STROCSS 2021: Strengthening the reporting of cohort, cross-sectional and case-control studies in surgery.

INTRODUCTION: Strengthening The Reporting Of Cohort Studies in Surgery (STROCSS) guidelines were developed in 2017 in order to improve the reporting quality of observational studies in surgery and updated in 2019. In order to maintain relevance and continue upholding good reporting quality among observational studies in surgery, we aimed to update STROCSS 2019 guidelines. METHODS: A STROCSS 2021 steering group was formed to come up with proposals to update STROCSS 2019 guidelines. An expert panel of researchers assessed these proposals and judged whether they should become part of STROCSS 2021 guidelines or not, through a Delphi consensus exercise. RESULTS: 42 people (89%) completed the DELPHI survey and hence participated in the development of STROCSS 2021 guidelines. All items received a score between 7 and 9 by greater than 70% of the participants, indicating a high level of agreement among the DELPHI group members with the proposed changes to all the items. CONCLUSION: We present updated STROCSS 2021 guidelines to ensure ongoing good reporting quality among observational studies in surgery.

Drug resistance mutations in protease gene of HIV-1 subtype C infected patient population.

Failure of antiretroviral therapy (ART) in HIV-1 infection is a critical issue for the physicians treating HIV patients. The major cause of drug failure is the development of resistance mutations in reverse transcriptase (RT) and/or protease (PR) genes. Mutations associated with drug resistance decrease drug effectiveness. This study was conducted to assess drug resistance profile of the entire PR gene in 90 HIV-1 patients consisting of 23 ART non-responsive, 32 ART responsive and 35 drug naive patients. It was observed that the majority of the sequences (94.4%) belonged to subtype C and (5.5%) to subtype A1. The ART non-responsive and responsive patients were treated with either first line of ART regimen (two NRTI and one NNRTI) or second line of ART regimen that included additional one protease inhibitor (PI). All the patients in each group except one responsive patient had various minor resistance mutations. Thus, drug failures in ART non-responsive patients may not always be due to drug resistance mutations instead other factors may also be responsible for drug failures such as non-compliance, suboptimal dose or drug interaction. The presence of minor drug resistance mutations in drug naive patients is suggestive of transmitted resistance mutations.

LMNB1 Duplication-Mediated Autosomal Dominant Adult-Onset Leukodystrophy in an Indian Family.

Autosomal dominant leukodystrophy is an adult onset neurodegenerative disorder presenting with progressive symptoms of ataxia and autonomic dysfunction in fourth or fifth decade in life. It has clinical similarity with multiple sclerosis, but shows characteristic magnetic resonance imaging findings of diffuse bilaterally symmetrical leukodystrophy which can distinguish this disorder. It is a rare disorder with no known treatment till date, and has never been described from the Indian subcontinent. We present an Indian family with autosomal dominant adult-onset demyelinating leukodystrophy with multiple members affected over four generations, and demonstrate a cheap and accurate molecular method of real-time polymerase chain reaction to detect the LMNB1 gene duplication, which is the genetic basis of this devastating disorder.

A competing risk analysis of death patterns in male genitourinary cancer.

BACKGROUND: Early diagnosis and improved therapeutic options have contributed to prolonged survival in male genitourinary cancer. However, these cancer survivors may die due to other causes. AIMS: This work is aimed to explore the death patterns among male genitourinary cancer patients due to other causes. The occurrence of death not related to cancer is defined as competing risk (CR). METHODS AND RESULTS: Data extracted between 1973 and 2014 for male patients (n = 638 393) diagnosed with genitourinary cancer and registered in the Surveillance, Epidemiology, and End Results (SEER) Program were included for analysis. A CR analysis was performed to explore the death patterns due to cancer or otherwise. Our study evidenced a huge proportion of patients' death due to associated factors including but not limited to cancer. Interestingly, the computed hazard ratios obtained in cancers of male organ sites such as prepuce, glans penis, penis, and spermatic cord were 1.28 (0.98-1.67), 1.53 (1.33-1.77), 1.35 (0.19-1.53), and 1.57 (1.24-2.0), respectively. However, the hazard ratios evaluated on factors other than cancer in the same organ sites were 0.95 (0.76-1.18), 1.14 (0.99-1.3), 1.09 (0.97-1.22), and 1.12 (0.86-1.46), respectively. CONCLUSION: This study shows that among the male genitourinary cancer patients, the significant proportion of deaths occurs due to reasons unrelated to cancer. It can be concluded that the magnitude of death due to only genitourinary cancer is minimal and is not as high as documented in the earlier literature.

WITHDRAWN: Commentary on: A systematic review and meta-analysis of risk factors for unruptured intracranial aneurysm growth.

The Publisher regrets that this article is an accidental duplication of an article that has already been published, http://dx.doi.org/10.1016/j.ijsu.2019.08.018. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

Expression signature of lysosomal-associated transmembrane protein 4B in hepatitis C virus-induced hepatocellular carcinoma.

INTRODUCTION: Hepatocellular carcinoma is a lethal disease worldwide and therefore the establishment of novel diagnostic biomarkers is imperative. In this study, it was hypothesized that an abnormal expression of the lysosomal-associated protein transmembrane 4 beta ( LAPTM4B) gene is crucial in the pathogenesis of hepatitis C virus-mediated hepatocellular carcinoma; hence we investigated the expression profile of LAPTM4B in hepatitis C virus-induced hepatocellular carcinoma. METHODS: A group of 189 consecutive patients (hepatitis C virus-related hepatocellular carcinoma as tumor cases; n=93, hepatitis C virus-related cirrhotics as disease controls; n=96) opting for living donor liver transplantation as a therapeutic surgical regimen were recruited with informed consent. Additionally, paired adjacent non-tumorous tissues (n=93) obtained from cases were also included. Serum LAPTM4B protein concentrations were assessed by third-generation enzyme-linked immunosorbent assay and LAPTM4B mRNA, and protein expressions at tissue level were determined by quantitative real time reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry techniques, respectively. RESULTS: LAPTM4B protein concentrations in sera of patients were higher ( p<0.001) in tumor cases (1.25±0.25 ng/ml) compared to disease controls (0.53±0.28 ng/ml). Our study also depicts positive clinicopathological correlations between alpha-fetoprotein titers (b=0.65; p<0.001), quantitative hepatitis C virus RNA copies (b=0.33; p<0.001), and LAPTM4B protein concentrations, all in sera of patients. In addition, qRT-PCR and immunohistochemistry analyses revealed a significantly higher ( p<0.05) tissue LAPTM4B mRNA and protein expression, respectively, in tumor cases rather than in non-tumorous tissues and disease controls. CONCLUSIONS: Together, our results illustrate the LAPTM4B gene as a diagnostic biomarker in patients with hepatocellular carcinoma having documented evidence of chronic hepatitis C virus infection.

Comparative analysis of drug resistance mutations in the human immunodeficiency virus reverse transcriptase gene in patients who are non-responsive, responsive and naive to antiretroviral therapy.

Drug resistance mutations in the Pol gene of human immunodeficiency virus 1 (HIV-1) are one of the critical factors associated with antiretroviral therapy (ART) failure in HIV-1 patients. The issue of resistance to reverse transcriptase inhibitors (RTIs) in HIV infection has not been adequately addressed in the Indian subcontinent. We compared HIV-1 reverse transcriptase (RT) gene sequences to identify mutations present in HIV-1 patients who were ART non-responders, ART responders and drug naive. Genotypic drug resistance testing was performed by sequencing a 655-bp region of the RT gene from 102 HIV-1 patients, consisting of 30 ART-non-responding, 35 ART-responding and 37 drug-naive patients. The Stanford HIV Resistance Database (HIVDBv 6.2), IAS-USA mutation list, ANRS_09/2012 algorithm, and Rega v8.02 algorithm were used to interpret the pattern of drug resistance. The majority of the sequences (96 %) belonged to subtype C, and a few of them (3.9 %) to subtype A1. The frequency of drug resistance mutations observed in ART-non-responding, ART-responding and drug-naive patients was 40.1 %, 10.7 % and 20.58 %, respectively. It was observed that in non-responders, multiple mutations were present in the same patient, while in responders, a single mutation was found. Some of the drug-naive patients had more than one mutation. Thymidine analogue mutations (TAMs), however, were found in non-responders and naive patients but not in responders. Although drug resistance mutations were widely distributed among ART non-responders, the presence of resistance mutations in the viruses of drug-naive patients poses a big concern in the absence of a genotyping resistance test.

Novel point and combo-mutations in the genome of hepatitis B virus-genotype D: characterization and impact on liver disease progression to hepatocellular carcinoma.

BACKGROUND: The contribution of chronic hepatitis B virus (HBV) infection in the pathogenesis of hepatocellular carcinoma (HCC) through progressive stages of liver fibrosis is exacerbated by the acquisition of naturally occurring mutations in its genome. This study has investigated the prevalence of single and combo mutations in the genome of HBV-genotype D from treatment naïve Indian patients of progressive liver disease stages and assessed their impact on the disease progression to HCC. METHODS: The mutation profile was determined from the sequence analysis of the full-length HBV genome and compared with the reference HBV sequences. SPSS 16.0 and R software were used to delineate their statistical significance in predicting HCC occurrence. RESULTS: Age was identified as associated risk factor for HCC development in chronic hepatitis B (CHB) patients (p ≤ 0.01). Beyond the classical mutations in basal core promoter (BCP) (A1762T/G1764A) and precore (G1862T), persistence of progressively accumulated mutations in enhancer-I, surface, HBx and core were showed significant association to liver disease progression. BCP_T1753C, core_T147C, surface_L213I had contributed significantly in the disease progression to HCC (p < 0.05) in HBeAg positive patients whereas precore_T1858C, core_I116L, core_P130Q and preS1_S98T in HBeAg negative patients. Furthermore, the effect of individual mutation was magnified by the combination with A1762T/G1764A in HCC pathogenesis. Multivariate risk analysis had confirmed that core_P130Q [OR 20.71, 95% CI (1.64-261.77), p = 0.019] in B cell epitope and core_T147C [OR 14.58, 95% CI (1.17-181.76), p = 0.037] in CTL epitope were two independent predictors of HCC in HBeAg positive and negative patients respectively. CONCLUSIONS: Thus distinct pattern of mutations distributed across the entire HBV genome may be useful in predicting HCC in high-risk CHB patients and pattern of mutational combinations may exert greater impact on HCC risk prediction more accurately than point mutations and hence these predictors may support the existing surveillance strategies in proper management of the patients.

Cartilage support for fascia graft in type I tympanoplasty.

To evaluate the success rate, in terms of anatomical and functional results, in our technique of cartilage support for fascia graft in type I tympanoplasty. Retrospective study of tragal cartilage support for fascia graft in tympanoplasty for large central perforation in 748 patients was carried at an academic institution during January 2004 to March 2012. Patients' age ranged from 11 to 65 years. 325 (43.4 %) male and 423 (56.6 %) female patients were operated and mean post-operative follow up was of 24 months (range 6-48 months). The inclusion criteria were large central or subtotal perforation, anterior quadrant perforation, anterior tympanosclerotic patch with perforation and revision myringoplasty. Small central perforation, posterior perforations, traumatic perforations and Ossiculplasty were excluded from this study. In this technique, a piece of tragal cartilage carved in semi lunar shape is inserted medial to anterior remnant of tympanic membrane. Temporalis fascia graft is sandwiched between cartilage and anterior remnant of tympanic membrane. Post-operative closure of perforation was noted. Pure-tone average pre and post-operative air-bone gap in dB at 250, 500, 1000, 2000, and 4,000 Hz were compared. The overall success rate of our technique was 98.3 % in terms of graft uptake and within 13.35 ± 5.22 dB of air bone gap closure in terms of hearing improvement. This study reveals that cartilage support for fascia graft in type I tympanoplasty is a highly reliable technique and gives significant improvement in graft take-up and hearing status.

Tackling hepatitis B virus-associated hepatocellular carcinoma--the future is now.

Hepatocellular carcinoma (HCC) is one of the most lethal and prevalent cancers in many developing countries including India. Among the various etiological factors being implicated in the cause of HCC, the most important cause, however, is hepatitis B virus (HBV) infection. Among all HBV genes, HBx is the most critical carcinogenic component, the molecular mechanisms of which have not been completely elucidated. Despite its clinical significance, there exists a very elemental understanding of the molecular, cellular, and environmental mechanisms that drive disease pathogenesis in HCC infected with HBV. Furthermore, there are only limited therapeutic options, the clinical benefits of which are insignificant. Therefore, the quest for novel and effective therapeutic regimen against HBV-related HCC is of paramount importance. This review attempts to epitomize the current state of knowledge of this most common and dreaded liver neoplasm, highlighting the putative treatment avenues and therapeutic research strategies that need to be implemented with immediate effect for tackling HBV-related HCC that has plagued the medical and scientific fraternity for decades. Additionally, this review proposes a novel "five-point" management algorithm for HBV-related HCC apart from portraying the unmet needs, principal challenges, and scientific perspectives that are relevant to controlling this accelerating global health crisis.