Sleep is crucial for the clearance of metabolic waste products. Sleep deprivation leads to the accumulation of amyloid-β (Aβ) and tau proteins, which may be mediated by impaired glymphatic clearance, thereby contributing to the hallmark pathologies of Alzheimer's disease (AD). The apolipoprotein E (APOE) gene, particularly the APOE ε4 allele, is a major genetic risk factor for AD and is also closely associated with sleep. Notably, the interaction between poor sleep and APOE ε4 may further enhance AD risk. However, prior studies have reported inconsistent effects of sleep deprivation on AD related biomarkers, and clinical studies stratified by APOE genotype are lacking. This study aims to investigate the effects of 24-h acute sleep deprivation on plasma AD biomarkers and to assess APOE genotype-dependent responses.

HbSC disease is the second most common type of sickle cell disease (SCD) in populations of African origin. Although it is often grouped together with other types of SCD, particularly sickle cell anemia (HbSS), it has unique pathophysiology and a different spectrum of laboratory and clinical features. Compared to HbSS, hemoglobin levels are higher, HbF is lower at less than 5%, and most vaso-occlusive and vasculopathic complications are less frequent, although retinopathy is more common. Despite these differences, there have been no specific guidelines on the management of HbSC disease. This clinical practice guideline was developed by the European Hematology Association (EHA) in accordance with the EHA Guidelines Methodology Framework to provide consensus-based guidance for the management of children and adults with HbSC disease. A multidisciplinary Guideline Panel was convened by the EHA Guidelines Committee and included hematologists, pediatricians, methodologists, and patient representatives with expertise in SCD and its complications. Panel members were assigned to thematic working groups based on their clinical expertise, and each group was responsible for drafting content and recommendations within their respective domains. Literature searches were conducted using PubMed for relevant studies published in English. A modified Delphi process was used to reach consensus on recommendations, and panel members voted anonymously using an online system. A predefined threshold of ≥70% agreement and <15% disagreement was required for adoption. Statements not reaching consensus were revised and subjected to further rounds of discussion and voting. Thirty-five recommendations were adopted, including guidance on the use of hydroxyurea and therapeutic venesection.

Mirizzi syndrome (MS) is a rare complication of long-standing cholelithiasis in which an impacted gallstone causes extrinsic compression of the common hepatic duct. Markedly elevated carbohydrate antigen 19-9 (CA 19-9) is strongly associated with pancreaticobiliary malignancies, but severe benign biliary obstruction can also cause substantial elevations, presenting a diagnostic challenge. We present a 50-year-old man with acute obstructive jaundice, fever, right upper quadrant pain, and a serum CA 19-9 level of 1000 U/mL. Triphasic contrast-enhanced computed tomography confirmed Type I Mirizzi syndrome caused by an 11.9-mm gallstone impacted in Hartmann's pouch, with no evidence of malignancy. Due to dense adhesions obliterating Calot's triangle, the patient underwent subtotal (fenestrating) cholecystectomy. Postoperatively, cholestatic liver tests markedly improved, and CA 19-9 decreased to 153 U/mL, supporting a benign obstructive and inflammatory etiology. This case highlights the importance of considering Mirizzi syndrome in patients with obstructive jaundice and markedly elevated CA 19-9 to avoid misdiagnosis and unnecessary aggressive surgical intervention.

Background Blood transfusion is frequently required in patients with chronic liver disease, particularly during episodes of gastrointestinal bleeding. However, excessive transfusion may increase portal venous pressure and adversely affect clinical outcomes. This study aimed to evaluate the association between transfusion volume and adverse clinical outcomes in patients with chronic liver disease. Objective This study aimed to assess the association between blood transfusion volume and adverse clinical outcomes, including rebleeding, hepatic encephalopathy, ascites, and prolonged hospital stay, among patients with chronic liver disease. Methods  This retrospective observational study was conducted at Assam Medical College, Dibrugarh, Assam, India, and utilized existing patient records collected between April 1, 2025, and March 31, 2026. A total of 240 adult patients with chronic liver disease who received blood transfusion during hospitalization were included. Patients were categorized into low-transfusion (≤2 units) and high-transfusion (>2 units) groups. Outcomes assessed included rebleeding, hepatic encephalopathy, ascites, and length of hospital stay. Categorical variables were analyzed using the chi-squared test, while continuous variables were compared using Student's t-test. Multivariate logistic regression analysis was performed to identify the independent predictors of rebleeding after adjustment for clinically relevant covariates. Results One hundred and thirty-eight (57.5%) received ≤2 units of blood transfusion, while 102 patients (42.5%) received >2 units. Rebleeding occurred more frequently in the high-transfusion group compared with the low-transfusion group (42 (41.2%) vs. 27 (19.6%); p<0.001). Hepatic encephalopathy was also more common among patients receiving >2 units (45 (44.1%) vs. 36 (26.1%); p=0.003). The mean hospital stay was significantly longer in the high-transfusion group (8.6±2.3 days vs. 5.9±1.8 days; p<0.001). On multivariate logistic regression analysis, transfusion volume >2 units independently predicted rebleeding (OR: 2.3; 95% CI: 1.1-4.8; p=0.02). Conclusions Higher transfusion volume was associated with increased rates of rebleeding, hepatic encephalopathy, and prolonged hospital stay in patients with chronic liver disease. These findings support careful transfusion practices and highlight the need for further prospective studies evaluating restrictive transfusion strategies.

The genetic and phenotypic heterogeneity of hereditary ataxias complicates the design of clinical trials since each ataxia progresses at different rates. Consequently, robust biomarkers are urgently needed to monitor therapeutic efficacy and safety of potential therapeutic interventions. Neurofilament light chain has emerged as a leading candidate, serving as a sensitive pharmacodynamic biomarker of neuronal injury and treatment response in neurodegenerative disorders. This review explores the utility of neurofilament light chain across various ataxias, including polyglutamine spinocerebellar ataxias, Friedreich's ataxia, multiple system atrophy, and other genetic ataxias, such as ataxias associated with RCF1 and SPG7 genes. We synthesize evidence from recent studies that have used ultra-sensitive assays. These studies consistently demonstrate elevated neurofilament light chain levels in cerebrospinal fluid and blood, correlating with disease severity, progression and neuroimaging findings. Notably, neurofilament light chain levels rise during the presymptomatic stage in spinocerebellar ataxias, highlighting its potential for stratifying individuals for trial enrolment and tracking therapeutic effects. A treatment-induced reduction in neurofilament light chain could function as a surrogate endpoint for target engagement, analogous to its validated use in amyotrophic lateral sclerosis. Finally, we discuss the results of other studies conducted on other biomarkers, including glial fibrillary acidic protein, total tau and phosphorylated tau, which may reflect complementary aspects of neurodegeneration and glial activation. Glial fibrillary acidic protein may provide insights into astroglial reactivity and neuroinflammation. Similarly, alteration in total tau and phosphorylated tau levels may suggest dysfunction in neuronal cytoskeleton and axonal integrity. The review also focuses on target-engagement biomarkers, including polyglutamine-expanded ataxin proteins in spinocerebellar ataxias and frataxin in Friedreich's ataxia, as critical tools to complement the ataxia biomarker toolkit. The quantification of mutant ataxin proteins provides a mechanistic readout for emerging gene-silencing or protein-lowering therapies. In parallel, the measurement of frataxin levels serves as a pharmacodynamic marker in therapeutic strategies aiming to restore frataxin expression. These target-engagement biomarkers are valuable in early phases of clinical trials, which mainly aim to demonstrate the biological activity of a treatment before later-phase trials assessing clinical efficacy. Finally, we report on somatic instability in polyglutamine spinocerebellar ataxias as an emerging and highly relevant therapeutic target. CAG repeat mosaicism is gene specific and correlates with disease progression. Integrating measures of repeat instability with neurodegenerative biomarkers could provide a comprehensive monitoring approach in clinical studies. This overview underscores the potential of fluid biomarkers, particularly neurofilament light chain, in accelerating therapeutic development for hereditary ataxias.

Sleep restriction disrupts circadian organization and represents a behavioral condition with systemic consequences that extend beyond the central nervous system. In this study, we evaluated structural and cellular changes in the distal colon of rats exposed to sustained sleep restriction. Sixteen male Rattus norvegicus were assigned to a control group (n = 8) or a sleep-restricted group (n = 8) and subjected to a modified multiple-platform protocol for 21 days. Blood samples were collected for inflammatory assessment, and the distal colon was analyzed using histochemical and immunohistochemical approaches. Sleep-restricted rats exhibited reduced body mass gain and an increased proportion of polymorphonuclear leukocytes. In the distal colon, sleep restriction increased mucosal thickness and crypt depth, depleted goblet cells, and caused mast cell hyperplasia. It also produced quantitative and morphometric changes in neurons and enteric glial cells in the myenteric and submucosal plexuses. Notably, these alterations occurred in the absence of macroscopic mucosal lesions. Together, these findings demonstrate that sustained sleep restriction promotes coordinated remodeling of distal colonic histoarchitecture, epithelial composition, immune-related cells and enteric neuro-glial organization. Considering that sleep restriction disrupts circadian entrainment and alters behavioral patterns such as feeding, these results support the concept that intestinal remodeling represents a peripheral consequence of circadian disruption.