Upregulation of Shiga Toxin Receptor CD77/Gb3 and Interleukin‐1β Expression in the Brain of EHEC Patients with Hemolytic Uremic Syndrome and Neurologic Symptoms

In 2011, a large outbreak of Shiga toxin‐producing enterohemorrhagic Escherichia coli (EHEC) infections occurred in northern Germany, which mainly affected adults. Out of 3842 patients, 104 experienced a complicated course comprising hemolytic uremic syndrome and neurological complications, including cognitive impairment, aphasia, seizures and coma. T2 hyperintensities on magnet resonance imaging (MRI) bilateral in the thalami and in the dorsal pons were found suggestive of a metabolic toxic effect. Five of the 104 patients died because of toxic heart failure. In the present study, the post‐mortem neuropathological findings of the five EHEC patients are described. Histological investigation of 13 brain regions (frontal, temporal, occipital cortex, corpora mammillaria, thalamus, frontal operculum, corona radiata, gyrus angularis, pons, medulla oblongata, cerebellar vermis and cerebellar hemisphere) showed no thrombosis, ischemic changes or fresh infarctions. Further, no changes were found in electron microscopy. In comparison with five age‐matched controls, slightly increased activation of microglia and a higher neuronal expression of interleukin‐1β and of Shiga toxin receptor CD77/globotriaosylceramide 3 was observed. The findings were confirmed by Western blot analyses. It is suggested that CD77/globotriaosylceramide upregulation may be a consequence to Shiga toxin exposure, whereas increased interleukin‐1β expression may point to activation of inflammatory cascades.     

Is small bowel biopsy necessary in adults with suspected celiac disease and IgA anti-endomysium antibodies?

The comparative diagnostic value of IgA anti-endomysium and IgA antigliadin antibodies in adults with histologically confirmed celiac disease is reported. Sera from 144 adult patients (without concurrent dermatitis herpetiformis or IgA deficiency) who underwent small bowel biopsy were analyzed for both IgA anti-endomysium and IgA anti-gliadin antibodies. Nineteen patients (13%) had celiac disease. The presence of IgA antiendomysium antibodies had a sensitivity of 74% and a specificity of 100%. The positive and negative predictive values were 100% and 96%, respectively, and the diagnostic accuracy was 97%. In contrast, IgA anti-gliadin antibodies had positive and negative predictive values of 28% and 96%, respectively, with a diagnostic accuracy of 71%. Based on these data, we suggest that small bowel biopsy is not necessary to diagnose celiac disease in symptomatic adults with IgA antiendomysium antibodies. Due to a negative predictive value of 96%, some symptomatic adults lacking anti-endomysium antibodies will not be correctly diagnosed without small bowel biopsy.     

Intraoperative liver steatosis characterization using diffuse reflectance spectroscopy

Background

Liver steatosis is associated with poor outcome after liver transplantation and liver resection. There is a need for an accurate and reliable intraoperative tool to identify and quantify steatosis. This study aimed to investigate whether surface diffuse reflectance spectroscopy (DRS) measurements could detect liver steatosis on humans during liver surgery.

Clinical significance of serum cytokine patterns during start of fever in patients with neutropenia

Summary. Serum concentrations of tumour necrosis factor alpha (TNF-α), interleukin-1 receptor antagonist (IL-1ra), interferon gamma (IFN-γ), interleukin-6 (IL-6) and interleukin-10 (IL-10) were studied in 31 patients with haematological malignancies during febrile neutropenia. Samples were obtained when blood cultures were performed (time 0) and, when possible, after 2, 4, 6, 12 and 24 h. Increased levels of all cytokines were detected after start of fever with peak values in gram-negative (Gr⁻) bacteraemias after 2 h (TNF-α, IL-lra and IFN-γ), 4h (IL-6) and 6 h (IL-10), respectively. At time 0 the median TNF-α value was higher in the Gr⁻ group (80 pg/ml; range 54-516 pg/ml) as compared to both gram-positive bacteraemias (Gr⁺, 14pg/ ml; range 7-60 pg/ml; P < 0 05) and blood culture negative episodes (BCN, 8pg/ml; range 0-87pg/ml; P<0 05).
Furthermore, the peak values of TNF-α, IL-lra, IL-6 and IL-10 during the 24 h study period were significantly and/or numerically higher in the ^Gr- group in comparison to the Gr⁺ and BCN groups, respectively. It may be concluded that neutropenic patients have increased levels of both pro- and anti-inflammatory cytokines at start of fever, with the highest values recorded during the first hours in ^Gr- bacteraemias. Prospective studies will show whether monitoring of serum cytokines may be used as an early diagnostic tool before results of blood cultures are available, which may have important therapeutic implications.     

Reported normal values and weighted means for commonly used echocardiography pulsed Doppler and tissue Doppler measurements

Pulsed Doppler (PW) and tissue Doppler imaging (TDI) measurements are part of every echocardiography examination for evaluation of left ventricular (LV) diastolic function and filling pressure. The purpose of this study was to summarize published data on normal values for PW and TDI measurements. A PubMed search was performed on the 10th of October 2016 to identify relevant articles. Studies were considered relevant if they included more than 200 healthy individuals. A total of 13 studies were identified. Of these, 13 studies with 7777 subjects reported PW measurement over the mitral valve, six studies with 4082 subjects reported PW measurement in the pulmonary vein and 10 studies with 5988 subjects reported TDI. We also report weighted mean values for 14 different variables. As expected, measurements varied with age. There were no major differences between men and women. In contrast, there was a large difference in reported values between studies, in corresponding age groups. This review therefore raises caution about relying on normal values from just one study.     

Association of acidosis with coagulopathy and transfusion requirements in liver transplantation

Journal of Thrombosis and Thrombolysis - The relationship between acidosis and coagulopathy has long been described in vitro and in trauma patients, but not yet in orthotopic liver transplantation...     

An Experimental Study of the Effects of Patient Race,Sexual Orientation,and Injection Drug Use on Providers’ PrEP-Related Clinical Judgments

AIDS and Behavior - Social biases may influence providers’ judgments related to pre-exposure prophylaxis (PrEP) and patients’ consequent PrEP access. US primary and HIV care providers...     

Simian AIDS-related lymphoma growth in severe combined immunodeficiency mice is independent of karyotypic abnormalities or Bcl-6 mutations

Simian AIDS-related lymphomas (sARL) of cynomolgus monkeys infected with a simian immunodeficiency virus (SIVsm) were studied in relation to growth in severe combined immunodeficient (SCID) mice, karyotype abnormalities, and DNA sequence of the first noncoding region of the Bcl-6 gene. The tumors were diffuse large B cell lymphomas and expressed a simian homolog to Epstein-Barr virus (HVMF-1) in 12 of 13 primary tumors and corresponding cell lines. A tested cell line was tumorigenic in SCID mice. Tumors in the SCID mice showed cell growth features similar to those in the original lymphoma, suggesting that no subpopulation with growth advantage was selected for in the mice. Spectral karyotype analysis of sARL cell lines showed normal cytogenetic features except for a trisomy of monkey chromosome 2 (corresponding to human chromosomes 7 and 21) in two of five sARL lines, which was not recovered in SCID tumors established from the same cell line. Sequence analysis of a Bcl-6 gene fragment showed sequence variations indicative of population polymorphism(s) in 10 of 13 sARLs, and no evidence of Bcl-6 mutations. Thus Bcl-6 mutations in the first noncoding region are irrelevant for sARL development in cynomolgus monkeys and for tumorigenicity of sARL cell lines. We also demonstrate that no cytogenetic alterations are needed for the development of highly aggressive lymphomas in the SIV-immunosuppressed host.