Antibiotic use in acute pancreatitis: An Indian multicenter observational study

Introduction

Prophylactic antibiotics are used frequently for acute pancreatitis (AP). Consensus guidelines do not recommend this currently, based on moderate quality evidence. In this study, we aimed to evaluate the antibiotic use pattern in AP in India and propose a risk-directed approach to antibiotic use in AP.

Material and Methods

This multicenter study was conducted from 1 May 2013 to 31 July 2013. Eleven participants from eight tertiary centers completed a questionnaire that captured patient demographics, etiology, admission status, presence of (peri)pancreatic necrosis, severity of pancreatitis, details of antibiotic use, and clinical outcomes (total hospital stay, persistent organ failure, need for ICU, total days in ICU, development of infections, in-hospital mortality).

Results

A total of 200 proformas were analyzed. Seventy-three (36.5 %) had acute necrotizing pancreatitis (ANP). Eighty-nine (44.5 %), 52 (26 %), and 55 (27.5 %) patients had mild AP (MAP), moderately severe AP (MSAP), and severe AP (SAP), respectively. Forty-five (22.5 %) patients developed infections (unifocal 29; multifocal 16). One hundred thirty-four (67 %) patients received antibiotics, of which 89 (66.4 %) received prophylactic, while 45 (33.6 %) received therapeutic antibiotics. The distribution of antibiotic use according to the severity of AP was 43 (48.3 %) in patients with MAP (prophylactic in 41; therapeutic in 2), 36 (69.2 %) in patients with MSAP (prophylactic in 29; therapeutic in 7), and 55 (100 %) in patients with SAP (prophylactic in 19; therapeutic in 36). Therapeutic antibiotics were prescribed based on culture and sensitivity in 21 (46.7 %) patients.

Conclusions

Despite nonrecommendation, prophylactic antibiotics are used frequently in AP. We emphasize on the need for multicenter randomized controlled trials on prophylactic antibiotics for AP based on a risk-directed approach, rather than a “blanket approach.”     

Donor insulin use predicts beta-cell function after islet transplantation

Insulin is routinely used to manage hyperglycaemia in organ donors and during the peri-transplant period in islet transplant recipients. However, it is unknown whether donor insulin use (DIU) predicts beta-cell dysfunction after islet transplantation. We reviewed data from the UK Transplant Registry and the UK Islet Transplant Consortium; all first-time transplants during 2008-2016 were included. Linear regression models determined associations between DIU, median and coefficient of variation (CV) peri-transplant glucose levels and 3-month islet graft function. In 91 islet cell transplant recipients, DIU was associated with lower islet function assessed by BETA-2 scores (β [SE] -3.5 [1.5], P = .02), higher 3-month post-transplant HbA1c levels (5.4 [2.6] mmol/mol, P = .04) and lower fasting C-peptide levels (−107.9 [46.1] pmol/l, P = .02). Glucose at 10 512 time points was recorded during the first 5 days peri-transplant: the median (IQR) daily glucose level was 7.9 (7.0-8.9) mmol/L and glucose CV was 28% (21%-35%). Neither median glucose levels nor glucose CV predicted outcomes post-transplantation. Data on DIU predicts beta-cell dysfunction 3 months after islet transplantation and could help improve donor selection and transplant outcomes.     

Percutaneous vertebroplasty in painful refractory vertebral hemangiomas

Background:

Painful vertebral hemangiomas are often inadequately managed medically. We evaluated the outcome of percutaneous vertebroplasty (PVP) in the treatment of painful vertebral hemangiomas refractory to medical management.

Materials and Methods:

14 patients (four thoracic and ten lumbar vertebra) with painful vertebral hemangiomas presenting with severe back pain for more than 6 months not responding to medical therapy were treated by vertebroplasty. Cross sectional imaging of the spine with magnetic resonance was done. Blood investigations were done to exclude coagulopathy excluded. PVP was performed under local anesthesia.

Results:

The pain intensity numeric rating scale (PI-NRS-11) of these patients was in the range of 7-10 (Severe Pain). After vertebroplasty 8 patients were completely free of pain (PI NRS Score 0) while 6 were significantly relieved (PI-NRS Score 1-3). No complications were observed. Two patients with associated radicular pain had good pain relief following PVP. No recurrence was found during 36 months of postoperative followup.

Conclusion:

PVP is a safe and effective procedure in patients with painful vertebral hemangiomas refractory to medical management.     

Metabolism of benzo[a]pyrene: conversion of (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene to highly mutagenic 7,8-diol-9,10-epoxides.

Metabolites of (+/-)-trans 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene formed by a rat liver microsomes and by a highly purified monoxygenase system were analyzed by high-pressure liquid chromatography. Four stereoisomeric tetraols of 7,8,9,10-tetrahydrobenzo[a]pyrene, known solvolysis products of the two highly mutagenic stereoisomers of the 9,10-epoxide of the 7,8-dihydrodiol, were identified as products. The ratio of the two highly unstable diol epoxides formed (7 beta,8alpha-dihydroxy-9beta,10beta-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene, diol epoxide 1; 7beta,8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene, diol epoxide 2) ranged from about 1.7 to 0.4. The diol epoxides are sufficiently reactive to alkylate phosphate buffer (pH 7.4) at 37 degrees. Microsomes, particularly those from control animals, formed a substantial amount of an additional metabolite that appears to be phenolic. In analogy to benzo[a]pyrene, the metabolism of the 7,8-dihydrodiol shows similar induction after pretreatment of rats with phenobarbital or 3-methylcholanthrene. Neither diol epoxide appears to be a substrate for epoxide hydrase based on the ratis of tetraols formed in the presence or absence of epoxide hydrase. In view of the known carcinogenicity of benzo[a]pyrene 7,8-oxide and 7,8-dihydrodiol and of the marked mutagenicity of the stereoisomeric diol epoxides, both of these diol epoxides qualify for consideration as "ultimate carcinogen(s)" of benzo[a]pyrene.     

Tumorigenicity of the optical enantiomers of the diastereomeric benzo[a]pyrene 7,8-diol-9,10-epoxides in newborn mice: exceptional activity of (+)-7beta,8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene.

The tumorigenicities of benzo[a]pyrene and each optical enantiomer of the diastereomeric benzo[a]pyrene 7,8-diol-9,10-epoxides derived from trans-7,8-dihydroxy-7,8-dihydrobenzol[a]pyrene were tested by sequential intraperitoneal injection of mice with 1,2, and 4 nmol, or with 2, 4, and 8 nmol of each compound on the 1st, 8th, and 15th day of life, respectively. The experiment was terminated when the animals were 34--37 weeks old. (+)-7beta, 8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzol[a]pyrene [(+)-BP-7beta,8alpha-diol-9alpha,10alpha-epoxide 2] had exceptional tumorigenicity, whereas benzo[a]-pyrene and the other three optically pure isomers of the benzo[a]pyrene 7,8-diol,9,10-epoxides had little or no activity. These results demonstrate differences in the carcinogenic activities of optically active isomers of a polycyclic hydrocarbon diol epoxide. Eleven percent of control mice had pulmonary tumors, whereas 71% and 100% of the mice treated with a total dose of 7 or 14 nmol of (+)-BP-7beta,8alpha-diol-9alpha,10alpha-epoxide 2, respectively, had pulmonary tumors. Control mice had an average of 0.12 pulmonary tumors per mouse, whereas mice treated with a total dose of 7 or 14 nmol of (+)-BP-7beta,8alpha-diol-9alpha,10alpha-epoxide 2 had 1.72 and 7.67 pulmonary tumors per mouse, respectively. Mice treated with 14 nmol of (-)-BP-7alpha,8beta-diol-9beta,10beta-epoxide 2, (-)-BP-7beta,8alpha-diol-9beta,10beta-epoxide 1, or (+)-BP-7alpha,8beta-diol-9alpha,10alpha-epoxide 1 had 0.13, 0.25, and 0.34 pulmonary tumors per animal, respectively.     

The Synergistic Impact of Sexual Stigma and Psychosocial Well-Being on HIV Testing: A Mixed-Methods Study Among Nigerian Men who have Sex with Men

Although sexual stigma has been linked to decreased HIV testing among men who have sex with men (MSM), mechanisms for this association are unclear. We evaluated the role of psychosocial well-being in connecting sexual stigma and HIV testing using an explanatory sequential mixed methods analysis of 25 qualitative and 1480 quantitative interviews with MSM enrolled in a prospective cohort study in Nigeria from March/2013–February/2016. Utilizing structural equation modeling, we found a synergistic negative association between sexual stigma and suicidal ideation on HIV testing. Qualitatively, prior stigma experiences often generated psychological distress and perceptions of feeling unsafe, which decreased willingness to seek services at general health facilities. MSM reported feeling safe at the MSM-friendly study clinic but still described a need for psychosocial support services. Addressing stigma and unmet mental health needs among Nigerian MSM has the potential to improve HIV testing uptake.