Portacaval shunt causes apoptosis and liver atrophy in rats despite increases in endogenous levels of major hepatic growth factors

BACKGROUND/AIMS: The response to the liver damage caused by portacaval shunt (PCS) is characterized by low-grade hyperplasia and atrophy. To clarify mechanisms of this dissociation, we correlated the expression of 'hepatotrophic factors' and the antihepatotrophic and proapoptotic peptide, transforming growth factor (TGF)-beta, with the pathologic changes caused by PCS in rats. METHODS: PCS was created by side-to-side anastomosis between the portal vein and inferior vena cava, with ligation of the hilar portal vein. Hepatic growth mediators were measured to 2 months. RESULTS: The decrease in the liver/body weight ratio during the first 7 days which stabilized by day 15, corresponded to parenchymal cell apoptosis and increases in hepatic TGF-beta concentration that peaked at 1.4 x baseline at 15 days before returning to control levels by day 30. Variable increases in the concentrations of growth promoters (hepatocyte growth factor, TGF-alpha and augmenter of liver regeneration) also occurred during the period of hepatocellular apoptosis. CONCLUSIONS: The development of hepatic atrophy was associated with changes in TGF-beta concentration, and occurred despite increased expression of multiple putative growth promoters. The findings suggest that apoptosis set in motion by TGF-beta constrains the amount of hepatocyte proliferation independently from control of liver volume.     

Differences in fetal growth, discordancy, and placental pathology in reduced versus nonreduced twins

This study evaluated the effect of multifetal pregnancy reduction on the incidence of small for gestational age (SGA) and discordance in reduced versus nonreduced twins and differences in placental pathology. A computerized ultrasound database was used to identify diamniotic-dichorionic twins who delivered at our institution. Reduced (n = 36) versus nonreduced twins (n = 243) were compared for differences in rates of SGA and discordancy (>or= 20%.) The groups were compared for differences in maternal and neonatal characteristics, as well as differences in placental pathology. Chi-square tests were used to compare differences in means. Stepwise logistic regression was used to adjust for potential confounders including placental pathology. The rate of SGA in either twin A or B remained nonsignificant after adjustment for the use of assisted reproductive technology and gestational age at delivery in the stepwise logistic model (odds ratio, 1.7 95%; confidence interval, 0.5, 5.2). The average discordance at delivery was 12.4% in reduced versus 11.4% in the nonreduced twins ( P = 0.54). We found no overall differences in placental pathology between the two groups. Reduced and nonreduced twins have no significant differences in SGA fetuses, growth discordancy, or placental pathology.     

Effect of COVID-19 lockdown on the pathway of care and treatment outcome among patients with tuberculosis in a rural part of northern India: a community-based study

Objectives: The coronavirus disease 2019 (COVID-19) pandemic affected routine healthcare services across all spectra, and tuberculosis (TB) care under the National Tuberculosis Elimination Program have been affected the most. However, evidence available at the community level is minimal. The clinical features, care cascade pathway, and treatment outcomes of TB patients pre- and during/post-COVID-19 pandemic lockdown in a rural community health block in northern India were assessed and compared.Materials and Methods: This was a retrospective cohort study that included all patients diagnosed with TB and initiated treatment under programmatic settings between January 1 and June 30, 2020, in a rural TB unit in northern India. The periods from January 1 to March 23 and March 24 to June 30 were marked as pre-lockdown and during/post-lockdown, respectively.Results: A total of 103 patients were diagnosed and treated for TB during the study period. A significantly higher proportion of pulmonary TB cases were reported during/post-lockdown (43, 82.7%) compared to that pre-lockdown (32, 62.7%), and a higher diagnostic delay was noted during/post-lockdown (35, 81.4%). Through adjusted analysis, patients diagnosed during/post-lockdown period (adjusted risk ratio [aRR], 0.85; 95% confidence interval [CI], 0.73–0.98) and previously treated (aRR, 0.77; 95% CI, 0.60–0.995) had significantly lower favorable treatment outcomes.Conclusions: The symptom and disease (pulmonary/extrapulmonary) pattern have changed during/post-lockdown. The care cascade delays are still high among TB patients, irrespective of the lockdown status. Lockdown had a significant adverse impact on the outcomes of TB treatment.     

Original research: Widespread gaps in the quality of care for primary biliary cholangitis in UK

ObjectivePrimary biliary cholangitis (PBC) is a progressive, autoimmune, cholestatic liver disease affecting approximately 15 000 individuals in the UK. Updated guidelines for the management of PBC were published by The European Association for the Study of the Liver (EASL) in 2017. We report on the first national, pilot audit that assesses the quality of care and adherence to guidelines.DesignData were collected from 11 National Health Service hospitals in England, Wales and Scotland between 2017 and 2020. Data on patient demographics, ursodeoxycholic acid (UDCA) dosing and key guideline recommendations were captured from medical records. Results from each hospital were evaluated for target achievement and underwent χ² analysis for variation in performance between trusts.Results790 patients’ medical records were reviewed. The data demonstrated that the majority of hospitals did not meet all of the recommended EASL standards. Standards with the lowest likelihood of being met were identified as optimal UDCA dosing, assessment of bone density and assessment of clinical symptoms (pruritus and fatigue). Significant variations in meeting these three standards were observed across UK, in addition to assessment of biochemical response to UDCA (all p<0.0001) and assessment of transplant eligibility in high-risk patients (p=0.0297).ConclusionOur findings identify a broad-based deficiency in ‘real-world’ PBC care, suggesting the need for an intervention to improve guideline adherence, ultimately improving patient outcomes. We developed the PBC Review tool and recommend its incorporation into clinical practice. As the first audit of its kind, it will be used to inform a future wide-scale reaudit.     

Impact of a structured training program to enhance skills in phacoemulsification surgery

Purpose:The aim of this study was to determine whether the introduction of a structured short-term phacoemulsification training program improved the ICO-OSCAR (International Council of Ophthalmology’s Ophthalmology Surgical Competency Assessment Rubric) score and the learning curve of the trainees and decreased the complication rates of the cases.Methods:This study was a retrospective, observational study conducted in a tertiary eye care hospital in India. The study was conducted from March 2018 to October 2019 based on a structured phacoemulsification training program introduced in January 2019. The trainees enrolled in the phacoemulsification training program were divided into two groups: Group 1 (n = 33), who underwent training before the introduction of the structured program, and Group 2 (n = 29), who underwent the training after the introduction of the structured training program. Each trainee performed 20 cases. Group 1 training consisted of wet-lab and phacoemulsification surgeries. Group 2 training program comprised three modules over 5 weeks and a preassessment examination. Premodule 1 imparted cognitive skills; Module 1 was on structured wet-lab, Module 2 was about phacoemulsification step surgery, and Module 3 had independent complete surgeries. Group 2 also underwent compulsory Observation of cases being performed in the operation theater, surgical video recording review, and formative feedback. Mean OSCAR score comparison was done for both the groups. The OSCAR score was also calculated case-wise to obtain the learning curve with respect to the entry and exit levels, by classifying the trainees in each group as Novice, Beginner, Advanced Beginner, or Competent. A comparison of the posterior capsular rupture (PCR) rates and vision at discharge of all the cases was done.Results:Group 2 had a significantly better mean OSCAR score than Group 1 (4.03 and 3.43, respectively; P < 0.001). The PCR rate of the cases was significantly lower in Group 2 than in Group 1 (9.14% and 20.30%, respectively; P < 0.001). Group 2 had a significantly better visual acuity outcome of the cases than Group 1. Group 1 started as Novice (OSCAR score: 2), whereas Group 2 started as Beginner (OSCAR score: 3). Group 2 reached the Advanced Beginner level eight to 10 cases prior to Group 1.Conclusion:A structured training curriculum can make a significant difference in the training experience of the trainees and enable better surgical outcomes and a decrease in the complication rates.     

Optimizing infant HIV diagnosis with additional screening at immunization clinics in three sub‐Saharan African settings: a cost‐effectiveness analysis

IntroductionUptake of early infant HIV diagnosis (EID) varies widely across sub‐Saharan African settings. We evaluated the potential clinical impact and cost‐effectiveness of universal maternal HIV screening at infant immunization visits, with referral to EID and maternal antiretroviral therapy (ART) initiation.MethodsUsing the CEPAC‐Pediatric model, we compared two strategies for infants born in 2017 in Côte d’Ivoire (CI), South Africa (SA), and Zimbabwe: (1) existing EID programmes offering six‐week nucleic acid testing (NAT) for infants with known HIV exposure (EID), and (2) EID plus universal maternal HIV screening at six‐week infant immunization visits, leading to referral for infant NAT and maternal ART initiation (screen‐and‐test). Model inputs included published Ivoirian/South African/Zimbabwean data: maternal HIV prevalence (4.8/30.8/16.1%), current uptake of EID (40/95/65%) and six‐week immunization attendance (99/74/94%). Referral rates for infant NAT and maternal ART initiation after screen‐and‐test were 80%. Costs included NAT ($24/infant), maternal screening ($10/mother–infant pair), ART ($5 to 31/month) and HIV care ($15 to 190/month). Model outcomes included mother‐to‐child transmission of HIV (MTCT) among HIV‐exposed infants, and life expectancy (LE) and mean lifetime per‐person costs for children with HIV (CWH) and all children born in 2017. We calculated incremental cost‐effectiveness ratios (ICERs) using discounted (3%/year) lifetime costs and LE for all children. We considered two cost‐effectiveness thresholds in each country: (1) the per‐capita GDP ($1720/6380/2150) per year‐of‐life saved (YLS), and (2) the CEPAC‐generated ICER of offering 2 versus 1 lifetime ART regimens (e.g. offering second‐line ART; $520/500/580/YLS).ResultsWith EID, projected six‐week MTCT was 9.3% (CI), 4.2% (SA) and 5.2% (Zimbabwe). Screen‐and‐test decreased total MTCT by 0.2% to 0.5%, improved LE by 2.0 to 3.5 years for CWH and 0.03 to 0.07 years for all children, and increased discounted costs by $17 to 22/child (all children). The ICER of screen‐and‐test compared to EID was $1340/YLS (CI), $650/YLS (SA) and $670/YLS (Zimbabwe), below the per‐capita GDP but above the ICER of 2 versus 1 lifetime ART regimens in all countries.ConclusionsUniversal maternal HIV screening at immunization visits with referral to EID and maternal ART initiation may reduce MTCT, improve paediatric LE, and be of comparable value to current HIV‐related interventions in high maternal HIV prevalence settings like SA and Zimbabwe.     

Health Care Surrogacy Laws Do Not Adequately Address the Needs of Minors

A couple and their five-year-old daughter are in a car accident. The parents are not expected to survive. The child is transported to a children's hospital, and urgent treatment decisions must be made. Whom should the attending physician approach to make decisions for the child? When such cases arise in, for example, the hospitals where we work, the social worker or chaplain is instructed to use the Illinois Health Care Surrogacy Act as a guidepost to identify a decision-maker. But in our state and the country overall, the limitations of such statutes leave hospital workers to make a judgment call among friends, family, and clergy who may come forward. While surrogate decision-making statutes comprehensively address surrogate decision-makers for adults, a patchwork of laws—permanency statutes, kinship provider statutes, standby guardianship statutes, and, in some cases, surrogate decision-making statutes—provide variable decision-making pathways for children.