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Sarcoidosis is an inflammatory disease known to be associated with multiple autoimmune disorders. There is a restricted number of descriptions of the association between sarcoidosis and autoimmune thrombotic thrombocytopenic purpura (aTTP). We present the case of a 63‐year‐old woman admitted to the hospital to investigate a possible sarcoidosis who had hemolytic anemia and thrombocytopenia, with low ADAMTS13 activity and anti‐ADAMTS13 antibodies, leading to a diagnosis of aTTP. Sarcoidosis was later confirmed and the two conditions evolved separately after 6 months, questioning the link between them. Clinicians should be aware of this rare cause of thrombocytopenia in patients with sarcoidosis, as aTTP is a life‐threatening condition.

Chronic kidney disease (CKD) is a frequent and serious complication of atypical haemolytic uremic syndrome (aHUS). We aimed to develop a simple accurate model to predict the risk of renal dysfunction in aHUS based on clinical and biological features available at hospital admission. Renal function at 1-year follow-up, based on an estimated glomerular filtration rate < 60mL/min/1.73m2 as assessed by the Modification of Diet in Renal Disease equation, was used as an indicator of significant CKD. Prospectively collected data from a cohort of 156 aHUS patients who did not receive eculizumab were used to identify predictors of CKD. Covariates associated with renal impairment were identified by multivariate analysis. The model performance was assessed and a scoring system for clinical practice was constructed from the regression coefficient. Multivariate analyses identified three predictors of CKD: a high serum creatinine level, a high mean arterial pressure and a mildly decreased platelet count. The prognostic model had a good discriminative ability (area under the curve = .84). The scoring system ranged from 0 to 5, with corresponding risks of CKD ranging from 18% to 100%. This model accurately predicts development of 1-year CKD in patients with aHUS using clinical and biological features available on admission. After further validation, this model may assist in clinical decision making.

One promising frontier within the field of Medical Botany is the study of the bioactivity of plant metabolites on human health. Although plant metabolites are metabolic byproducts that commonly regulate ecological interactions and biochemical processes in plant species, such metabolites also elicit profound effects on the cellular processes of human and other mammalian cells. In this regard, due to their potential as therapeutic agents for a variety of human diseases and induction of toxic cellular responses, further research advances are direly needed to fully understand the molecular mechanisms induced by these agents. Herein, we focus our investigation on metabolites from the Cucurbitaceae, Ericaceae, and Rosaceae plant families, for which several plant species are found within the state of Florida in Hillsborough County. Specifically, we compare the molecular mechanisms by which metabolites and/or plant extracts from these plant families modulate the cytoskeleton, protein trafficking, and cell signaling to mediate functional outcomes, as well as a discussion of current gaps in knowledge. Our efforts to lay the molecular groundwork in this broad manner hold promise in supporting future research efforts in pharmacology and drug discovery.

Clostridium haemolyticum is a sporulating Gram-positive anaerobic rod that is considered to be one of the most fastidious and oxygen-sensitive anaerobes. It is a well-known animal pathogen and the cause of bacillary hemoglobinuria primarily in cattle. To date, human infections caused by C. haemolyticum have been reported in three patients with malignant underlying diseases. We present herein the case of a 30-year-old obese woman with no significant past medical history who developed bacteremia caused by C. haemolyticum with massive intravascular hemolysis associated with bone marrow necrosis and acute renal failure. Because of subculture failure, the diagnosis was made on the basis of 16S rDNA sequencing and next-generation sequencing. The patient, who had been afebrile for 20 days after a 17-day-course of antibiotics, experienced a second bacteremic episode caused by C. haemolyticum. After having been successfully treated for 42 days with clindamycin and amoxicillin-clavulanic acid, the patient developed acute myeloid leukemia as a result of bone marrow regeneration. Although uncommon in humans, infections caused by C. haemolyticum are severe and should be considered in a febrile patient who has severe hemolytic anemia. This case also highlights the importance of using molecular techniques for the identification of this fastidious anaerobic organism.

The purpose of the study is to improve our ability to detect catecholamine dependency and refractory septic shock. Fifty-one patients with septic shock were studied within the first 4 hours of norepinephrine administration. Patients were divided into 2 groups according to their evolution in the intensive care unit, namely, group A, shock reversal, and group B, no shock reversal. Reversal of shock was defined as the maintenance of a systolic blood pressure greater than or equal to 90 mm Hg without vasopressor support for 24 hours or more. Vascular reactivity was tested using incremental doses of phenylephrine. Muscle tissue oxygen saturation and its changes during a vascular occlusion test were measured. Group B patients had a higher Sequential Organ Failure Assessment (SOFA) score and lactate level and more frequently received norepinephrine and renal replacement. Overall mortality was 100% in group B (16/16) and 20% (7/35) in group A. Phenylephrine increased mean arterial pressure in a dose-dependent manner more significantly in group A patients than in group B (P = .0004). Basal tissue oxygen saturation and the recovery slope after vascular occlusion test were lower in group B. In multivariate analysis, 4 parameters remained independently associated with mortality: the increase in mean arterial pressure at phenylephrine 6 μg/kg per minute, the recovery slope, SOFA score, and norepinephrine doses at H0. The intensity of septic shock–induced vascular hyporesponsiveness to vasopressor is tightly linked to septic shock severity and evolution and may potentially be identified early with simple to obtain parameters such as near-infrared spectroscopy value, SOFA score, or norepinephrine dose.

Epidemiological studies of neurological complications in patients with hematological malignancies are scant. The objective of the study was to identify determinants of survival in patients with hematological malignancy and neurological failure. Post hoc analysis of a prospective study of adults with hematological malignancies admitted for any reason to one of 17 university or university-affiliated participating ICUs in France and Belgium (2010-2012). The primary outcome was vital status at hospital discharge. Of the 1011 patients enrolled initially, 226 (22.4%) had neurological failure. Presenting manifestations were dominated by drowsiness or stupor (65%), coma (32%), weakness (26%), and seizures (19%). Neuroimaging, lumbar puncture, and electroencephalography were performed in 113 (50%), 73 (32%), and 63 (28%) patients, respectively. A neurosurgical biopsy was done in 1 patient. Hospital mortality was 50%. By multivariate analysis, factors independently associated with higher hospital mortality were poor performance status (odds ratio [OR], 3.99; 95%CI, 1.82-9.39; P = 0.0009), non-Hodgkin's lymphoma (OR, 2.60; 95%CI, 1.35-5.15; P = 0.005), shock (OR, 1.95; 95%CI, 1.04-3.72; P = 0.04), and respiratory failure (OR, 2.18; 95%CI, 1.14-4.25; P = 0.02); and factors independently associated with lower hospital mortality were GCS score on day 1 (OR, 0.88/point; 95%CI, 0.81-0.95; P = 0.0009) and autologous stem cell transplantation (OR, 0.25; 95%CI, 0.07-0.75; P = 0.02). In ICU patients with hematological malignancies, neurological failure is common and often fatal. Independent predictors of higher hospital mortality were type of underlying hematological malignancy, poor performance status, hemodynamic and respiratory failures, and severity of consciousness impairment. Knowledge of these risk factors might help to optimize management strategies.

Purpose Little attention has been given to ARDS in cancer patients, despite their high risk for pulmonary complications. We sought to describe outcomes in cancer patients with ARDS meeting the Berlin definition. Methods Data from a cohort of patients admitted to 14 ICUs between 1990 and 2011 were used for a multivariable analysis of risk factors for hospital mortality. Results Of 1,004 included patients (86 % with hematological malignancies and 14 % with solid tumors), 444 (44.2 %) had neutropenia. Admission SOFA score was 12 (10–13). Etiological categories were primary infection-related ARDS ( n  = 662, 65.9 %; 385 bacterial infections, 213 invasive aspergillosis, 64 Pneumocystis pneumonia); extrapulmonary septic shock-related ARDS ( n  = 225, 22.4 %; 33 % candidemia); noninfectious ARDS ( n  = 76, 7.6 %); and undetermined cause ( n  = 41, 4.1 %). Of 387 (38.6 %) patients given noninvasive ventilation (NIV), 276 (71 %) subsequently required endotracheal ventilation. Hospital mortality was 64 % overall. According to the Berlin definition, 252 (25.1 %) patients had mild, 426 (42.4 %) moderate and 326 (32.5 %) severe ARDS; mortality was 59, 63 and 68.5 %, respectively ( p  = 0.06). Mortality dropped from 89 % in 1990–1995 to 52 % in 2006–2011 ( p  < 0.0001). Solid tumors, primary ARDS, and later admission period were associated with lower mortality. Risk factors for higher mortality were allogeneic bone-marrow transplantation, modified SOFA, NIV failure, severe ARDS, and invasive fungal infection. Conclusions In cancer patients, 90 % of ARDS cases are infection-related, including one-third due to invasive fungal infections. Mortality has decreased over time. NIV failure is associated with increased mortality. The high mortality associated with invasive fungal infections warrants specific studies of early treatment strategies.

Abstract Rationale Noninvasive diagnostic multiplex molecular tests may enable the early identification and treatment of viral infections in critically ill immunocompromised patients. Objectives To assess the association between viral detection in nasopharyngeal swabs and ICU mortality in critically ill hematology patients. Methods This was a post hoc analysis of a prospective cohort of critically ill hematology patients admitted to 17 ICUs. Nasal swabs sampled and frozen at ICU admission were tested using a multiplex PCR assay. Predictors of ICU mortality and assay positivity were identified. Measurements and Main Results Of the 747 patients (447 with acute respiratory failure [ARF]), 21.3% had a virus detected (56.4% rhinovirus/enterovirus and 30.7% influenza/parainfluenza/respiratory syncytial viruses). Overall ICU and hospital mortality rates were 26% and 37%, respectively. Assay positivity was associated with lymphoproliferative disorders, hematopoietic stem cell transplantation, treatment with steroids or other immunosuppressants, ARF (25.5% vs. 16.3%; P = 0.004), and death in the ICU (28.9% vs. 19.3%; P = 0.008). The association with ICU mortality was significant for all viruses and was strongest for influenza/parainfluenza/respiratory syncytial viruses. In patients with ARF, detection of any respiratory virus was independently associated with ICU mortality (odds ratio, 2.07; 95% confidence interval, 1.22–3.50). Conclusions Respiratory virus detection in the upper airway by multiplex PCR assay is common in critically ill hematology patients. In patients with ARF, respiratory virus detection was independently associated with ICU mortality. Multiplex PCR assay may prove helpful for the risk stratification of hematology patients with ARF. Studies to understand whether respiratory tract viruses play a causal role in outcomes are warranted.

Introduction. The PiCCO transpulmonary thermodilution technique provides two indices of cardiac systolic function, the cardiac function index (CFI) and the global ejection fraction (GEF). Both appear to be correlated with left ventricular ejection fraction (LVEF) measured by echocardiography in patients with circulatory failure, especially in septic shock. The aim of the present study was to test the reliability of CFI as an indicator of LVEF in patients with cardiogenic shock. Methods. In thirty-five patients with cardiogenic shock, we performed (i) simultaneous measurements of echocardiography LVEF and cardiac function index assessed by transpulmonary thermodilution (n=72) and (ii) transpulmonary thermodilution before/after increasing inotropic agents (n=18). Results. Mean LVEF was 31% (+/−11.7), CFI 3/min (+/−1), and GEF 14.2% (+/−6). CFI and GEF were both positively correlated with LVEF (P<0.0001, r2=0.27). CFI and GEF were significantly increased with inotropic infusion (resp., P=0.005, P=0.007). A cardiac function index <3.47/min predicted a left ventricular ejection fraction ≤35% (sensitivity 81.1% and specificity 63%). In patients with right ventricular dysfunction, CFI was not correlated with LVEF. Conclusion. CFI is correlated with LVEF provided that patient does not present severe right ventricular dysfunction. Thus, the PiCCO transpulmonary thermodilution technique is useful for the monitoring of inotropic therapy during cardiogenic shock.

PurposeStudies have suggested benefits from magnesium sulphate in thrombotic thrombocytopenic purpura (TTP). We aimed to measure the effects of magnesium sulphate supplementation on TTP recovery.MethodsIn this multicenter, randomised, double-blind, controlled, superiority study, we enrolled adults with a clinical diagnosis of TTP. Patients were randomly allocated to receive magnesium sulphate (6 g intravenously followed by a continuous infusion of 6 g/24 h for 3 days) or placebo, in addition to the standard treatment. The primary outcome was the median time to platelet normalisation (defined as a platelet count ≥ 150 G/L). Efficacy and safety were assessed by intention-to-treat.ResultsOverall, we enrolled 74 participants, including one who withdrew his/her consent. Seventy-three patients were further analyzed, 35 (48%) allocated to magnesium sulphate and 38 (52%) to placebo. The median time to platelet normalisation was 4 days (95% confidence interval [CI], 3–4) in the magnesium sulphate group and 4 days (95% CI 3–5) in the placebo group. The cause-specific hazard ratio of response was 0.93 (95% CI 0.58–1.48, p = 0.75). The number of patients with ≥ 1 serious adverse reactions was similar in the two groups. By day 90, four patients in the magnesium sulphate group and two patients in the placebo group had died (p = 0.42). The most frequent adverse event was low blood pressure occurring in 34% in the magnesium sulphate group and 29% in the placebo group (p = 0.80).ConclusionAmong patients with TTP, the addition of magnesium sulphate to the standard of care did not result in a significant improvement in time to platelet normalisation.