventricular contractility with an ejection fraction of less than 45%. In contrast, diastolic dysfunction is evidenced by impaired ventricular relaxation and an ejection fraction greater than 45%. The diagnosis of HF is challenging with patients who present with acute dyspnea and a history of chronic obstructive pulmonary disease or pneumonia. The pathophysiology of HF and the resulting compensatory mechanisms involve a complex neuroendocrine response that includes a release of natriuretic peptides including B-type natriuretic peptides (BNPs). Elevation of BNP is in response to ventricular wall stress and volume overload from HF. BNP promotes natriuresis, diuresis, and vasodilitation and therefore counteracts some of the deleterious effects of the neuroendocrine response in HF Recently, a new laboratory test for BNP has been developed to assist in rapid identification of patients with HF. Research studies have shown that BNP testing assists in differentiating between cardiac and pulmonary causes of acute dyspnea and could be used to evaluate effectiveness of therapy and as a predictor for length of stay and readmission.

Neuromuscular signs associated with acute hypophosphatemia in a dog.

PubMed

Claus, Kimberly N; Day, Thomas K; Wolf, Christina

2015-01-01

The purpose of this report was to describe the successful recognition and management of neuromuscular dysfunction secondary to severe, acute hypophosphatemia in an adult dog with a 2 day history of vomiting, anorexia, and abdominal pain. Radiographs were suggestive of a foreign body obstruction, and surgery was recommended. Resection and anastomosis of the distal duodenum and proximal jejunum was performed. The dog recovered uneventfully, but approximately 36 hr postoperatively, he was found to have significant weakness and muscle tremors that were accompanied by hyperthermia. The only significant abnormality on a serum biochemical profile was a phosphorous level of 0.26 mmol/L. Within 6 hr of initiating phosphorous supplementation, the patient fully recovered and had no residual signs of neuromuscular dysfunction. Signs of neurologic dysfunction secondary to hypophosphatemia are commonly recognized in human patients. Reports of patients with severe muscle weakness, some of which necessitate ventilation due to weakening of muscles of respiration, are common throughout the literature. Less commonly, tremors are noted. This is the first known report of neuromuscular signs recognized and rapidly corrected in a dog. Although it is likely to be uncommon, hypophosphatemia should be recognized as a differential diagnosis in patients with tremors and/or muscle weakness.

Loss of PAFR prevents neuroinflammation and brain dysfunction after traumatic brain injury

PubMed Central

Yin, Xiang-Jie; Chen, Zhen-Yan; Zhu, Xiao-Na; Hu, Jin-Jia

2017-01-01

Traumatic brain injury (TBI) is a principal cause of death and disability worldwide, which is a major public health problem. Death caused by TBI accounts for a third of all damage related illnesses, which 75% TBI occurred in low and middle income countries. With the increasing use of motor vehicles, the incidence of TBI has been at a high level. The abnormal brain functions of TBI patients often show the acute and long-term neurological dysfunction, which mainly associated with the pathological process of malignant brain edema and neuroinflammation in the brain. Owing to the neuroinflammation lasts for months or even years after TBI, which is a pivotal causative factor that give rise to neurodegenerative disease at late stage of TBI. Studies have shown that platelet activating factor (PAF) inducing inflammatory reaction after TBI could not be ignored. The morphological and behavioral abnormalities after TBI in wild type mice are rescued by general knockout of PAFR gene that neuroinflammation responses and cognitive ability are improved. Our results thus define a key inflammatory molecule PAF that participates in the neuroinflammation and helps bring about cerebral dysfunction during the TBI acute phase. PMID:28094295

REVIEWING THE KETAMINE MODEL FOR SCHIZOPHRENIA

PubMed Central

Frohlich, Joel

2014-01-01

The observation that antagonists of the N-methyl-D-aspartate glutamate receptor (NMDAR), such as phencyclidine (PCP) and ketamine, transiently induce symptoms of acute schizophrenia had led to a paradigm shift from dopaminergic to glutamatergic dysfunction in pharmacological models of schizophrenia. The glutamate hypothesis can explain negative and cognitive symptoms of schizophrenia better than the dopamine hypothesis, and has the potential to explain dopamine dysfunction itself. The pharmacological and psychomimetic effects of ketamine, which is safer for human subjects than phencyclidine, are herein reviewed. Ketamine binds to a variety of receptors, but principally acts at the NMDAR, and convergent genetic and molecular evidence point to NMDAR hypofunction in schizophrenia. Furthermore, NMDAR hypofunction can explain connectional and oscillatory abnormalities in schizophrenia in terms of both weakened excitation of inhibitory -aminobutyric acidergic (GABAergic) interneurons that synchronize cortical networks and disinhibition of principal cells. Individuals with prenatal aberrations of NMDAR might experience the onset of schizophrenia towards the completion of synaptic pruning in adolescence, when network connectivity drops below a critical value. We conclude that ketamine challenge is useful for studying the positive, negative, and cognitive symptoms, dopaminergic and GABAergic dysfunction, age of onset, functional dysconnectivity, and abnormal cortical oscillations observed in acute schizophrenia. PMID:24257811

Pathophysiology of pulmonary hypertension in acute lung injury

PubMed Central

Price, Laura C.; McAuley, Danny F.; Marino, Philip S.; Finney, Simon J.; Griffiths, Mark J.

2012-01-01

Acute lung injury (ALI) and acute respiratory distress syndrome are characterized by protein rich alveolar edema, reduced lung compliance, and acute severe hypoxemia. A degree of pulmonary hypertension (PH) is also characteristic, higher levels of which are associated with increased morbidity and mortality. The increase in right ventricular (RV) afterload causes RV dysfunction and failure in some patients, with associated adverse effects on oxygen delivery. Although the introduction of lung protective ventilation strategies has probably reduced the severity of PH in ALI, a recent invasive hemodynamic analysis suggests that even in the modern era, its presence remains clinically important. We therefore sought to summarize current knowledge of the pathophysiology of PH in ALI. PMID:22246001

Acute catecholamine cardiomyopathy in patients with phaeochromocytoma or functional paraganglioma.

PubMed

Giavarini, Alessandra; Chedid, Antoine; Bobrie, Guillaume; Plouin, Pierre-François; Hagège, Albert; Amar, Laurence

2013-10-01

Phaeochromocytomas and paragangliomas (PPGL) can cause acute catecholamine cardiomyopathy (ACC). We assessed the prevalence of ACC and compared the presentation of cases with and without ACC in a large series of PPGL. Single centre retrospective study. Hypertension Unit, University Hospital, Paris. 140 consecutive patients with PPGL, referred from January 2003 to September 2012. Left ventricular ejection fraction (LVEF), perioperative mortality. Fifteen patients (11%) had suffered an ACC, occurring in 14 cases before the diagnosis of PPGL. Precipitating factors were identified in 11 cases. Twelve patients presented with acute pulmonary oedema, including 10 with cardiogenic shock, requiring life support in eight cases. Seven patients (five with pulmonary oedema) presented with acute chest pain and cardiac dysfunction. Electrocardiographic abnormalities were present in 14 cases: ST segment elevation or pathological Q waves, ST segment depression, and/or diffuse T wave inversion. Six patients displayed classical (apical ballooning) or inverted (basal/mid ventricular stunning) takotsubo-like cardiomyopathy. Coronary arteries were always normal on angiography. In patients with ACC, median LVEF rose from 30% (IQR 23-33%) during ACC to 71% (50-72%) before surgery (n=11, p<0.001). Median LVEF before PPGL surgery was 65% (51-72%) and 65% (60-70%) in patients with and without a history of ACC, respectively (not significant). PPGL may present as ACC in 11% of cases, excluding patients dying from undiagnosed tumours. Left ventricular dysfunction is usually reversible before surgery. PPGL should be suspected in patients with acute heart failure without evidence of valvular or coronary artery disease.

Sepsis and Acute Kidney Injury.

PubMed

Bilgili, Beliz; Haliloğlu, Murat; Cinel, İsmail

2014-12-01

Acute kindney injury (AKI) is a clinical syndrome which is generally defined as an abrupt decline in glomerular filtration rate, causing accumulation of nitrogenous products and rapid development of fluid, electrolyte and acid base disorders. In intensive care unit sepsis and septic shock are leading causes of AKI. Sepsis-induced AKI literally acts as a biologic indicator of clinical deterioration. AKI triggers variety of immune, inflammatory, metabolic and humoral patways; ultimately leading distant organ dysfunction and increases morbidity and mortality. Serial mesurements of creatinine and urine volume do not make it possible to diagnose AKI at early stages. Serum creatinine influenced by age, weight, hydration status and become apparent only when the kidneys have lost 50% of their function. For that reason we need new markers, and many biomarkers in the diagnosis of early AKI activity is assessed. Historically "Risk-Injury-Failure-Loss-Endstage" (RIFLE), "Acute Kidney Injury Netwok" (AKIN) and "The Kidney Disease/ Improving Global Outcomes" (KDIGO) classification systems are used for diagnosing easily in clinical practice and research and grading disease. Classifications including diagnostic criteria are formed for the identification of AKI. Neutrophil gelatinase associated lipocalin (NGAL), cystatin-C (Cys-C), kidney injury molecule-1 (KIM-1) and also "cell cycle arrest" molecules has been concerned for clinical use. In this review the pathophysiology of AKI, with the relationship of sepsis and the importance of early diagnosis of AKI is evaluated.

Heart failure and kidney dysfunction: epidemiology, mechanisms and management.

PubMed

Schefold, Joerg C; Filippatos, Gerasimos; Hasenfuss, Gerd; Anker, Stefan D; von Haehling, Stephan

2016-10-01

Heart failure (HF) is a major health-care problem and the prognosis of affected patients is poor. HF often coexists with a number of comorbidities of which declining renal function is of particular importance. A loss of glomerular filtration rate, as in acute kidney injury (AKI) or chronic kidney disease (CKD), independently predicts mortality and accelerates the overall progression of cardiovascular disease and HF. Importantly, cardiac and renal diseases interact in a complex bidirectional and interdependent manner in both acute and chronic settings. From a pathophysiological perspective, cardiac and renal diseases share a number of common pathways, including inflammatory and direct, cellular immune-mediated mechanisms; stress-mediated and (neuro)hormonal responses; metabolic and nutritional changes including bone and mineral disorder, altered haemodynamic and acid-base or fluid status; and the development of anaemia. In an effort to better understand the important crosstalk between the two organs, classifications such as the cardio-renal syndromes were developed. This classification might lead to a more precise understanding of the complex interdependent pathophysiology of cardiac and renal diseases. In light of exceptionally high mortality associated with coexisting HF and kidney disease, this Review describes important crosstalk between the heart and kidney, with a focus on HF and kidney disease in the acute and chronic settings. Underlying molecular and cellular pathomechanisms in HF, AKI and CKD are discussed in addition to current and future therapeutic approaches.

Influence of experimental rat model of multiple organ dysfunction on cefepime and amikacin pharmacokinetics.

PubMed Central

Mimoz, O; Jacolot, A; Padoin, C; Quillard, J; Tod, M; Louchahi, K; Samii, K; Petitjean, O

1996-01-01

We adapted an experimental model of multiple organ dysfunction to study the alterations it induces in the pharmacology of cefepime and amikacin. The half-lives of both antibiotics were significantly prolonged because of nonsignificant enhancement of the volume of distribution and reduced renal elimination. In the presence of multiple organ dysfunction, the concentration of each antibiotic in the lungs, compared with that in the lungs of healthy controls, was significantly decreased, despite similar concentrations in plasma, indicating that the application of a standard antibiotic concentration in plasma could lead to underdosage in tissues during the initial days of therapy. PMID:8851623

Blood-brain barrier dysfunction in brain diseases: clinical experience.

PubMed

Schoknecht, Karl; Shalev, Hadar

2012-11-01

The blood-brain barrier, a unique feature of the cerebral vasculature, is gaining attention as a feature in common neurologic disorders including stroke, traumatic brain injury, epilepsy, and schizophrenia. Although acute blood-brain barrier dysfunction can induce cerebral edema, seizures, or neuropsychiatric symptoms, epileptogenesis and cognitive decline are among the chronic effects. The mechanisms underlying blood-brain barrier dysfunction are diverse and may range from physical endothelial damage in traumatic brain injury to degradation of extracellular matrix proteins via matrix metalloproteinases as part of an inflammatory response. Clinically, blood-brain barrier dysfunction is often detected using contrast-enhanced imaging. However, these techniques do not give any insights into the underlying mechanism. Elucidating the specific pathways of blood-brain barrier dysfunction at different time points and in different brain diseases using novel imaging techniques promises a more accurate blood-brain barrier terminology as well as new treatment options and personalized treatment. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

[A case of rupture of the left ventricle free wall with papillary muscle dysfunction following acute myocardial infarction, operated on successfully].

PubMed

de Lima, R; Perdigão, C; Neves, L; Cravino, J; Dantas, M; Bordalo, A; Pais, F; Diogo, A N; Ferreira, R; Ribeiro, C

1990-09-01

The authors present a case of left ventricular free wall rupture post acute myocardial infarction, associated with mitral papillary posterior muscle necrosis, operated by infartectomy and mitral valvular protesis replacement. They refer the various complications occurred during the hospital staying, and discuss its medical and surgical approach. The patient was discharged alive and six months after the infarction keeps a moderate activity.

Multiorgan failure during a sickle cell crisis in sickle/beta-thalassemia.

PubMed

Tedla, Fasika M; Friedman, Eli A

2003-08-01

In contrast to the chronic nephropathy associated with sickle cell syndromes, acute renal failure and multiorgan dysfunction caused by acute sickling crisis are encountered infrequently. The authors present the first case of extensive multiorgan failure during a sickling episode in a patient with sickle/beta+thalassemia. The authors also review the interaction of the thalassemias with sickle cell disease and outline the distinctive course of their patient in comparison with previous reports.

Postoperative Takotsubo cardiomyopathy triggered by intraoperative fluid overload and acute hypertensive crisis

PubMed Central

Varutti, Rosanna; Setti, Tommaso; Ezri, Tiberiu; Nicolosi, Gianluigi; Rellini, Gianluigi; Cassin, Matteo; Leykin, Yigal

2015-01-01

The Takotsubo cardiomyopathy is a rare haemodynamic dysfunction, only recently reported perioperatively. While the diagnostic criteria have been established and the outcome is known as favorable, the pathophysiological mechanisms are not entirely understood. Here we present the case of a patient scheduled for laparoscopic hysterectomy and adnexectomy, who early postoperatively developed a Takotsubo cardiomyopathy supposedly triggered by an acute hypertensive crisis due to intraoperative fluid overload. PMID:28913455

Impaired Epstein-Barr Virus-Specific Neutralizing Antibody Response during Acute Infectious Mononucleosis Is Coincident with Global B-Cell Dysfunction

PubMed Central

Panikkar, Archana; Hislop, Andrew; Tellam, Nick; Dasari, Vijayendra; Hogquist, Kristin A.; Wykes, Michelle; Moss, Denis J.; Rickinson, Alan; Balfour, Henry H.

2015-01-01

Here we present evidence for previously unappreciated B-cell immune dysregulation during acute Epstein-Barr virus (EBV)-associated infectious mononucleosis (IM). Longitudinal analyses revealed that patients with acute IM have undetectable EBV-specific neutralizing antibodies and gp350-specific B-cell responses, which were associated with a significant reduction in memory B cells and no evidence of circulating antibody-secreting cells. These observations correlate with dysregulation of tumor necrosis factor family members BAFF and APRIL and increased expression of FAS on circulating B cells. PMID:26109734

Acute Heart Failure Triggered by Coronary Spasm With Transient Left Ventricular Dysfunction.

PubMed

Adachi, Yusuke; Sakakura, Kenichi; Ibe, Tatsuro; Yoshida, Nanae; Wada, Hiroshi; Fujita, Hideo; Momomura, Shin-Ichi

2017-04-06

Coronary spasm is abnormal contraction of an epicardial coronary artery resulting in myocardial ischemia. Coronary spasm induces not only depressed myocardial contractility, but also incomplete myocardial relaxation, which leads to elevated ventricular filling pressure. We herein report the case of a 55-year-old woman who had repeated acute heart failure caused by coronary spasm. Acetylcholine provocation test with simultaneous right heart catheterization was useful for the diagnosis of elevated ventricular filling pressure as well as coronary artery spasm. We should add coronary spasm to a differential diagnosis for repeated acute heart failure.

Urocortin Treatment Improves Acute Hemodynamic Instability and Reduces Myocardial Damage in Post-Cardiac Arrest Myocardial Dysfunction

PubMed Central

Huang, Chien-Hua; Wang, Chih-Hung; Tsai, Min-Shan; Hsu, Nai-Tan; Chiang, Chih-Yen; Wang, Tzung-Dau; Chang, Wei-Tien; Chen, Huei-Wen; Chen, Wen-Jone

2016-01-01

Aims Hemodynamic instability occurs following cardiac arrest and is associated with high mortality during the post-cardiac period. Urocortin is a novel peptide and a member of the corticotrophin-releasing factor family. Urocortin has the potential to improve acute cardiac dysfunction, as well as to reduce the myocardial damage sustained after ischemia reperfusion injury. The effects of urocortin in post-cardiac arrest myocardial dysfunction remain unclear. Methods and Results We developed a preclinical cardiac arrest model and investigated the effects of urocortin. After cardiac arrest induced by 6.5 min asphyxia, male Wistar rats were resuscitated and randomized to either the urocortin treatment group or the control group. Urocortin (10 μg/kg) was administrated intravenously upon onset of resuscitation in the experimental group. The rate of return of spontaneous circulation (ROSC) was similar between the urocortin group (76%) and the control group (72%) after resuscitation. The left ventricular systolic (dP/dt40) and diastolic (maximal negative dP/dt) functions, and cardiac output, were ameliorated within 4 h after ROSC in the urocortin-treated group compared to the control group (P<0.01). The neurological function of surviving animals was better at 6 h after ROSC in the urocortin-treated group (p = 0.023). The 72-h survival rate was greater in the urocortin-treated group compared to the control group (p = 0.044 by log-rank test). Cardiomyocyte apoptosis was lower in the urocortin-treated group (39.9±8.6 vs. 17.5±4.6% of TUNEL positive nuclei, P<0.05) with significantly increased Akt, ERK and STAT-3 activation and phosphorylation in the myocardium (P<0.05). Conclusions Urocortin treatment can improve acute hemodynamic instability as well as reducing myocardial damage in post-cardiac arrest myocardial dysfunction. PMID:27832152

Validating the WHO maternal near miss tool: comparing high- and low-resource settings.

PubMed

Witteveen, Tom; Bezstarosti, Hans; de Koning, Ilona; Nelissen, Ellen; Bloemenkamp, Kitty W; van Roosmalen, Jos; van den Akker, Thomas

2017-06-19

WHO proposed the WHO Maternal Near Miss (MNM) tool, classifying women according to several (potentially) life-threatening conditions, to monitor and improve quality of obstetric care. The objective of this study is to analyse merged data of one high- and two low-resource settings where this tool was applied and test whether the tool may be suitable for comparing severe maternal outcome (SMO) between these settings. Using three cohort studies that included SMO cases, during two-year time frames in the Netherlands, Tanzania and Malawi we reassessed all SMO cases (as defined by the original studies) with the WHO MNM tool (five disease-, four intervention- and seven organ dysfunction-based criteria). Main outcome measures were prevalence of MNM criteria and case fatality rates (CFR). A total of 3172 women were studied; 2538 (80.0%) from the Netherlands, 248 (7.8%) from Tanzania and 386 (12.2%) from Malawi. Total SMO detection was 2767 (87.2%) for disease-based criteria, 2504 (78.9%) for intervention-based criteria and 1211 (38.2%) for organ dysfunction-based criteria. Including every woman who received ≥1 unit of blood in low-resource settings as life-threatening, as defined by organ dysfunction criteria, led to more equally distributed populations. In one third of all Dutch and Malawian maternal death cases, organ dysfunction criteria could not be identified from medical records. Applying solely organ dysfunction-based criteria may lead to underreporting of SMO. Therefore, a tool based on defining MNM only upon establishing organ failure is of limited use for comparing settings with varying resources. In low-resource settings, lowering the threshold of transfused units of blood leads to a higher detection rate of MNM. We recommend refined disease-based criteria, accompanied by a limited set of intervention- and organ dysfunction-based criteria to set a measure of severity.

Cardiac dysfunctions following spinal cord injury

PubMed Central

Sandu, AM; Popescu, M; Iacobini, MA; Stoian, R; Neascu, C; Popa, F

2009-01-01

The aim of this article is to analyze cardiac dysfunctions occurring after spinal cord injury (SCI). Cardiac dysfunctions are common complications following SCI. Cardiovascular disturbances are the leading causes of morbidity and mortality in both acute and chronic stages of SCI. We reviewed epidemiology of cardiac disturbances after SCI, and neuroanatomy and pathophysiology of autonomic nervous system, sympathetic and parasympathetic. SCI causes disruption of descendent pathways from central control centers to spinal sympathetic neurons, originating into intermediolateral nuclei of T1–L2 spinal cord segments. Loss of supraspinal control over sympathetic nervous system results in reduced overall sympathetic activity below the level of injury and unopposed parasympathetic outflow through intact vagal nerve. SCI associates significant cardiac dysfunction. Impairment of autonomic nervous control system, mostly in patients with cervical or high thoracic SCI, causes cardiac dysrrhythmias, especially bradycardia and, rarely, cardiac arrest, or tachyarrhytmias and hypotension. Specific complication dependent on the period of time after trauma like spinal shock and autonomic dysreflexia are also reviewed. Spinal shock occurs during the acute phase following SCI and is a transitory suspension of function and reflexes below the level of the injury. Neurogenic shock, part of spinal shock, consists of severe bradycardia and hypotension. Autonomic dysreflexia appears during the chronic phase, after spinal shock resolution, and it is a life–threatening syndrome of massive imbalanced reflex sympathetic discharge occurring in patients with SCI above the splanchnic sympathetic outflow (T5–T6). Besides all this, additional cardiac complications, such as cardiac deconditioning and coronary heart disease may also occur. Proper prophylaxis, including nonpharmacologic and pharmacological strategies and cardiac rehabilitation diminish occurrence of the cardiac dysfunction following SCI. Each type of cardiac disturbance requires specific treatment. PMID:20108532

Mitochondria-targeted antioxidant (MitoQ) ameliorates age-related arterial endothelial dysfunction in mice.

PubMed

Gioscia-Ryan, Rachel A; LaRocca, Thomas J; Sindler, Amy L; Zigler, Melanie C; Murphy, Michael P; Seals, Douglas R

2014-06-15

Age-related arterial endothelial dysfunction, a key antecedent of the development of cardiovascular disease (CVD), is largely caused by a reduction in nitric oxide (NO) bioavailability as a consequence of oxidative stress. Mitochondria are a major source and target of vascular oxidative stress when dysregulated. Mitochondrial dysregulation is associated with primary ageing, but its role in age-related endothelial dysfunction is unknown. Our aim was to determine the efficacy of a mitochondria-targeted antioxidant, MitoQ, in ameliorating vascular endothelial dysfunction in old mice. Ex vivo carotid artery endothelium-dependent dilation (EDD) to increasing doses of acetylcholine was impaired by ∼30% in old (∼27 months) compared with young (∼8 months) mice as a result of reduced NO bioavailability (P < 0.05). Acute (ex vivo) and chronic (4 weeks in drinking water) administration of MitoQ completely restored EDD in older mice by improving NO bioavailability. There were no effects of age or MitoQ on endothelium-independent dilation to sodium nitroprusside. The improvements in endothelial function with MitoQ supplementation were associated with the normalization of age-related increases in total and mitochondria-derived arterial superoxide production and oxidative stress (nitrotyrosine abundance), as well as with increases in markers of vascular mitochondrial health, including antioxidant status. MitoQ also reversed the age-related increase in endothelial susceptibility to acute mitochondrial damage (rotenone-induced impairment in EDD). Our results suggest that mitochondria-derived oxidative stress is an important mechanism underlying the development of endothelial dysfunction in primary ageing. Mitochondria-targeted antioxidants such as MitoQ represent a promising novel strategy for the preservation of vascular endothelial function with advancing age and the prevention of age-related CVD. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

Mitochondria-targeted antioxidant (MitoQ) ameliorates age-related arterial endothelial dysfunction in mice

PubMed Central

Gioscia-Ryan, Rachel A; LaRocca, Thomas J; Sindler, Amy L; Zigler, Melanie C; Murphy, Michael P; Seals, Douglas R

2014-01-01

Age-related arterial endothelial dysfunction, a key antecedent of the development of cardiovascular disease (CVD), is largely caused by a reduction in nitric oxide (NO) bioavailability as a consequence of oxidative stress. Mitochondria are a major source and target of vascular oxidative stress when dysregulated. Mitochondrial dysregulation is associated with primary ageing, but its role in age-related endothelial dysfunction is unknown. Our aim was to determine the efficacy of a mitochondria-targeted antioxidant, MitoQ, in ameliorating vascular endothelial dysfunction in old mice. Ex vivo carotid artery endothelium-dependent dilation (EDD) to increasing doses of acetylcholine was impaired by ∼30% in old (∼27 months) compared with young (∼8 months) mice as a result of reduced NO bioavailability (P < 0.05). Acute (ex vivo) and chronic (4 weeks in drinking water) administration of MitoQ completely restored EDD in older mice by improving NO bioavailability. There were no effects of age or MitoQ on endothelium-independent dilation to sodium nitroprusside. The improvements in endothelial function with MitoQ supplementation were associated with the normalization of age-related increases in total and mitochondria-derived arterial superoxide production and oxidative stress (nitrotyrosine abundance), as well as with increases in markers of vascular mitochondrial health, including antioxidant status. MitoQ also reversed the age-related increase in endothelial susceptibility to acute mitochondrial damage (rotenone-induced impairment in EDD). Our results suggest that mitochondria-derived oxidative stress is an important mechanism underlying the development of endothelial dysfunction in primary ageing. Mitochondria-targeted antioxidants such as MitoQ represent a promising novel strategy for the preservation of vascular endothelial function with advancing age and the prevention of age-related CVD. PMID:24665093

Chlorine-induced cardiopulmonary injury

PubMed Central

Carlisle, Matthew; Lam, Adam; Svendsen, Erik R.; Aggarwal, Saurabh; Matalon, Sadis

2016-01-01

Chlorine (Cl2) is utilized worldwide for a diverse range of industrial applications, including pulp bleaching, sanitation, and pharmaceutical development. Though Cl2 has widespread use, little is known regarding the mechanisms of toxicity associated with Cl2 exposure, which occurs during industrial accidents or acts of terrorism. Previous instances of Cl2 exposure have led to reported episodes of respiratory distress that result in high morbidity and mortality. Furthermore, studies suggest that acute Cl2 exposure also results in systemic vascular injury and subsequent myocardial contractile dysfunction. Here we review both lung and cardiac pathology associated with acute Cl2 inhalation and discuss recently published data that suggests that mitochondrial dysfunction underlies the pathogenesis of Cl2-induced toxicity. Lastly, we discuss our findings that suggest that upregulation of autophagy protects against Cl2-induced lung inflammation and can be a potential therapeutic target for ameliorating the toxic effects of Cl2 exposure. PMID:27303906

Fiber optic probe enabled by surface-enhanced Raman scattering for early diagnosis of potential acute rejection of kidney transplant

NASA Astrophysics Data System (ADS)

Chi, Jingmao; Chen, Hui; Tolias, Peter; Du, Henry

2014-06-01

We have explored the use of a fiber-optic probe with surface-enhanced Raman scattering (SERS) sensing modality for early, noninvasive and, rapid diagnosis of potential renal acute rejection (AR) and other renal graft dysfunction of kidney transplant patients. Multimode silica optical fiber immobilized with colloidal Ag nanoparticles at the distal end was used for SERS measurements of as-collected urine samples at 632.8 nm excitation wavelength. All patients with abnormal renal graft function (3 AR episodes and 2 graft failure episodes) who were clinically diagnosed independently show common unique SERS spectral features in the urines collected just one day after transplant. SERS-based fiber-optic probe has excellent potential to be a bedside tool for early diagnosis of kidney transplant patients for timely medical intervention of patients at high risk of transplant dysfunction.

Chlorine-induced cardiopulmonary injury.

PubMed

Carlisle, Matthew; Lam, Adam; Svendsen, Erik R; Aggarwal, Saurabh; Matalon, Sadis

2016-06-01

Chlorine (Cl2 ) is utilized worldwide for a diverse range of industrial applications, including pulp bleaching, sanitation, and pharmaceutical development. Though Cl2 has widespread use, little is known regarding the mechanisms of toxicity associated with Cl2 exposure, which occurs during industrial accidents or acts of terrorism. Previous instances of Cl2 exposure have led to reported episodes of respiratory distress that result in high morbidity and mortality. Furthermore, studies suggest that acute Cl2 exposure also results in systemic vascular injury and subsequent myocardial contractile dysfunction. Here, we review both lung and cardiac pathology associated with acute Cl2 inhalation and discuss recently published data that suggest that mitochondrial dysfunction underlies the pathogenesis of Cl2 -induced toxicity. Last, we discuss our findings that suggest that upregulation of autophagy protects against Cl2 -induced lung inflammation and can be a potential therapeutic target for ameliorating the toxic effects of Cl2 exposure. © 2016 New York Academy of Sciences.

Predictors of Long-Term Mortality and Frequent Re-Hospitalization in Patients with Acute Decompensated Heart Failure and Kidney Dysfunction Treated with Renin-Angiotensin System Blockers.

PubMed

Baydemir, Canan; Ural, Dilek; Karaüzüm, Kurtuluş; Balci, Sibel; Argan, Onur; Karaüzüm, Irem; Kozdağ, Güliz; Ağır, Ayşen A

2017-07-10

BACKGROUND Assessment of risk for all-cause mortality and re-hospitalization is an important task during discharge of acute heart failure (AHF) patients, as they warrant different management strategies. Treatment with optimal medical therapy may change predictors for these 2 end-points in AHF patients with renal dysfunction. The aim of this study was to evaluate the predictors for long-term outcome in AHF patients with kidney dysfunction who were discharged on optimal medical therapy. MATERIAL AND METHODS The study was conducted retrospectively. The study group consisted of 225 AHF patients with moderate-to-severe kidney dysfunction, who were hospitalized at Kocaeli University Hospital Cardiology Clinic and who were prescribed beta-blockers and ACE-inhibitors or angiotensin II receptor blockers at discharge. Clinical, echocardiographic, and biochemical predictors of the composite of total mortality and frequent re-hospitalization (≥3 hospitalizations during the follow-up) were assessed using Cox regression and the predictors for each end-point were assessed by competing risk regression analysis. RESULTS Incidence of all-cause mortality was 45.3% and frequent readmissions were 49.8% in a median follow-up of 54 months. The associates of the composite end-point were age, NYHA class, respiration rate on admission, eGFR, hypoalbuminemia, mitral valve E/E' ratio, and ejection fraction. In competing risk regression analysis, right-sided HF, hypoalbuminemia, age, and uric acid appeared as independent associates of all-cause mortality, whereas NYHA class, NT-proBNP, mitral valve E/E' ratio, and uric acid were predictors for re-hospitalization. CONCLUSIONS Predictors for all-cause mortality in AHF with kidney dysfunction treated with optimal therapy are mainly related to advanced HF with right-sided dysfunction, whereas frequent re-hospitalization is associated with volume overload manifested by increased mitral E/E' ratio and NT-proBNP levels.

Overdose pattern and outcome in paracetamol-induced acute severe hepatotoxicity

PubMed Central

Craig, Darren G N; Bates, Caroline M; Davidson, Janice S; Martin, Kirsty G; Hayes, Peter C; Simpson, Kenneth J

2011-01-01

AIMS Paracetamol (acetaminophen) hepatotoxicity is the commonest cause of acute liver failure (ALF) in the UK. Conflicting data regarding the outcomes of paracetamol-induced ALF resulting from different overdose patterns are reported. METHODS Using prospectively defined criteria, we have analysed the impact of overdose pattern upon outcome in a cohort of 938 acute severe liver injury patients admitted to the Scottish Liver Transplantation Unit. RESULTS Between 1992 and 2008, 663 patients were admitted with paracetamol-induced acute severe liver injury. Of these patients, 500 (75.4%) had taken an intentional paracetamol overdose, whilst 110 (16.6%) had taken an unintentional overdose. No clear overdose pattern could be determined in 53 (8.0%). Unintentional overdose patients were significantly older, more likely to abuse alcohol, and more commonly overdosed on compound narcotic/paracetamol analgesics compared with intentional overdose patients. Unintentional overdoses had significantly lower admission paracetamol and alanine aminotransferase concentrations compared with intentional overdoses. However, unintentional overdoses had greater organ dysfunction at admission, and subsequently higher mortality (unintentional 42/110 (38.2%), intentional 128/500 (25.6%), P < 0.001). The King's College poor prognostic criteria had reduced sensitivity in unintentional overdoses (77.8%, 95% confidence intervals (CI) 62.9, 88.8) compared with intentional overdoses (89.9%, 95% CI 83.4, 94.5). Unintentional overdose was independently predictive of death or liver transplantation on multivariate analysis (odds ratio 1.91 (95% CI 1.07, 3.43), P= 0.032). CONCLUSIONS Unintentional paracetamol overdose is associated with increased mortality compared with intentional paracetamol overdose, despite lower admission paracetamol concentrations. Alternative prognostic criteria may be required for unintentional paracetamol overdoses. PMID:21219409

Identifying and Extinguishing Dysfunctional and Deadly Organizational Practices

ERIC Educational Resources Information Center

Mawhinney, Thomas C.

2009-01-01

It is possible to define an organization's culture in terms of its dominant behavioral practices and their molar consequences, from the shop floor to the executive suite (Redmon & Mason, 2001). Dysfunctional and potentially deadly practices (for the organization as a whole) can be "latent." They often go undetected until their…

Blood markers of coagulation, fibrinolysis, endothelial dysfunction and inflammation in lacunar stroke versus non-lacunar stroke and non-stroke: systematic review and meta-analysis.

PubMed

Wiseman, Stewart; Marlborough, Fergal; Doubal, Fergus; Webb, David J; Wardlaw, Joanna

2014-01-01

The cause of cerebral small vessel disease is not fully understood, yet it is important, accounting for about 25% of all strokes. It also increases the risk of having another stroke and contributes to about 40% of dementias. Various processes have been implicated, including microatheroma, endothelial dysfunction and inflammation. A previous review investigated endothelial dysfunction in lacunar stroke versus mostly non-stroke controls while another looked at markers of inflammation and endothelial damage in ischaemic stroke in general. We have focused on blood markers between clinically evident lacunar stroke and other subtypes of ischaemic stroke, thereby controlling for stroke in general. We systematically assessed the literature for studies comparing blood markers of coagulation, fibrinolysis, endothelial dysfunction and inflammation in lacunar stroke versus non-stroke controls or other ischaemic stroke subtypes. We assessed the quality of included papers and meta-analysed results. We split the analysis on time of blood draw in relation to the stroke. We identified 1,468 full papers of which 42 were eligible for inclusion, including 4,816 ischaemic strokes, of which 2,196 were lacunar and 2,500 non-stroke controls. Most studies subtyped stroke using TOAST. The definition of lacunar stroke varied between studies. Markers of coagulation/fibrinolysis (tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI), fibrinogen, D-dimer) were higher in lacunar stroke versus non-stroke although fibrinogen was no different to non-stroke in the acute phase. tPA and PAI were no different between lacunar and non-lacunar stroke. Fibrinogen and D-dimer were significantly lower in lacunar stroke compared to other ischaemic strokes, both acutely and chronically. Markers of endothelial dysfunction (homocysteine, von Willebrand Factor (vWF), E-selectin, P-selectin, intercellular adhesion molecule-1 (ICAM), vascular cellular adhesion molecule-1 (VCAM)) were higher or had insufficient or conflicting data (P-selectin, VCAM) in lacunar stroke versus non-stroke. Compared to other ischaemic stroke subtypes, homocysteine did not differ in lacunar stroke while vWF was significantly lower in lacunar stroke acutely [atherothrombotic standardized mean difference, SMD, -0.34 (-0.61, -0.08); cardioembolic SMD -0.38 (-0.62, -0.14)], with insufficient data chronically. Markers of inflammation (C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6)) were higher in lacunar stroke versus non-stroke, although there were no studies measuring TNF-α chronically and the sole study measuring IL-6 chronically showed no difference between lacunar stroke and non-stroke. Compared to other ischaemic stroke subtypes, there was no difference (CRP) or insufficient or conflicting data (TNF-α) to lacunar stroke. IL-6 was significantly lower [atherothrombotic SMD -0.37 (-0.63, -0.10); cardioembolic SMD -0.52 (-0.82, -0.22)] in lacunar stroke acutely, with insufficient data chronically. Lacunar stroke is an important stroke subtype. More studies comparing lacunar stroke to non-lacunar stroke specifically, rather than to non-stroke controls, are needed. Prospective studies with measurements taken well after the acute event are more likely to be helpful in determining pathogenesis. The available data in this review were limited and do not exclude the possibility that peripheral inflammatory processes including endothelial dysfunction are associated with lacunar stroke and cerebral small vessel disease. © 2013 S. Karger AG, Basel

Cognitive predictors and moderators of winter depression treatment outcomes in cognitive-behavioral therapy vs. light therapy.

PubMed

Sitnikov, Lilya; Rohan, Kelly J; Evans, Maggie; Mahon, Jennifer N; Nillni, Yael I

2013-12-01

There is no empirical basis for determining which seasonal affective disorder (SAD) patients are best suited for what type of treatment. Using data from a parent clinical trial comparing light therapy (LT), cognitive-behavioral therapy (CBT), and their combination (CBT + LT) for SAD, we constructed hierarchical linear regression models to explore baseline cognitive vulnerability constructs (i.e., dysfunctional attitudes, negative automatic thoughts, response styles) as prognostic and prescriptive factors of acute and next winter depression outcomes. Cognitive constructs did not predict or moderate acute treatment outcomes. Baseline dysfunctional attitudes and negative automatic thoughts were prescriptive of next winter treatment outcomes. Participants with higher baseline levels of dysfunctional attitudes and negative automatic thoughts had less severe depression the next winter if treated with CBT than if treated with LT. In addition, participants randomized to solo LT who scored at or above the sample mean on these cognitive measures at baseline had more severe depressive symptoms the next winter relative to those who scored below the mean. Baseline dysfunctional attitudes and negative automatic thoughts did not predict treatment outcomes in participants assigned to solo CBT or CBT + LT. Therefore, SAD patients with extremely rigid cognitions did not fare as well in the subsequent winter if treated initially with solo LT. Such patients may be better suited for initial treatment with CBT, which directly targets cognitive vulnerability processes. Copyright © 2013 Elsevier Ltd. All rights reserved.

Toxins in Botanical Dietary Supplements: Blue Cohosh Components Disrupt Cellular Respiration and Mitochondrial Membrane Potential

PubMed Central

Datta, Sandipan; Mahdi, Fakhri; Ali, Zulfiqar; Jekabsons, Mika B.; Khan, Ikhlas A.; Nagle, Dale G.; Zhou, Yu-Dong

2014-01-01

Certain botanical dietary supplements have been associated with idiosyncratic organ-specific toxicity. Similar toxicological events, caused by drug-induced mitochondrial dysfunction, have forced the withdrawal or U.S. FDA “Black Box” warnings of major pharmaceuticals. To assess the potential mitochondrial liability of botanical dietary supplements, extracts from 352 authenticated plant samples used in traditional Chinese, Ayurvedic, and Western herbal medicine were evaluated for the ability to disrupt cellular respiration. Blue cohosh (Caulophyllum thalictroides) methanol extract exhibited mitochondriotoxic activity. Used by some U.S. midwives to help induce labor, blue cohosh has been associated with perinatal stroke, acute myocardial infarction, congestive heart failure, multiple organ injury, and neonatal shock. The potential link between mitochondrial disruption and idiosyncratic herbal intoxication prompted further examination. The C. thalictroides methanol extract and three saponins, cauloside A (1), saponin PE (2), and cauloside C (3) exhibited concentration- and time-dependent mitochondriotoxic activities. Upon treatment, cell respiration rate rapidly increased and then dramatically decreased within minutes. Mechanistic studies revealed that C. thalictroides constituents impair mitochondrial function by disrupting membrane integrity. These studies provide a potential etiological link between this mitochondria-sensitive form of cytotoxicity and idiosyncratic organ damage. PMID:24328138

Bringing in vitro analysis closer to in vivo: Studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling.

PubMed

Verheijen, Marcha; Schrooders, Yannick; Gmuender, Hans; Nudischer, Ramona; Clayton, Olivia; Hynes, James; Niederer, Steven; Cordes, Henrik; Kuepfer, Lars; Kleinjans, Jos; Caiment, Florian

2018-05-24

Doxorubicin (DOX) is a chemotherapeutic agent of which the medical use is limited due to cardiotoxicity. While acute cardiotoxicity is reversible, chronic cardiotoxicity is persistent or progressive, dose-dependent and irreversible. While DOX mechanisms of action are not fully understood yet, 3 toxicity processes are known to occur in vivo: cardiomyocyte dysfunction, mitochondrial dysfunction and cell death. We present an in vitro experimental design aimed at detecting DOX-induced cardiotoxicity by obtaining a global view of the induced molecular mechanisms through RNA-sequencing. To better reflect the in vivo situation, human 3D cardiac microtissues were exposed to physiologically-based pharmacokinetic (PBPK) relevant doses of DOX for 2 weeks. We analysed a therapeutic and a toxic dosing profile. Transcriptomics analysis revealed significant gene expression changes in pathways related to "striated muscle contraction" and "respiratory electron transport", thus suggesting mitochondrial dysfunction as an underlying mechanism for cardiotoxicity. Furthermore, expression changes in mitochondrial processes differed significantly between the doses. Therapeutic dose reflects processes resembling the phenotype of delayed chronic cardiotoxicity, while toxic doses resembled acute cardiotoxicity. Overall, these results demonstrate the capability of our innovative in vitro approach to detect the three known mechanisms of DOX leading to toxicity, thus suggesting its potential relevance for reflecting the patient situation. Our study also demonstrated the importance of applying physiologically relevant doses during toxicological research, since mechanisms of acute and chronic toxicity differ. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Administration of exogenous acylated ghrelin or rikkunshito, an endogenous ghrelin enhancer, improves the decrease in postprandial gastric motility in an acute restraint stress mouse model

PubMed Central

Nahata, M; Saegusa, Y; Sadakane, C; Yamada, C; Nakagawa, K; Okubo, N; Ohnishi, S; Hattori, T; Sakamoto, N; Takeda, H

2014-01-01

Background Physical or psychological stress causes functional disorders in the upper gastrointestinal tract. This study aims to elucidate the ameliorating effect of exogenous acylated ghrelin or rikkunshito, a Kampo medicine which acts as a ghrelin enhancer, on gastric dysfunction during acute restraint stress in mice. Methods Fasted and postprandial motor function of the gastric antrum was wirelessly measured using a strain gauge force transducer and solid gastric emptying was detected in mice exposed to restraint stress. Plasma corticosterone and ghrelin levels were also measured. To clarify the role of ghrelin on gastrointestinal dysfunction in mice exposed to stress, exogenous acylated ghrelin or rikkunshito was administered, then the mice were subjected to restraint stress. Key Results Mice exposed to restraint stress for 60 min exhibited delayed gastric emptying and increased plasma corticosterone levels. Gastric motility was decreased in mice exposed to restraint stress in both fasting and postprandial states. Restraint stress did not cause any change in plasma acylated ghrelin levels, but it significantly increased the plasma des-acyl ghrelin levels. Administration of acylated ghrelin or rikkunshito improved the restraint stress-induced delayed gastric emptying and decreased antral motility. Ameliorating effects of rikkunshito on stress-induced gastric dysfunction were abolished by simultaneous administration of a ghrelin receptor antagonist. Conclusions & Inferences Plasma acylated/des-acyl ghrelin imbalance was observed in acute restraint stress. Supplementation of exogenous acylated ghrelin or enhancement of endogenous ghrelin signaling may be useful in the treatment of decreased gastric function caused by stress. PMID:24684160

CD147/basigin reflects renal dysfunction in patients with acute kidney injury.

PubMed

Nagaya, Hiroshi; Kosugi, Tomoki; Maeda-Hori, Mayuko; Maeda, Kayaho; Sato, Yuka; Kojima, Hiroshi; Hayashi, Hiroki; Kato, Noritoshi; Ishimoto, Takuji; Sato, Waichi; Yuzawa, Yukio; Matsuo, Seiichi; Kadomatsu, Kenji; Maruyama, Shoichi

2014-10-01

Acute tubular necrosis (ATN) describes a form of intrinsic acute kidney injury (AKI) that results from persistent hypoperfusion and subsequent activation of the immune system. A glycosylated transmembrane protein, CD147/basigin, is involved in the pathogenesis of renal ischemia and fibrosis. The present study investigated whether CD147 can reflect pathological features and renal dysfunction in patients with AKI. Plasma and spot urine samples were collected from 24 patients (12 controls and 12 with ATN) who underwent renal biopsy between 2008 and 2012. In another study, patients undergoing open surgery to treat abdominal aortic aneurysms (AAAs) were enrolled in 2004. We collected urine and plasma samples from seven patients with AKI and 33 patients without AKI, respectively. In these experiments, plasma and urinary CD147, and urinary L-fatty acid-binding protein (L-FABP) levels were measured, and the former expression in kidneys was examined by immunostaining. In biopsy tissues of ATN with severe histological features, CD147 induction was strikingly present in inflammatory cells such as macrophages and lymphocytes in the injured interstitium, but not in damaged tubules representing atrophy. Both plasma and urinary CD147 levels were strikingly increased in ATN patients; both values showed greater correlations with renal dysfunction compared to urinary L-FABP. In patients who had undergone open AAA surgery, urinary and plasma CD147 values in AKI patients were significantly higher than in non-AKI patients at post-operative day 1, similar to the profile of urinary L-FABP. CD147 was prominent in its ability to detect AKI and may allow the start of preemptive medication.

Acute recurrent pancreatitis: Etiopathogenesis, diagnosis and treatment

PubMed Central

Testoni, Pier Alberto

2014-01-01

Acute recurrent pancreatitis (ARP) refers to a clinical entity characterized by episodes of acute pancreatitis which occurs on more than one occasion. Recurrence of pancreatitis generally occurs in a setting of normal morpho-functional gland, however, an established chronic disease may be found either on the occasion of the first episode of pancreatitis or during the follow-up. The aetiology of ARP can be identified in the majority of patients. Most common causes include common bile duct stones or sludge and bile crystals; sphincter of oddi dysfunction; anatomical ductal variants interfering with pancreatic juice outflow; obstruction of the main pancreatic duct or pancreatico-biliary junction; genetic mutations; alcohol consumption. However, despite diagnostic technologies, the aetiology of ARP still remains unknown in up to 30% of cases: in these cases the term “idiopathic” is used. Because occult bile stone disease and sphincter of oddi dysfunction account for the majority of cases, cholecystectomy, and eventually the endoscopic biliary and/or pancreatic sphincterotomy are curative in most of cases. Endoscopic biliary sphincterotomy appeared to be a curative procedure per se in about 80% of patients. Ursodeoxycholic acid oral treatment alone has also been reported effective for treatment of biliary sludge. In uncertain cases toxin botulin injection may help in identifying some sphincter of oddi dysfunction, but this treatment is not widely used. In the last twenty years, pancreatic endotherapy has been proven effective in cases of recurrent pancreatitis depending on pancreatic ductal obstruction, independently from the cause of obstruction, and has been widely used instead of more aggressive approaches. PMID:25493002

Sacral Herpes Zoster Associated with Voiding Dysfunction in a Young Patient with Scrub Typhus.

PubMed

Hur, Jian

2015-06-01

When a patient presents with acute voiding dysfunction without a typical skin rash, it may be difficult to make a diagnosis of herpes zoster. Here, we present a case of scrub typhus in a 25-year-old man with the complication of urinary dysfunction. The patient complained of loss of urinary voiding sensation and constipation. After eight days, he had typical herpes zoster eruptions on the sacral dermatomes and hypalgesia of the S1-S5 dermatomes. No cases of dual infection with varicella zoster virus and Orientia tsutsugamushi were found in the literature. In the described case, scrub typhus probably induced sufficient stress to reactivate the varicella zoster virus. Early recognition of this problem is imperative for prompt and appropriate management, as misdiagnosis can lead to long-term urinary dysfunction. It is important that a diagnosis of herpes zoster be considered, especially in patients with sudden onset urinary retention.

Sacral Herpes Zoster Associated with Voiding Dysfunction in a Young Patient with Scrub Typhus

PubMed Central

2015-01-01

When a patient presents with acute voiding dysfunction without a typical skin rash, it may be difficult to make a diagnosis of herpes zoster. Here, we present a case of scrub typhus in a 25-year-old man with the complication of urinary dysfunction. The patient complained of loss of urinary voiding sensation and constipation. After eight days, he had typical herpes zoster eruptions on the sacral dermatomes and hypalgesia of the S1-S5 dermatomes. No cases of dual infection with varicella zoster virus and Orientia tsutsugamushi were found in the literature. In the described case, scrub typhus probably induced sufficient stress to reactivate the varicella zoster virus. Early recognition of this problem is imperative for prompt and appropriate management, as misdiagnosis can lead to long-term urinary dysfunction. It is important that a diagnosis of herpes zoster be considered, especially in patients with sudden onset urinary retention. PMID:26157595

Sleep-Disordered Breathing in Acute Ischemic Stroke: A Mechanistic Link to Peripheral Endothelial Dysfunction.

PubMed

Scherbakov, Nadja; Sandek, Anja; Ebner, Nicole; Valentova, Miroslava; Nave, Alexander Heinrich; Jankowska, Ewa A; Schefold, Jörg C; von Haehling, Stephan; Anker, Stefan D; Fietze, Ingo; Fiebach, Jochen B; Haeusler, Karl Georg; Doehner, Wolfram

2017-09-11

Sleep-disordered breathing (SDB) after acute ischemic stroke is frequent and may be linked to stroke-induced autonomic imbalance. In the present study, the interaction between SDB and peripheral endothelial dysfunction (ED) was investigated in patients with acute ischemic stroke and at 1-year follow-up. SDB was assessed by transthoracic impedance records in 101 patients with acute ischemic stroke (mean age, 69 years; 61% men; median National Institutes of Health Stroke Scale, 4) while being on the stroke unit. SDB was defined by apnea-hypopnea index ≥5 episodes per hour. Peripheral endothelial function was assessed using peripheral arterial tonometry (EndoPAT-2000). ED was defined by reactive hyperemia index ≤1.8. Forty-one stroke patients underwent 1-year follow-up (390±24 days) after stroke. SDB was observed in 57% patients with acute ischemic stroke. Compared with patients without SDB, ED was more prevalent in patients with SDB (32% versus 64%; P <0.01). After adjustment for multiple confounders, presence of SDB remained independently associated with ED (odds ratio, 3.1; [95% confidence interval, 1.2-7.9]; P <0.05). After 1 year, the prevalence of SDB decreased from 59% to 15% ( P <0.001). Interestingly, peripheral endothelial function improved in stroke patients with normalized SDB, compared with patients with persisting SDB ( P <0.05). SDB was present in more than half of all patients with acute ischemic stroke and was independently associated with peripheral ED. Normalized ED in patients with normalized breathing pattern 1 year after stroke suggests a mechanistic link between SDB and ED. URL: https://drks-neu.uniklinik-freiburg.de. Unique identifier: DRKS00000514. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Continuous infusion or bolus injection of loop diuretics for patients admitted for severe acute heart failure: is one strategy better than the other?

PubMed

Caetano, Francisca; Mota, Paula; Almeida, Inês; Fernandes, Andreia; Botelho, Ana; Leitão Marques, António

2015-02-01

Intravenous loop diuretics are an essential part of acute heart failure management; however, data to guide their use is sparse. Our aim was to compare continuous intravenous infusion of loop diuretics with intravenous bolus administration in terms of efficacy and adverse events in patients admitted with severe acute heart failure. Over a period of three years, 110 patients were admitted to our cardiac intensive care unit with acute heart failure. Clinical, laboratory and prognostic parameters were compared according to the diuretic strategy used and mortality and readmission for acute heart failure during follow-up were analyzed. Previous medical history was similar in the two groups. At admission, the continuous infusion group met criteria for worse prognosis: lower systolic blood pressure (p=0.011), more severe renal injury (p=0.008), lower left ventricular ejection fraction (p=0.016) and higher incidence of restrictive pattern of diastolic dysfunction (p=0.032). They were more often treated with vasopressors (p=0.003), inotropes (p=0.010), renal support therapy (p=0.003) and non-invasive ventilation (p<0.001). They had longer hospitalizations (p=0.014) and a higher incidence of cardiorenal syndrome (p=0.009); however, at discharge, there were no differences in renal function between the groups. In-hospital mortality was similar, and during follow-up there were no differences in mortality or readmission for acute heart failure. Continuous infusion was preferred in patients presenting with worse clinical status, in whom renal dysfunction was transiently worse. However, in-hospital mortality and creatinine at discharge were similar. Continuous infusion thus appears to counteract the initial dire prognosis of more unstable patients. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Acute and chronic hypothyroidism are associated with similar left ventricular diastolic dysfunction relative to the euthyroid state: results of doppler echocardiographic comparisons.

PubMed

Gauna, A; Messuti, H; Papadopulos, G; Benchuga, G; Viale, F; Marlowe, R J; Silva Croome, M C

2011-10-01

How the duration of hypothyroidism affects left ventricular diastolic function is not well-characterized. We sought to compare left ventricular diastolic function in acutely vs chronically hypothyroid patients vs euthyroid controls, and within individuals while on vs off T4. We prospectively performed such comparisons measuring pulsed-wave and color M-mode Doppler echocardiographic variables: early or late mitral peak velocities (E wave or A wave, respectively), E wave/A wave ratio, E wave deceleration time, isovolumic relaxation time (IVRT), mitral flow propagation velocity (Vp), E wave/Vp ratio. Subjects comprised the acute HYPO group, 10 patients undergoing T4 withdrawal ≥ 6 months post-primary treatment for differentiated thyroid cancer (DTC); the chronic HYPO group, 23 treatment-naïve Hashimoto thyroiditis patients; and 21 healthy euthyroid controls. Subjects were adults aged ≤ 60 yr, predominantly female, with sinus rhythm; exclusion criteria were cardiovascular or thyroid disorder besides DTC (Hashimoto thyroiditis) in acute (chronic) HYPO patients or medication (besides thyroid hormone) affecting cardiac or thyroid function. Mean IVRT was significantly delayed and mean Vp, significantly slowed in both HYPO groups vs controls (p<0.0005), but did not differ between HYPO groups. These variables also were significantly impaired (p<0.05) within individuals when off vs on T4 (no.=8 acute, 10 chronic HYPO patients). Both HYPO groups had elevated mean E wave/Vp ratios vs controls, but the elevation reached significance (p<0.05) only in the larger chronic HYPO group. Left ventricular diastolic dysfunction is largely similar in acutely or chronically hypothyroid patients off T4 vs healthy controls or the same patients on T4.

Protective Effects of Emodin-Induced Neutrophil Apoptosis via the Ca2+-Caspase 12 Pathway against SIRS in Rats with Severe Acute Pancreatitis.

PubMed

Wang, Gui-Jun; Wang, Yue; Teng, Yong-Sheng; Sun, Fa-Lv; Xiang, Hong; Liu, Jian-Jun; Xia, Shi-Lin; Zhang, Gui-Xin; Chen, Hai-Long; Shang, Dong

2016-01-01

Severe acute pancreatitis (SAP) results in high mortality. This is partly because of early multiple organ dysfunction syndromes that are usually caused by systemic inflammatory response syndrome (SIRS). Many studies have reported the beneficial effects of emodin against SAP with SIRS. However, the exact mechanism underlying the effect of emodin remains unclear. This study was designed to explore the protective effects and underlying mechanisms of emodin against SIRS in rats with SAP. In the present study, cytosolic Ca 2+ levels, calpain 1 activity, and the expression levels of the active fragments of caspases 12 and 3 decreased in neutrophils from rats with SAP and increased after treatment with emodin. Delayed neutrophil apoptosis occurred in rats with SAP and emodin was able to reverse this delayed apoptosis and inhibit SIRS. The effect of emodin on calpain 1 activity, the expression levels of the active fragments of caspases 12 and 3, neutrophil apoptosis, and SIRS scores were attenuated by PD150606 (an inhibitor of calpain). These results suggest that emodin inhibits SIRS in rats with SAP by inducing circulating neutrophil apoptosis via the Ca 2+ -calpain 1-caspase 12-caspase 3 signaling pathway.

Protective Effects of Emodin-Induced Neutrophil Apoptosis via the Ca2+-Caspase 12 Pathway against SIRS in Rats with Severe Acute Pancreatitis

PubMed Central

Wang, Gui-Jun; Wang, Yue; Teng, Yong-Sheng; Sun, Fa-Lv; Xiang, Hong; Liu, Jian-Jun; Xia, Shi-Lin; Zhang, Gui-Xin

2016-01-01

Severe acute pancreatitis (SAP) results in high mortality. This is partly because of early multiple organ dysfunction syndromes that are usually caused by systemic inflammatory response syndrome (SIRS). Many studies have reported the beneficial effects of emodin against SAP with SIRS. However, the exact mechanism underlying the effect of emodin remains unclear. This study was designed to explore the protective effects and underlying mechanisms of emodin against SIRS in rats with SAP. In the present study, cytosolic Ca2+ levels, calpain 1 activity, and the expression levels of the active fragments of caspases 12 and 3 decreased in neutrophils from rats with SAP and increased after treatment with emodin. Delayed neutrophil apoptosis occurred in rats with SAP and emodin was able to reverse this delayed apoptosis and inhibit SIRS. The effect of emodin on calpain 1 activity, the expression levels of the active fragments of caspases 12 and 3, neutrophil apoptosis, and SIRS scores were attenuated by PD150606 (an inhibitor of calpain). These results suggest that emodin inhibits SIRS in rats with SAP by inducing circulating neutrophil apoptosis via the Ca2+-calpain 1-caspase 12-caspase 3 signaling pathway. PMID:28078280

[Definition and biomarkers of acute renal damage: new perspectives].

PubMed

Seijas, M; Baccino, C; Nin, N; Lorente, J A

2014-01-01

The RIFLE and AKIN criteria have definitely help out to draw attention to the relationship between a deterioration of renal function that produces a small increase in serum creatinine and a worse outcome. However, the specific clinical utility of using these criteria remains to be well-defined. It is believed that the main use of these criteria is for the design of epidemiological studies and clinical trials to define inclusion criteria and objectives of an intervention. AKI adopting term, re-summoning former ARF terminology, it is appropriate to describe the clinical condition characterized by damage to kidney, in the same way as the term is used to describe acute lung damage where the lung injury situation still has not increased to a situation of organ failure (dysfunction). The serum and urine biomarkers (creatinine, urea, and diuresis) currently in use are not sensitive or specific for detecting kidney damage, limiting treatment options and potentially compromising the outcome. New biomarkers are being studied in order to diagnose an earlier and more specific AKI, with the potential to change the definition criteria of AKI with different stages, currently based in diuresis and serum creatinine. Copyright © 2013 Elsevier España, S.L. and SEMICYUC. All rights reserved.

[Urinary tract infections--pediatric urologist point of view].

PubMed

Baka-Ostrowska, Małgorzata

2008-01-01

Urinary tract infections (UTI) could present with different clinical forms dependent on intensity and localization of infection and child's age. The symptoms could be non specific in children. Condition that provoke to urinary stasis, especially voiding dysfunction is the favourable factor for UTI appearance. Gram-negative enteric bacteria is the most common pathogen. Urine culture is the basic investigation that allow to identify pathogen and its drug sensitiveness but simultaneous urinalysis is necessary to recognize the inflammation of urinary organs. In addition, the number of leukocytes gives an idea about inflammation intensity. Ultrasonographic (USG) scan is necessary to examine urostasis. DMSA study performed during febrile UTI allow to identify children with acute pyelonephritis and when repeated 6 months later - those with renal scars. A normal USG and DMSA scan during infection makes voiding cystourethrography (VCU) unnecessary in the primary examination. The presence of vesicoureteric reflux (VUR) not always predispose children to renal lesions. Early and appropriate treatment of UTI, especially during the first 24 hours, diminishes the likelihood of renal involvement during the acute phase of infection but does not prevent scar formation. The proper hygiene of the urethral meatus, voiding and drinking habits and preventing of constipation are crucial in UTI prophylaxis.

Comparative study of single/combination use of Huang-Lian-Jie-Du decoction and berberine on their protection on sepsis induced acute liver injury by NMR metabolic profiling.

PubMed

Lv, Yan; Wang, Junsong; Xu, Dingqiao; Liao, Shanting; Li, Pei; Zhang, Qian; Yang, Minghua; Kong, Lingyi

2017-10-25

Sepsis is a serious clinical disease with a high mortality rate all around the world. Liver organ dysfunction is an important sign for the severity and outcome of sepsis in patients. In this study, 1 H NMR-based metabolomics approach and biochemical assays were applied to investigate the metabolic profiling for cecal ligation and puncture (CLP) induced acute liver injury, the therapeutical effect of single/combination use of Huang-Lian-Jie-Du decoction (HLJDD) and berberine, and the interaction of them. Metabolomics analysis revealed significant perturbations in livers of septic rats, which could be ameliorated by HLJDD, berberine and their combination treatment. Berberine could better rectified glycolysis and nucleic acid metabolism in the liver. HLJDD had exceptional better anti-inflammatory, antibacterial and antioxidative effects than berberine. The interaction of berberine and HLJDD could further strengthen the anti-inflammation and anti-oxidation, but with poor effect on amino acids metabolism. These findings highlighted the feasibility of the integrated NMR based metabolomics approach to understand the pathogenesis of diseases, the action mechanisms of therapy and the herb-drug interaction. Copyright © 2017 Elsevier B.V. All rights reserved.

Acute bile nephropathy secondary to anabolic steroids.

PubMed

Alkhunaizi, Ahmed M; ElTigani, Mohamed A; Rabah, Rola S; Nasr, Samih H

2016-02-01

Renal dysfunction in cholestatic liver disease is multifactorial. Acute kidney injury may develop secondary to renal vasoconstriction in the setting of peripheral vasodilation and relative hypovolemia, tubular obstruction by bile casts, and direct tubular toxicity from bile. Anabolic steroids are frequently used by athletes to boost endurance and increase muscle mass. These agents are a recently recognized cause of hepatotoxicity and jaundice and may lead to acute kidney injury. To increase awareness about this growing problem and to characterize the pathology of acute kidney injury in this setting, we report on a young male who developed acute kidney injury in the setting of severe cholestatic jaundice related to ingestion of anabolic steroids used for bodybuilding. Kidney biopsy showed bile casts within distal tubular lumina, filamentous bile inclusions within tubular cells, and signs of acute tubular injury. This report supports the recently re-emerged concept of bile nephropathy cholemic nephrosis.

Endothelial Effects of Emission Source particles: Acute Toxic Response Gene Expression Profiles

EPA Science Inventory

Air pollution epidemiology has established a strong association between exposure to ambient particulate matter (PM) and cardiovascular outcomes. Experimental studies in both humans and laboratory animals support varied biological mechanisms including endothelial dysfunction as po...

Intra-operative hemodialysis during liver transplantation: an expanded role of the nephrology nurse.

PubMed

Henson, Angela; Carpenter, Sally

2010-01-01

Hemodialysis is widely acknowledged as a treatment option to stabilize acute medical conditions where biochemistry management is paramount. One of the most challenging situations is during liver transplantation, when patients with moderate renal dysfunction are likely to become acutely acidotic. For nephrology nurses, this extended role requires increased knowledge, advanced skills, and a high level of communication with unfamiliar team members. With appropriate procedures and a supportive environment, delivering such a service is feasible.

Automated Comprehensive Evaluation of mTBI Visual Dysfunction

DTIC Science & Technology

2016-10-01

of this study is to validate the Neuro-Ophthalmic Device (NODe) test battery that provides the highest sensitivity and specificity for the detection...that the tests within the NODe test battery can serve as objective biomarkers for acute mTBI. Two hundred acute mTBI (≤72 hrs post injury) and 200 age...post-mTBI-related vision problems. The purpose of this study is to validate the Neuro-Ophthalmic Device (NODe) test battery that provides the

Acute Korsakoff syndrome following mammillothalamic tract infarction.

PubMed

Yoneoka, Yuichiro; Takeda, Norio; Inoue, Akira; Ibuchi, Yasuo; Kumagai, Takashi; Sugai, Tsutomu; Takeda, Ken-ichiro; Ueda, Kaoru

2004-01-01

There are limited case reports of structural lesions causing Korsakoff syndrome. This report describes acute Korsakoff syndrome following localized, bilateral infarction of the mammillothalamic tracts (MTTs). Axial T2-weighted imaging revealed the lesions at the lateral wall level of the third ventricle and diffusion-weighted imaging confirmed that the left lesion was new and the right old. Korsakoff syndrome persisted 6 months after the onset. This case suggests that bilateral MTT dysfunction can lead to Korsakoff syndrome.

Molecular Classifiers for Acute Kidney Transplant Rejection in Peripheral Blood by Whole Genome Gene Expression Profiling

PubMed Central

Kurian, S. M.; Williams, A. N.; Gelbart, T.; Campbell, D.; Mondala, T. S.; Head, S. R.; Horvath, S.; Gaber, L.; Thompson, R.; Whisenant, T.; Lin, W.; Langfelder, P.; Robison, E. H.; Schaffer, R. L.; Fisher, J. S.; Friedewald, J.; Flechner, S. M.; Chan, L. K.; Wiseman, A. C.; Shidban, H.; Mendez, R.; Heilman, R.; Abecassis, M. M.; Marsh, C. L.; Salomon, D. R.

2015-01-01

There are no minimally invasive diagnostic metrics for acute kidney transplant rejection (AR), especially in the setting of the common confounding diagnosis, acute dysfunction with no rejection (ADNR). Thus, though kidney transplant biopsies remain the gold standard, they are invasive, have substantial risks, sampling error issues and significant costs and are not suitable for serial monitoring. Global gene expression profiles of 148 peripheral blood samples from transplant patients with excellent function and normal histology (TX; n = 46), AR (n = 63) and ADNR (n = 39), from two independent cohorts were analyzed with DNA microarrays. We applied a new normalization tool, frozen robust multi-array analysis, particularly suitable for clinical diagnostics, multiple prediction tools to discover, refine and validate robust molecular classifiers and we tested a novel one-by-one analysis strategy to model the real clinical application of this test. Multiple three-way classifier tools identified 200 highest value probesets with sensitivity, specificity, positive predictive value, negative predictive value and area under the curve for the validation cohort ranging from 82% to 100%, 76% to 95%, 76% to 95%, 79% to 100%, 84% to 100% and 0.817 to 0.968, respectively. We conclude that peripheral blood gene expression profiling can be used as a minimally invasive tool to accurately reveal TX, AR and ADNR in the setting of acute kidney transplant dysfunction. PMID:24725967

CORTISOL CORRELATES WITH SEVERITY OF ILLNESS AND POORLY REFLECTS ADRENAL FUNCTION IN PEDIATRIC ACUTE RESPIRATORY DISTRESS SYNDROME

PubMed Central

Yehya, Nadir; Vogiatzi, Maria G.; Thomas, Neal J.; Srinivasan, Vijay

2016-01-01

Objective To test the association between random cortisol and severity of illness in a “real-world” application of current guidelines. Study design We performed a secondary analysis of a prospective observational cohort of acute respiratory distress syndrome (ARDS). Children with ARDS and vasopressor-dependent shock were identified and random cortisol levels prior to potential hydrocortisone initiation recorded. The cohort was dichotomized to cortisol < 18 μg/dL and ≥ 18 μg/dL, and hydrocortisone use and outcomes compared. Results Of 357 children with ARDS, 155 (15 non-survivors, 10%) had vasopressors initiated with cortisol drawn prior to possible hydrocortisone use. Patients with cortisol < 18 μg/dL had lower severity of illness scores, fewer organ failures, and lower vasopressor scores (all rank-sum p < 0.05). No benefit was seen with hydrocortisone in either the entire cohort, or when dichotomized by a cortisol cutoff of 18 μg/dL. In patients with cortisol ≥ 18 μg/dL, hydrocortisone was associated with increased mortality after adjustment for either organ dysfunction or vasopressor score. Conclusions In children with ARDS with vasopressor-dependent shock, low cortisol correlated with lower severity of illness. Random cortisol was a poor method of diagnosing adrenal insufficiency, and a strategy of hydrocortisone replacement for cortisol < 18 μg/dL did not target a population likely to benefit from hydrocortisone. Future guidelines should reconsider using random cortisol levels alone for assessing adrenal function. PMID:27283464

Cortisol Correlates with Severity of Illness and Poorly Reflects Adrenal Function in Pediatric Acute Respiratory Distress Syndrome.

PubMed

Yehya, Nadir; Vogiatzi, Maria G; Thomas, Neal J; Srinivasan, Vijay

2016-10-01

To test the association between random cortisol and severity of illness in a "real-world" application of current guidelines. We performed a secondary analysis of a prospective observational cohort of acute respiratory distress syndrome (ARDS). Children with ARDS and vasopressor-dependent shock were identified and random cortisol levels before potential hydrocortisone initiation recorded. The cohort was dichotomized to cortisol < 18 and ≥ 18 μg/dL, and hydrocortisone use and outcomes compared. Of 357 children with ARDS, 155 (15 nonsurvivors; 10%) had vasopressors initiated with cortisol drawn before possible hydrocortisone use. Patients with cortisol < 18 μg/dL had lower severity of illness scores, fewer organ failures, and lower vasopressor scores (all rank-sum P < .05). No benefit was seen with hydrocortisone in either the entire cohort, or when dichotomized by a cortisol cutoff of 18 μg/dL. In patients with cortisol ≥ 18 μg/dL, hydrocortisone was associated with increased mortality after adjustment for either organ dysfunction or vasopressor score. In children with ARDS with vasopressor-dependent shock, low cortisol correlated with lower severity of illness. Random cortisol was a poor method of diagnosing adrenal insufficiency, and a strategy of hydrocortisone replacement for cortisol < 18 μg/dL did not target a population likely to benefit from hydrocortisone. Future guidelines should reconsider using random cortisol levels alone for assessing adrenal function. Copyright © 2016 Elsevier Inc. All rights reserved.

Principals Of Radiation Toxicology: Important Aspects.

NASA Astrophysics Data System (ADS)

Popov, Dmitri; Maliev, Slava; Jones, Jeffrey

“All things are poison, and nothing is without poison; only the dose permits something not to be poisonous.” Paracelsus Key Words: Radiation Toxins (RT), Radiation Toxicants (RTc), Radiation Poisons (RP), Radiation Exposure (RE), Radiation Toxicology is the science about radiation poisons. [D.Popov et al. 2012,J.Zhou et al. 2007,] Radiation Toxins is a specific proteins with high enzymatic activity produced by living irradiated mammals. [D.Popov et al. 2012,] Radiation Toxicants is a substances that produce radiomimetics effects, adverse biological effects which specific for radiation. [D.Popov et al. 2012,] Radiation Toxic agent is specific proteins that can produce pathological biological effects specific for physical form of radiation.[D.Popov et al. 1990,2012,V. Maliev 2007] Different Toxic Substances isolated from cells or from blood or lymph circulation. [Kudriashov I. et al. 1970, D.Popov et al. 1990,2012,V. Maliev et al. 2007,] Radiation Toxins may affects many organs or specific organ, tissue, specific group of cells. [Kudriashov I. et al. 1970, D.Popov et al. 1990,2012,V. Maliev et al. 2007] For example: Radiation Toxins could induce collective toxic clinical states to include: systemic inflammatory response syndrome (SIRS),toxic multiple organ injury (TMOI), toxic multiple organ dysfunction syndromes (TMODS),and finally, toxic multiple organ failure (TMOF). [T. Azizova et al. 2005, Konchalovsky et al., 2005, D. Popov et al 2012] However, Radiation Toxins could induce specific injury of organs or tissue and induce Acute Radiation Syndromes such as Acute Radiation Cerebrovascular Syndrome, Acute Radiation Cardiovascular Syndrome, Acute Radiation Hematopoietic Syndrome, Acute Radiation GastroIntestinal Syndrome. [ D.Popov et al. 1990, 2012, V. Maliev et al. 2007] Radiation Toxins correlates with Radiation Exposure and the dose-response relationship is a fundamental and essential concept in classic Toxicology and Radiation Toxicology.[ D.Popov et al. 1990, 2012] Moderate and high doses of radiation induces necrosis of radiosensitive cells with the subsequent formation of radiation toxins and their induced acute inflammatory processes. Radiation necrosis is the most substantial and most severe form of radiation induced injury, and when widespread, has grave therapeutic implications. [D. Popov et al. 1990, 2012,Claudio A. et al. 2002, Robertson J. et al. 2002, ] Relatively small doses of Radiation Toxins induce apoptosis and high doses of Radiation Toxins induce necrosis. [Rastogi P. et al. 2009, D. Popov et al. 1990, 2012,] Threshold of Toxic Effects occurs and can be defined. [D. Popov et al. 2012, ] Radiation Toxins affects Somatic cells and Germ Cells. Radiation Toxins can induce teratogenic processes. Specific Toxicity of Radiation Toxins can affects developing fetus. Material and Methods, Results: http://www.intechopen.com/books/current-topics-in-ionizing-radiation-research/radiation-toxins-molecular-mechanisms-of-toxicity-and-radiomimetic-properties- Conclusion: Radiation is a physical agent - induce activation of some secretory proteins with high enzymatic activity. This proteins called as Radiation Toxins can produce specific for radiation biological and toxic effects after administration to radiation naive mammals. [V. Maliev et al. 2007, D. Popov et al. 1990, 2012] Radiation Toxins are teratogenic and oncogenic. Radiation Toxins effects depend on Administered Dose and Radiation effects depend on Exposure Dose and Absorbed Dose. The levels of Radiation Toxins correlates with Radiation Exposure.

Right-Sided Cardiac Dysfunction in Heart Failure With Preserved Ejection Fraction and Worsening Renal Function.

PubMed

Mukherjee, Monica; Sharma, Kavita; Madrazo, Jose A; Tedford, Ryan J; Russell, Stuart D; Hays, Allison G

2017-07-15

In urban populations, worsening renal function (WRF) is well established in patients hospitalized with acute decompensated heart failure with preserved ejection fraction (HFpEF). However, the mechanisms for development of WRF in the setting of acute HF in HFpEF are unclear. In the present study, we sought to characterize conventional echocardiographic measures of right ventricular (RV) chamber size and function to determine whether RV dysfunction and/or adverse RV remodeling is related to WRF in patients with HFpEF. Our study included 104 adult patients with HFpEF (EF ≥ 55%) with technically adequate 2-dimensional echocardiograms performed during their hospitalization for acute decompensated HF to determine echocardiographic predictors of WRF, defined as a serum creatinine (Cr) increase of ≥ 0.3 mg/dl within 72 hours of hospitalization. Thirty-eight of the 104 patients (36%) developed WRF (mean Cr increase = 0.9 ± 0.1 mg/dl) during the hospitalization (mean age ± SD of 64 ± 12 years, 27 women [71%], 29 black [76%]). There were no significant differences in LV medial E/e' ratio and RV systolic pressure by WRF status or in linear dimensions of RV and right atrial size. RV fractional area change, a measure of RV function, however, was significantly decreased in HFpEF patients with WRF compared with the no WRF group (p = 0.003), whereas RV free wall thickness (p = 0.001) was increased. In conclusion, linear and volumetric measures of dimensions of right atrial and RV chamber size did not distinguish HFpEF patients with and without WRF. However, in HFpEF patients with WRF during acute HF hospitalization, there was a significant decrease in RV function and a significant increase in RV free wall thickness compared with matched patients with no WRF. These findings suggest that adverse RV remodeling and RV dysfunction occur in HFpEF patients with WRF. Copyright © 2017 Elsevier Inc. All rights reserved.

β-Blocker Therapy Prior to Admission for Acute Coronary Syndrome in Patients Without Heart Failure or Left Ventricular Dysfunction Improves In-Hospital and 12-Month Outcome: Results From the GULF-RACE 2 (Gulf Registry of Acute Coronary Events-2).

PubMed

Abi Khalil, Charbel; AlHabib, Khalid F; Singh, Rajvir; Asaad, Nidal; Alfaleh, Hussam; Alsheikh-Ali, Alawi A; Sulaiman, Kadhim; Alshamiri, Mostafa; Alshaer, Fayez; AlMahmeed, Wael; Al Suwaidi, Jassim

2017-12-20

The prognostic impact of β-blockers (BB) in acute coronary syndrome (ACS) patients without heart failure (HF) or left ventricular dysfunction is controversial, especially in the postreperfusion era. We sought to determine whether a BB therapy before admission for ACS has a favorable in-hospital outcome in patients without HF, and whether they also reduce 12-month mortality if still prescribed on discharge. The GULF-RACE 2 (Gulf Registry of Acute Coronary Events-2) is a prospective multicenter study of ACS in 6 Middle Eastern countries. We studied in-hospital cardiovascular events in patients hospitalized for ACS without HF in relation to BB on admission, and 1-year mortality in relation to BB on discharge. Among the 7903 participants, 7407 did not have HF, of whom 5937 (80.15%) patients were on BB. Patients on BB tended to be older and have more comorbidities. However, they had a lower risk of in-hospital mortality, mitral regurgitation, HF, cardiogenic shock, and ventricular tachycardia/ventricular fibrillation. Furthermore, 4208 patients were discharged alive and had an ejection fraction ≥40%. Among those, 84.1% had a BB prescription. At 12 months, they also had a reduced risk of mortality as compared with the non-BB group. Even after correcting for confounding factors in 2 different models, in-hospital and 12-month mortality risk was still lower in the BB group. In this cohort of ACS, BB therapy before admission for ACS is associated with decreased in-hospital mortality and major cardiovascular events, and 1-year mortality in patients without HF or left ventricular dysfunction if still prescribed on discharge. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Rhabdomyolysis in a patient complicated with hypopituitarism and multiple organ dysfunction syndrome and the literature review.

PubMed

Zhou, Chuan; Lai, Shichao; Xie, Yong; Zhang, Shu; Lu, Yiping

2018-06-07

Muscular symptoms, including stiffness, myalgia, cramps, and fatigue, are present in the majority of the patients with hypopituitarism, adrenal insufficiency and hypothyroidism, but rhabdomyolysis, the rapid breakdown of skeletal muscle, is a rare manifestation. In most patients who develop rhabdomyolysis, precipitating factors, such as strenuous exercise or use of lipid-lowering drugs, can be identified. We report the case of a 23-year-old male with primary hypopituitarism who developed acute renal impairment (AKI) with rhabdomyolysis after strenuous physical activity (push-ups). His blood test confirmed marked hypopituitarism. Severe elevation of serum CK consistent with rhabdomyolysis was noted and an elevated creatinine indicated AKI and multiple organ dysfunction syndrome (MODS). Patient's condition improved significantly after continuous renal replacement therapy (CRRT), glucocorticoid hormone replacement therapy and aggressive hydration. MODS with rhabdomyolysis in patients with hypothyroidism is quite rare and we expect that this case report adds to the existing literature on this subject. We also emphasize that thyroid and adrenal gland status should be evaluated in patients with unexplained AKI, MODS and presenting with the symptoms of muscle involvement. We respectively reviewed 23 patients with hypopituitarism, adrenal Insufficiency and hypothyroidism induced rhabdomyolysis who were involved in the past 40 years relevant literatures. We report a successfully treated case of rhabdomyolysis, which is a rare but potentially serious complication of hypopituitarism. Screening for endocrine abnormality in patients with elevated muscle enzymes should be considered, since an early diagnosis and prompt treatment is essential to prevent rhabdomyolysis and its consequences. Copyright © 2018. Published by Elsevier Inc.

Severe scrub typhus infection: Clinical features, diagnostic challenges and management

PubMed Central

Peter, John Victor; Sudarsan, Thomas I; Prakash, John Anthony J; Varghese, George M

2015-01-01

Scrub typhus infection is an important cause of acute undifferentiated fever in South East Asia. The clinical picture is characterized by sudden onset fever with chills and non-specific symptoms that include headache, myalgia, sweating and vomiting. The presence of an eschar, in about half the patients with proven scrub typhus infection and usually seen in the axilla, groin or inguinal region, is characteristic of scrub typhus. Common laboratory findings are elevated liver transaminases, thrombocytopenia and leukocytosis. About a third of patients admitted to hospital with scrub typhus infection have evidence of organ dysfunction that may include respiratory failure, circulatory shock, mild renal or hepatic dysfunction, central nervous system involvement or hematological abnormalities. Since the symptoms and signs are non-specific and resemble other tropical infections like malaria, enteric fever, dengue or leptospirosis, appropriate laboratory tests are necessary to confirm diagnosis. Serological assays are the mainstay of diagnosis as they are easy to perform; the reference test is the indirect immunofluorescence assay (IFA) for the detection of IgM antibodies. However in clinical practice, the enzyme-linked immuno-sorbent assay is done due to the ease of performing this test and a good sensitivity and sensitivity when compared with the IFA. Paired samples, obtained at least two weeks apart, demonstrating a ≥ 4 fold rise in titre, is necessary for confirmation of serologic diagnosis. The mainstay of treatment is the tetracycline group of antibiotics or chloramphenicol although macrolides are used alternatively. In mild cases, recovery is complete. In severe cases with multi-organ failure, mortality may be as high as 24%. PMID:26261776

Has the survival of the graft improved after renal transplantation in the era of modern immunosuppression?

PubMed

Moreso, Francesc; Hernández, Domingo

2013-01-18

The introduction of new immunosuppressant drugs in recent years has allowed for a reduction in acute rejection rates along with highly significant improvements in short-term kidney transplantation results. Nonetheless, this improvement has not translated into such significant changes in long-term results. In this manner, late graft failure continues to be a frequent cause of readmission onto dialysis programmes and re-entry onto the waiting list. Multiple entities of immunological and non-immunological origin act together and lead to chronic allograft dysfunction. The characteristics of the transplanted organ are a greater determinant of graft survival, and although various algorithms have been designed as a way of understanding the risk of the transplant organ and assigning the most adequate recipient accordingly. They are applied in the clinical setting only under exceptional circumstances. Characterising, for each patient, the immune factors (clinical and subclinical rejection, reactivation of dormant viral infections, adherence to treatment) and non-immune factors (hypertension, diabetes, anaemia, dyslipidaemia) that contribute to chronic allograft dysfunction could allow us to intervene more effectively as a way of delaying the progress of such processes. Therefore, identifying the causes of graft failure and its risk factors, applying predictive models, and intervening in causal factors could constitute strategies for improving kidney transplantation results in terms of survival. This review analyses some of the evidences conditioning graft failure as well as related therapeutic and prognostic aspects: 1) magnitude of the problem and causes of graft failure; 2) identification of graft failure risk factors; 3) therapeutic strategies for reducing graft failure, and; 4) graft failure prediction.

Clinical features and outcomes in patients with disseminated toxoplasmosis admitted to intensive care: a multicenter study.

PubMed

Schmidt, Matthieu; Sonneville, Romain; Schnell, David; Bigé, Naike; Hamidfar, Rebecca; Mongardon, Nicolas; Castelain, Vincent; Razazi, Keyvan; Marty, Antoine; Vincent, François; Dres, Martin; Gaudry, Stephane; Luyt, Charles Edouard; Das, Vincent; Micol, Jean-Baptiste; Demoule, Alexandre; Mayaux, Julien

2013-12-01

Characteristics and outcomes of adult patients with disseminated toxoplasmosis admitted to the intensive care unit (ICU) have rarely been described. We performed a retrospective study on consecutive adult patients with disseminated toxoplasmosis who were admitted from January 2002 through December 2012 to the ICUs of 14 university-affiliated hospitals in France. Disseminated toxoplasmosis was defined as microbiological or histological evidence of disease affecting >1 organ in immunosuppressed patients. Isolated cases of cerebral toxoplasmosis were excluded. Clinical data on admission and risk factors for 60-day mortality were collected. Thirty-eight patients were identified during the study period. Twenty-two (58%) had received an allogeneic hematopoietic stem cell transplant (median, 61 [interquartile range {IQR}, 43-175] days before ICU admission), 4 (10%) were solid organ transplant recipients, and 10 (27%) were infected with human immunodeficiency virus (median CD4 cell count, 14 [IQR, 6-33] cells/µL). The main indications for ICU admission were acute respiratory failure (89%) and shock (53%). The 60-day mortality rate was 82%. Allogeneic hematopoietic stem cell transplant (hazard ratio [HR] = 2.28; 95% confidence interval [CI], 1.05-5.35; P = .04) and systolic cardiac dysfunction (HR = 3.54; 95% CI, 1.60-8.10; P < .01) within 48 hours of ICU admission were associated with mortality. Severe disseminated toxoplasmosis leading to ICU admission has a poor prognosis. Recipients of allogeneic hematopoietic stem cell transplant appear to have the highest risk of mortality. We identified systolic cardiac dysfunction as a major determinant of outcome. Strategies aimed at preventing this fatal opportunistic infection may improve outcomes.

Right Ventricular Dysfunction in Chronic Lung Disease

PubMed Central

Kolb, Todd M.; Hassoun, Paul M.

2012-01-01

Right ventricular dysfunction arises in chronic lung disease when chronic hypoxemia and disruption of pulmonary vascular beds contribute to increase ventricular afterload, and is generally defined by hypertrophy with preserved myocardial contractility and cardiac output. Although the exact prevalence is unknown, right ventricular hypertrophy appears to be a common complication of chronic lung disease, and more frequently complicates advanced lung disease. Right ventricular failure is rare, except during acute exacerbations of chronic lung disease or when multiple co-morbidities are present. Treatment is targeted at correcting hypoxia and improving pulmonary gas exchange and mechanics. There are presently no convincing data to support the use of pulmonary hypertension-specific therapies in patients with right ventricular dysfunction secondary to chronic lung disease. PMID:22548815

Obscured hemorrhagic pancreatitis after orthotopic heart transplantation complicated with acute right heart failure and hepatic dysfunction: a case report.

PubMed

Lin, Ting-Wei; Tsai, Meng-Ta; Roan, Jun-Neng; Liu, Yi-Sheng; Tsai, Hong-Ming; Luo, Chwan-Yau

2016-12-01

Pancreatitis is a serious complication after cardiac surgery and can lead to significant morbidities and mortality. The incidence of pancreatitis is even higher in patients undergoing heart transplantation than in those undergoing other cardiac surgeries. Nevertheless, the clinical presentations of pancreatitis are frequently atypical in these patients. We report a heart recipient who was complicated with acute right heart failure initially after orthotopic heart transplantation and developed devastating unanticipated hemorrhagic pancreatitis 1 month after the transplantation. This crypto-symptomatic pancreatitis was not diagnosed until massive internal bleeding and hemorrhagic shock occurred, because the typical presentations of acute pancreatitis were masked by the intra-abdominal manifestations caused by right heart failure and congestive liver dysfunction. The patient underwent a successful transarterial embolization. The causes of pancreatitis after heart transplantation include low cardiac output, immunosuppressant use and cytomegalovirus infection. The typical symptoms of pancreatitis might be not apparent in patients after heart transplantation because of their immunosuppressive status. Furthermore, in patients complicated with right heart failure after transplantation, the manifestation of pancreatitis could be even more obscure. The prompt diagnosis is highly depended on the clinician's astuteness.

Microscale frictional strains determine chondrocyte fate in loaded cartilage.

PubMed

Bonnevie, Edward D; Delco, Michelle L; Bartell, Lena R; Jasty, Naveen; Cohen, Itai; Fortier, Lisa A; Bonassar, Lawrence J

2018-06-06

Mounting evidence suggests that altered lubricant levels within synovial fluid have acute biological consequences on chondrocyte homeostasis. While these responses have been connected to increased friction, the mechanisms behind this response remain unknown. Here, we combine a frictional bioreactor with confocal elastography and image-based cellular assays to establish the link between cartilage friction, microscale shear strain, and acute, adverse cellular responses. Our incorporation of cell-scale strain measurements reveals that elevated friction generates high shear strains localized near the tissue surface, and that these elevated strains are closely associated with mitochondrial dysfunction, apoptosis, and cell death. Collectively, our data establish two pathways by which chondrocytes negatively respond to friction: an immediate necrotic response and a longer term pathway involving mitochondrial dysfunction and apoptosis. Specifically, in the surface region, where shear strains can exceed 0.07, cells are predisposed to acute death; however, below this surface region, cells exhibit a pathway consistent with apoptosis in a manner predicted by local shear strains. These data reveal a mechanism through which cellular damage in cartilage arises from compromised lubrication and show that in addition to boundary lubricants, there are opportunities upstream of apoptosis to preserve chondrocyte health in arthritis therapy. Copyright © 2018 Elsevier Ltd. All rights reserved.

Transient Retinal Dysfunctions after Acute Cannabis Use.

PubMed

Schwitzer, Thomas; Robert, Matthieu P; Giersch, Anne; Angioi-Duprez, Karine; Ingster-Moati, Isabelle; Pon-Monnier, Amandine; Schwan, Raymund; Laprevote, Vincent

2016-01-01

Although cannabis is very widespread worldwide, the impact of cannabis on visual function remains poorly understood. This is partly due to numerous difficulties met in developing clinical studies in cannabis users. Here, we report the first documented case of neuroretinal dysfunction after acute cannabis smoking. This observation was favored by the need of an annual ophthalmic evaluation in the context of a chloroquine intake for a systemic lupus erythematosus in a 47-year-old heavy cannabis user. A complete ophthalmic evaluation including visual acuity tests, intraocular pressure, fundoscopic examination, automated 10° central visual field, full-field electroretinogram (ERG) and multifocal ERG was performed twice - 30 min and 5 h after cannabis smoking. A strong decrease (up to 48%) in the a-wave amplitude of the full-field ERG was measured 30 min after cannabis smoking for all scotopic responses compared with the responses 5 h after smoking. Other tests showed reproducible results between the 2 series of measurements. This clinical case suggests that acute inhalation of cannabis affects the photoreceptors functioning. This rare situation suggests further investigations are required on the impact of cannabis on retinal processing, especially since cannabis has been incriminated in car injuries. © 2016 S. Karger AG, Basel.

Clinical features and treatment of hypertriglyceridemia-induced acute pancreatitis during pregnancy: A retrospective study.

PubMed

Huang, Chunlan; Liu, Jie; Lu, Yingying; Fan, Junjie; Wang, Xingpeng; Liu, Jun; Zhang, Wei; Zeng, Yue

2016-12-01

To analyze the features and treatment of hypertriglyceridemia-induced acute pancreatitis (HTGP) during pregnancy. A retrospective study of 21 pregnant women diagnosed with acute pancreatitis (AP) was performed. Patients were divided into acute biliary pancreatitis (ABP), HTGP, and idiopathic groups according to etiology. 95% of the patients were in the third trimester of gestation. The percentage of patients with HTGP was higher than that of ABP (48% vs.14%). The percentage of severe acute pancreatitis (SAP) in the HTGP group was higher than that in the ABP group (40.0% vs.0%). The Ranson scores for moderately severe acute pancreatitis (MSAP) and SAP in the HTGP group were significantly different (2.50 ± 0.58 vs.3.60 ± 0.89, P < 0.05, respectively). The mean serum triglyceride (TG) levels in the MSAP and SAP HTGP groups were not significantly different (18.81 ± 11.13 vs. 30.53 ± 24.20 mmol/L, P > 0.05, respectively). In the HTGP group, there were five patients given plasma exchange therapy and five not. Plasmapheresis decreased the incidence of systemic inflammatory response syndrome (SIRS) from 100% to 28.6% and the TG level from 20.36 ± 7.41 mmol/L to 5.23 ± 3.62 mmol/L (P < 0.05). The length of hospitalization of the plasmapheresis group was shorter than that of the nonplasmapheresis group (17.3 ± 6.7 days vs. 37.0 ± 20.8 days). Plasma exchange may be safe and effectively administered for HTGP patients during pregnancy with SIRS or multiple organ dysfunction syndrome (MODS). J. Clin. Apheresis 31:571-578, 2016. © 2015 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Medical management of the acute radiation syndrome.

PubMed

López, Mario; Martín, Margarita

2011-07-13

The acute radiation syndrome (ARS) occurs after whole-body or significant partial-body irradiation (typically at a dose of >1 Gy). ARS can involve the hematopoietic, cutaneous, gastrointestinal and the neurovascular organ systems either individually or in combination. There is a correlation between the severity of clinical signs and symptoms of ARS and radiation dose. Radiation induced multi-organ failure (MOF) describes the progressive dysfunction of two or more organ systems over time. Radiation combined injury (RCI) is defined as radiation injury combined with blunt or penetrating trauma, burns, blast, or infection. The classic syndromes are: hematopoietic (doses >2-3 Gy), gastrointestinal (doses 5-12 Gy) and cerebrovascular syndrome (doses 10-20 Gy). There is no possibility to survive after doses >10-12 Gy. The Phases of ARS are-prodromal: 0-2 days from exposure, latent: 2-20 days, and manifest illness: 21-60 days from exposure. Granulocyte-colony stimulating factor (G-CSF) at a dose of 5 μg/kg body weight per day subcutaneously has been recommended as treatment of neutropenia, and antibiotics, antiviral and antifungal agents for prevention or treatment of infections. If taken within the first hours of contamination, stable iodine in the form of nonradioactive potassium iodide (KI) saturates iodine binding sites within the thyroid and inhibits incorporation of radioiodines into the gland. Finally, if severe aplasia persists under cytokines for more than 14 days, the possibility of a hematopoietic stem cell (HSC) transplantation should be evaluated. This review will focus on the clinical aspects of the ARS, using the European triage system (METREPOL) to evaluate the severity of radiation injury, and scoring groups of patients for the general and specific management of the syndrome.

Vaspin protects against LPS-induced ARDS by inhibiting inflammation, apoptosis and reactive oxygen species generation in pulmonary endothelial cells via the Akt/GSK-3β pathway

PubMed Central

Qi, Di; Wang, Daoxin; Zhang, Chunrong; Tang, Xumao; He, Jing; Zhao, Yan; Deng, Wang; Deng, Xinyu

2017-01-01

Acute respiratory distress syndrome (ARDS) is characterized by uncontrolled extravasation of protein-rich fluids, which is caused by disruption and dysfunction of the barrier of pulmonary endothelial cells (ECs). Visceral adipose tissue-derived serine protease inhibitor (vaspin) is a novel adipokine with pleiotropic properties, which has been reported to exert beneficial effects against obesity-associated systemic vascular diseases; however, its effects on ARDS remain unknown. In the present study, mice were subjected to systemic administration of adenoviral vector expressing vaspin (Ad-vaspin) to examine its effects on lipopolysaccharide (LPS)-induced ARDS in vivo. Histological analysis was then conducted, and cytokine [tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10] levels, and intercellular cell adhesion molecule-1 (ICAM-1) and adherens junctions (AJs) expression were detected. In addition, human pulmonary microvascular ECs (HPMECs) were treated with recombinant human (rh)-vaspin to further investigate its molecular basis and underlying mechanism. The mRNA expression levels of inflammatory cytokines (TNF-α and IL-6) and endothelial-specific adhesion markers [vascular cell adhesion molecule-1 and E-selectin], activation of nuclear factor-κB, and cell viability and apoptosis were then examined. Furthermore, the expression of AJs and organization of the cytoskeleton, as well as expression and activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and generation of reactive oxygen species (ROS) were determined. The results indicated that Ad-vaspin protected against LPS-induced ARDS by alleviating the pulmonary inflammatory response and pulmonary EC barrier dysfunction in mice, which was accompanied by activation of the protein kinase B (Akt)/glycogen synthase kinase (GSK)-3β pathway. In addition, pretreatment of HPMECs with rh-vaspin attenuated inflammation, apoptosis and ROS generation without alterations in AJs and cytoskeletal organization following LPS insult, which was accompanied by activation of the Akt/GSK3β pathway. In conclusion, the present study demonstrated that vaspin protects against LPS-induced ARDS by reversing EC barrier dysfunction via the suppression of inflammation, apoptosis and ROS production in pulmonary ECs, at least partially via activation of the Akt/GSK3β pathway. These findings provide evidence of a causal link between vaspin and EC dysfunction in ARDS, and suggest a potential therapeutic intervention for patients with ARDS. PMID:29039444

Vaspin protects against LPS‑induced ARDS by inhibiting inflammation, apoptosis and reactive oxygen species generation in pulmonary endothelial cells via the Akt/GSK‑3β pathway.

PubMed

Qi, Di; Wang, Daoxin; Zhang, Chunrong; Tang, Xumao; He, Jing; Zhao, Yan; Deng, Wang; Deng, Xinyu

2017-12-01

Acute respiratory distress syndrome (ARDS) is characterized by uncontrolled extravasation of protein‑rich fluids, which is caused by disruption and dysfunction of the barrier of pulmonary endothelial cells (ECs). Visceral adipose tissue‑derived serine protease inhibitor (vaspin) is a novel adipokine with pleiotropic properties, which has been reported to exert beneficial effects against obesity‑associated systemic vascular diseases; however, its effects on ARDS remain unknown. In the present study, mice were subjected to systemic administration of adenoviral vector expressing vaspin (Ad‑vaspin) to examine its effects on lipopolysaccharide (LPS)‑induced ARDS in vivo. Histological analysis was then conducted, and cytokine [tumor necrosis factor (TNF)‑α, interleukin (IL)‑6 and IL‑10] levels, and intercellular cell adhesion molecule‑1 (ICAM‑1) and adherens junctions (AJs) expression were detected. In addition, human pulmonary microvascular ECs (HPMECs) were treated with recombinant human (rh)‑vaspin to further investigate its molecular basis and underlying mechanism. The mRNA expression levels of inflammatory cytokines (TNF‑α and IL‑6) and endothelial‑specific adhesion markers [vascular cell adhesion molecule‑1 and E‑selectin], activation of nuclear factor‑κB, and cell viability and apoptosis were then examined. Furthermore, the expression of AJs and organization of the cytoskeleton, as well as expression and activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and generation of reactive oxygen species (ROS) were determined. The results indicated that Ad‑vaspin protected against LPS‑induced ARDS by alleviating the pulmonary inflammatory response and pulmonary EC barrier dysfunction in mice, which was accompanied by activation of the protein kinase B (Akt)/glycogen synthase kinase (GSK)‑3β pathway. In addition, pretreatment of HPMECs with rh‑vaspin attenuated inflammation, apoptosis and ROS generation without alterations in AJs and cytoskeletal organization following LPS insult, which was accompanied by activation of the Akt/GSK3β pathway. In conclusion, the present study demonstrated that vaspin protects against LPS‑induced ARDS by reversing EC barrier dysfunction via the suppression of inflammation, apoptosis and ROS production in pulmonary ECs, at least partially via activation of the Akt/GSK3β pathway. These findings provide evidence of a causal link between vaspin and EC dysfunction in ARDS, and suggest a potential therapeutic intervention for patients with ARDS.

Neuromodulation by implant for treating lower urinary tract symptoms and dysfunction.

PubMed

Bemelmans, B L; Mundy, A R; Craggs, M D

1999-08-01

Patients with irritative micturition complaints, pelvic pain, involuntary urine loss or urinary retention are sometimes difficult to treat. The advent of direct sacral nerve stimulation offers a therapeutic alternative if conservative measures fail and surgery is considered. This paper reviews therapeutic neuromodulation by implant for treating lower urinary tract symptoms and dysfunction. The international literature is reviewed on topics such as the physiological basis of neuromodulation, techniques of acute testing and chronic implantation, and clinical results. Future developments and ways for possible improvement are discussed. The mode of action of neuromodulation is probably through restoring the correct balance between excitatory and inhibitory impulses from and to the pelvic organs at a sacral and supra-sacral level. Depending on the predefined success criteria, average success rates of definitive implants vary from 50 to 70%. From the data it seems that patients with urge incontinence and urinary retention are the best candidates for neuromodulation. In the literature the lack of standardisation of selection criteria, stimulation parameters and definitions of success is striking. Neuromodulation by implant is a useful therapeutic alternative. It should at least be considered in patients with therapy-resistant urge incontinence and urinary retention before proceeding to surgery. Issues such as underlying physiology, methodological standardisation, technical improvements, and patient selection must be addressed in future research.

Models of Lung Transplant Research: a consensus statement from the National Heart, Lung, and Blood Institute workshop

PubMed Central

Lama, Vibha N.; Belperio, John A.; Christie, Jason D.; El-Chemaly, Souheil; Fishbein, Michael C.; Gelman, Andrew E.; Hancock, Wayne W.; Keshavjee, Shaf; Kreisel, Daniel; Looney, Mark R.; McDyer, John F.; Shilling, Rebecca A.; Panoskaltsis-Mortari, Angela; Wilkes, David S.; Eu, Jerry P.; Nicolls, Mark R.

2017-01-01

Lung transplantation, a cure for a number of end-stage lung diseases, continues to have the worst long-term outcomes when compared with other solid organ transplants. Preclinical modeling of the most common and serious lung transplantation complications are essential to better understand and mitigate the pathophysiological processes that lead to these complications. Various animal and in vitro models of lung transplant complications now exist and each of these models has unique strengths. However, significant issues, such as the required technical expertise as well as the robustness and clinical usefulness of these models, remain to be overcome or clarified. The National Heart, Lung, and Blood Institute (NHLBI) convened a workshop in March 2016 to review the state of preclinical science addressing the three most important complications of lung transplantation: primary graft dysfunction (PGD), acute rejection (AR), and chronic lung allograft dysfunction (CLAD). In addition, the participants of the workshop were tasked to make consensus recommendations on the best use of these complimentary models to close our knowledge gaps in PGD, AR, and CLAD. Their reviews and recommendations are summarized in this report. Furthermore, the participants outlined opportunities to collaborate and directions to accelerate research using these preclinical models. PMID:28469087

[Acute non-traumatic myelopathy in children and adolescents].

PubMed

Arroyo, Hugo A

2013-09-06

The term 'acute myelopathies'--referred to a spinal cord dysfunction--represent a heterogeneous group of disorders with distinct etiologies, clinical and radiologic features, and prognoses. The objective of this review is to discuss the non-traumatic acute myelopathies. Acute myelopathy can be due to several causes as infective agents or inflammatory processes, such as in acute myelitis, compressive lesions, vascular lesions, etc. The clinical presentation is often dramatic with tetraparesis or paraparesis, sensory disturbances and bladder and/or bowel dysfunction. History and physical examination are used to localize the lesion to the root or specific level of the cord, which can guide imaging. Different syndromes are recognized: complete transverse lesion, central grey matter syndrome, anterior horn syndrome, anterior spinal artery syndrome, etc). The first priority is to rule out a compressive lesion. If a myelopathy is suspected, a gadolinium-enhanced MRI of the spinal cord should be obtained as soon as possible. If there is no structural lesion such as epidural blood or a spinal mass, then the presence or absence of spinal cord inflammation should be documented with a lumbar puncture. The absence of pleocytosis would lead to consideration of non inflammatory causes of myelopathy such as arteriovenous malformations, fibrocartilaginous embolism, or possibly early inflammatory myelopathy. In the presence of an inflammatory process (defined by gadolinium enhancement, cerebrospinal fluid pleocytosis, or elevated cerebrospinal fluid immunoglobulin index), one should determine whether there is an inflammatory or an infectious cause. Different virus, bacterias, parasites and fungi have to be considered as autoimmune and inflammatory diseases that involve the central nervous system.

Assessment of adrenal function in patients with acute hepatitis using serum free and total cortisol.

PubMed

Degand, Thibault; Monnet, Elisabeth; Durand, François; Grandclement, Emilie; Ichai, Philippe; Borot, Sophie; Qualls, Clifford R; Agin, Arnaud; Louvet, Alexandre; Dumortier, Jérôme; Francoz, Claire; Dumoulin, Gilles; Di Martino, Vincent; Dorin, Richard; Thevenot, Thierry

2015-09-01

Adrenal dysfunction is frequently reported in severe acute hepatitis using serum total cortisol. Because 90% of serum cortisol is bound to proteins that are altered during stress, we investigated the effect of decreased cortisol-binding proteins on serum total and free cortisol in severe acute hepatitis. 43 severe and 31 non-severe acute hepatitis and 29 healthy controls were enrolled consecutively and studied prospectively. Baseline (T0) and cosyntropin-stimulated (T60) serum total and free cortisol concentrations were measured. T0 and T60 serum total cortisol did not differ significantly between severe, non-severe hepatitis and healthy controls. Conversely, serum free cortisol (T0p=0.012; T60p<0.001) concentrations increased from healthy controls to severe hepatitis, accompanied by a decrease in corticosteroid-binding globulin and albumin (all p<0.001). In acute hepatitis (n=74), patients with "low" corticosteroid-binding globulin (<28mg/L) had higher T0 serum free cortisol than others (103.1 [61.2-157] vs. 56.6 [43.6-81.9]nmol/L, p=0.0024). Analysis of covariance showed that at equal concentration of total cortisol, the free cortisol concentration was significantly higher in severe than in non-severe hepatitis (p<0.001) or healthy controls (p<0.001). In severe hepatitis, the decrease in cortisol-binding proteins impairs correct diagnosis of adrenal dysfunction. This could be corrected by measuring or estimating free cortisol. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

21 CFR 522.1145 - Hyaluronate sodium.

Code of Federal Regulations, 2011 CFR

2011-04-01

... equine osteoarthritis. (iii) Limitations. For intra-articular injection in horses only. Treatment may be... osteoarthritis. (iii) Limitations. For intraarticular injection in horses only. Treatment may be repeated at... dysfunction in horses due to acute or chronic noninfectious synovitis associated with equine osteoarthritis...