Acute on chronic liver failure because of acute hepatic insults: Etiologies, course, extrahepatic organ failure and predictors of mortality.

BACKGROUND AND AIM: Acute on chronic liver failure (ACLF) because of precipitating factors (variceal bleed/infections) identifies cirrhotics at risk for high short-term mortality. Information on ACLF because of acute hepatic insults is lacking. The aim of the study was to evaluate acute hepatic insults in ACLF and their effect on the course and outcome. METHODS: In a prospective study, 213 consecutive patients of ACLF because of acute hepatic insults were included. Etiology of acute hepatic insult, frequency of silent, and overt chronic liver disease (CLD), organ failure (OF), and outcomes were assessed. Prognostic models such as model for endstage liver disease (MELD), acute physiology and chronic health evaluation (APACHE II), and chronic liver failure-sequential organ failure (CLIF-SOFA) were evaluated. RESULTS: Etiologies of acute hepatic insult were hepatitis virus(es)- 81 (38%; HBV-42, HEV-39), continuous alcohol consumption-77 (33.3%), antituberculosis drugs-11 (5.2%), autoimmune hepatitis flare-5(2.3%), cryptogenic-44 (20.7%). The common causes of CLD were alcohol (n = 85/40%), HBV(n = 52/24%), and cryptogenic(n = 50/20%). The MELD, APACHE II, and CLIF-SOFA scores were similar among silent and overt CLD and did not influence outcome. Predominant etiologies of ACLF were hepatitis virus(es) reactivation or superinfection in silent CLD(52/112, 46.4%) and alcohol among overt CLD(43/101, 43%). Independent predictors of mortality included hepatic-encephalopathy (early, HR: 4.01; advanced, HR: 6.10), serum creatinine ≥1.5 mg/dl (HR: 4.53), CLIF-SOFA ≥8(HR: 1.69), and etiology of acute hepatic insult (alcohol, HR: 4.08; cryptogenic, HR: 3.18). HEV-ACLF had lower mortality (12.8% vs. 33-54% in other etiologies;P < 0.001). OF was major determinant of mortality. With increasing number of OF, mortality increased linearly(P = 0.001). CONCLUSIONS: Hepatitis virus(es) and continuous alcohol consumption are important causes of ACLF caused by acute hepatic insults. HEV-ACLF has lower mortality. OF is an important prognostic predictor.

Demographic profile, host, disease & viral predictive factors of response in patients with chronic hepatitis C virus infection at a tertiary care hospital in north India.

BACKGROUND & OBJECTIVES: Standard of care for chronic hepatitis C (CHC) in India is peginterferon and ribavirin (RBV). The response to treatment in real life stetting is unclear. The objectives of this study were to evaluate the demographic profile and assess the virological response and predictors of response in CHC patients. METHODS: Consecutive patients with CHC were included in this study. Detailed clinical history, risk factors, and predictive factors of response were noted. Patients were treated with peginterferon α2b (1.5 µg/kg/wk) and RBV (12 mg/kg/day) for 6 to 18 months based on response. RESULTS: A total of 211 patients were included in the analysis, mean age 40.6±12.3 yr, 144 (68%) were males and 71 (34%) had compensated cirrhosis. Commonest risk factor for acquiring CHC was previous transfusion and surgery (51%). Genotype 3 (72%) was most common followed by genotype 1 (23%). Overall sustained virologic response (SVR) was 64 per cent [95% CI 57.1%-70.4%]. The SVR was 66.5 per cent [95% CI 58.34-73.89%] for genotype 3 and 61.2 per cent [95% CI 46.23 to 74.80%] for genotype 1. Non-cirrhotics had better SVR rates compared to cirrhotics (76 vs 41%, p<0.001). On multivariate analysis, BMI ≥23 kg/m2, HOMA-IR ≥2, compliance (≤80%), and fibrosis >2 were predictors of low SVR. INTERPRETATION & CONCLUSIONS: Genotype 3 was the commonest HCV genotype. The commonest source of infection was previous transfusion and surgery. SVR rates for genotypes 3 were better than genotype 1 patients. Predictors of non-response were high BMI, insulin resistance, significant fibrosis and inadequate compliance.

Recombinant Hepatitis E virus like particles can function as RNA nanocarriers.

BACKGROUND: Assembled virus-like particles (VLPs) without genetic material, with structure similar to infectious virions, have been successfully used as vaccines. We earlier described in vitro assembly, characterisation and tissue specific receptor dependent Clathrin mediated entry of empty HEV VLPs, produced from Escherichia coli expressed HEV capsid protein (pORF2). Similar VLP's have been described as a potential candidate vaccine (Hecolin) against HEV. FINDINGS: We have attempted to use such recombinant assembled Hepatitis E virus (HEV) VLPs as a carrier for heterologous RNA with protein coding sequence fused in-frame with HEV 5' region (containing cap and encapsidation signal) and investigated, if the relevant protein could be expressed and elicit an immune response in vivo. In vitro transcribed red fluorescent protein (RFP)/Hepatitis B virus surface antigen (HBsAg) RNA, fused to 5'-HEV sequence with cap and encapsidation signal (1-249 nt), was packaged into the recombinant HEV-VLPs and incubated with five different cell lines (Huh7, A549, Vero, HeLa and SiHa). The pORF2-VLPs could specifically transfer exogenous coding RNA into Huh7 and A549 cells. In vivo, Balb/c mice were immunized (intramuscular injections) with 100 µg pORF2-VLP encapsidated with 5'-methyl-G-HEV (1-249 nt)-HBsAg RNA, blood samples were collected and screened by ELISA for anti-pORF2 and anti-HBsAg antibodies. Humoral immune response could be elicited in Balb/c mice against both HEV capsid protein and cargo RNA encoded HBsAg protein. CONCLUSIONS: These findings suggest that other than being a possible vaccine, HEV pORF2-VLPs can be used as a promising non-replicative tissue specific gene delivery system.

Hepatitis E virus (HEV) protease: a chymotrypsin-like enzyme that processes both non-structural (pORF1) and capsid (pORF2) protein.

Hepatitis E virus (HEV), a major cause of acute viral hepatitis across the world, is a non-enveloped, plus-strand RNA virus. Its genome codes three proteins, pORF1 (multifunctional polyprotein), pORF2 (capsid protein) and pORF3 (multi-regulatory protein). pORF1 encodes methyltransferase, putative papain-like cysteine protease, helicase and replicase enzymes. Of these, the protease domain has not been characterized. On the basis of sequence analysis, we cloned and expressed a protein covering aa 440-610 of pORF1, expression of which led to cell death in Escherichia coli BL-21 and Huh7 hepatoma cells. Finally, we expressed and purified this protein from E. coli C43 cells (resistant to toxic proteins). The refolded form of this protein showed protease activity in gelatin zymography. Digestion assays showed cleavage of both pORF1 and pORF2 as observed previously. MS revealed digestion of capsid protein at both the N and C termini. N-terminal sequencing of the ~35 kDa methyltransferase, ~35 kDa replicase and ~56 kDa pORF2 proteins released by protease digestion revealed that the cleavage sites were alanine15/isoleucine16, alanine1364/valine1365 in pORF1 and leucine197/valine198 in pORF2. Specificity of these cleavage sites was validated by site-directed mutagenesis. Further characterization of the HEV protease, carried out using twelve inhibitors, showed chymostatin and PMSF to be the most efficient inhibitors, indicating this protein as a chymotrypsin-like protease. The specificity was further confirmed by cleavage of the chymotrypsin-specific fluorogenic peptide N-succinyl-Leu-Leu-Val-Tyr-7-amido-4-methylcoumarin. Mutational analysis of the conserved serine/cysteine/histidine residues suggested that H443 and C472/C481/C483 are possibly the active site residues. To our knowledge, this is the first direct demonstration of HEV protease and its function.

A Cross-Sectional Observational Study Analyzing the Knowledge, Attitude, and Practice of Young Female Nursing Officers and Female Doctors About the Human Papillomavirus Vaccine.

Background Cervical cancer (CC) is the second most common cancer among Indian women and is caused by a human papillomavirus (HPV) infection. To achieve its global commitment to the elimination of CC, India is planning to include the HPV vaccine in its national immunization program. The success of the prevention of CC mostly depends on the level of awareness and knowledge among healthcare providers about different aspects of the disease and the vaccine. We aimed to evaluate the knowledge, attitudes, and practices (KAP) regarding CC, HPV, and the HPV vaccine in first-contact young female doctors and nursing officers. Methodology This cross-sectional study was conducted at the All India Institute of Medical Sciences, Kalyani, between February and June 2024 among young female health workers aged between 20 and 35 years. To evaluate KAP we used a validated, self-administered questionnaire. Results There were a total of 204 participants, whose median age was 26 (interquartile range = 25 to 29) years; among them, 114 (55.9%) were nursing officers and 90 (44.1%) were junior doctors. Good knowledge was found among 85.5% of doctors and 70.2% of nursing officers (p < 0.01). A positive attitude was found in 81.1% of doctors and 67.5% of nursing officers (p < 0.01). The overall good practice score was low (31.3%). A higher level of education was associated with good knowledge (ß = -1.16, 95% confidence interval (CI) = -1.76, -0.55, p < 0.01) and positive attitude (ß = -0.53, 95% CI = -0.9, 0.16, p = 0.005) toward HPV, CC, and the HPV vaccine. Conclusions Our cohort showed good knowledge and attitude toward CC, HPV, and the HPV vaccine, but poor HPV vaccine uptake and practice. Therefore, health education programs focused on increasing awareness and uplifting confidence are needed to accept and recommend the HPV vaccine in developing countries like India.

Fibroscan can avoid liver biopsy in Indian patients with chronic hepatitis B.

BACKGROUND AND AIM: Liver fibrosis is an established determinant of prognosis and therapy in chronic hepatitis B (CHB). The role of fibroscan in assessing fibrosis in CHB remains unclear. Present study was designed to correlate fibroscan with liver biopsy and determine whether fibroscan can avoid liver biopsy in patients with CHB. METHODS: Fibroscan and liver biopsy were performed in 382 consecutive patients with CHB. Biopsies were reviewed by pathologist blinded to the fibroscan value. Discriminant values of liver stiffness measurement (LSM) to reasonably exclude and predict significant fibrosis were calculated from receiver operating characteristic (ROC) curves. The factors affecting LSM independent of fibrosis were assessed. RESULTS: Three hundred fifty-seven patients were included (mean age 30.1 ± 9.7 years, male : female 17 : 3). There was significant correlation between LSM and histological fibrosis (r = 0.58, P < 0.001). The area under ROC curve of LSM for significant fibrosis (F0-1 vs. F2-4), bridging fibrosis (F0-2 vs. F3-4), and cirrhosis (F0-3 vs. F4) was 0.84 (95% CI: 0.78-0.89), 0.94 (95% CI: 0.89-0.99), and 0.93 (95% CI: 0.85-1.00), respectively. LSM < 6.0 KPa could exclude significant (F ≥ 2) and bridging fibrosis (F ≥ 3) with a negative predictive value (NPV) of 92.4% and 99.5%, respectively. Cut-off of 9 KPa could detect significant (F ≥ 2) and bridging fibrosis (F ≥ 3) with specificity of 95% and 97%, respectively, and had a positive predictive value (PPV) of 84.3% in predicting significant fibrosis. LSM < 6 KPa and > 9 KPa matched with histological fibrosis in 227/250 (91%) patients. Therefore, fibroscan could avoid liver biopsy in 70% (250/357) patients with an accuracy > 90%. Histological fibrosis, ALT > 5 times, and age > 40 years were independent determinants of increased liver stiffness. CONCLUSIONS: Fibroscan accurately assessed fibrosis and could avoid liver biopsy in more than two-thirds of patients with CHB.

Role of hepatitis B virus genotype D & its mutants in occult hepatitis B infection.

BACKGROUND & OBJECTIVES: Non-detection of hepatitis B virus (HBV) envelope protein (hepatitis B surface antigen, HBsAg) in a chronically HBV infected individual has been described as occult infection. One possible reason for this phenotype is alteration in large (L-HBsAg) to small (S-HBsAg) envelope protein ratio associated with reduced or non secretion of HBsAg. This results in quantitative levels of serum HBsAg below the detection limit of enzyme immunoassays. Genotype D of HBV has a characteristic 33 nucleotide (nt) deletion upstream of the pre-S2/S promoter. This deletion may reduce HBsAg secretion in occult infection patients infected with genotype D HBV. Additional deletions in the pre-S2/S promoter may further aggravate reduced HBsAg secretion in patients infected with genotype D HBV. Thus, the aim of the present study was to determine the role of genotype D specific 33nt deletion and additional pre-S2/S promoter deletions in causing reduced or no secretion of HBsAg, in occult infection. Since these deletions overlap virus polymerase, their effect on virus replication was also investigated. METHODS: We examined the in vitro expression of HBsAg, ratio of cure and 'e' antigen (HBcAg/HBeAg), their secretion and virus replication, using overlength 1.3 mer/1.86 mer genotype A replicons, and genotype D replicons with and without additional pre-S2/S promoter deletions from cases of occult infection. RESULTS: Genotype D replicon showed a decrease in HBsAg secretion compared to the wild-type genotype A. Genotype D replicons carrying additional pre-S2/S promoter deletions, showed further reduction in HBsAg secretion, demonstrated presence of intracellular HBcAg/HBeAg, virus replication intermediates and 'e' antigen secretion. INTERPRETATION & CONCLUSIONS: The characteristic 33 nt deletion of genotype D HBV reduces HBsAg secretion. Additional pre-S2/S promoter deletions may further diminish HBsAg secretion, leading to occult infection. Pre-S2/S promoter deletions do not affect HBV replication.

Prospective derivation and validation of early dynamic model for predicting outcome in patients with acute liver failure.

OBJECTIVE: It is difficult to predict the outcome in patients with acute liver failure (ALF) using existing prognostic models. This study investigated whether early changes in the levels of dynamic variables can predict outcome better than models based on static baseline variables. DESIGN: 380 patients with ALF (derivation cohort n=244, validation cohort n=136) participated in a prospective observational study. The derivation cohort was used to identify predictors of mortality. The ALF early dynamic (ALFED) model was constructed based on whether the levels of predictive variables remained persistently high or increased over 3 days above the discriminatory cut-off values identified in this study. The model had four variables: arterial ammonia, serum bilirubin, international normalised ratio and hepatic encephalopathy >grade II. The model was validated in a cohort of 136 patients with ALF. RESULTS: The ALFED model demonstrated excellent discrimination with an area under the receiver operator characteristic curve of 0.91 in the derivation cohort and of 0.92 in the validation cohort. The model was well calibrated in both cohorts and showed a similar increase in mortality with increasing risk scores from 0 to 6. The performance of the ALFED model was superior to the King's College Hospital criteria and the Model for End stage Liver Disease score, even when their 3-day serial values were taken into consideration. An ALFED score of ≥4 had a high positive predictive value (85%) and negative predictive value (87%) in the validation cohort. CONCLUSION: The ALFED model accurately predicted outcome in patients with ALF, which may be useful in clinical decision-making.

Unveiling Preeclampsia Prognosis: Uterine Artery Doppler Indices in Low-Risk Pregnancies.

Background Anticipating preeclampsia's onset is pivotal in mitigating adverse maternal and perinatal outcomes. This study aims to prognosticate preeclampsia within low-risk pregnancies by evaluating uterine artery Doppler indices within the 14-28 week gestation. Methodology An observational cohort comprising 360 low-risk pregnancies (14-28 weeks gestation) underwent serial uterine artery Doppler assessments at 14-20 and 20-28 weeks. Follow-up was extended to delivery to detect preeclampsia incidence. Results Among 360 participants, 56 (15.5%) developed preeclampsia. Sensitivity values for resistance index (RI), pulsatility index (PI), and bilateral notching were 17.6%, 56.25%, and 71%, respectively, during 14-20 weeks. Similarly, during 20-28 weeks, sensitivities for RI, PI, and bilateral notching were 16.6%, 36.8%, and 55.5%, respectively, with specificity exceeding 90%. Notch depth index (NDI) >0.14 emerged as a better predictor of preeclampsia between both intervals (area under the curve = 0.686 and 0.646). Conclusions Bilateral notching during 14-20 weeks and NDI >0.14 within 14-20 and 20-28 weeks indicate preeclampsia susceptibility in low-risk pregnancies. Conversely, uterine artery Doppler indices at 14-28 weeks effectively rule out preeclampsia development, exhibiting a specificity of >90%.

Persistent hyperammonemia is associated with complications and poor outcomes in patients with acute liver failure.

BACKGROUND & AIMS: Patients admitted to the hospital with acute liver failure (ALF) and high arterial levels of ammonia are more likely to have complications and poor outcomes than patients with lower levels of ammonia. ALF is a dynamic process; ammonia levels can change over time. We investigated whether early changes (first 3 days after admission) in arterial levels of ammonia were associated with complications and outcomes and identified factors associated with persistent hyperammonemia. METHODS: We performed a prospective observational study that measured arterial ammonia levels each day for 5 days in 295 consecutive patients with ALF. We analyzed associations of changes in ammonia levels during the first 3 days with complications and outcomes. RESULTS: Patients with persistent arterial hyperammonemia (≥122 µmol/L for 3 consecutive days), compared with those with decreasing levels, had lower rates of survival (23% vs 72%; P < .001) and higher percentages of cerebral edema (71% vs 37%; P < .001), infection (67% vs 28%; P = .003), and seizures (41% vs 7.7%; P < .001). Patients with persistent hyperammonemia had greater mortality, with an odds ratio (OR) of 10.7, compared with patients with baseline levels of ammonia ≥122 µmol/L (OR, 2.4). Patients with persistent hyperammonemia were more likely to progress to and maintain advanced hepatic encephalopathy than those with decreasing levels. Patients with persistent, mild hyperammonemia (≥85 µmol/L for 3 days) were also more likely to have complications or die (P < .001) than patients with serial ammonia levels <85 µmol/L. Infections (OR, 4.17), renal failure (OR, 2.20), and decreased arterial pH (OR, 0.003) were independent predictors of persistent hyperammonemia. CONCLUSIONS: Patients with ALF and persistent arterial hyperammonemia for 3 days after admission are more likely to develop complications and have greater mortality than patients with decreasing levels or high baseline levels. Infection, renal failure, and decreased arterial pH are independent predictors of persistent hyperammonemia.

Effect of addition of short course of prednisolone to gluten-free diet on mucosal epithelial cell regeneration and apoptosis in celiac disease: a pilot randomized controlled trial.

BACKGROUND: Identification of adjuvant treatment is necessary for rapid and effective treatment in patients with celiac disease. In a pilot randomized controlled trial, the effect of prednisolone on enterocyte apoptosis and regeneration in celiac disease was investigated. PATIENTS AND METHODS: Thirty-three treatment-naïve patients with celiac disease were randomized to either gluten-free diet (GFD, n = 17) or GFD + prednisolone (1 mg/kg for 4 weeks, n = 16). Duodenal biopsies were taken at baseline and at 4 and 8 weeks posttreatment. Six patients with functional dyspepsia were recruited as controls. All these biopsies were stained for markers of intrinsic apoptotic pathway (AIF, H2AX, p53), common apoptotic pathway (CC3, M30), apoptotic inhibitors (XIAP, Bcl2), and epithelial proliferation (Ki-67). Apoptotic (AI) and proliferation indices (PI) were compared. RESULTS: At baseline duodenal biopsies, the end apoptotic products H2AX and M30 were significantly increased. In comparison with those treated with GFD alone, after 4 weeks of GFD + prednisolone treatment, some markers of both intrinsic and common apoptotic pathways showed rapid decline. After prednisolone withdrawal, there was overexpression of H2AX, CC3, and p53 in the latter group. In comparison with those treated with only GFD, patients treated with prednisolone showed suppression of mucosal PI, which started rising again after withdrawal of prednisolone. CONCLUSIONS: Apoptosis takes place in mucosal epithelium in celiac disease. Addition of short course of prednisolone suppresses apoptosis rapidly. However, it also suppresses epithelial regeneration; hence, if used, it should be withdrawn after an initial short course.

Association of pro-inflammatory cytokines, adipokines & oxidative stress with insulin resistance & non-alcoholic fatty liver disease.

BACKGROUND & OBJECTIVES: The cytokines, adipokines, and oxidative stress have been implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD); however, such data remain scarce in India. The present study evaluated pro-inflammatory cytokines, adipokines, and markers of oxidative stress in patients with non-alcoholic fatty liver disease (NAFLD), and their association with degree of adiposity, insulin resistance and markers of disease severity. METHODS: The present prospective cross-sectional pilot study included 79 subjects; 34 NAFLD, 22 chronic hepatitis B (CH-B) and 23 healthy controls (HC). The parameters studied were adiponectin, leptin, tumour necrosis factor α (TNFα), interleukin-1 and 6 (IL-1, IL-6), and systemic markers of oxidative stress. RESULTS: The mean body mass index (kg/m 2 ) in NAFLD patients, CHB, and HC were 26.4±3.7, 21.3±2.3, and 22.3±2.7, respectively. The median serum levels of all pro-inflammatory cytokines were significantly higher (P<0.001) in NAFLD compared to control groups. Compared to HC, levels of adiponectin and leptin were significantly (P<0.05, P<0.01) reduced in both NAFLD and CHB. IL-6 showed marked and selective increase only in NAFLD patients. The levels of IL-6 were significantly (P<0.02) higher in NAFLD patients with advanced histology grade and correlated with IR (r=0.42, P=0.02). In a sub-group, markers of oxidative stress were significantly higher, and that of antioxidant potential were significantly lower among NAFLD patients compared to control subjects. INTERPRETATION & CONCLUSIONS: Patients with NAFLD revealed significantly elevated levels of pro-inflammatory cytokines, increased oxidative stress, and a significant association of IL-6 with IR and advanced histopathology.

A rare case of misoprostol hypersensitivity.

Medical abortion using mifepristone-misoprostol regimen has been considered to be a safe and effective method for pregnancy termination. Misoprostol is a frequently used well tolerated drug with mild and transient side effects. Considering the safety profile mifepristone-misoprostol regimen has also been advocated by many for home-based medical abortion. However, we report herein a rare case of hypersensitivity reaction to sublingual misoprostol administered for first trimester medical abortion, where timely diagnosis and prompt intervention prevented life-threatening airway obstruction. The possibility of such rare event should be kept in mind and included in patient counselling and information especially for those who opt for outpatient abortion care so that they can seek medical help at the earliest.

Maternal mortality and predictors of adverse outcome in patients with heart disease in pregnancy.

Introduction: Heart disease in pregnancy possesses a great haemodynamic challenge and is a known risk for increased maternal morbidity and mortality. The functional status of the patient is one of the most significant parameters which can impact the feto-maternal outcome. Many predictors have been studied and compiled in various scoring systems time and again. The most updated and validated is the modified WHO classification, according to which the presence of pulmonary artery hypertension (PAH) and severe ventricular dysfunction (ejection fraction <30%) mandates the patient to be under class IV, which along with another important risk factor, i.e., New York heart association (NYHA) class, is revaluated under the present study. The objective of this study is to examine three of the most important predictors of adverse outcomes, i.e., functional status (NYHA class), PAH, and left ventricular ejection fraction (LVEF) in patients with heart disease in pregnancy. Methods: It's a prospective study from January 2016 to August 2017 wherein pregnant patients with heart disease were divided on the basis of NYHA class, PAH, and LVEF, and the feto-maternal outcome was recorded and evaluated in terms of maternal mortality, fetal demise, the occurrence of major cardiac complication, and risk of preterm delivery. Results: A total of three out of 29 (10.34%) maternal deaths were attributed to a cardiac cause. 5.45% of patients with heart disease had maternal mortality, which is in contrast to the 1.12% maternal mortality rate in general at our centre. Three out of 17 (17.64%) patients in NYHA classes 3 and 4 ended in maternal deaths, while there were no mortalities in classes 1 and 2. Intrauterine fetal demise (23.52%), risk of preterm delivery (relative risk = 0.4688; 95% CI: 0.2320 to 0.9470) was significantly higher in patients belonging to NYHA classes 3 and 4 as compared to those in classes 1 and 2. All of the ten (100%) patients who developed cardiac complications belonged to classes 3 and 4. The percentage of abortions (20.00%), intra uterine fetal demise (IUFD) (40.00%), and cardiac complication (80%) in patients with LVEF <44% were significantly more than in patients with better ejection fraction. Pulmonary artery systolic pressure (PASP) ≥ is associated with higher maternal mortality, a greater number of abortions and IUFD (22.62%), cardiac complication (22.72%), and increased risk of preterm birth (0.5769; 95% CI: 0.2801 to 1.188), but these associations are not found to be significant. Conclusion: NYHA class was found to be a very strong predictor followed by left ventricular ejection fraction for poor outcome. Maternal mortality in asymptomatic patients or patients with mild symptoms (NYHA classes 1 and 2) is comparable to that found in the general population. However, pulmonary artery systolic pressure is not found to be significantly associated with worse outcomes in our study.

Amniotic Fluid Embolism After First-Trimester Abortion.

Amniotic fluid embolism (AFE) may be a rare event in pregnancy, especially after a first-trimester medical termination of pregnancy (MTP). A 35-year-old G3P2L2 came to our outpatient department at six weeks of pregnancy for medical termination of pregnancy and bilateral tubal ligation. After around one hour of surgery, she developed respiratory distress with abdominal distension, hypotension, tachycardia and tachypnoea. On laparotomy, we found ascitic fluid, bowels with petechia, and oozing all over the wounds. Finally, within 24 hours of surgery, she expired. Strong clinical suspicion of AFE should prompt a multidisciplinary team including anaesthesia, respiratory therapy, critical care, and maternal-foetal medicine to be involved in the ongoing care of women with AFE.

An Unusual Case of Retained Foreign Body in the Vagina With Vaginal Fibrosis.

Vaginal foreign bodies can cause long haul, foul-smelling vaginal discharge and vaginal bleeding and are typically found in female youngsters while looking into vaginitis and urinary tract diseases. There are many causes for vaginal discharges. Among them, vaginal foreign bodies are uncommon but not a very rare presentation. We had a case of a 49-year-old female, a widow, with para 2 living 2 and a history of menopause since three years; she was referred from a district hospital with a diagnosis of carcinoma of the cervix and was later found to have a foreign body, which was removed surgically through the vagina. A foreign body in the vagina is usually seen in children than in adults. Foreign bodies are inserted vaginally for treatment purposes, contraception, induced abortion, and sexual stimulation in adults. Here, we report a case of retained vaginal foreign body with vaginal fibrosis.

Teaching and Learning Medical Professionalism: an Input from Experienced Faculty and Young Graduates in a Tertiary Care Institute.

Introduction: Medical professionalism is of paramount importance especially in today's day and age. This study gives an insight on the preferred methods of teaching and learning professionalism among the young MBBS graduates and experienced faculty in a medical teaching institute. Material and methods: This was an observational study conducted in the Department of Obstetrics and Gynaecology from January 2019 to January 2020. It included 60 interns and 60 faculty members, who were interviewed for nine different methods of teaching and learning professionalism: (a) professional role model; (b) early clinical exposure; (c) recruiting faculty who had compressive training in medical education before joining the medical institute; (d) teaching and assessing communication skills to each student; (e) conducting seminar, didactic lecture and small group discussion; (f) reflective practice; (g) mentorship; (h) faculty development programme; (i) hidden curriculum. Each participant's response was analyzed using Wilcoxon rank-sum test on SPSS software version 22. Results:Interns preferred early clinical exposure, recruiting faculty with prior comprehensive training in medical education and reflective practice as preferred methods, while faculty members preferred teaching and assessing communication skills for every student, early clinical exposure and mentorship. Conclusion:Early clinical exposure, teaching and assessing communication skills, mentorship and reflective practice are the preferred methods of teaching and learning medical professionalism.

Analysis of Different Routes of Hysterectomy Based on a Prospective Algorithm and Their Complications in a Tertiary Care Institute.

Introduction: Hysterectomy is the most common gynaecological operation worldwide. The objective of the study is to analyze the various routes of hysterectomy and its complications when the decision of route is based on using a prospective algorithm tree. Methodology. It is an observational study to analyze the route of hysterectomy based on using a prospective algorithm. The decision tree is based on pelvic pathology, uterine size, vaginal access, pelvic adhesion, competency of the surgeon, choice of the patient, and complication of different routes of hysterectomy. Data were collected from preoperative, intraoperative, and postoperative records. Demographic factors, indications, routes of hysterectomy, and complications were recorded and analyzed by using SPSS software version 22. Observation. Among the malignant or suspected malignant pathology groups, TAH was performed in 89 cases and TLH was performed in 3 cases. Among the benign disease groups, VH was performed in 137(38.2%) cases, TAH was performed in 118(32.9%) cases, and TLH was performed in 104 (28.9%) cases. Operative time and a number of blood transfusions were significantly less with VH (p value < 0.0001 and 0.004) compared to abdominal and total laparoscopic hysterectomy. Postoperative complication such as fever was more with abdominal hysterectomy (p-value<0.00001) compared to VH and TLH. Vaginal discharge was more with VH and TLH compared to TAH (p value -0.004) and wound infection was more in the abdominal route (p value 0.001). Conclusion: The abdominal route was the route of choice for surgery in malignancy or suspected malignant pathology. In benign pathology, VH was the most common and preferable route of surgery. Complications were found to be minimal with vaginal hysterectomy.

Hepatitis E virus replication involves alternating negative- and positive-sense RNA synthesis.

Hepatitis E virus (HEV) is the major cause of epidemic hepatitis and many outbreaks of sporadic hepatitis. The virus responsible has a single-stranded, positive-sense RNA. Its replication and the regulatory process involved therein are poorly understood. Much of the HEV biology studied has been done by using full-length capped RNA transcripts (replicons) and transient transfections in cell cultures. We investigated replicon replication using negative-sense strand-specific molecular beacons in live cell imaging, and quantifying intracellular viral RNA using strand-specific real-time PCR every 2 h until 24 h post-transfection. A graph of the copy numbers of both positive- and negative-sense RNA at the different time points was plotted. This showed a temporal separation and alternating cycles of negative- and positive-sense RNA formation. As a control, a dysfunctional replicase mutant (GDD→GAA) was used, which showed no increase in copy number. The live cell imaging corroborated the quantitative data, in that the maximal amount of negative-sense RNA was observed at 8 h post-transfection. The real-time-PCR copy-number analysis of the subgenome showed the presence of a single subgenomic RNA. Using fluorescent protein genes mCherry and EGFP fused in-frame to ORF2 and ORF3 in separate constructs and immunofluorescence, we showed the formation of both proteins pORF2 and pORF3 from a single subgenomic RNA. Our study demonstrated cyclical bursts of virus replication and the role of subgenomic RNA in the HEV life cycle.

Antituberculosis therapy-induced acute liver failure: magnitude, profile, prognosis, and predictors of outcome.

UNLABELLED: Antituberculosis therapy (ATT)-associated acute liver failure (ATT-ALF) is the commonest drug-induced ALF in South Asia. Prospective studies on ATT-ALF are lacking. The current study prospectively evaluated the magnitude, clinical course, outcome, and prognostic factors in ATT-ALF. From January 1986 to January 2009, 1223 consecutive ALF patients were evaluated: ATT alone was the cause in 70 (5.7%) patients. Another 15 (1.2%) had ATT and simultaneous hepatitis virus infection. In 44 (62.8%) patients, ATT was prescribed empirically without definitive evidence of tuberculosis. ATT-ALF patients were younger (32.87 [+/-15.8] years), and 49 (70%) of them were women. Most had hyperacute presentation; the median icterus encephalopathy interval was 4.5 (0-30) days. The median duration of ATT before ALF was 30 (7-350) days. At presentation, advanced encephalopathy and cerebral edema were present in 51 (76%) and 29 (41.4%) patients, respectively. Gastrointestinal bleed, seizures, infection, and acute renal failure were documented in seven (10%), five (7.1%), 26 (37.1%), and seven (10%) patients, respectively. Compared with hepatitis E virus (HEV) and non-A non-E-induced ALF, ATT-ALF patients had nearly similar presentations except for older age and less elevation of liver enzymes. The mortality rate among patients with ATT-ALF was high (67.1%, n = 47), and only 23 (32.9%) patients recovered with medical treatment. In multivariate analysis, three factors independently predicted mortality: serum bilirubin (>or=10.8 mg/dL), prothrombin time (PT) prolongation (>or=26 seconds), and grade III/IV encephalopathy at presentation. CONCLUSION: ATT-ALF constituted 5.7% of ALF at our center and had a high mortality rate. Because the mortality rate is so high, determining which factors are predictors is less important. A high proportion of patients had consumed ATT empirically, which could have been prevented.