Depression is Associated with Weight Gain in Patients Transplanted for NASH Cirrhosis but Not Other Etiologies of Cirrhosis

The present study was to bridge this gap in knowledge by evaluating the relationship between depression, liver disease and weight change after LT. Weight gain after liver transplantation (LT) is common, particularly in patients transplanted for NASH cirrhosis, and is associated with reduced survival. In non-LT patients, presence and sub-optimal management of depression is closely associated with weight gain and obesity. The impact of depression as predictor of post-LT weight gain is currently not known. Method:All adult patients receiving LT between 7/2007 to 7/2017 were included in the analysis. Patients with graft failure or death within 6 months after LT were excluded. Baseline weight was weight 2 weeks after LT to avoid contribution of peri-transplant edema. Screening for depression was performed by a psychologist or psychiatrist using DSM-IV/V guidelines. Antidepressant use was quantified through chart review. Results: The presence of depression did not affect weight change in patients transplanted for HCV and alcoholic cirrhosis; however, in patients transplanted for NASH cirrhosis depression was positively associated with 60 months post-LT weight gain. Patients receiving treatment for depression, the weight gain was mitigated, whereas in patients with NASH cirrhosis and depression not on anti-depressants the weight gain was significantly more profound at each follow up.Conclusion: Presence and under-treatment of depression are associated with more profound weight gain in patients transplanted for NASH cirrhosis, likely reflecting poor coping mechanisms. Additional trials with aggressive screening and treatment of depression in patients transplanted for NASH cirrhosis are essential to mitigate post-LT weight gai

Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs

The global retinoblastoma outcome study : a prospective, cluster-based analysis of 4064 patients from 149 countries

DATA SHARING : The study data will become available online once all analyses are complete.BACKGROUND : Retinoblastoma is the most common intraocular cancer worldwide. There is some evidence to suggest that major differences exist in treatment outcomes for children with retinoblastoma from different regions, but these differences have not been assessed on a global scale. We aimed to report 3-year outcomes for children with retinoblastoma globally and to investigate factors associated with survival. METHODS : We did a prospective cluster-based analysis of treatment-naive patients with retinoblastoma who were diagnosed between Jan 1, 2017, and Dec 31, 2017, then treated and followed up for 3 years. Patients were recruited from 260 specialised treatment centres worldwide. Data were obtained from participating centres on primary and additional treatments, duration of follow-up, metastasis, eye globe salvage, and survival outcome. We analysed time to death and time to enucleation with Cox regression models. FINDINGS : The cohort included 4064 children from 149 countries. The median age at diagnosis was 23·2 months (IQR 11·0–36·5). Extraocular tumour spread (cT4 of the cTNMH classification) at diagnosis was reported in five (0·8%) of 636 children from high-income countries, 55 (5·4%) of 1027 children from upper-middle-income countries, 342 (19·7%) of 1738 children from lower-middle-income countries, and 196 (42·9%) of 457 children from low-income countries. Enucleation surgery was available for all children and intravenous chemotherapy was available for 4014 (98·8%) of 4064 children. The 3-year survival rate was 99·5% (95% CI 98·8–100·0) for children from high-income countries, 91·2% (89·5–93·0) for children from upper-middle-income countries, 80·3% (78·3–82·3) for children from lower-middle-income countries, and 57·3% (52·1-63·0) for children from low-income countries. On analysis, independent factors for worse survival were residence in low-income countries compared to high-income countries (hazard ratio 16·67; 95% CI 4·76–50·00), cT4 advanced tumour compared to cT1 (8·98; 4·44–18·18), and older age at diagnosis in children up to 3 years (1·38 per year; 1·23–1·56). For children aged 3–7 years, the mortality risk decreased slightly (p=0·0104 for the change in slope). INTERPRETATION : This study, estimated to include approximately half of all new retinoblastoma cases worldwide in 2017, shows profound inequity in survival of children depending on the national income level of their country of residence. In high-income countries, death from retinoblastoma is rare, whereas in low-income countries estimated 3-year survival is just over 50%. Although essential treatments are available in nearly all countries, early diagnosis and treatment in low-income countries are key to improving survival outcomes.The Queen Elizabeth Diamond Jubilee Trust and the Wellcome Trust.https://www.thelancet.com/journals/langlo/homeam2023Paediatrics and Child Healt

Risk of cardio-nephro-metabolic disease from NAFLD to MAFLD: fact or fiction?

Nonalcoholic fatty liver disease (NAFLD) is emerging as the most common etiology for chronic liver disease. Despite this, our understanding of this illness is lacking. The previous paradigm is that central adiposity, hyperlipidemia, hypertension, and insulin resistance, also known as metabolic syndrome, lead to NAFLD, and this relationship is unidirectional. However, recent evidence clearly shows that the clinical burden of this illness extends well beyond liver-related morbidity and mortality and is associated with multiple extrahepatic complications, particularly metabolic consequences. Due to this, the professional consensus has proposed using the term metabolic associated fatty liver disease (MAFLD) to more accurately reflect pathogenesis and help in patient stratification for management. This review discusses the shared pathophysiological mechanisms that link these diseases and how this can be leveraged to prevent these complications in individuals with NAFLD/MAFLD

Current and Emerging Therapies for Non-alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease is the most common cause of chronic liver disease in the developed world and commonly associated with metabolic comorbidities such as diabetes mellitus, hypertension, dyslipidemia, and obesity. Non-alcoholic steatohepatitis is an aggressive form of non-alcoholic fatty liver disease, associated with an increased risk of liver and non-liver-related mortality. Currently there are no approved therapies for non-alcoholic fatty liver disease/non-alcoholic steatohepatitis and standard-of-care lifestyle advice is rarely effective. This has spurned intense drug development efforts and several agents are in clinical trials to address this major gap in non-alcoholic fatty liver disease. Drug development efforts have focused on pathogenic mechanisms including pathways involving lipid metabolism, inflammation, and fibrosis. This review presents the overview of the trials and agents in the pipeline of emerging therapies for non-alcoholic fatty liver disease/non-alcoholic steatohepatitis