Impact of gender-affirming hormone therapy on the development of COVID-19 infections and associated complications:A systematic review

BACKGROUND Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)can produce a wide range of clinical manifestations from asymptomatic to life-threatening.Various researchers have worked to elucidate the pathogenic mechanisms underlying these variable presentations.Differences in individual responses to systemic inflammation and coagulopathy appear to be modulated by several factors,including sex steroid hormones.Transgender men or non-binary individuals who undergo gender-affirming hormone therapy(GAHT)are a unique population of interest for exploring the androgen-mediated coronavirus disease 2019(COVID-19)hypothesis.As the search for reliable and effective COVID-19 treatments continues,understanding the risks and benefits of GAHT may mitigate COVID-19 related morbidity and mortality in this patient population.AIM To investigate the potential role of GAHT in the development of COVID-19 infections and complications.METHODS This systematic review implemented an algorithmic approach using PRISMA guidelines.PubMed,Scopus,Google Scholar top 100 results,and archives of Plastic and Reconstructive Surgery was on January 12,2022 using the key words“gender”AND“hormone”AND“therapy”AND“COVID-19”as well as associated terms.Non-English articles,articles published prior to 2019(prior to COVID-19),and manuscripts in the form of reviews,commentaries,or letters were excluded.References of the selected publications were screened as well.RESULTS The database search resulted in the final inclusion of 14 studies related to GAHT COVID-19.Of the included studies,only two studies directly involved and reported on COVID-19 in transgender patients.Several clinical trials looked at the relationship between testosterone,estrogen,and progesterone in COVID-19 infected cis-gender men and women.It has been proposed that androgens may facilitate initial COVID-19 infection,however,once this occurs,testosterone may have a protective effect.Multiple clinical studies have shown that low baseline testosterone levels in men with COVID-19 are associated with worsening outcomes.The role of female sex hormones,including estrogen and progesterone have also been proposed as potential protective factors in COVID-19 infection.This was exemplified in multiple studies investigating different outcomes in pre-and post-menopausal women as well as those taking hormone replacement therapy.Two studies related specifically to transgender patients and GAHT found that estrogen and progesterone could help protect men against COVID-19,and that testosterone hormone therapy may increase the risk of contracting COVID-19.CONCLUSION Few studies were found related to the role of GAHT in COVID-19 infections.Additional research is necessary to enhance our understanding of this relationship and provide better care for transgender patients.

Lung cancer screening: Should we be excluding people with previous malignancy?

The National Lung Screening Trial(NLST) was a large,randomized, controlled study showing a 20% reduction of lung cancer mortality and 7% reduction of all cause mortality using annual low dose computed tomography(LDCT) in a high risk population. NLST excluded people with a previous history of cancer treatment within the past 5 years and all people with a history lung cancer. The aim of this work is to review how lung cancer screening trials addressed the confounding effect of previous malignancy. We also review the subsequent recommendations by the United States Preventative Task Force Services, multiple professional societies and the Center for Medicaid and Medicare Services which defer either to NLST criteria or, clinician judgment or refrain from asserting any recommendation on the topic, respectively. Implications of lung cancer screening in the setting of previous malignancies, specifically lung, head and neck, esophageal, gastric, breast, colorectal cancer and lymphoma are also discussed. With lung cancer screening, an antecedent malignancy introduces the possibility of discovering metastasis as well as lung cancer. In some circumstances diagnosis and treatment of oligometastatic disease may confer a survival benefit. The survival benefit of treating either lung cancer or oligometastatic disease as result of lung cancer screening has yet to be determined. Further studies are needed to determine the role of lung cancer screening in the setting of previous malignancy.

Apolipoprotein B100 is required for hepatitis C infectivity and Mipomersen inhibits hepatitis C

AIM To characterize the role of apolipoprotein B100(apoB 100) in hepatitis C viral(HCV) infection. METHODS In this study, we utilize a gene editing tool, transcription activator-like effector nucleases(TALENs), to generate human hepatoma cells with a stable genetic deletion of APOB to assess of apoB in HCV. Using infectious cell culture-competent HCV, viral pseudoparticles, replicon models, and lipidomic analysis we determined the contribution of apoB to each step of the viral lifecycle. We further studied the effect of mipomersen, an FDAapproved antisense inhibitor of apoB 100, on HCV using in vitro cell-culture competent HCV and determined itsimpact on viral infectivity with the TCID50 method. RESULTS We found that apo B100 is indispensable for HCV infection. Using the JFH-1 fully infectious cell-culture competent virus in Huh 7 hepatoma cells with TALENmediated gene deletion of apoB(APOB KO), we found a significant reduction in HCV RNA and protein levels following infection. Pseudoparticle and replicon models demonstrated that apo B did not play a role in HCV entry or replication. However, the virus produced by APOB KO cells had significantly diminished infectivity as measured by the TCID-50 method compared to wildtype virus. Lipidomic analysis demonstrated that these virions have a fundamentally altered lipidome, with complete depletion of cholesterol esters. We further demonstrate that inhibition of apoB using mipomersen, an FDA-approved anti-sense oligonucleotide, results in a potent anti-HCV effect and significantly reduces the infectivity of the virus. CONCLUSION Apo B is required for the generation of fully infectious HCV virions, and inhibition of apo B with mipomersen blocks HCV. Targeting lipid metabolic pathways to impair viral infectivity represents a novel host targeted strategy to inhibit HCV.

Robotic management of urinary fistula

Objectives:To highlight critical preoperative and intraoperative considerations in approaching fistula repair robotically.Methods:A search of the literature was conducted to identify relevant articles pertaining to robotic management of urinary fistulae.Results:Fistulae of the genitourinary tract can be a challenging dilemma for urologists,as definitive management may require surgical intervention.Pathogenesis of both enteric and non-enteric fistulae are multifactorial,and successful repair hinges on the meticulous perioperative evaluation,planning,and execution.Traditional open techniques can subject patients to increased morbidity and prolonged hospitalizations.Since its introduction,the robotic surgical platform has continued to expand its indications.Its three-dimensional visualization and tremor free wristed instrument movements have made the robotic platform an attractive option for genitourinary fistula reconstruction.Conclusion:Robotic management of complex urinary fistulae is feasible in expert hands;more studies are needed to define its role in the treatment algorithm of this devastating conditions.