Incidence, risk factors and outcomes of de novo malignancies post liver transplantation

Liver transplantation (LT) is associated with a 2 to 7 fold higher, age and gender adjusted, risk of de novo malignancy. The overall incidence of de novo malignancy post LT ranges from 2.2% to 26%, and 5 and 10 years incidence rates are estimated at 10% to 14.6% and 20% to 32%, respectively. The main risk factors for de novo malignancy include immunosuppression with impaired immunosurveillance, and a number of patient factors which include; age, latent oncogenic viral infections, tobacco and alcohol use history, and underlying liver disease. The most common cancers after LT are non-melanoma skin cancers, accounting for approximately 37% of de novo malignancies, with a noted increase in the ratio of squamous to basal cell cancers. While these types of skin cancer do not impact patient survival, post-transplant lymphoproliferative disorders and solid organ cancer, accounting for 25% and 48% of malignancies, are associated with increased mortality. Patients developing these types of cancer are diagnosed at more advanced stages, and their cancers behave more aggressively compared with the general population. Patients undergoing LT for primary sclerosing cholangitis (particularly with inflammatory bowel disease) and alcoholic liver disease have high rates of malignancies compared with patients undergoing LT for other indications. These populations are at particular risk for gastrointestinal and aerodigestive cancers respectively. Counseling smoking cessation, skin protection from sun exposure and routine clinical follow-up are the current approach in practice. There are no standardized surveillance protocol, but available data suggests that regimented surveillance strategies are needed and capable of yielding cancer diagnosis at earlier stages with better resulting survival. Evidence-based strategies are needed to guide optimal surveillance and safe minimization of immunosuppression

Most Individuals With Advanced Cirrhosis Have Sleep Disturbances, Which Are Associated With Poor Quality of Life

Background & Aims Sleep disturbances are common in patients with cirrhosis, but their determinants and effects on health-related quality of life are not well-understood. We investigated the prevalence of disturbed sleep in these patients, factors associated with sleep disruption, and effects on quality of life. Methods We performed a prospective, cross-sectional study of 193 stable ambulatory patients with cirrhosis (154 with decompensated cirrhosis). Participants completed the Pittsburgh Sleep Quality Index (to assess sleep quality), the Chronic Liver Disease Questionnaire (CLDQ), and muscle cramp questionnaires and underwent neurocognitive testing. Actigraphy was performed in a subset of patients with normal and disturbed sleep. We collected serum samples from subjects with normal and disturbed sleep and performed non-targeted metabolomic analyses. Results Of the study subjects, 157 (81%) had disturbed sleep, with Pittsburgh Sleep Quality Index scores >5. Disturbed sleep was associated with muscle cramps, daytime somnolence, and decreased quality of life on the basis of CLDQ scores. Factors independently associated with disturbed sleep in logistic regression analysis included hypoalbuminemia, opiate therapy, and muscle cramps. Disturbed sleep was independently associated with CLDQ score (correlation parameter, –36.6; 95% confidence interval, –24 to –49; P < .001) on linear regression. Disturbed sleep was associated with neurocognitive impairment and with significantly delayed bedtime and decreased total sleep time, measured by actigraphy. Disturbed sleep was associated with metabolome signatures of alterations to the intestinal microbiome and lipid, arginine, and urea cycle metabolism. Conclusions Most patients with advanced cirrhosis (81%) have disturbed sleep. This has negative effects on quality of life and is associated with disruptions of several metabolic pathways, including metabolism by the intestinal microbiota

Relationship Between Characteristics of Medications and Drug-Induced Liver Disease Phenotype and Outcome

Background & Aims: It is not known if specific characteristics of medication are associated with type of drug-induced liver injury (DILI) or outcome. We examined the relationships among select characteristics of medications and DILI phenotype and outcome. Methods: We analyzed 383 cases of DILI caused by a single orally administered prescription agent from the DILI Network Prospective Study with causalities of definite, highly likely, or probable. Relationship of daily dosage (≥ 50 mg vs. ≤ 49 mg), preponderance of hepatic metabolism (≥50% vs <50%), or Biopharmaceutics Drug Disposition Classification System (BDDCS) class (1–4, based on solubility and metabolism of the drug) were compared with clinical characteristics and outcomes. Results: Compared to cases of DILI in the <50 mg/day group, those associated with daily dosages ≥50 mg had shorter latency (median 38 days vs 56 days; P=.03) and a different biochemical pattern of liver injury (P=.04); no differences in pattern of injury, recovery, severity, or outcome were observed. Patients with DILI caused by medications with or without preponderant hepatic metabolism did not differ in clinical characteristics or outcomes. Compared to other classes of BDDCS, DILI caused by BDDCS class 1 medications had significantly longer latency (P<.001) and greater proportion of hepatocellular injury (P=.001). However, peak liver biochemical values and patients’ time to recovery, disease severity, and outcomes did not differ among the 4 BDDCS classes. Conclusions: Characteristics of medications (dosage, hepatic metabolism, and solubility) are associated with features of DILI such as latency and pattern of liver injury, but not with recovery, severity, or outcome

Case report of congenital rubella syndrome with sub aortic membrane non-coronary cusp perforation and patent ductus arteriosus

Rubella, a common viral infection caused primarily by the rubella virus, is still a global public health concern. Every year, about 30000 instances of congenital rubella syndrome are reported in India, according to health ministry surveillance. A case study of a 6-year-old boy with congenital rubella syndrome was presented here. The child presented with classic abnormalities of congenital rubella syndrome like hearing loss, vision problems, heart defects and intellectual disabilities. Among its many manifestations, congenital heart defects are life threatening, this child was planned for surgical correction of above cardiac lesions. Treatment modalities differ in each type of congenital heart defects and its early detection and surgical intervention can reduce childhood mortality and morbidity

A review on processing and properties of aluminum based metal matrix composites

This journal paper presents an in-depth exploration of Metal Matrix Composites (MMCs), a vital class of composite materials extensively employed in diverse sectors such as aerospace, automotive, defense, and marine due to their exceptional combination of high strength and reduced weight. The review focuses on various processing methods for MMCs, emphasizing the range of fabrication techniques available. The experimental evaluation of these composites is discussed, encompassing essential assessments like hardness, tensile strength, compression resistance, fatigue behavior, and tribological performance, all conducted in accordance with ASTM standards. The objective of the paper is to provide a thorough understanding of MMCs, from their fabrication processes to the systematic evaluation of their properties, contributing valuable insights to the field

Clinical impact of idiopathic pulmonary fibrosis on SARS-CoV-2 patient outcomes: a comprehensive analysis in the pre-vaccination era

IntroductionOur retrospective study aimed to evaluate the impact of idiopathic pulmonary fibrosis (IPF) on the clinical outcomes of COVID-19 admissions using data from the 2020 nationwide inpatient sample (NIS).MethodsWe performed multivariate adjustment for baseline comorbidities and demographics after univariate screening.ResultsAmong the 1,018,915 adults hospitalized with COVID-19 in 2020, 910 were also diagnosed with IPF. Patients admitted with both COVID-19 and IPF had a higher risk of mortality compared to those without IPF [adjusted OR 1.87 (95% CI 1.13-2.70), p &lt; 0.01]. Additionally, patients with both conditions had higher odds of requiring mechanical ventilation [adjusted OR 1.66 (95 % CI 1.13–2.42) p = 0.01] and needing mechanical ventilation within the first 24 h of admission [adjusted OR 1.87 (95% CI 1.013–3.39) p = 0.04]. IPF patients incurred higher mean total hospitalization charges [$140,790 vs.$79,045, adjusted difference + $60,577 (SD ± 52,460)] and had a longer mean length of stay [11.2 vs. 7.5 days, adjusted difference 3.3 days longer (SD ± 2.0)] compared to the non-IPF cohort (p = 0.02).DiscussionOur findings suggest that IPF significantly worsens the clinical outcomes of COVID-19 hospitalizations, leading to increased healthcare utilization and costs. Further studies are needed to study this subpopulation during the postvaccination era to understand the effects on patient outcomes and to explore potential targeted interventions for improving prognosis in patients with both COVID-19 and IPF

UK imports, third country effect and the global financial crisis: Evidence from the asymmetric ARDL method

This paper examines the role of exchange rate volatility in determining real imports. As a robustness check, it further explores the impact of the recent global financial crisis which is a period characterized by heightened exchange rate volatility. More specifically, we investigate the impact of exchange rate volatility on UK real imports from Germany, Japan and the US during the period January 1991–March 2013. In contrast to most studies which focus on bilateral trade, we additionally explore the third country exchange rate volatility effect on UK imports. To capture the nonlinear features which often characterize macroeconomic data, we employ the asymmetric autoregressive distributed lag (ARDL) approach to cointegration. Our results suggest that exchange rate volatility plays an important role and reveal that there is a significant effect of the recent financial crisis on UK imports. This finding is consistent when we test for the third country volatility effect. Finally, we find that there is a significant causal relationship between exchange rate volatility and UK imports both in bilateral tests and in tests which account for the third country exchange rate volatility

Exchange Rate Uncertainty and Import Demand of Thailand

This study investigates the impact of real exchange rate uncertainty on import demand of Thailand. The period of study is during July 1997 to December 2011. The results from bounds testing for cointegration show that all variables are cointegrated. Even though there is no short-run impact, but the long-run negative impact of real exchange rate uncertainty on real imports is large and highly significant under the floating exchange rate regime. In the long run, a rise in real exchange rate uncertainty can improve the country’s trade balance by substantially lowering import demand, but can harm industrial production at the same time. Therefore, stabilization of real effective exchange rate via major nominal exchange rates may deem necessary