Prevalence of advanced liver fibrosis and steatosis in type-2 diabetics with normal transaminases: A prospective cohort study

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)and type-2 diabetes mellitus(T2DM)have an intricate bidirectional relationship.Individuals with T2DM,not only have a higher prevalence of non-alcoholic steatosis,but also carry a higher risk of progression to nonalcoholic steatohepatitis.Experts still differ in their recommendations of screening for NAFLD among patients with T2DM.AIM To study the prevalence of NAFLD and advanced fibrosis among our patient population with T2DM.METHODS During the study period(November 2018 to January 2020),59 adult patients with T2DM and 26 non-diabetic control group individuals were recruited prospectively.Patients with known significant liver disease and alcohol use were excluded.Demographic data and lab parameters were recorded.Liver elastography was performed in all patients.RESULTS In the study group comprised of patients with T2DM and normal alanine aminotransferase levels(mean 17.8±7 U/L),81%had hepatic steatosis as diagnosed by elastography.Advanced hepatic fibrosis(stage F3 or F4)was present in 12%of patients with T2DM as compared to none in the control group.Patients with T2DM also had higher number of individuals with grade 3 steatosis[45.8%vs 11.5%,(P<0.00001)and metabolic syndrome(84.7%vs 11.5%,P<0.00001)].CONCLUSION A significant number of patients with T2DM,despite having normal transaminase levels,have NAFLD,grade 3 steatosis and advanced hepatic fibrosis as measured by liver elastography.     

Incidence and predictors of de novo late-onset persistent atrial fibrillation in postoperative rheumatic heart disease patients (LOAF-RHD study)

Journal of Interventional Cardiac Electrophysiology - Late-onset atrial fibrillation (LOAF) after valve surgery for degenerative mitral valve disease often with underlying mitral valve prolapse is...     

State-of-the-art review on management of end-stage heart failure in amyloidosis: transplant and beyond

Heart Failure Reviews - Cardiac involvement occurs in light-chain (AL), transthyretin wild-type (wtATTR), and hereditary (hATTR) amyloidosis; other types of amyloidosis account...     

Alcohol-induced increases in insulin-like growth factor binding protein-1 are partially mediated by TNF

BACKGROUND: Alcohol (EtOH) alters the plasma and tissue content of insulin-like growth factor (IGF)-I, an important anabolic hormone. However, the bioavailability and bioactivity of IGF-I can also be modulated by changes in soluble proteins that bind IGF-I (IGFBPs). The purpose of the present study was to determine whether EtOH intoxication in rats alters the plasma concentration and tissue mRNA content of various IGFBPs. Based on initial results subsequent studies were performed to assess potential mechanisms by which EtOH increased IGFBP-1. METHODS: Rats were administered EtOH (75 mmol/kg) and blood and tissues collected at various times thereafter. Separate groups of rats were also pretreated with 4-methylpyrazole (4-MP; alcohol dehydrogenase inhibitor), cyanamide (inhibitor of acetaldehyde metabolism), RU486 (glucocorticoid receptor antagonist) or the tumor necrosis factor (TNF) antagonist (TNF(BP)) prior to EtOH administration. RESULTS: Acute EtOH intoxication did not alter the mRNA content of IGFBP-3, -4 or -5 in liver or kidney. However, EtOH increased IGFBP-1 in blood (5-fold), which was associated with an up-regulation of IGFBP-1 mRNA content in liver and kidney (2- to 3-fold). Likewise, the injection of the nonmetabolizable alcohol -butanol also increased IGFBP-1 in plasma, liver, and kidney. The increased IGFBP-1 in blood and tissues was not prevented by inhibiting alcohol metabolism with 4-MP. However, pretreatment with cyanamide markedly accentuated the EtOH-induced increase in IGFBP-1 in blood (20-fold), liver (3.5-fold), and kidney (12-fold), indicating that accumulation of acetaldehyde can enhance IGFBP-1 synthesis. A time course study indicated that EtOH increased plasma IGFBP-1 levels as early as 0.5-1 hr, and that this response was associated with elevated IGFBP-1 mRNA in liver but not kidney. Pretreatment with RU486 did not prevent or attenuate the EtOH-induced increase in IGFBP-1. However, the alcohol-induced increase in IGFBP-1 was attenuated by TNF(BP). CONCLUSIONS: These data suggest that the acute alcohol-induced increase in IGFBP-1 is mediated, at least in part, by TNF and is independent of EtOH metabolism and increases in endogenous glucocorticoids.     

Age-dependent impairment of IgG responses to glycosylphosphatidylinositol with equal exposure to Plasmodium falciparum among Javanese migrants to Papua,Indonesia

Immune responses directed at glycosylphosphatidylinositol (GPI) anchors of Plasmodium falciparum may offer protection against symptomatic malaria. To independently explore the effect of age on generation of the anti-GPI IgG response, we measured serum anti-GPI IgGs in a longitudinal cohort of migrant Javanese children (6-12 years old) and adults (> or = 20 years old) with equivalent numbers of exposures to P. falciparum in Papua, Indonesia. While the peak response in adults was achieved after a single infection, comparable responses in children required > or = 3-4 infections. Significantly fewer children (16%) than adults (41%) showed a high (optical density > 0.44) anti-GPI IgG response (odds ratio [OR] = 3.8, 95% confidence interval [CI] = 2.3-6.3, P < 0.0001), and adults were more likely to show a persistently high response (OR = 5.5, 95% CI = 1.0-56.8, P = 0.03). However, the minority of children showing a strong response were significantly less likely to experience symptoms with subsequent parasitemia compared with those with a weak response (OR = 4.0, 95% CI = 1.1-13.8, P = 0.02). This effect was not seen among high- and low-responding adults (OR = 1.2, 95% CI = 0.5-2.8, P = 0.60). Host age, independent of cumulative exposure, apparently represents a key determinant of the quantitative and qualitative nature of the IgG response to P. falciparum GPI.     

Pulmonary vascular disease in neonates with transposition of the great arteries and intact ventricular septum.

BACKGROUND--Progressive pulmonary vascular disease in surgically unrepaired transposition of the great arteries with or without ventricular septal defect had been frequently described in the past. Occurrence of progressive pulmonary vascular disease has been reported even after atrial switch procedure done at three months of age. With the advent of neonatal surgical repair, this problem is virtually non-existent. There is a small subgroup of infants with transposition of the great arteries who show pulmonary vascular disease in the neonatal period that can adversely affect the surgical outcome. The clinico-pathological correlation in this group of patients was studied. OBSERVATIONS--Three patients, with transposition of the great arteries and intact ventricular septum, who showed histological evidence of pulmonary vascular disease in the neonatal period or early infancy are described. Two of these patients, continued to have poor systemic oxygenation despite adequate atrial communication. One patient had a close ductus arteriosus within the first two hours of birth while on prostaglandin E1 infusion. CONCLUSIONS--In the absence of left ventricular outflow tract obstruction, a poor response to atrial septostomy suggests pulmonary hypertension and pulmonary vascular disease. Antenatal constriction of the ductus arteriosus may contribute to such changes in pulmonary vasculature.     

A community-based, comparative evaluation of direct agglutination and rK39 strip tests in the early detection of subclinical Leishmania donovani infection

In the Indian state of Bihar, the sensitivities and specificities of direct agglutination tests (DAT) and rK39 test strips for the detection of Leishmania donovani infection in humans were explored and found to be generally good (92%-100%). When 172 asymptomatic individuals [16 'case-contacts' who lived in the same households as past or current, confirmed cases of visceral leishmaniasis (VL) and 156 other subjects from neighbouring households] were tested, the same 36 (21%) individuals, including all 16 'case-contacts', were found seropositive using each type of test. When followed-up after 3 months, 18 of the individuals who had been found seropositive in the baseline survey remained seropositive, and eight (44%) of these had developed symptomatic VL, with amastigotes in their splenic aspirates. Seven (44%) of the 16 'case-contacts' but only one (5%) of the other 20 subjects found seropositive at baseline went on to develop VL within 3 months. Although the strip test appeared slightly better than DAT for predicting the development of VL in the 172 subjects, either type of test may be very useful for the early detection of asymptomatic L. donovani infection and thus the identification of those at relatively high risk of developing VL.