Introduction: Staphylococcus aureus is the leading biofilmforming microorganisms in orthopaedic implant infections. The biofilms formed are difficult to eradicate and resistance to antibiotics. This current study aims to determine the effectiveness of povidone-iodine; an antiseptic solution in eradicating S. aureus biofilm on stainless steel alloy. In addition to the usual Colony-Forming Unit (CFU) used for verification, Scanning Electron Microscope (SEM) is used to validate the formation and eradication of the biofilms. Materials and methods: This is an in vitro study where the biofilm is formed by inoculating clinically isolated S. aureus, incubated for 24 hours onto stainless steel alloy 316L implants. The implants are then irrigated using povidoneiodine solution with varying concentrations (5 and 10%) and durations (30, 60, and 180 seconds). The anti-biofilm effect was evaluated using plating and SEM methods to confirm its effectiveness. The process is repeated after 24 hours of postirrigation reincubation to detect any rebound growth. Results: No biofilm seen after irrigation with povidoneiodine at 5% and 10% concentrations at 30, 60 and 180 seconds, respectively, in both CFU count and SEM. This result is replicated after 24 hours of reincubation, in assessing for rebound growth. Conclusion: Our study supports that a minimum of 5% povidone-iodine with a minimum irrigation time of 30 seconds are effective at eliminating S. aureus biofilm on stainless steel alloy implants. Both CFU count and SEM yield similar value in validating the presence of biofilm. Additionally, SEM allows visualisation of the morphology of the biofilm.

Objective To systematically evaluate the risk prediction models for postoperative delirium in adults with cardiac surgery. Methods The SinoMed, CNKI, Wanfang, VIP, PubMed, EMbase, Web of Science, and Cochrane Library databases were searched to collect studies on risk prediction models for postoperative delirium in cardiac surgery published up to January 29, 2025. Two researchers screened the literature according to inclusion and exclusion criteria, used the PROBAST bias tool to assess the quality of the literature, and conducted a meta-analysis of common predictors in the model using Stata 17.0 software. Results A total of 21 articles were included, establishing 45 models with 28733 patients. Age, cardiopulmonary bypass time, history of diabetes, history of cerebrovascular disease, and gender were the top five common predictors. The area under the curve (AUC) of the 45 models ranged from 0.544 to 0.98. Fourteen out of the 21 studies had good applicability, while the applicability of the remaining seven was unclear; 20 studies had a high risk of bias. Meta-analysis showed that the incidence of postoperative delirium in adults with cardiac surgery was 18.6% [95%CI (15.7%, 21.6%)], and age [OR=1.045 (1.036, 1.054), P<0.001], history of cerebrovascular disease [OR=1.758 (1.459, 2.057), P<0.001], gender [OR=1.732 (1.430, 2.034), P<0.001], mini-mental state examination score [OR=3.930 (1.859, 8.309), P<0.001], and length of ICU stay [OR=5.586 (4.289, 6.883), P<0.001] were independent influencing factors for postoperative delirium after cardiac surgery. Conclusion The risk prediction models for postoperative delirium after cardiac surgery have good predictive performance, but there is a high overall risk of bias. In the future, large-sample, multicenter, high-quality prospective clinical studies should be conducted to construct the optimal risk prediction model for postoperative delirium in adults with cardiac surgery, aiming to identify and prevent the occurrence of postoperative delirium as early as possible.

Background: Access to advanced histomolecular diagnostic testing for central nervous system(CNS) tumors is limited in low and middle-income countries (LMICs), hindering adequate characterization and failure to reach a WHO CNS 2021 diagnosis. LMICs also lack access to targeted therapies, and even conventional chemotherapy and radiation therapies vary between LMICs and high-income countries. Consequently, whether histomolecular subclassification is clinically beneficial and if it provides prognostic information in an LMIC setting is not clear. Here, we address this question by presenting the first systematic prospective study of CNS glioma patients from Pakistan, examining differences in overall survival (OS) by histomolecular subtype. Methods: A total of 194 patients with CNS tumors were enrolled at a single tertiary-care centerin Karachi, Pakistan. Routine histochemical processing, immunohistochemistry, and molecular testing using fluorescence in situ hybridization analysis, limited targeted-panel next-generation sequencing, and polymerase chain reaction were performed to test for isocitrate dehydrogenase (IDH) 1 and 2, P53, ATRX, Ki-67, 1p/19q co-deletion, and MGMT promoter methylation. Results: The results revealed that IDH status was a significant independent prognostic factor,regardless of age (p=0.016), with a 1-year survival rate of 76% and median OS of 16.15 months in IDH-wildtype high-grade gliomas. Conversely, the 1-year survival rate was 95% for IDH-mutant gliomas. Significant survival differences were observed for ATRX status (retained vs. loss) in IDH-mutant gliomas (p=0.046), P53 mutations in IDH-wildtype high-grade gliomas (p=0.05), and 1p/19q co-deletion in grade 3 gliomas (log-rank p=0.023). Conclusion We provide empirical evidence supporting a role for histo-morphological and limitedmolecular testing in neuro-oncology practice in LMICs.

Objective: Cyclophosphamide (CP), a chemotherapeutic agent, has been shown to inhibit spermatogenesis. Accordingly, the primary objective of this study was to evaluate the potential therapeutic benefits of quercetin‑loaded nanoselenium (quercetin‑loaded selenium nanoparticles [SeNPs]) in mice treated with CP. Methods: Thirty‑five adult male mice were randomly assigned to five groups (n=7 per group): control, quercetin‑loaded SeNPs (20 mg/kg, daily for 5 weeks), CP (200 mg/kg, single dose), treatment A (CP+quercetin‑loaded SeNPs), and treatment B (CP+quercetin, 20 mg/kg daily for 5 weeks). Sperm parameters, DNA fragmentation index, catalase activity, levels of glutathione (GSH), glutathione disulfide (GSSG), malondialdehyde (MDA), and reactive oxygen species (ROS) were evaluated in all groups, along with histological assessments of testicular tissue. Results: In CP‑treated mice, administration of quercetin‑loaded SeNPs (treatment A) significantly improved sperm parameters, including total count, motility, morphology, and DNA integrity. Treatment also markedly increased the numbers of spermatogonia, primary spermatocytes, spermatids, Sertoli cells, and Leydig cells in testicular tissue. Furthermore, treatment with quercetin‑loaded SeNPs resulted in a significant increase in catalase activity and GSH levels while significantly reducing GSSG, MDA, and ROS levels in CP‑induced testicular damage. Conclusion These findings suggest that quercetin‑loaded SeNPs enhance spermatogenesis in a CP‑induced mouse model by improving the antioxidant profile and testicular stereological parameters.

Introduction: Obesity is a complex metabolic condition associated with significant cardiometabolic risks. The Comprehensive Metabolic Therapy (CoMeT) programme is a multidisciplinary intervention designed to address these risks through integrated medical management, physiotherapy, and dietary counseling. This pilot study aimed to evaluate the effectiveness of the CoMeT programme on anthropometric, metabolic, and body composition parameters in adults with obesity. Methodology: We conducted a pilot pre–post study involving 11 adults with obesity (BMI ≥27.5 kg/m²) enrolled in the CoMeT programme at Hospital Putrajaya. Assessments at baseline and post-intervention included anthropometric measures (weight, BMI, waist circumference), metabolic parameters (hemoglobin A1c [HbA1c]), and body composition (skeletal muscle mass [SMM], body fat percentage) using InBody 970 bioelectrical impedance analysis. Data were analyzed using SPSS version 29.0. Results: The mean age was 38.5 ± 8.9 years, with baseline weight 134.7 ± 20.9 kg and BMI 49.8 ± 9.0 kg/m². Three participants defaulted follow-up, leaving eight for post-intervention analysis. The mean weight reduction was 2.1 ± 6.4 kg (1.6 ± 5.0%). Notably, the greatest reduction (−12.5%) occurred in a participant with high adherence to both the dietary and physiotherapy components of the intervention. Participants receiving GLP-1 receptor agonists (oral semaglutide) also demonstrated weight reduction (mean −2.5 kg). Conversely, weight gain was observed in some participants despite diet modifications, potentially due to low physiotherapy attendance or baseline metabolic factors. HbA1c improved modestly (−0.19 ± 0.29%). Body composition changes were minimal, with slight reductions in body fat percentage (−0.13 ± 1.2%) and SMM (−0.49 ± 1.88 kg). Conclusion The CoMeT programme shows promising early-stage effectiveness in improving anthropometric and metabolic outcomes with the greatest benefits observed in patients achieving high multidisciplinary adherence and adjunct pharmacotherapy. These findings highlight the potential of a multidisciplinary approach in managing high-grade obesity and emphasize the need for larger-scale studies to further validate these outcomes and optimize targeted lifestyle and therapeutic interventions
Body Composition ; Adult ; Obesity

Introduction: The growing popularity of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for weight management has inadvertently perpetuated demand for unregulated experimental peptides procured through gray markets. Retatrutide, a novel triple GLP-1/glucose-dependent insulinotropic polypeptide (GIP)/glucagon receptor agonist undergoing Phase III trials; AOD -9604, an abandoned synthetic human growth hormone fragment; and tesamorelin, a synthetic GHRH analogue, are increasingly self-administered without medical supervision. Their combined metabolic and thromboembolic risks remain unknown and unreported. Case: A 50-year-old Malaysian female with morbid obesity and poorly controlled type 2 diabetes mellitus (hemoglobin A1c 13%) presented with acute dyspnea, chest tightness, syncope, and cardiogenic shock. Three weeks prior, she had self-initiated subcutaneous retatrutide, AOD-9604, and tesamorelin procured through unregulated online platforms, achieving rapid weight loss of 10 kg. Despite markedly reduced oral intake from GLP-1-mediated gastrointestinal side effects, she continued her prescribed high-dose insulin regimen and sodium-glucose cotransporter-2 (SGLT2) inhibitor without dose adjustment. She developed concurrent diabetic ketoacidosis, confirmed biochemically, alongside massive saddle pulmonary embolism with right ventricular strain on echocardiography and computed tomography pulmonary angiography. She was successfully treated with systemic thrombolysis using alteplase, guideline-directed diabetic ketoacidosis management including fixed-rate insulin infusion and fluid resuscitation, and anticoagulation. The SGLT2 inhibitor was withheld throughout admission. She was discharged on rivaroxaban with counseling to cease all unregulated compounds. All three agents were submitted to the National Pharmaceutical Regulatory Authority/Malaysian Adverse Drug Reactions Advisory Committee for adverse drug reaction reporting. Conclusion To our knowledge, this is the first reported case of concurrent massive pulmonary embolism and diabetic ketoacidosis precipitated by unsupervised gray-market retatrutide, AOD-9604, and tesamorelin. Clinicians should enquire about unregistered supplement use, counsel insulin-dependent patients on sick-day rules when appetitesuppressing agents are initiated, and report adverse events to pharmacovigilance authorities.
AOD 9604 ; tesamorelin ; Diabetic Ketoacidosis ; Pulmonary Embolism ; Peptides

Introduction: New-onset diabetes after transplantation (NODAT) is a clinically significant complication associated with adverse metabolic and graft outcomes and affects patients’ quality of life. Data in paediatric populations are limited. This case series describes the incidence, clinical characteristics, and early outcomes of NODAT in a paediatric kidney transplant cohort. Cases: Thirty patients (aged 5–17 years; 16 males, 14 females; 14 Malay, 15 Chinese, 1 Indian) underwent renal transplantation at Hospital Tunku Azizah between 2019 and 2025. NODAT was identified using standard diagnostic criteria and occurred in four patients (13.3%). Among patients who developed NODAT, three were Malay and one Chinese; all were aged 10–17 years, with a predominance of females (n = 3). All were non-obese (body mass index [BMI]: 11–21.4 kg/m²), and only one had a family history of type 2 diabetes mellitus. Underlying causes of ESRF in these patients included focal segmental glomerulosclerosis (FSGS, n = 2), CAKUT (n = 1), and unknown etiology (n = 1). Two patients received kidneys from living donors, and two from cadaveric donors. Two patients demonstrated reduced C-peptide levels, consistent with impaired insulin secretion. All patients received steroid induction and maintenance therapy alongside tacrolimus-based immunosuppression, with one patient also receiving everolimus. Two patients developed post-transplant CMV viremia, which has been associated with NODAT. The onset of NODAT was early, occurring within 2 weeks post-transplant in three patients and at 1 month in one patient. Insulin therapy achieved glycemic control in all cases. Two patients were able to discontinue insulin within 3–4 months, suggesting recovery of endogenous glycemic regulation, while the remaining two required ongoing insulin therapy. Conclusion NODAT affects a substantial proportion of paediatric kidney transplant recipients and may present despite the absence of conventional risk factors. Early surveillance is essential. The observed potential for insulin independence may indicate a reversible component of β-cell dysfunction, which warrants further investigation in larger cohorts.
Child ; Kidney Transplantation ; Hospitals

Introduction: RENI syndrome (renal, endocrine, neurologic, and immune syndrome), also known as sphingosine-1-phosphate lyase insufficiency syndrome (SPLIS), is a rare autosomal recessive disorder caused by pathogenic variants in the SGPL1 gene. This gene encodes sphingosine-1- phosphate lyase, an enzyme responsible for the final step in sphingolipid degradation. Impaired enzyme activity results in the accumulation of sphingolipid intermediates, leading to multisystem involvement affecting the kidneys, adrenal glands, skin, immune system, and nervous system. Frequently reported manifestations include steroid-resistant nephrotic syndrome, primary adrenal insufficiency, ichthyosis, and neurological abnormalities. Case: We report a 15-year-old male with a history of primary adrenal insufficiency diagnosed at age three after presenting with recurrent vomiting and abdominal pain. He was started on steroid replacement therapy and remained stable without episodes of adrenal crisis. He also had ichthyosis requiring dermatological follow-up. During routine surveillance, persistent proteinuria was detected, and urinary protein excretion increased over time. Ultrasound showed renal parenchymal changes despite preserved renal function. Whole-exome sequencing identified a homozygous variant of uncertain significance in the SGPL1 gene, consistent with RENI syndrome. He was started on enalapril for his proteinuria and continues to undergo multidisciplinary follow-ups. Both parents are consanguineous, but were not screened. Mutations in SGPL1 have increasingly been recognized as a monogenic cause of syndromic steroid-resistant nephrotic syndrome, associated with endocrine and dermatological features. Renal histopathology in cases reported often shows focal segmental glomerulosclerosis, reflecting podocyte injury due to disruption of sphingolipid signaling pathways. Early recognition is crucial, as patients need multidisciplinary care. Conclusion This case highlights the importance of considering RENI syndrome in patients presenting with early-onset primary adrenal insufficiency accompanied by renal and dermatological symptoms. Increased clinical awareness and prompt genetic testing can enable earlier diagnosis, guide long-term monitoring, and support appropriate genetic counseling.
Adrenal Insufficiency ; Proteinuria ; Ichthyosis

Introduction: Growth hormone deficiency (GHD) is a recognized endocrine complication among childhood cancer survivors resulting from disruption of hypothalamic–pituitary axis due to tumors, neurosurgery, or cranial irradiation. While recombinant human growth hormone (rhGH) therapy improves growth and metabolic outcome, concerns remain regarding its long-term safety with risk of tumor recurrence and secondary neoplasm. We present a case series of five paediatric oncology survivors with confirmed GHD receiving rhGH in Hospital Tunku Azizah, highlighting our clinical experience in comparison with international practice. Case: Five paediatric oncology survivors (acute lymphoblastic leukemia, craniopharyngioma, medulloblastoma, and supratentorial PNET) with GHD were commenced on rhGH therapy 2.5–5.5 years after completion of cancer treatment. All patients had significant short stature with a mean height SDS of −3.22 prior to the initiation of therapy. GHD was confirmed biochemically with low IGF-1 level and dynamic testing (peak GH 0.35–4.61 ng/mL). Among the four patients with brain tumors, two had stable residual disease while the remaining were tumor-free. rhGH therapy was temporarily ceased in two patients due to minor increment in tumor size but was successfully resumed following stabilization without further complications to date. Two patients are concurrently on pubertal induction. Most patients demonstrated catch-up growth with increased height velocity, supporting the efficacy of rhGH in this population. No secondary malignancies or significant adverse events were observed during follow-up. Conclusion Paediatric oncology survivors with GHD in this series demonstrated a favorable response to rhGH therapy, evidenced by improvements in height SDS and growth velocity, while maintaining oncological stability in the majority of cases. Our findings are consistent with international data, supporting cautious but appropriate use of rhGH in this population. Careful patient selection and close multidisciplinary monitoring remain essential.
Child ; Neoplasms ; Growth Hormone ; Survivors

Background: The most common clinical manifestation of HCV infection, which includes both hepatic and extrahepatic manifestations, is mixed cryoglobulinemia, which is characterized by the precipitation of certain proteins in the blood at temperatures below 37°C (in vitro), aggregation, and deposition in the walls of small and medium-sized vessels, causing vasculitis, which is clinically manifested by a triad of joint pain, fatigue, and rash on the soles of the feet. Cryoglobulinemia is commonly diagnosed in people with HCV infection, with a prevalence ranging from 10% to 70%. Vasculitis that occurs when cryoglobulinemia is detected mainly affects the small vessels of the skin, kidneys, and peripheral nerves, causing complications in other organ systems. Aim : To determine the prevalence of cryoglobulinemia in people with HCV infection, study it in relation to the stage of liver fibrosis, and determine its clinical relevance. Materials and Methods : 200 chronic HCV infected individuals were included in the study according to the inclusion and exclusion criteria. After obtaining informed consent from each participant, a questionnaire was used to collect information, perform physical measurements, and collect peripheral blood samples. Complete blood count and biochemical tests (liver and kidney function) were performed. The degree of liver fibrosis was assessed non-invasively (APRI, FIB4). The glomerular filtration rate was calculated electronically using the MDRD GFR Equation. Skin examination was performed to assess the presence of rash, ulcers, and scarring on the shins and ankles of cryoglobulinemia. To determine cryoglobulinemia, 8 ml of blood was collected in a tube without anticoagulant, and the sample was kept motionless for 1 hour at room temperature until clotting was complete. After centrifugation, the samples were separated and stored in a refrigerator at +4°C for 7 days, and then at room temperature for 30 minutes, the precipitate was detected. Results : A total of 200 people participated in the study, of which 71 were men (35.5%), the average age was 53.39±13.0. Cryoglobulinemia protein precipitates were determined in a total of 148 people, of which 50 were men (33.8%), the average age was 52.95±13.0. Cryoglobulinemia protein precipitates were detected in 89 people, or 60.1% of the study participants. Of the total study participants, 176 (88.0%) had chronic hepatitis C (CHC). Of these, 57 people had CHC with cryoglobulinemia. Comparing laboratory parameters, the mean GGT level in the cryoglobulinemia group was statistically significantly higher than in the non-cryoglobulinemia group (p=0.039). However, when laboratory parameters were grouped by increasing or decreasing, AST and ALT levels were significantly higher in the cryoglobulinemia group, indicating more hepatocellular damage (p<0.000). Increased creatinine levels may be associated with the risk of renal dysfunction. The FIB-4 index and APRI index showed a more severe degree of fibrosis in the cryoglobulinemia group (p<0.005; p<0.000). Univariate logistic regression analysis showed that age was associated with the occurrence of cryoglobulinemia (OR=2.48; 95% CI:1.31–4.70; p=0.005). Platelet count had a statistically significant positive effect in multivariate analysis (OR=14.38; 95% CI:1.26–163.89; p=0.032). Conclusion The prevalence of cryoglobulinemia among HCV-infected patients was 60.1%, and older age and decreased platelet count among infected individuals were associated with the occurrence of cryoglobulinemia.