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Abstract Background Acute myeloid leukemia, constituting a majority of leukemias, grapples with a 24% 5-year survival rate. Recent strides in research have unveiled fresh targets for drug therapies. LIM-only, a pivotal transcription factor within LIM proteins, oversees cell development and is implicated in tumor formation. Among these critical LIM proteins, CSRP1, a Cysteine-rich protein, emerges as a significant player in various diseases. Despite its recognition as a potential prognostic factor and therapeutic target in various cancers, the specific link between CSRP1 and acute myeloid leukemia remains unexplored. Our previous work, identifying CSRP1 in a prognostic model for AML patients, instigates a dedicated exploration into the nuanced role of CSRP1 in acute myeloid leukemia. Methods R tool was conducted to analyze the public data. qPCR was applied to evaluate the expression of CSRP1 mRNA for clinical samples and cell line. Unpaired t test, Wilcoxon Rank Sum test, KM curves, spearman correlation test and Pearson correlation test were included in this study. Results CSRP1 displays notable expression variations between normal and tumor samples in acute myeloid leukemia (AML). It stands out as an independent prognostic factor for AML patients, showing correlations with clinical factors like age and cytogenetics risk. Additionally, CSRP1 correlates with immune-related pathways, immune cells, and immune checkpoints in AML. Furthermore, the alteration of CSRP1 mRNA levels is observed upon treatment with a DNMT1 inhibitor for THP1 cells. Conclusion The CSRP1 has potential as a novel prognostic factor and appears to influence the immune response in acute myeloid leukemia. Additionally, there is an observed association between CSRP1 and DNA methylation in acute myeloid leukemia.

Introduction: The burden of chronic liver disease (CLD) is on the rise and liver transplantation remains the best treatment modality for the end stage liver disease (ESLD). Tribhuvan University Teaching Hospital has started doing living donor liver transplantation (LDLT) and we aim to report our experience and early postoperative outcomes of the first 10 living donor liver transplants performed in our institute. Methods: This is a retrospective review and included all patients who were operated for LDLT from the year 2019 to 2023 for various indications. Demographic data, Model for End-Stage Liver Disease score, Child score, etiology of CLD, liver graft type, graft-to-recipient weight ratio, operative time, blood transfusion and complications were analysed. Results: From 2019 to 2023, in total, 10 patients underwent LDLT, including one paediatric transplant. The most common etiology was alcohol (50%) and right lobe was the preferred graft. The average operative time was 7.9 ± 2.56 hours. There were no re exploration or re transplantation. The mean duration of hospital stay was around 21.37 ± 6.43 days. All patients were followed for one to five years. Four recipients had Clavien Dindo Grade II and above complications, including bile leak and post-operative bleeding. One mortality occurred on 27th post-operative day due to covid infection. Conclusions: Living donor liver transplantation is a feasible option for patients with end stage liver disease and is safe to be performed in low volume centre with the help of expertise and good team work.

Background: Combined heart-liver transplantation (CHLT) is a complex procedure with rising demand and is subject to ongoing assessment. Here, we provide an update on indications, patient outcomes, and risk factors. Methods: This retrospective study utilized CHLT data from the United Network for Organ Sharing registry between 1990 and 2023. Recipient and donor characteristics, and risk factors for mortality were analyzed using Cox regression hazard models. Recipient and graft survival at 30 days, 1 year, and 5 years were analyzed using the Kaplan-Meier method. Results: This cohort included 532 patients with median survival of 16.9 years (SD: 1.09). The most common indications for CHLT were congenital heart disease (36%) and dilated cardiomyopathy (31%). Patient survival at 30 days, 1 year, and 5 years were 94%, 85%, and 77%, respectively. Combined heart-liver graft survival was 93%, 85%, and 77%, respectively. Diabetes (hazard ratio [HR]: 1.74; p = 0.04) was associated with multigraft failure and mortality in multivariate analysis. Compared to congenital heart disease, dilated (HR: 0.55; p = 0.03) and restrictive myopathies (HR: 0.5; p = 0.03) were associated with improved graft and overall survival. Higher donor left ventricular ejection fraction (EF) was also associated with improved graft and overall survival (HR: 0.96; p = 0.008). Conclusions: CHLTs are being performed at increasingly higher rates with comparable survival to single-organ transplants. Diabetes was associated with increased mortality. Recipient dilated or restrictive myopathies and higher donor EF were correlated with improved survival compared to congenital heart disease. Further studies are needed to better understand these observations.

Asthma is an obstructive lung disease with high prevalence. Symptom control in asthma remains poor despite significant advancements in treatment guidelines and inhalational devices. This is often attributed to inadequate patient adherence to the inhaler technique and insufficient education on its long-term use. Through this study, we aimed to assess the impact of reinforcement of proper inhaler technique on asthma symptom control and quality of life. A prospective cohort of 400 asthma patients using dry powder inhalers and metered dose inhalers was recruited in the outpatient clinic of our hospital. At the time of recruitment, the correctness of inhaler technique usage was assessed, and the pre-test Inhaler Technique Score (ITS) was recorded for each patient. Then, a ten-step inhalation technique was taught through demonstration, and the post-test ITS score was recorded again. This was done for each patient at monthly intervals for 3 months. Along with it, two tailored questionnaires, the Asthma Control Test (ACT) and Asthma Quality of Life Questionnaire (AQLQ), were administered at each visit to assess disease control and quality of life. Significant enhancements in inhalation technique were noted from the first to the third visit using the ten-step inhalation usage scores, which improved from 6.91 to 9.87 (out of 10) (p

Abstract Cancer stem cells (CSCs) are widely acknowledged as the drivers of tumor initiation, epithelial‐mesenchymal transition (EMT) progression, and metastasis. Originating from both hematologic and solid malignancies, CSCs exhibit quiescence, pluripotency, and self‐renewal akin to normal stem cells, thus orchestrating tumor heterogeneity and growth. Through a dynamic interplay with the tumor microenvironment (TME) and intricate signaling cascades, CSCs undergo transitions from differentiated cancer cells, culminating in therapy resistance and disease recurrence. This review undertakes an in‐depth analysis of the multifaceted mechanisms underlying cancer stemness and CSC‐mediated resistance to therapy. Intrinsic factors encompassing the TME, hypoxic conditions, and oxidative stress, alongside extrinsic processes such as drug efflux mechanisms, collectively contribute to therapeutic resistance. An exploration into key signaling pathways, including JAK/STAT, WNT, NOTCH, and HEDGEHOG, sheds light on their pivotal roles in sustaining CSCs phenotypes. Insights gleaned from preclinical and clinical studies hold promise in refining drug discovery efforts and optimizing therapeutic interventions, especially chimeric antigen receptor (CAR)‐T cell therapy, cytokine‐induced killer (CIK) cell therapy, natural killer (NK) cell‐mediated CSC‐targeting and others. Ultimately use of cell sorting and single cell sequencing approaches for elucidating the fundamental characteristics and resistance mechanisms inherent in CSCs will enhance our comprehension of CSC and intratumor heterogeneity, which ultimately would inform about tailored and personalized interventions.

Chronic obstructive pulmonary disease (COPD) presents as a multifaceted clinical landscape with various hematological manifestations. Among these, polycythemia and anemia pose distinct challenges. While the prevalence of polycythemia has decreased in recent years, anemia remains a prevalent concern, impacting patient outcomes. This study investigated the incidence and clinical characteristics of polycythemia in COPD patients, focusing on a diverse cohort in India. Methodological approaches included comprehensive evaluations of clinical parameters, pulmonary function, and hematological profiles. Results revealed significant variations in COPD severity, pulmonary function, and respiratory symptoms among patients with different hemoglobin levels. The findings shed light on the complex interplay between hematological variations and clinical manifestations in COPD, providing valuable insights for disease management strategies.

Acute kidney injury (AKI) is a growing epidemic and is independently associated with increased risk of death, chronic kidney disease (CKD) and cardiovascular events. Randomized-controlled trials (RCTs) in this domain are notoriously challenging and many clinical studies in AKI have yielded inconclusive findings. Underlying this conundrum is the inherent heterogeneity of AKI in its etiology, presentation and course. AKI is best understood as a syndrome and identification of AKI subphenotypes is needed to elucidate the disease's myriad etiologies and to tailor effective prevention and treatment strategies. Conventional RCTs are logistically cumbersome and often feature highly selected patient populations that limit external generalizability and thus alternative trial designs should be considered when appropriate. In this narrative review of recent developments in AKI trials based on the Kidney Disease Clinical Trialists (KDCT) 2020 meeting, we discuss barriers to and strategies for improved design and implementation of clinical trials for AKI patients, including predictive and prognostic enrichment techniques, the use of pragmatic trials and adaptive trials.