Posttransplant Metabolic Syndrome

Metabolic syndrome (MS) is a cluster of metabolic derangements associated with insulin resistance and an increased risk of cardiovascular mortality. MS has become a major health concern worldwide and is considered to be the etiology of the current epidemic of diabetes and cardiovascular disease. In addition to cardiovascular disease, the presence of MS is also closely associated with other comorbidities including nonalcoholic fatty liver disease (NAFLD). The prevalence of MS in patients with cirrhosis and end-stage liver disease is not well established and difficult to ascertain. Following liver transplant, the prevalence of MS is estimated to be 44–58%. The main factors associated with posttransplant MS are posttransplant diabetes, obesity, dyslipidemia, and hypertension. In addition to developing NAFLD, posttransplant MS is associated with increased cardiovascular mortality that is 2.5 times that of the age- and sex-matched individuals. Additionally, the presence of posttransplant MS has been associated with rapid progression to fibrosis in individuals transplanted for HCV cirrhosis. There is an urgent need for well-designed prospective studies to fully delineate the natural history and risk factors associated with posttransplant MS. Until then, early recognition, prevention, and treatment of its components are vital in improving outcomes in liver transplant recipients

Histopathological Study of Subacute Toxic Effects of Chloroacetic Acid on Albino Rats and its Correlation with Serum Levels of Malondialdehyde

Human beings are increasingly being exposed to chloroacetic acid (CAA), a type of halo acetic acid. It would not be an exaggeration to say that almost the whole humankind today is affected by it or its metabolites. The concern over the carcinogenicity of haloacetic acids led the United States Environmental Protection Agency to regulate the allowable concentration of haloacetic acids in drinking water as part of the Disinfectants and Disinfection Byproducts Rule promulgated in 1998. Keeping this view in mind, the present study on histolopathological evaluation of different types of tissues viz., brain, kidney, liver, spleen and testes of Rattus norvegicus was performed, to find out the subacute toxicity of chloroacetic acid and correlation between CAA administration and changes in malondialdehyde (MDA) level in blood

Effect of Kohl-Chikni Dawa – a compound ophthalmic formulation of Unani medicine on naphthalene-induced cataracts in rats

BACKGROUND: Cataracts are the leading cause of blindness worldwide, accounting for 13-27% of cases. Kohl-Chikni Dawa (KCD) is reputed for its beneficial effects in the treatment of premature cataracts. However, its efficacy is yet to be tested. To investigate the rationality of the therapeutic use of Kohl-Chikni Dawa (KCD) in Unani medicine. METHODS: The effect of Kohl-Chikni Dawa eye drops on naphthalene-induced cataracts in rats was investigated by slit-lamp biomicroscopic analysis. The normal group of experimental animals was administered with mineral oil (orally), while other groups were given naphthalene (orally) along with local application of KCD eye drops (once and twice daily), placebo and distilled water (twice daily). Initial morphological changes of the lenses were observed twice a week for two weeks, and thereafter once a week for four weeks. RESULTS: Local application of KCD (twice daily) caused significant reduction in the lens opacification after 2 to 4 weeks of naphthalene administration. CONCLUSION: KCD eye drops may have the potential to delay progression of naphthalene-induced cataracts in rats

A qualitative systematic review of anonymous/unspecified living kidney and liver donors’ perspectives

Objectives & background: Anonymous live organ donors or unspecified donors are individuals willing to be organ donors for any transplant recipient with whom they have no biological or antecedent emotional relationship. Despite excellent recipient outcomes and the potential to help address organ scarcity, controversy surrounds the unconditional act of gifting one’s organs to an unrelated recipient. This qualitative systematic review provides insights into the first-hand experiences, motivations, and challenges that unspecified donors face. Methods: A systematic search was conducted on Medline, Embase, CINAHL, PsycINFO, and Web of Science database for qualitative literature regarding unspecified living donors’ motivations and experiences in liver and kidney transplantation. An inductive thematic analysis was conducted to generate themes and supportive subthemes. Results: 12 studies were included. The four major themes were (i) motivations, (ii) perception of risks, (iii) donor support, and (iv) benefits of donation. Unspecified donors demonstrated a deep sense of social responsibility but tended to underestimate health risks in favour of benefits for recipients. Despite the lack of emotional support from family and friends, the decision to donate was a resolute personal decision for donors. Majority benefitted emotionally and did not express regret. Conclusion: This qualitative review bridges the gap in literature on unspecified living donor psychology and provides a comprehensive understanding of the decision-making matrix and experiences of donors

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

Evaluation of the central depressant activity of Jadwar (<i>Delphinium denudatum </i>Wall.) in<b> </b>mice

59-64In Unani medicine, Jadwar (Delphinium denudatum Wall.) is reputed for its beneficial effects in various neurological disorders. The present investigation was undertaken to evaluate the central depressant activity of the aqueous extract of Delphinium denudatum (Dd) in mice, using various experimental paradigms of depression viz. pentobarbitone sodium induced hypnosis (PSH), spontaneous motor activity (SMA) and open- field behaviour (OFB) tests. Pilot studies indicated that single dose (2000 mg/kg) administration of Dd had little to no acute behavioural effects, hence the extract of Dd was administered orally at different dose levels. Dd extract (200-1600 mg/kg, orally) showed significant depressant effects on all the paradigms of depression. The results indicate that Dd induced a significant increase in sleeping time of pantobarbitone sodium induced hypnosis. In SMA test, significant decrease was observed in activity counts on photoactometer readings. In OFB test, there was significant decrease in openfield ambulation, sniffing, defecation and slight decrease in preening whereas rearing remained unchanged. The Dd extract showed consistent and significant depressant activity in all the tests. The effects induced by aqueous extract of Dd were less marked at lower dose than at higher dose

Vascular Disease in Patients with Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is increasingly being diagnosed and is considered to be the most frequent chronic liver disorder in Western countries. It represents a histopathological spectrum ranging from simple hepatic steatosis to steatohepatitis and finally cirrhosis. NAFLD is considered as the hepatic manifestation of the metabolic syndrome and is associated with increased mortality. Increasing evidence now suggests that NAFLD is also associated with higher cardiovascular disease (CVD) morbidity and mortality independent of conventional cardiometabolic risk factors (such as obesity, insulin resistance, and diabetes mellitus). The exact mechanisms linking NAFLD to increased CVD risk are still incompletely understood and likely reflect multiple coexisting pathways. Recent evidence suggests a contributive effect of an altered hemostasis in patients with NAFLD. For example, patients with NAFLD have higher levels of prothrombotic factors (e.g., von Willebrand factor, fibrinogen, factor VII activity, and plasminogen activator inhibitor-1), which correlate with underlying histological severity of the disease. The current review focuses on these hemostatic abnormalities in NAFLD and the link with increased CVD risk