Bile Culture May Guide Antibiotic Stewardship in Acute Bacterial Cholangitis.

BACKGROUND: Bile cultures are often sent with blood cultures in patients with acute bacterial cholangitis. AIMS: To assess the yield of blood and bile cultures in patients with cholangitis and the clinical utility of bile cultures in guiding therapy. METHODS: All patients diagnosed with cholangitis, based on the Tokyo 2013/2018 guidelines were recruited retrospectively over ten years. The clinical and investigation details were recorded. The results of bile and blood cultures including antibiotic sensitivity patterns were noted. The concordance of microorganisms grown in blood and bile cultures and their sensitivity pattern were assessed. RESULTS: A total of 1063 patients with cholangitis were included. Their mean age was 52.7 ± 14 years and 65.4% were males. Blood cultures were positive in 372 (35%) patients. Bile culture was performed in 384 patients with 84.4% being positive, which was significantly higher than the yield of blood culture (p < 0.001). Polymicrobial growth was more in bile (59.3%) than in blood cultures (13.5%, p < 0.001). E.coli, Klebsiella, Enterococcus and Pseudomonas were the four most common organisms isolated from both blood and bile. Extended spectrum betalactamase producing organisms were isolated in 57.7% and 58.8% of positive blood and bile cultures, respectively. Among 127 patients with both blood and bile cultures positive, complete or partial concordance of organisms was noted in about 90%. CONCLUSION: Bile and blood cultures have a similar microbial profile in most patients with cholangitis. As bile cultures have a significantly higher yield than blood cultures, they could effectively guide antimicrobial therapy, especially in those with negative blood cultures.

Clinical profile and treatment outcomes of Boerhaave's syndrome: A 13-year experience from an upper gastrointestinal surgical unit.

Objectives: IBoerhaave's syndrome (BS) is a rare, but potentially fatal condition, characterized by barogenic esophageal rupture and carries a high mortality. We aimed to study our institutional experience of managing patients with BS. Material and Methods: A retrospective review of patients with BS presenting to a tertiary care centre from 2005 to 2018 was carried out in this study. Clinical presentation, diagnostic evaluations, treatments received, and treatment outcomes were studied. Perforations were classified as early (<24 hours) and delayed (>24 hours), based on the time elapsed. Surgical complications were graded using Clavien-Dindo grade. The Pittsburgh perforation severity score was correlated with short-term treatment outcomes. Results: Of the 12 patients [male, 75%; mean (range) age, 53 (28-80) years] included, 10 patients had a delayed (>24 hours) presentation. Chest pain was the dominant symptom (58.3%); six patients presented either in shock (n= 1) or with organ failure (n= 3) or both (n= 2). All the perforations were sited in the lower thoracic esophagus, of which three were contained and nine were uncontained. The seal of the perforation was achieved by surgical repair in four patients (primary repair, 2; repair over a T-tube, 2) and endoscopic techniques in four patients (clipping, 1; stenting, 3). Sepsis drainage [surgical, 7 (open-5, minimally-invasive-2); non-surgical, 5] and feeding jejunostomy were performed in all patients. Five (41.7%) patients received a re-intervention. Median (range) hospital stay was 25.5 (12-101) days, 30-day operative morbidity was 50%, and there was one in-hospital death. The Pittsburgh perforation severity score was as follows: 2-5 in two patients and >5 in 10 patients; there were more delayed presentations, increased surgical interventions, post-procedure morbidity, and in-hospital mortality in the latter group, but the differences were statistically not significant. In 11 patients followed-up [median (range):1507 (17-5929) days], there was no disease recurrence, symptomatic reflux or dysphagia. Conclusion: Favourable treatment outcomes, including reduced mortality and organ preservation can be achieved for Boerhaave's perforations, through a multimodality approach. Minimally invasive, endoluminal or open surgical techniques may be safely utilized in its management. The Pittsburgh severity score can be a useful clinical tool that can be used to select the initial intervention and to predict treatment outcomes.

Common polymorphisms of protein tyrosine phosphate non-receptor type 2 gene are not associated with risk of Crohn's disease in Indian.

BACKGROUND: Multiple genetic risk factors for Crohn's disease (CD) have been identified. However, these observations are not consistent across different populations. The protein tyrosine phosphate non-receptor type 2 (PTPN2) gene plays a role in various aspects of host defense including epithelial barrier function, autophagy, and innate and adaptive immune response. Two common polymorphisms in the PTPN2 gene (rs2542151 and rs7234029) have been associated with risk of CD in Western countries. AIM: To evaluate the association of PTPN2 gene polymorphisms with risk of CD in Indian population. METHODS: We conducted a prospective case-control study. Patients with CD were recruited, and their clinical and investigation details were noted. Controls were patients without organic gastrointestinal disease or other comorbid illnesses. Two common polymorphisms in the PTPN2 gene (rs2542151 and rs7234029) were assessed. DNA was extracted from peripheral blood samples of cases and controls and target DNA was amplified using specific sets of primers. The amplified fragments were digested with restriction enzymes and the presence of polymorphism was detected by restriction fragment length polymorphism. The frequency of alleles was determined. The frequencies of genotypes and alleles were compared between cases and controls to look for significant differences. RESULTS: A total of 108 patients with CD (mean age 37.5 ± 12.7 years, females 42.6%) and 100 controls (mean age 39.9 ± 13.5 years, females 37%) were recruited. For the single nucleotide polymorphism (SNP) rs7234029, the overall frequency of G variant genotype (AG or GG) was noted to be significantly lower in the cases compared to controls (35.2% vs 50%, P = 0.05). For the SNP rs2542151, the overall frequency of G variant genotype (GT or GG) was noted to be similar in cases compared to controls (43.6% vs 47%, P = 0.73). There were no significant differences in minor allele (G) frequency for both polymorphisms between the cases and controls. Both the SNPs had no significant association with age of onset of illness, gender, disease location, disease behaviour, perianal disease, or extraintestinal manifestations of CD. CONCLUSION: Unlike observation form the West, polymorphisms in the PTPN2 gene (rs7234029 and rs2542151) are not associated with an increased risk of developing CD in Indian patients.

Patients With Un-Displaced Or Displaced Intra Capsular Proximal Femur Fractures Do Not Represent A Different Patient Group And Have Similar Short And Long Term Mortality.

BACKGROUND: Proximal femur fractures in geriatric patients are associated with substantial mortality. Management of intracapsular proximal femur fractures has been based on age, displacement, cognition, and pre-injury mobility. However, over the last decade, there has been a tendency to offer arthroplasty rather than internal fixation for these patients irrespective of displacement, to allow early mobilisation and negate the higher rate of reoperation due to failed internal fixation. There are no previous investigations analysing whether the severity of fracture displacement is related to different patient characteristics. AIM: This study examines whether patients sustaining undisplaced or displaced intracapsular proximal femur fractures represent different patient groups with different pre-injury characteristics and post-operative mortality, irrespective of treatment modality. METHODS: A retrospective series of 329 consecutive patients over the age of 55 years who sustained intracapsular proximal femur fractures, who underwent surgical management at a district general hospital over a period of 2 years (2012-2013) were identified using the national hip fracture database. Demographics, American Society of Anaesthesiologist (ASA) grade, pre-injury outdoor mobility status, cognitive status, and admission serum investigations, fracture displacement, type of surgery, and mortality rates at short term (2 years) & long-term (7-9 years) were reviewed. RESULTS: There were 109 male and 220 female patients with a minimum follow-up of 7 years. The mean age at surgery was 81.6 years (range 55-103 years). There were 63 (19.1%) undisplaced fractures (Garden 1 &2) and, 265 (80.5%) displaced fractures (Garden 3 & 4). The median survival in this cohort was 2.95 years (95% CI 2.3-3.6). Mortality rates were 77.4% (n=257) at long-term (7-9 years) follow-up. Admission patient characteristics showed no statistically significant difference between displaced and undisplaced fracture groups. This included ASA, pre-operative cognition, and mobility status. Fracture displacement was not an independent predictor of mortality at short or long term. CONCLUSION: In patients sustaining intracapsular proximal femur fractures, the degree of displacement is not a caveat for a different patient group. Fracture displacement is not predicted by the pre-injury level of function and does not predict short or long-term mortality.

STEPS - a patient centric and low-cost solution to ensure standards of TB care to patients reaching private sector in India.

BACKGROUND: More than half of the TB patients in India seek care from the private sector. Two decades of attempts by the National TB Program to improve collaboration between the public and private sectors have not worked except in a few innovative pilots. The System for TB Elimination in Private Sector (STEPS) evolved in 2019 as a solution to ensure standards of TB care to every patient reaching the private sector. We formally evaluated the STEPS to judge the success of the model in achieving its outcomes and to inform decisions about scaling up of the model to other parts of the country. METHODS: An evaluation team was constituted involving all relevant stakeholders. A logic framework for the STEPS model was developed. The evaluation focused on (i) processes - whether the activities are taking place as intended and (ii) proximal outcomes - improvements in quality of care and strengthening of TB surveillance system. We (i) visited 30 randomly selected STEPS centres for assessing infrastructure and process using a checklist, (ii) validated the patient data with management information system of National TB Elimination Program (NTEP) by telephonic interview of 57 TB patients (iii) analysed the quality of patient care indicators over 3 years from the management information system (iv) conducted in-depth interviews (IDI) with 33 beneficiaries and stakeholders to understand their satisfaction and perceived benefits of STEPS and (v) performed cost analysis for the intervention from the perspective of NTEP, private hospital and patients. RESULTS: Evaluation revealed that STEPS is an acceptable model to all stakeholders. IDIs revealed that all patients were satisfied about the services received. Data in management information system of NTEP were consistent with the hospital records and with the information provided by the patient. Quality of TB care indicators for patients diagnosed in private hospitals showed improvements over years as proportion of TB patients notified from private sector with a microbiological confirmation of diagnosis improved from 25% in 2018 to 38% in 2020 and the documented treatment success rate increased from 33% (2018 cohort) to 88% (2019 cohort). Total additional programmatic cost (deducting cost for patient entitlements) per additional patient with successful treatment outcome was estimated to be 67 USD. Total additional expense/business loss for implementing STEPS for the hospital diagnosing 100 TB patients in a year was estimated to be 573 USD while additional minimum returns for the hospital was estimated to be 1145 USD. CONCLUSION: Evaluation confirmed that STEPS is a low cost and patient-centric strategy. STEPS successfully addressed the gaps in the quality of care for patients seeking care in the private sector and ensured that services are aligned with the standards of TB care. STEPS could be scaled up to similar settings.

"Surgically Treated COVID-19-Positive Trauma Patients Had a Higher Fatality Rate" - A Rural District General Hospital's Perspective in the United Kingdom.

Introduction Our study analyses the influence of the COVID-19 pandemic on perioperative death in elderly patients undergoing surgery for fractures who test positive for the virus during their admission in a rural hospital setting in the UK. Methods One hundred and fifty-six consecutive patients with age more than 75 years, who underwent surgery for fractures in Glangwili General Hospital during the second wave of the pandemic between 20th November 2020 and 20th January 2021, were included in this study. The 28-day mortality rate was estimated, and the results were compared to a matched cohort of patients from a similar duration before the pandemic (20th November 2019 to 20th January 2020). Results A total of 41 out of 156 patients were tested positive for COVID-19 in this study cohort. The overall 28-day mortality rate was 8.9% (n=15 patients) in comparison to 4% (n=8) in the comparative cohort of 196 patients from the pre-pandemic era. Of the 41 patients who tested positive for COVID-19, 11 patients died within 28 days of surgery, resulting in a mortality rate of 26.8% with a relative risk of 7.7(p=0.0461). Furthermore, 91% (n=10) of COVID-19-positive patients who died had an underlying cardiac disease and/or proximal femoral fractures. The 28-day mortality rate in those tested negative for COVID-19 was 3.5% (n=4). Conclusion There is a significantly increased risk of death in the perioperative period on contracting COVID-19, in patients who are 75 years of age or older, especially those with associated cardiac comorbidities and who have sustained proximal femoral fractures.

Maternal and neonatal outcomes in extra hepatic portal vein obstruction: Our experience.

BACKGROUND: Women with Extra hepatic portal vein obstruction (EHPVO) are mostly young and belong to Asian countries. In the Indian subcontinent, 20-30% variceal bleeds are caused by EHPVO. Hence pregnancy is a concern in such patients. The objective of this study is to observe the maternal and neonatal outcomes in women with EHPVO. MATERIALS AND METHOD: Extra hepatic portal vein obstruction was studied retrospectively in 28 pregnancies in 20 women from Jan 2011 to July 2018 at a tertiary hospital in South India and the pregnancy outcomes were observed during this period. Institutional Review Board approval obtained. RESULTS: The mean age of the women was 24.3 years and the mean age of diagnosis was 18.5 years. Splenomegaly, thrombocytopenia and anaemia were seen in 22 (78.5%), 17 (60.7%) and 8 (28.5%) of pregnancies, respectively. Rate of abortions and preterm deliveries were 2 (7.1%, n =28) and 10 (35.7%, n =28). There was one stillbirth (3.6%) in the study group. EHPVO was diagnosed in 25 (89.3%) women prenatally in our series. During pregnancy only one woman had variceal bleed, which was managed conservatively. Blood and blood product transfusion was required in 7(25%) of women and there was no maternal mortality. CONCLUSION: Pregnancies in EHPVO have good maternal and neonatal outcomes, provided they are taken care of by a multidisciplinary approach in a tertiary care centre.

Prevalence of past hepatitis A infection among Crohn's patients and controls - An examination of the 'hygiene hypothesis', and the need for hepatitis A vaccination.

Our study aimed to determine the prevalence of prior exposure to hepatitis A virus in Crohn's disease patients, whose IgG antibody levels against hepatitis A virus were compared with age and sex-matched controls. All of the 41 cases with Crohn's disease and 43 controls included in the study tested positive for IgG anti-hepatitis A virus antibody, with titres (38.8 IU/ml, 22-63.9; median, IQR) similar to those in controls (40.7 IU/ml, 17.3-66.7; p = 0.75). Environmental sanitation remains poor in India, despite reasonable economic gains as reflected by universal exposure to hepatitis A virus infection. Vaccination against hepatitis A may not be important in patients attending inflammatory bowel disease clinic, owing to natural immunity provided by prior infection. The observed rise in inflammatory bowel disease incidence seems to be increasing despite persistently poor environmental hygiene.

Self-expanding metal stent in esophageal perforations and anastomotic leaks.

BACKGROUND AND AIMS: Placement of self-expanding metal stents (SEMS) has emerged as a minimally invasive treatment option for esophageal perforation and leaks. The aim of our study was to assess the role of SEMS for the management of benign esophageal diseases such as perforations and anastomotic leaks. METHODS: All patients (n = 26) who underwent SEMS placement for esophageal perforation and anastomotic leaks between May 2012 and February 2019 were included. Data were analyzed in relation to the indications, type of stent used, complications, and outcomes. RESULTS: Indications for stent placement included anastomotic leaks 65% (n = 17) and perforations 35% (n = 9). Fully covered SEMS (FCSEMS) was placed in 25 patients, and in 1, partially covered SEMS (PCSEMS) was placed. Stent placement was successful in all the patients (n = 26). Four patients did not report for follow-up after stenting. Among the patients on follow-up, 91% (20/22) had healing of the mucosal defect. Stent-related complications were seen in 5 (23%) patients and included stent migration [3], reactive hyperplasia [1] and stricture [1]. CONCLUSION: Covered stent placement for a duration of 8 weeks is technically safe and clinically effective as a first-line procedure for bridging and healing benign esophageal perforation and leaks.

Codon Usage Selection Can Bias Estimation of the Fraction of Adaptive Amino Acid Fixations.

A growing number of molecular evolutionary studies are estimating the proportion of adaptive amino acid substitutions (α) from comparisons of ratios of polymorphic and fixed DNA mutations. Here, we examine how violations of two of the model assumptions, neutral evolution of synonymous mutations and stationary base composition, affect α estimation. We simulated the evolution of coding sequences assuming weak selection on synonymous codon usage bias and neutral protein evolution, α = 0. We show that weak selection on synonymous mutations can give polymorphism/divergence ratios that yield α-hat (estimated α) considerably larger than its true value. Nonstationary evolution (changes in population size, selection, or mutation) can exacerbate such biases or, in some scenarios, give biases in the opposite direction, α-hat < α. These results demonstrate that two factors that appear to be prevalent among taxa, weak selection on synonymous mutations and non-steady-state nucleotide composition, should be considered when estimating α. Estimates of the proportion of adaptive amino acid fixations from large-scale analyses of Drosophila melanogaster polymorphism and divergence data are positively correlated with codon usage bias. Such patterns are consistent with α-hat inflation from weak selection on synonymous mutations and/or mutational changes within the examined gene trees.

Ancestral inference and the study of codon bias evolution: implications for molecular evolutionary analyses of the Drosophila melanogaster subgroup.

Reliable inference of ancestral sequences can be critical to identifying both patterns and causes of molecular evolution. Robustness of ancestral inference is often assumed among closely related species, but tests of this assumption have been limited. Here, we examine the performance of inference methods for data simulated under scenarios of codon bias evolution within the Drosophila melanogaster subgroup. Genome sequence data for multiple, closely related species within this subgroup make it an important system for studying molecular evolutionary genetics. The effects of asymmetric and lineage-specific substitution rates (i.e., varying levels of codon usage bias and departures from equilibrium) on the reliability of ancestral codon usage was investigated. Maximum parsimony inference, which has been widely employed in analyses of Drosophila codon bias evolution, was compared to an approach that attempts to account for uncertainty in ancestral inference by weighting ancestral reconstructions by their posterior probabilities. The latter approach employs maximum likelihood estimation of rate and base composition parameters. For equilibrium and most non-equilibrium scenarios that were investigated, the probabilistic method appears to generate reliable ancestral codon bias inferences for molecular evolutionary studies within the D. melanogaster subgroup. These reconstructions are more reliable than parsimony inference, especially when codon usage is strongly skewed. However, inference biases are considerable for both methods under particular departures from stationarity (i.e., when adaptive evolution is prevalent). Reliability of inference can be sensitive to branch lengths, asymmetry in substitution rates, and the locations and nature of lineage-specific processes within a gene tree. Inference reliability, even among closely related species, can be strongly affected by (potentially unknown) patterns of molecular evolution in lineages ancestral to those of interest.

Molecular evolution in the Drosophila melanogaster species subgroup: frequent parameter fluctuations on the timescale of molecular divergence.

Although mutation, genetic drift, and natural selection are well established as determinants of genome evolution, the importance (frequency and magnitude) of parameter fluctuations in molecular evolution is less understood. DNA sequence comparisons among closely related species allow specific substitutions to be assigned to lineages on a phylogenetic tree. In this study, we compare patterns of codon usage and protein evolution in 22 genes (>11,000 codons) among Drosophila melanogaster and five relatives within the D. melanogaster subgroup. We assign changes to eight lineages using a maximum-likelihood approach to infer ancestral states. Uncertainty in ancestral reconstructions is taken into account, at least to some extent, by weighting reconstructions by their posterior probabilities. Four of the eight lineages show potentially genomewide departures from equilibrium synonymous codon usage; three are decreasing and one is increasing in major codon usage. Several of these departures are consistent with lineage-specific changes in selection intensity (selection coefficients scaled to effective population size) at silent sites. Intron base composition and rates and patterns of protein evolution are also heterogeneous among these lineages. The magnitude of forces governing silent, intron, and protein evolution appears to have varied frequently, and in a lineage-specific manner, within the D. melanogaster subgroup.