Misoprostol for non-alcoholic steatohepatitis: a randomised control trial.

INTRODUCTION: The management of non-alcoholic steatohepatitis (NASH) is an unmet clinical need. Misoprostol, a structural analogue of naturally occurring prostaglandin E1, has been reported to decrease proinflammatory cytokine production and may have a potential role in treating NASH. We aimed to evaluate the efficacy and safety of misoprostol in treating patients with NASH. METHODS: In this phase 2, double-blind, randomised, placebo-controlled trial, patients with NASH were randomly assigned in a 1:1 ratio to receive 200 µg of misoprostol or placebo thrice daily for 2 months. The primary endpoint was an improvement in liver function tests (LFTs), interleukin-6 (IL-6) and endotoxin levels. The secondary endpoint was improvement in insulin resistance, dyslipidaemia, hepatic fibrosis and hepatic steatosis. RESULTS: A total of 50 patients underwent randomisation, of whom 44 (88%) were males. The age range was 25-64 years (mean±SE of mean (SEM) 38.1±1.4). 19 (38%) patients had concomitant type 2 diabetes mellitus. 32 (64%) patients were either overweight or obese. At the end of 2 months' treatment, a reduction in total leucocyte count (TLC) (p=0.005), alanine aminotransferase (ALT) (p<0.001), aspartate aminotransferase (AST) (p=0.002) and controlled attenuation parameter (CAP) (p=0.003) was observed in the misoprostol group, whereas placebo ensued a decline in ALT (p<0.001), AST (p=0.018), gamma-glutamyl transferase (GGT) (p=0.003), CAP (p=0.010) and triglycerides (p=0.048). There was no diminution in insulin resistance, hepatic fibrosis (elastography) and dyslipidaemia in both groups. However, misoprostol resulted in a significant reduction in CAP as compared with the placebo group (p=0.039). Moreover, in the misoprostol group, pretreatment and post-treatment IL-6 and endotoxin levels remained stable, while in the placebo group, an increase in the IL-6 levels was noted (p=0.049). Six (12%) patients had at least one adverse event in the misoprostol group, as did five (10%) in the placebo group. The most common adverse event in the misoprostol group was diarrhoea. No life-threatening events or treatment-related deaths occurred in each group. CONCLUSION: Improvement in the biochemical profile was seen in both misoprostol and placebo groups without any statistically significant difference. However, there was more improvement in steatosis, as depicted by CAP, in the misoprostol group and worsening of IL-6 levels in the placebo group. TRIAL REGISTRATION NUMBER: NCT05804305.

Mesenteric panniculitis associated with non-alcoholic fatty liver disease: A case series.

Mesenter ic p anniculitis (MP) is a b enign infla mmatory condi tion of the abdomin al mesentery, whi ch presents with a wid e variety of symptoms. I t is diagnosed non - invasively through com puted to mography (CT ) scan, whereas biopsy is still co nside red th e gold standa rd. Steroids are the first line of treatment. Here, we report four cases who presented with abdominal pain. These patients were overweight and the CT scan findings were suggestive of mese nte ric panniculitis. Three cases had concomitant non- alcoholic steatohep atitis w ith el evated alanine transaminase levels, dyslipidaemia, and insulin resistance. FibroSca n showed moderate to severe steatosis. PNPLA3 rs738409 genotype was homozygous positive (GG) in one patient, whereas two patients were heterozygous positive (CG ). This a ssociat io n has not been well-described so far and w arrants f ur ther inve s tigation. There may be some common predisposing factors.

Predictors of fatal neurological complications among admitted COVID-19 patients with their implication in outcome: A Case Control study.

BACKGROUND: COVID-19 is known to be associated to potentially fatal neurological complications; therefore, it is essential to understand the risk factors for its development and the impact they have on the outcome of COVID-19 patients. AIMS: To determine the risk factors for developing fatal neurological complications and their outcome in hospitalized COVID-19 patients. MATERIAL AND METHODS: Case control study based on hospitalized patients was conducted from July 15th 2021 to December 15th 2021. Cases and controls were COVID-19 confirmed patients with and without severe neurological manifestations. Age, comorbid conditions, vaccination status, Blood Sugar Random (BSR), D-dimers levels, anticoagulation type and dosage were taken as predictors (exposure variables) for developing neurological complications. In the case-only (subgroup) analysis, 28-day mortality were analyzed using the same predictors including admission hypoxemia. Chi square test and regression model were built to calculate OR with 95%CI. RESULTS: Among 383 patients (median age, 56 years [IQR, 24-110]; 49.9% men); 95 had neurological complications (cases) and 288 did not (controls). Development of neurological complications among COVID-19 related hospitalizations was significantly associated with old age >71 yrs. (cases, 23.2%; controls, 13.5%; OR, 3.31; 95% CI, 1.28-8.55), presence of diabetes mellitus (37.9% vs. 24%; OR, 1.9; 95% CI, 1.2-3.1), admission hyperglycemia (BSR 351-600 mg/dl), (29.5% vs. 7.6%; OR, 3.11; 95%CI, 1.54-6.33), raised D-dimer levels 5000-10,000 ng/ml (41% vs. 11.8%; OR, 5.2; 95% CI, 3.02-8.9), prophylactic dose anticoagulation (43.2% vs. 28.1%; OR, 1.9; 95%CI, 1.2-3.1), and unvaccinated status of COVID-19 patients (90.5% vs. 75.6%; OR, 3.01; 95% CI, 1.44-6.25). Neurological complications with COVID-19 were associated with increased likelihood of death or invasive mechanical ventilation by day 28 (86.3% vs. 45.1%; OR, 7.66; 95% CI, 4.08-14.4). In case-only analysis (median age, 56 years [IQR, 27,110]; 50.5% women), 67 (70.5%) had CVE, 21 (22.1%) had Encephalitis, and 7 (7.4%) had GBS as neurological manifestations. 28-day mortality among these patients was strongly associated with a lower likelihood of vaccination. (6.1% cases vs. 30.8% controls; OR, .146; 95%CI, .033- .64), being younger 17-45 yrs. (12.2% vs. 46.2%; OR, .162; 95%CI, .045-.58), having no comorbid condition (19.5% vs. 61.5%; OR, .151; 95%CI, .044- .525), having cerebrovascular events and GBS as type of neurological manifestation (76.8% vs.30.8%; OR, 7.46; 95%CI, 2.06-26.96), (2.4% vs. 38.4%; OR, .04; 95%CI, .007- 0.24) respectively, and presence of hypoxemia at admission (91.5% vs. 15.4%; OR, 58.92; 95%CI, 10.83-320.67). CONCLUSION: Old age, presence of Diabetes Mellitus, unvaccinated status of patients, high BSR at admission, high D-dimers, and prophylactic dose anticoagulation were identifies as increased risk factors for developing serious neurological complications among COVID-19 patients. Neurological problems in COVID-19 patients raised death risk 7.6-fold. The most common neurological complication was cerebrovascular events, followed by encephalitis and GBS. Unvaccinated status, cerebrovascular events, and admission hypoxemia are associated with an increased likelihood of 28-day mortality among these patients.

The Spectrum of Autoimmune Liver Disorders, Clinical Presentation, and Autoantibodies in Patients From a Tertiary Care Center in Pakistan.

Background The autoimmune illnesses that affect the liver include autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and overlap syndrome. In our patients, we aimed to address the complete spectrum of autoimmune liver disorders, clinical presentation, and autoantibodies. Methods The study included all the patients diagnosed with autoimmune liver disorder irrespective of age, gender, and ethnic background presented at the liver clinic of the hospital in the last two years. The diagnosis was based on characteristic clinical and laboratory findings, the presence of one or more characteristic autoantibodies, and/or histological abnormalities. The diagnosis of AIH was further validated by revised International AIH Group criteria using a scoring calculator. The diagnostic criteria for PBC required the presence of chronic elevation of alkaline phosphatase (ALP) with positive antimitochondrial antibody (AMA) or positive PBC-specific anti-nuclear antibodies (ANA) (sp-100, gp-210) tests and/or compatible histology. The patients of AIH-PBC overlap syndrome fulfilled the criteria for AIH in the setting of PBC. Patients having liver involvement in other autoimmune disorders were included in the study. Results The total number of patients was 124; 83 (67%) were females; mean age ± standard error of mean (SEM) was 44.97 ± 1.47 years with a range of 09-84 years. Type-1 AIH was seen in 68 (54.8%) patients, type-2 AIH in 10 (8.1%) patients, PBC in 22 (17.7%) patients, overlap of PBC with AIH in 10 (8.1%) patients, IgG4 disease in four (3.2%) patients, psoriasis-specific immune hepatitis in four (3.2%) patients, celiac disease-related hepatitis in three (2.4%) patients, sarcoidosis in two (1.6%) patients, and ichthyosis-associated hepatitis in one (0.8%) patient. There was a high prevalence of cirrhosis (50%) at the time of presentation; 19% of patients had decompensated liver disease. ANA was positive in 52/68 cases of AIH type-1, but anti-smooth muscle antibody (ASMA) was reactive only in nine cases and anti-soluble liver antigen (SLA) in five cases. There was no female preponderance in type-2 AIH (M:F = 6:4). AMA was reactive in 25 (78%) cases of PBC and overlap syndrome. Antibodies prevalent in PBC (AMA-M2, AMA-M2-3E, sp-100, gp-210, anti-Ro52) were also seen in some cases of AIH, though they did not fulfill the criteria of the overlap syndrome. Conclusion There is an unmet need for the early diagnosis of autoimmune liver diseases and the initiation of appropriate management to prevent complications.

Prevalence of Nocturnal Enuresis Among Children Dwelling in Rural Areas of Sindh.

Introduction Nocturnal enuresis (NE) is usually a condition of childhood and refers to involuntary urinary incontinence during sleep. Due to its impact on a child's mental and social health, it is important to determine the prevalence of this condition among a population. Therefore, the aim of our study is to evaluate its prevalence and associated risk factors among children living in rural areas of Sindh province, Pakistan. Methods Fifteen-hundred children aged between three and 12 years of age who lived in rural areas of Sindh and visited a tertiary care hospital for various complaints were selected at random. Their parents were asked to fill in a questionnaire regarding the symptoms and risk factors of NE. The data were gathered over a period of three months, starting from June 2019 to August 2019. The data were then analyzed to draw associations between the findings. Results Out of the total 1500 participants, 570 (38%) were male and the remaining 930 (62%) were female. Among these, the majority with NE were males (70%) and children between the age of six and seven years (65%). The first and fourth to fifth born were more likely to develop symptoms of NE. There was also a positive association between family history (P=0.003), delayed milestones (0.001), psychological problems (0.005), and urinary tract infection (P=0.001). However, a child suffering from chronic illness, parasitic infection, or anemia did not have a significant relationship with developing NE. Conclusion The total prevalence of NE among rural areas was 40%, which was higher than in urban areas. This could be due to limited awareness among parents and limited healthcare facilities to manage the condition in rural areas. However, it is important to identify the symptoms of NE earlier among children to reduce the impact it leaves on them.

The Importance of Serum N-Terminal Pro-Brain Natriuretic Peptide and Endogenous Hydrogen Sulfide for Predicting Coronary Artery Lesions in Pediatric Kawasaki Disease Patients: Findings From a Tertiary Care Hospital in Karachi, Pakistan.

Introduction Kawasaki disease (KD) is an idiopathic, acute systemic vasculitis typically affecting medium-sized blood vessels with an inclination towards the coronary arteries. There is no specific diagnostic test established for it yet. Hence, our study aims to evaluate serum N-terminal pro-brain natriuretic peptide (NT-proBNP), hydrogen sulfide (H2S), and interleukin-6 (IL-6) levels as potential diagnostic tools in children with KD and determine its relationship with the development of coronary artery lesions (CAL) in the pediatric population visiting a tertiary care hospital in Karachi. Methods A prospective observational study was performed on a sample of 500 children at a tertiary care hospital over a period of two years from June 2017 to June 2019. Blood samples were collected from two groups labeled CAL and non-coronary artery lesion (NCAL), and different biomarkers including NT-proBNP, IL-6, and H2S were compared between them to predict the diagnostic properties of each marker. Results Among the 500 children, 50% were between the age of one to five years. All presented with fever and varying degrees of associated symptoms. On lab investigations, levels of NT-proBNP and IL-6 during the acute phase of the disease were found to be higher in the CAL group than the NCAL and control groups (p<0.001). However, H2S levels during the acute attack were significantly lower in the CAL group when compared to the NCAL or control groups (p<0.001). Conclusion Elevated levels of NT-proBNP and IL-6 can be utilized as potential clinical markers for identifying children at risk of developing CAL as a complication of KD. Reduced H2S levels are also proposed as an indicator of progress towards CAL and should be considered in reaching a diagnosis.

Prevalence and Risk Factors of Hypertension Among Children Attending Out Patient Department of a Tertiary Care Hospital in Karachi.

INTRODUCTION: The childhood obesity epidemic has caused the global prevalence of hypertension (HTN) in children to increase from 2% to 4%. However, there is limited data regarding this issue in Pakistan. Hence this cross-sectional study aims to document the prevalence of HTN and its risk factors among children visiting the out patient department (OPD) of a government hospital in Karachi, which is one of the largest cities in Pakistan. METHODS: One thousand children aged between 4 and 12 years who visited the OPD in October 2019 were included. Blood pressures (BPs) for each child were measured manually and recorded. Their guardians were then interviewed to assess the risk factors present in each child. Data collected were analyzed using SPSS (Statistical Package for the Social Sciences). RESULTS: Among all the children, those between 4 and 7 years of age had a higher prevalence of HTN (19.2%; 9.2% stage 1 and 10.0% stage 2) than children aged between 8 and 12 years (14.5%; 8.0% stage 1 and 6.5% stage 2). Obese children between the age of 4 and 7 years (OR = 3.11) were more likely to develop HTN. Moreover, children with a positive family history of HTN were 1.43 times more likely to have HTN and 1.32 times more likely to have pre-HTN. There was no significant association of gender, artificial feeding, low birth weight, and maternal smoking with HTN. CONCLUSION: The prevalence is particularly higher in children aged between 4 and 7 years (19.2%) and there is a strong association between high BMI (body mass index), family history of HTN, and high-fat diet intake with HTN in children. There was no significant variation of prevalence between both genders.