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Abstract Background and Aims Strictures are the most common biliary complication after liver transplantation, and endoscopic retrograde cholangiopancreatography (ERCP) is considered the gold standard in its management. Failure to cross the biliary anastomosis requires a repeated attempt with ERCP, referral for percutaneous transhepatic cholangiography (PTC) or surgery. We present our experience with the digital single operator cholangioscope (D‐SOC) in achieving guidewire access in a liver transplant cohort with difficult biliary strictures who have failed conventional ERCP methods. Methods This was a retrospective study involving two adult liver transplant centers servicing the two most populated states in Australia. Deceased‐donor liver transplant recipients undergoing D‐SOC for biliary strictures who have failed conventional methods to achieve biliary access were included. Results Between July 2017 to April 2022, eighteen patients underwent D‐SOC after failing to achieve guidewire placement through standard ERCP techniques. Thirteen out of eighteen (72%) had successful guidewire placement with index D‐SOC. Five of eighteen patients (28%) had unsuccessful guidewire placement with D‐SOC. In two of these patients, use of D‐SOC informed further endoscopic management, with one avoiding PTC and the other avoiding surgery. Two of the five patients required PTC and one patient was left unstented. Three patients developed post D‐SOC cholangitis. Conclusions D‐SOC is effective at achieving guidewire access in post‐liver transplant patients who fail conventional ERCP techniques and should be considered in the treatment algorithm as a step before PTC and surgery.

Abstract Background Despite the availability of an effective vaccine, chronic hepatitis B virus (HBV) infections remain a major cause of liver cirrhosis and hepatocellular carcinoma. HBV burden in pregnancy, risk factors and the timing of mother to child transmission remain poorly described especially during this era of lifelong use of Tenofovir/Lamivudine/Efavirenz as firstline for HIV treatment. We aimed to determine the burden of HBV in pregnancy and infants receiving their first dose of HBV vaccine 6 weeks after birth in a high HIV-prevalence setting. Methods Pregnant women ≥ 20 weeks’ gestational age were enrolled and followed up as mother-infant dyads from delivery, 6, 24 and 96 weeks after birth. HBV surface antigen (HBsAg) was tested (fresh plasma, immunochromatography) in pregnancy. Women testing HBsAg-seropositive were further evaluated for other four HBV-biomarkers. Maternally HBV exposed babies were tested for HBsAg from birth and HBs-antibodies from 6 months of age. Maternal-infant factors were tested in univariable and multivariable analyses for predictors of HBsAg-seropositivity. Results Six hundred HIV-uninfected and 608 HIV-infected women on Tenofovir/Lamivudine/Efavirenz-regimen with median (interquartile range) 350: (87–1477) days of therapy use were enrolled. The overall HBsAg-seroprevalence was 32/1208: 2.65%, 95% confidence interval (CI) [1.74, 3.55]; being 7/600: 1.17%, 95% CI [0.37, 1.97] and 25/608: 4.11%, 95% CI [2.52, 5.68] in HBsAg-monoinfected and HBsAg/HIV-coinfected respectively, disproportionately detected in 31/32: 96.9%, 95% CI [90.8, 100] women presumably HBV-unvaccinated in infancy. HBV exposed babies tended to be born prematurely (

IntroductionCombination antiretroviral therapy (cART) effectively controls HIV; however, chronic low-level viremia and gut microbiota dysbiosis remain significant drivers of gut and systemic inflammation. In this study, we explored the relationship between gut microbiota composition, intestinal inflammation, microbial translocation, and systemic inflammation in women on cART in Sub-Saharan Africa.MethodsWe conducted a study in HIV-infected and HIV-uninfected lactating women followed up at 6 weeks and 6 months postpartum in Harare, Zimbabwe. We used 16S ribosomal Ribonucleic Acid (rRNA) sequencing and MesoScale Discovery V-Plex assays to examine the gut microbiome and to quantify plasma inflammatory biomarkers, respectively. In addition, we measured fecal calprotectin, plasma lipopolysaccharide-binding protein (LBP), and soluble cluster of differentiation 14 (sCD14) by enzyme-linked immunosorbent assay to assess gut inflammation, microbial translocation, and monocyte/macrophage activation.ResultsA group of 77 lactating women were studied, of which 35% were HIV-infected. Fecal calprotectin levels were similar by HIV status at both follow-up time points. In the HIV-infected group at 6 weeks postpartum, fecal calprotectin was elevated: median (interquartile range) [158.1 µg/g (75.3–230.2)] in women who had CD4+ T-lymphocyte counts

Abstract Background Human immunodeficiency virus (HIV) severely damages the epithelial cells of the gut lining leading to an inflamed leaky gut, translocation of microbial products, and dysbiosis resulting in systemic immune activation. Also, microbiota composition and maternal gut function can be altered in pregnancy through changes in the immune system and intestinal physiology. The aim of this study was to investigate the gut microbiota in HIV-infected and HIV-uninfected pregnant women and to compare and identify the association between gut microbial composition and adverse birth outcomes. Results A total of 94 pregnant women (35 HIV-infected and 59 HIV-uninfected controls) were recruited in Harare from 4 polyclinics serving populations with relatively poor socioeconomic status. Women were of a median age of 28 years (interquartile range, IQR: 22.3–32.0) and 55% of women were 35 weeks gestational age at enrolment (median 35.0 weeks, IQR: 32.5–37.2). Microbiota profiling in these participants showed that species richness was significantly lower in the HIV-infected pregnant women compared to their HIV-uninfected peers and significant differences in β-diversity using Bray–Curtis dissimilarity were observed. In contrast, there was no significant difference in α-diversity between immune-compromised (CD4+

BACKGROUND:Resistant starch is a prebiotic metabolized by the gut bacteria. It has been shown to attenuate chronic kidney disease (CKD) progression in rats. Previous studies employed taxonomic analysis using 16S rRNA sequencing and untargeted metabolomics profiling. Here we expand these studies by metaproteomics, gaining new insight into the host-microbiome interaction. METHODS:Differences between cecum contents in CKD rats fed a diet containing resistant starch with those fed a diet containing digestible starch were examined by comparative metaproteomics analysis. Taxonomic information was obtained using unique protein sequences. Our methodology results in quantitative data covering both host and bacterial proteins. RESULTS:5,834 proteins were quantified, with 947 proteins originating from the host organism. Taxonomic information derived from metaproteomics data surpassed previous 16S RNA analysis, and reached species resolutions for moderately abundant taxonomic groups. In particular, the Ruminococcaceae family becomes well resolved-with butyrate producers and amylolytic species such as R. bromii clearly visible and significantly higher while fibrolytic species such as R. flavefaciens are significantly lower with resistant starch feeding. The observed changes in protein patterns are consistent with fiber-associated improvement in CKD phenotype. Several known host CKD-associated proteins and biomarkers of impaired kidney function were significantly reduced with resistant starch supplementation. Data are available via ProteomeXchange with identifier PXD008845. CONCLUSIONS:Metaproteomics analysis of cecum contents of CKD rats with and without resistant starch supplementation reveals changes within gut microbiota at unprecedented resolution, providing both functional and taxonomic information. Proteins and organisms differentially abundant with RS supplementation point toward a shift from mucin degraders to butyrate producers.

The human immunodeficiency virus (HIV) heavily affects women from resource-limited settings who are vulnerable to potentially harmful mycotoxins including aflatoxin B1 (AFB1), fumonisin B1 (FB1) and ochratoxin A (OTA). We aimed to conduct biomonitoring and ascertain the determinants of maternal mycotoxin exposure in pregnancy, lactation and post-lactation periods. We conducted a retrospective longitudinal study in HIV-infected and HIV-uninfected women from Harare, Zimbabwe. 175 and 125 random urine samples in pregnancy and 24 months after delivery (post-lactation) respectively were analysed for aflatoxin M1 (AFM1) and FB1 by ELISA. 6 weeks after delivery (lactation), 226 and 262 breast milk (BM) samples were analysed for AFM1 and OTA respectively by ELISA. The association of demographics and food consumption with mycotoxins was evaluated using multivariable logistic regression. In HIV-infected, urinary AFM1 was detected in 46/94 (Median: 0.05; Range: 0.04–0.46 ng mL−1) in pregnancy and 47/66 (Median: 0.05; Range: 0.04–1.01 ng mL−1) post-lactation. Urinary FB1 was detected in 86/94 (Median: 1.39; Range: 0.17–6.02 ng mL−1) in pregnancy and 56/66 (Median: 0.72; Range: 0.20–3.81 ng mL−1) post-lactation. BM AFM1 was detected in 28/110 (Median: 7.24; Range: 5.96–29.80 pg mL−1) and OTA in 11/129 (Median: 0.20; Range: 0.14–0.65 ng mL−1). In HIV-uninfected, urinary AFM1 was detected in 48/81 (Median: 0.05; Range: 0.04–1.06 ng mL−1) in pregnancy and 41/59 (Median: 0.05; Range: 0.04–0.52 ng mL−1) post-lactation. Urinary FB1 was detected in 74/81 (Median: 1.15; Range: 0.17–6.16 ng mL−1) in pregnancy and 55/59 (Median: 0.96; Range: 0.20–2.82 ng mL−1) post-lactation. BM AFM1 was detected in 38/116 (Median: 7.70; Range: 6.07–31.75 pg mL−1) and OTA in 4/133 (Median: 0.24; Range: 0.18–0.83 ng mL−1). Location, wealth, and peanut butter consumption were determinants of AFB1 exposure. HIV infection, BMI, location, rainy season, unemployment, and age were determinants of FB1 exposure. Women especially those pregnant and/or HIV-infected are at risk of adverse effects of mycotoxins. [ABSTRACT FROM AUTHOR]

As management of upper gastrointestinal malignancies improves, and with popularization of bariatric surgery, endoscopists are likely to meet patients with altered upper gastrointestinal anatomy. Short‐term, the surgery can cause complications like bleeding, leaks, and fistulas, and longer‐term problems such as intestinal or biliary anastomotic strictures or biliary stones can arise, all necessitating endoscopy. In addition, the usual upper gastrointestinal pathologies can also still occur. These patients pose unique challenges. To proceed, understanding the new layout of the upper gastrointestinal tract is essential. The endoscopist, armed with a clear plan for navigation, can readily diagnose and manage most commonly occurring conditions, such as marginal ulcers and proximal anastomotic strictures with standard endoscopic instruments. With complex reconstructions involving long segments of small bowel, such as Roux‐en‐Y gastric bypass, utilization of balloon‐assisted enteroscopy may be necessary, mandating modification of procedures such as endoscopic retrograde cholangiopancreatography. Successful endoscopic management of patients with altered anatomy will require prior planning and preparation to ensure the appropriate equipment, setting, and skill set is provided. [ABSTRACT FROM AUTHOR]

Background and Aims: Strictures are the most common biliary complication after liver transplantation, and endoscopic retrograde cholangiopancreatography (ERCP) is considered the gold standard in its management. Failure to cross the biliary anastomosis requires a repeated attempt with ERCP, referral for percutaneous transhepatic cholangiography (PTC) or surgery. We present our experience with the digital single operator cholangioscope (D‐SOC) in achieving guidewire access in a liver transplant cohort with difficult biliary strictures who have failed conventional ERCP methods. Methods: This was a retrospective study involving two adult liver transplant centers servicing the two most populated states in Australia. Deceased‐donor liver transplant recipients undergoing D‐SOC for biliary strictures who have failed conventional methods to achieve biliary access were included. Results: Between July 2017 to April 2022, eighteen patients underwent D‐SOC after failing to achieve guidewire placement through standard ERCP techniques. Thirteen out of eighteen (72%) had successful guidewire placement with index D‐SOC. Five of eighteen patients (28%) had unsuccessful guidewire placement with D‐SOC. In two of these patients, use of D‐SOC informed further endoscopic management, with one avoiding PTC and the other avoiding surgery. Two of the five patients required PTC and one patient was left unstented. Three patients developed post D‐SOC cholangitis. Conclusions: D‐SOC is effective at achieving guidewire access in post‐liver transplant patients who fail conventional ERCP techniques and should be considered in the treatment algorithm as a step before PTC and surgery. [ABSTRACT FROM AUTHOR]

This paper engaged the qualitative method of structured interviews with Christian men due to non-functioning in the family and church. The paper emphasises the leadership role of the man in context of family and church. The purpose of this paper was to evaluate how men function in their leadership role in context of family and church so that challenges may be identified, and practical solutions be recommended to the church for the equipping of Christian men. The question that this paper endeavoured to answer was: Which detrimental factors have contributed to the non-functioning of Christian men in their role as spiritual leaders in context of family and church? The structured interviews used in this study involved fifteen male participants selected from the surroundings of evangelical churches in Johannesburg, South Africa. This paper provides a description of the research process related to the qualitative data analysis and its results related to the participant responses. The feedback from the respondents shed light on the need for the equipping of Christian men in the selected churches for their leadership role in the mentioned contexts. This paper contributes to Christian families and churches having a sound biblical worldview of the leadership role of the man, and a clear understanding of the authority of Scripture in their lives and ministry. This paper comes from a chapter in a larger study from a PhD thesis: The leadership role of the man in context of the family and church: A pastoral-theological study.

Background and study aims The increase in hepaticojejunostomies has led to an increase in benign strictures of the anastomosis. Double balloon enteroscopy-assisted ERCP (DBE-ERCP) and percutaneous transhepatic biliary drainage (PTBD) are treatment options; however, there is lack of long-term outcomes, with no consensus on management. We performed a retrospective study assessing the outcomes of patients referred for endoscopic management of hepaticojejunostomy anastomotic strictures (HJAS). Patients and methods All consecutive patients at a tertiary institution underwent endoscopic intervention for suspected HJAS between 2009 and 2021 were enrolled. Results Eighty-two subjects underwent DBE-ERCP for suspected HJAS. The technical success rate was 77 % (63/82). HJAS was confirmed in 41 patients. The clinical success rate for DBE-ERCP ± PTBD was 71 % (29/41). DBE-ERCP alone achieved clinical success in 49 % of patients (20/41). PTBD was required in 49 % (20/41). Dual therapy was required in 22 % (9/41). Those with liver transplant had less technical success compared to other surgeries (72.1 % vs 82.1 % P = 0.29), less clinical success with DBE-ERCP alone (40 % vs 62.5 % P = 0.16) and required more PTBD (56 % vs 37.5 % P = 0.25). All those with ischemic biliopathy (n = 9) required PTBD for clinical success, required more DBE-ERCP (4.4 vs 2.0, P = 0.004), more PTBD (4.7 vs 0.3, P

Background : : Five to ten percent of all patients undergoing radiofrequency ablation (RFA), which is the most established technique for Barrett's esophagus (BE) ablation-develop strictures. Hybrid-argon plasma coagulation (APC) combines APC with submucosal saline injection that was recently developed to tackle this problem. The aims of this pilot study were to evaluate the feasibility, tolerance, safety and long-term efficacy of hybrid-APC for the treatment of BE. Methods : : Patients with histological proven BE were selected for hybrid-APC. Prior to APC thermal ablation the mucosa was lifted using a submucosal high-pressure water jet injection system (Erbejet 2; Erbe, Tuebingen, Germany). Short-term (< 48 hours) and long-term (> 48 hours) safety were evaluated. Efficacy of ablation was measured at 3, 6, 12 and 24 months at follow-up endoscopy by evidence of macroscopically complete resolution of BE mucosa and/or histologically complete resolution of intestinal metaplasia (CRIM). Results : : Eleven patients were included in the study (average age, 68.2 years; male 72.7%). Eight patients (72.7%) were treatment naive, 9.1% (n = 1) had prior RFA and 18.2% (n = 2) had prior endoscopic mucosal resection. Two patients were excluded from the study. Nine patients (100%) had macroscopic remission and 88.9% (n = 8) had macroscopic remission and microscopic CRIM at 24 months after hybrid-APC ablation. No treatment-related stricture or other major complications were observed, 1 patient (11.1%) reported minor adverse effects. Conclusion : : In this prospective pilot study, hybrid-APC appears safe, feasible and effective after 24 months, which has not been evaluated so far. Further large, multi-centre trials are warranted to confirm the present results.

IntroductionMother-to-child-transmission (MTCT) of human immunodeficiency virus (HIV) can occur in pregnancy/in utero (IU), during childbirth/intrapartum (IP), or postpartum (PP) through breastfeeding from an infected mother to her infant. Burden of PP-MTCT and associated risk factors remain poorly described, especially in adolescent girls and young women (AGYW) aged 15–24 years. Furthermore, despite concerns on high postnatal seroconversions, there is paucity of data on the burden of subsequent MTCT rates.MethodsPregnant women ≥20 weeks of gestation were enrolled into the University of Zimbabwe Birth Cohort from four primary health centers in Harare, Zimbabwe. Mother–infant dyads were followed up from delivery, week(s) 1, 6, 10, 14, 24, 36, 48, 72, and 96 after birth. Women who were uninfected at baseline were re-tested for HIV on subsequent visits. Plasma HIV RNA was quantified using reverse transcriptase polymerase chain reaction. Exposed babies were tested for HIV using qualitative/quantitative proviral DNA PCR on dried blood spots. Maternal–infant factors were tested in univariable/multivariable regression analyses for HIV-MTCT predictors.ResultsA total of 600 HIV-uninfected and 608 HIV-infected pregnant women on Tenofovir/Lamivudine/Efavirenz regimen were enrolled from 2016 to 2019. Postnatal HIV incidence was 0.42 cases/100 women-years [95% confidence interval (CI): 0.12–1.1]. Postnatal seroconverters were less likely to have children/pregnancies sharing same father and unaware of their spouses/intimate partner’s HIV status: p = 0.008 and p = 0.02, respectively, compared with non-seroconverters.Overall HIV-MTCT rate was (15/549): 2.7% (CI: 1.3–4.1%); (7/93) 7.5% observed in AGYW against 1.7%; in women aged >24, p = 0.008. PP-MTCT was the predominant 9/15 (60%) route, followed by IP-MTCT 4/15 (26.6%), whereas IU and postnatal MTCT rates each contributed 6.7% of all infant infections. Postnatal MTCT incidence was 12.8 (CI: 0.3–71.4) infant HIV infections/100 child-years of breastfeeding; a rate 14 times higher than PP-MTCT rate in babies born to women HIV-infected pre/post-conception whose babies were HIV DNA PCR–negative at six weeks.Antenatal HIV RNA >1,000 copies/ml was independently associated with MTCT; odds ratio [CI: 9.3 (2.6–43.1)]. Infected infants’ pre–HIV treatment HIV RNA levels correlated positively with maternal viral load; Spearman’s rank correlation. r = 0.6; p = 0.03.DiscussionMothers were 9.3 times more likely to transmit if HIV RNA was >1,000 copies/ml, disproportionately occurring in vulnerable AGYW. Breastfeeding-associated PP-MTCT remains high; therefore, it is imperative that HIV-infected women commence antiretroviral therapy early in pregnancy to suppress HIV RNA until weaning to decrease the risk of MTCT and possibly reduce the severity of disease in infected infants. HIV-uninfected lactating mothers should be continuously counseled on the risks of postnatal seroconversion.www.clinicaltrials.gov, trial registration number: NCT04087239.

BackgroundAchieving and maintaining viral suppression (VS) in people living with HIV/AIDS on antiretroviral therapy (ART) remains a crucial clinical goal, more so in pregnancy to prevent mother-to-child-transmission (MTCT). There is a need to understand VS kinetics and barriers to achieving it in order to meet the target of eliminating HIV-MTCT by 2030.MethodsHIV-infected pregnant women ≥20 weeks of gestation with different durations of Tenofovir/Lamivudine/Efavirenz exposures seeking antenatal care services at four primary health centres in high-density residential areas in Harare, Zimbabwe were enrolled in the University of Zimbabwe Birth Cohort Study. Plasma viral load (VL) was quantified by reverse transcriptase–polymerase chain reaction. Demographic, clinical, socio-economic and HIV- and ART-related factors were tested in multivariable logistic regression analyses as potential predictors for VS and undetectable VL.ResultsFrom March 2016 to June 2019, 608 HIV-infected pregnant women were enrolled. 63 (10.4%) were self-reported-ART-naïve; 324 (53.3%) and 221 (36.3%) initiated ART pre- and post-conception, respectively. Time from ART initiation to VS (VL ≤ 1,000 copies/ml) in 95% of the women was 126 days. Overall lack of VS (VL > 1,000 copies/ml) was observed in 133 (21.9%) women being 76.2, 27.4 and 7.7% in self-reported-ART-naïve, post-conception and pre-conception groups, respectively. Undetectable VL (≤ 50 copies/ml) was observed in 371 (61.2%) and low-level viremia (51–1,000 copies/ml) in 102 (16.8%) women.In multivariable models for all participants regardless of ART exposure, being on ART was the strongest predictor for both VS and undetectable VL (odds ratio 95% confidence interval, OR (CI): 8.9(4.2–19.5) and 8.1(3.2–24.4), respectively). For women on ART, duration of ART use >126 days was the strongest predictor with OR (CI): 6.7(3.3–14.0) for VS and 8.5(5.6–13.1) for undetectable VL. Other relevant predictors for favourable virological outcomes were older maternal age, HIV-status disclosure, absence of ART side effects and self-reported depression. Having a spouse/intimate partner on ART predicted a 4 times higher likelihood for VS.DiscussionLack of VS was frequently observed in this Harare cohort of pregnant women, mainly due to new HIV diagnosis, hence not being on ART and suboptimal duration of ART exposure. Since VS for 95% of women needed about 4 months of ART exposure, eliminating HIV-MTCT will require timely screening and commencing women together with their spouses/intimate partners on ART before pregnancy or early after conception.Clinical Trial Registrationwww.ClinicalTrials.gov, identifier: NCT04087239.

Abstract Objectives Colonoscopy is the gold standard diagnostic test used to detect early colorectal lesions and prevent colorectal carcinoma. Narrow band imaging (NBI) is an imaging technique that provides improved image resolution of the mucosa during endoscopy. Whether NBI improves the detection of sessile serrated lesion (SSL) is controversial—our aim was to assess this during routine colonoscopy. Methods We conducted a multicenter, prospective, randomized, controlled trial. Patients underwent colonoscopy for screening, surveillance, or symptoms. They were randomized to either high‐definition white light (HD‐WL) or NBI in a 1:1 ratio. The primary outcome was SSL detection rate. Secondary outcomes were adenoma detection rate (ADR) and polyp detection rate (PDR). Results A total of 400 patients were randomized to NBI (N = 200) or HD‐WL (N = 200). The total colonoscopy time was slightly longer in the NBI group compared to HD‐WL (median time 14 vs. 12 min, p = 0.033). There were no statistically significant differences in SSL detection rate (7.5% NBI vs. 8.0% HD‐WL; p = 0.852), ADR (41.0% NBI vs. 37.5% HD‐WL; p = 0.531), or PDR (61.0% NBI vs. 54.0% HD‐WL; p = 0.157) between the two groups. No significant predictors of SSL detection were found on univariable or multivariable analysis. Increasing age and increased withdrawal time were an independent predictors of polyp detection and increasing age was also an independent predictor of adenoma detection on multivariable analysis. Conclusion In the hands of experienced colonoscopists, NBI does not improve SSL detection compared to HD‐WL. Withdrawal time and patient age remain important factors for polyp and adenoma detection.