The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily affects the respiratory system but can also involve multiple organs, including the often-overlooked ocular system. An increasing number of population-based and retrospective case series studies have reported that ocular and neuro-ophthalmic complications are temporally associated with COVID-19 infection and vaccination. Furthermore, some data suggest a modest increase in ocular adverse events (OAEs) following infection or vaccination, particularly among individuals with autoimmune or pre-existing ocular conditions. The proposed immune-mediated mechanisms include immune responses following vaccination that may contribute to demyelination through molecular mimicry, a phenomenon in which antigens share structural or functional similarities with host self-antigens. In this review, we summarize studies published between 2019 and June 2025, retrieved from PubMed and Google Scholar databases. Studies were selected based on their clinical relevance and contribution to the understanding of OAEs in the context of SARS-CoV-2 infection and COVID-19 vaccination. Thematic tables highlight the clinical spectrum of reported ocular manifestations, ranging from common conditions such as uveitis, optic neuritis, retinal vascular occlusions, and cranial nerve palsies to rarer entities, including acute macular neuroretinopathy, thyroid eye disease, and papillophlebitis. This review presents recent evidence on the proposed pathophysiological mechanisms and risk profiles of COVID-19-related OAEs, with the aim of improving awareness, promoting timely ophthalmic evaluation, and supporting surveillance and future research to clarify causality and inform preventive strategies.

Introduction: Insulin deintensification is an emerging strategy to reduce hypoglycemia and treatment burden in patients on multiple daily injection (MDI ≥3), with potential to improve adherence and glycemic control. However, evidence in poorly controlled type 2 diabetes mellitus (T2DM) remains limited. This study evaluated its effectiveness and identified factors associated with achieving adequate glycemic control following deintensification among patients with poorly controlled T2DM attending Malaysian primary care. Methodology: A retrospective cohort study was conducted among 107 T2DM patients with hemoglobin A1c (HbA1c) >9%, attending Enhanced Diabetic Clinic at Cheras Health Clinic between 2021 and 2025. All patients on basal-bolus insulin (BBI) underwent deintensification. Multivariate logistic regression was performed to identify factors associated with achieving adequate glycemic control (HbA1c <7.5%). Changes in HbA1c following deintensification were assessed using paired t-tests. Results: Overall, 50.5% of patients achieved adequate glycemic control. Hypoglycemia events (AOR 9.5, 95% confidence interval [CI] 1.6–58.3; p = 0.015), MDI (AOR 9.6, 95% CI 1.4–67.1; p = 0.023) and Diabetes Medication Therapy Adherence Clinic (DMTAC) visits (AOR 1.1, 95% CI 1.0– 1.2; p = 0.039) were significantly associated with achieving HbA1c <7.5%. Conversely, patients transitioned from BBI to premixed regimens were less likely to achieve HbA1c <7.5% (AOR 0.22, 95% CI 0.05–0.93, p = 0.039). All insulin deintensification strategies were associated with significant HbA1c improvements with transitioned from BBI to premixed human insulin (mean difference -2.54%, 95% CI 1.77–3.31, p <0.001, Cohen’s d = 1.09), BBI to premixed analogue insulin (mean difference -3.38%, 95% CI 2.26– 4.49, p <0.001, Cohen’s d = 1.62), BBI to basal insulin (mean difference -3.67%, 95% CI 1.79–5.54, p = 0.004, Cohen’s d = 2.05). Conclusion Insulin deintensification is an effective strategy for improving glycemic control in poorly controlled T2DM. These findings highlight the importance of deintensification with careful consideration of hypoglycemia, MDI-related treatment burden, and patient engagement through regular DMTAC visits, which are integral to achieving optimal outcomes and support a personalized approach to diabetes management in primary care.
Diabetes Mellitus, Type 2 ; Glycemic Control ; Retrospective Studies ; Primary Health Care ; Insulins

Introduction: Polycystic ovarian syndrome (PCOS) is a complex endocrine disorder that significantly affects adolescent girls, particularly those with overweight or obesity. However, data examining the determinants and metabolic profiles of PCOS among adolescents with overweight and obesity remain limited, especially in Malaysia. This protocol describes a case-control study investigating the cardiometabolic, dietary, and psychosocial determinants of PCOS among adolescents with overweight and obesity. Methodology: This study is designed as a case-control study involving adolescent girls aged 13–16 years with a body mass index z-score >+1 standard deviation. Cases are defined as adolescent girls with a confirmed diagnosis of PCOS based on the recommendations of the 2017 International Consortium of Paediatric Endocrinology (ICPE), while controls are those who do not meet the diagnostic criteria for PCOS. A total sample size of 440 participants is required. Participants will be recruited from 22 secondary schools selected from a list of schools in Kuala Lumpur. Data on sociodemographic characteristics, psychosocial health, physical activity, and dietary intake will be collected using structured questionnaires. Blood samples will be obtained and analyzed for diagnostic testing (free testosterone), exclusion tests (thyroid-stimulating hormone, folliclestimulating hormone, luteinizing hormone, estradiol, prolactin, and dehydroepiandrosterone sulfate), and biochemical parameters (liver function tests, lipid profile, hemoglobin A1c, fasting glucose, fasting insulin, and inflammatory markers). Results: The study is expected to generate comprehensive data on the cardiometabolic, dietary, and psychosocial determinants of PCOS among adolescents with overweight and obesity. The findings will inform early screening strategies and targeted interventions aimed at reducing long-term reproductive and cardiometabolic complications. Conclusion This protocol outlines a structured approach to investigating PCOS in adolescence and addresses current gaps in early identification and risk stratification among highrisk populations.
Adolescent ; Humans ; Case-Control Studies ; Overweight ; Polycystic Ovary Syndrome ; Obesity

Introduction: Pituitary stalk interruption syndrome (PSIS) is a rare congenital disorder characterized by the neuroradiological triad of an absent or interrupted pituitary stalk, ectopic posterior pituitary, and anterior pituitary hypoplasia. It is typically diagnosed in infancy or childhood due to growth failure or delayed puberty. Diagnosis in adulthood is uncommon and may occur after decades of untreated hypopituitarism. Case: A 34-year-old Malay male with underlying physical and intellectual disability presented after a mechanical fall resulting in left slipped capital femoral epiphysis, an unusual pathological fracture in adulthood. Clinical examination revealed marked infantilism with complete absence of secondary sexual characteristics (Tanner stage I). Laboratory evaluation demonstrated combined pituitary hormone deficiency, including severe central hypothyroidism, profound hypogonadotropic hypogonadism, and central adrenal insufficiency. Growth hormone and insulin-like growth factor 1 were undetectable, while prolactin was mildly elevated, consistent with pituitary stalk disruption due to loss of hypothalamic dopaminergic inhibition. Bone age assessment showed severe delay, corresponding to 15 years. Pituitary magnetic resonance imaging demonstrated the classical PSIS triad: anterior pituitary hypoplasia with partial empty sella, a high T1 signal nodule at the median eminence representing ectopic posterior pituitary, and non-visualization of the infundibulum, consistent with an absent pituitary stalk. Birth history revealed premature breech delivery, a recognized perinatal risk factor. The patient was commenced on hormone replacement therapy, including levothyroxine, hydrocortisone, testosterone undecanoate, and calcium–vitamin D supplementation. Conclusion This case illustrates that PSIS may remain undiagnosed into adulthood, leading to severe consequences of long-standing hypopituitarism such as osteoporosis and pathological fractures. Clinicians should consider hypopituitarism in adults presenting with unexplained fractures and delayed sexual maturation, particularly when supported by a suggestive perinatal history.
Fractures, Spontaneous ; Pituitary Gland

Microangiopathic hemolytic anemia (MAHA) is a rare subtype of hemolytic anemia characterized by elevated hemolytic markers and red blood cell destruction. Though uncommon, MAHA can occur as a complication of acute pancreatitis because of the associated inflammatory response. Patients with MAHA secondary to pancreatitis show favorable outcomes when treated with plasma exchange.This paper presents the case of a patient diagnosed with acute pancreatitis-induced hemolytic anemia and thrombocytopenia, who was managed successfully with plasma exchange, steroids, and rituximab. Clinicians should maintain a high index of suspicion in patients with acute pancreatitis who present with anemia, thrombocytopenia, and schistocytes on peripheral smears, even in the absence of end-organ injuries and with normal ADAMTS13 activity. The early initiation of plasmapheresis can be lifesaving. The timely introduction of rituximab in cases where plasma exchange and steroids are insufficient, despite the ADAMTS13 activity status, may lead to better outcomes.

Microangiopathic hemolytic anemia (MAHA) is a rare subtype of hemolytic anemia characterized by elevated hemolytic markers and red blood cell destruction. Though uncommon, MAHA can occur as a complication of acute pancreatitis because of the associated inflammatory response. Patients with MAHA secondary to pancreatitis show favorable outcomes when treated with plasma exchange.This paper presents the case of a patient diagnosed with acute pancreatitis-induced hemolytic anemia and thrombocytopenia, who was managed successfully with plasma exchange, steroids, and rituximab. Clinicians should maintain a high index of suspicion in patients with acute pancreatitis who present with anemia, thrombocytopenia, and schistocytes on peripheral smears, even in the absence of end-organ injuries and with normal ADAMTS13 activity. The early initiation of plasmapheresis can be lifesaving. The timely introduction of rituximab in cases where plasma exchange and steroids are insufficient, despite the ADAMTS13 activity status, may lead to better outcomes.

Microangiopathic hemolytic anemia (MAHA) is a rare subtype of hemolytic anemia characterized by elevated hemolytic markers and red blood cell destruction. Though uncommon, MAHA can occur as a complication of acute pancreatitis because of the associated inflammatory response. Patients with MAHA secondary to pancreatitis show favorable outcomes when treated with plasma exchange.This paper presents the case of a patient diagnosed with acute pancreatitis-induced hemolytic anemia and thrombocytopenia, who was managed successfully with plasma exchange, steroids, and rituximab. Clinicians should maintain a high index of suspicion in patients with acute pancreatitis who present with anemia, thrombocytopenia, and schistocytes on peripheral smears, even in the absence of end-organ injuries and with normal ADAMTS13 activity. The early initiation of plasmapheresis can be lifesaving. The timely introduction of rituximab in cases where plasma exchange and steroids are insufficient, despite the ADAMTS13 activity status, may lead to better outcomes.

Colorectal cancer (CRC), a major global health concern, necessitates innovative treatments. Chimeric antigen receptor (CAR) T cells have shown promises, yet they grapple with challenges. The spotlight pivots to the rising heroes: CAR natural killer (NK) cells, offering advantages such as higher safety profiles, cost-effectiveness, and efficacy against solid tumors. Nevertheless, the specific mechanisms underlying CAR NK cell trafficking and their interplay within the complex tumor microenvironment require further in-depth exploration. Herein, we provide insights into the design and engineering of CAR NK cells, antigen targets in CRC, and success in overcoming resistance mechanisms with an emphasis on the potential for clinical trials.
Colorectal Neoplasms/immunology* ; Humans ; Killer Cells, Natural/metabolism* ; Receptors, Chimeric Antigen/genetics* ; Immunotherapy, Adoptive/methods* ; Tumor Microenvironment/immunology* ; Animals

Multiple morphological abnormalities of the flagella (MMAF) represent a severe form of sperm defects leading to asthenozoospermia and male infertility. In this study, we identified a novel homozygous splicing mutation (c.871-4 ACA>A) in the adenylate kinase 7 (AK7) gene by whole-exome sequencing in infertile individuals. Spermatozoa from affected individuals exhibited typical MMAF characteristics, including coiled, bent, short, absent, and irregular flagella. Transmission electron microscopy analysis showed disorganized axonemal structure and abnormal mitochondrial sheets in sperm flagella. Immunofluorescence staining confirmed the absence of AK7 protein from the patients' spermatozoa, validating the pathogenic nature of the mutation. This study provides direct evidence linking the AK7 gene to MMAF-associated asthenozoospermia in humans, expanding the mutational spectrum of AK7 and enhancing our understanding of the genetic basis of male infertility.
Humans ; Male ; Sperm Tail/ultrastructure* ; Homozygote ; Consanguinity ; Asthenozoospermia/pathology* ; Infertility, Male/genetics* ; Mutation ; Pakistan ; Adenylate Kinase/genetics* ; Adult ; Pedigree ; RNA Splicing ; Exome Sequencing ; Spermatozoa