Abstract Hyperkalemia (serum potassium >5.0 mEq/l) is a significant complication in patients with heart failure, chronic kidney disease, and diabetes mellitus, particularly when treated with renin-angiotensin-aldosterone system inhibitors (RAASi). Both hyperkalemia and RAASi interruption are associated with increased cardiovascular events, hospitalizations, and mortality. This expert opinion document, developed between January and December 2024 through a systematic process, aims to establish guidance for hyperkalemia treatment in Indonesian patients with cardiorenal diseases receiving RAASi therapy, addressing the unique challenges within the Indonesian healthcare context. A comprehensive literature review of international guidelines and regional studies was conducted by a panel of 11 expert specialists (3 cardiologists, 6 internist-nephrologists, and 2 internist-cardiologists), who evaluated 29 statements covering diagnosis, monitoring, prevention, and treatment of hyperkalemia. Of the 29 statements, 26 reached consensus: 17 statements achieved very high agreement (≥90%) and 9 attained high agreement (≥67% – <90%). The agreed statements covered key areas, including potassium monitoring frequency, RAASi dose optimization strategies, dietary modifications, and treatment thresholds. Three statements regarding alternative therapeutic approaches did not receive agreement (<67%) due to limited local availability and cost considerations. Key recommendations include structured monitoring protocols for high-risk patients, strategies for RAASi dose optimization while managing hyperkalemia risk, and specific interventions adapted to local resources. This document provides a practical approach for managing hyperkalemia in Indonesian patients with cardiorenal diseases while maintaining optimal RAASi therapy, considering local Indonesian healthcare resources and constraints.
Hyperkalemia ; Cardio-Renal Syndrome ; Renin-Angiotensin System ; Indonesia

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.

Purpose: The present study investigates the psychological factors impacting female cancer patients receiving radiotherapy and the individuals providing care for them, within a sociocultural environment that frequently marginalizes and depends on women. This research highlights a strategy for cancer care that may enhance results for both patients and caregivers by attending to psychosocial needs. The primary objectives are to measure the levels of anxiety, depression, quality of life, and perceived stress in both patients and caregivers, as well as to determine how psychosocial counseling affects these factors. Methods: It was a single-group pre-post observational study. Before starting radiotherapy, assessment of various psychosocial factors was done in female cancer patients and their respective caregivers. Psychosocial counseling sessions were conducted at weekly intervals during radiotherapy. At the 6th week after radiotherapy, assessment of same psychosocial factors was done again in both the patients as well as their caregivers. Results: The results show that both patients and caregivers had serious psychological disorders, such as anxiety, depression, perceived stress, and decreased quality of life. Psychosocial modulation was associated with improvement in quality of life measures like overall health and emotional and physical functioning. Conclusion The findings highlight how crucial it is to include psychological support in radiotherapy regimens. Despite limitations of the study, such as its exclusive focus on female patients, the results highlight the need to provide clinical staff with psycho-oncological training. The study recommends further investigation to ascertain the long-term effects of psychological health on treatment compliance and patient survival.

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: 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

AIM: To identify various risk factors that may play a significant role in the development of congenital nasolacrimal duct obstruction(CNLDO).METHODS: This observational case-control study included a case group of 122 children less than two years of age with CNLDO who underwent probing and irrigation treatment at the ophthalmology department of Imam Khomeini Hospital in Ahvaz, Iran, from June 2022 to June 2024. A control group of 122 age-matched children without CNLDO was also included for comparison. Data was collected from the children's medical records. RESULTS:The study found a significant correlation between the occurrence of CNLDO and several maternal factors, such as preeclampsia, the use of levothyroxine, hypothyroidism, having more than three pregnancies(gravidity >3), natural pregnancy, and gestational diabetes mellitus. Additionally, in children, factors, such as oxygen therapy, anemia, reflux, jaundice, and a family history of CNLDO in first-degree relatives were associated with CNLDO, and maternal preeclampsia and hypothyroidism were found to significantly increase the risk of developing CNLDO in children.CONCLUSION: Given that CNLDO affects both premature and full-term children, the present findings may potentially facilitate the early identification of children and infants at risk of nasolacrimal duct obstruction, thereby preventing the onset of chronic dacryocystitis.

Breast cancer is one of the most common causes of death all over the world. Therapeutic options applied to the patients include surgery, chemotherapy, and radiotherapy.However, far advanced disease often leads to chemoresistance and toxicity. Innovative therapies are needed to address these challenges. Melatonin has the potential to prevent and treat cancer, as it has been revealed in numerous clinical studies. Melatonin is a nontoxic agent that is mostly produced in the pineal gland, inducing various mechanisms of action such as the induction of apoptosis, antiangiogenic, antiproliferative, and metastasis-inhibitory effects. Therefore, melatonin increases therapeutic sensitivity when combined with conventional medication in breast cancer. Melatonin (3-20 mg/day) may reduce breast cancer cell growth in preclinical studies and enhance chemotherapy efficacy. Small human trials suggest potential benefits, but larger studies are needed. Higher doses (≥20 mg/day) are sometimes used alongside chemotherapy. This manuscript reviews research that has demonstrated the antitumor properties of melatonin, thereby focusing on its actions on angiogenesis, apoptosis, metastasis, and antiproliferative properties. We also discuss recent advances in the understanding of the actions of melatonin on epigenetic mechanisms (especially DNA methylation) and telomere length. The data in this review were obtained from journal articles up to May 2024.Regarding the study, Google Scholar and ScienceDirect were used as engines to search for open access. We searched the ISI, Pubmed and Scopus as valid external databases, and as internal databases, ISC and Iran medex. By finding mean keywords such as ‘breast cancer’, ‘estrogen’, ‘melatonin’, ‘cell death’, ‘cell proliferation’, ‘telomerase’ and ‘DNA methylation’, we reached to the formula with maximum collectivity in searching, then equivalent terms were found by Mesh database. The review also covers recent clinical investigations of melatonin in breast cancer.

Background: Fine needle aspiration (FNA) is a widely utilized technique for assessing thyroid nodules; however, its inherent non-diagnostic rate poses diagnostic challenges. The present study aimed to evaluate and compare the diagnostic efficacy of FNA, core needle biopsy (CNB), and their combined application in the assessment of thyroid nodules. Methods: A total of 56 nodules from 50 patients was analyzed using both FNA and simultaneous CNB. The ultrasound characteristics were categorized according to the American College of Radiology Thyroid Imaging Reporting and Data Systems classification system. The study compared the sensitivity, specificity, and accuracy of FNA, CNB, and the combination of the two techniques. Results: The concordance between FNA and CNB was notably high, with a kappa coefficient of 0.837. The sensitivity for detecting thyroid malignancy was found to be 25.0% for FNA, 66.7% for CNB, and 83.3% for the combined FNA/CNB approach, with corresponding specificities of 84.6%, 97.4%, and 97.4%. The accuracy of the FNA/CNB combination was the highest at 94.1%. Conclusions The findings of this study indicate that both CNB and the FNA/CNB combination offer greater diagnostic accuracy for thyroid malignancy compared to FNA alone, with no significant complications reported. Integrating CNB with FNA findings may enhance management strategies and treatment outcomes for patients with thyroid nodules.

Purpose: Curcumin as a potent anti-inflammatory and cancer-prevention molecule was labeled with n.c.a 177Lu. The combi-nation of 177Lu as a theranostic agent and curcumin as an anti-cancer can be considered for nuclear medicine. Methods: First, n.c.a 177Lu (specific activity = 48 Ci/mg) was prepared using the extraction chromatography method. Then,semi-empirical quantum chemical calculations were applied to get a deeper insight into the complexation reaction between Lu+3 and curcumin ligand. UV-Vis spectrophotometry was used for the determination of the metal-to-curcumin ratio. Sub-sequently, a mixture of (111–333 MBq) n.c.a 177Lu, 50 µL curcumin solution in ethanol, and 450 µL acetate buffer at pH = 5was incubated for 1  h at 95 ºC. The Lu-curcumin complex chemical structure was characterized using IR spectroscopy.Finally, the prepared complex was analyzed by different quality control tests. Results: Complexometry using UV-Vis studies showed a 1:2 ratio for Lutetium: curcumin complex which is in agreement with theoretical calculations. The IR-spectra analysis also confirmed the complex formation. The radiochemical purity of n.c.a 177Lu -curcumin was more than 95% as determined by radio-TLC. The stability of up to 48 h was observed for theprepared complex in serum. The partition coefficient was calculated for the compound (logP = -0.31). Evaluating biodistri-bution in tumoral mice exhibited high tumor uptake (%ID/gtissue = 2.03). Conclusion The promising results showed that n.c.a 177Lu-curcumin can be considered as a possible radiopharmaceutical agent for therapeutic applications.

Purpose: Curcumin as a potent anti-inflammatory and cancer-prevention molecule was labeled with n.c.a 177Lu. The combi-nation of 177Lu as a theranostic agent and curcumin as an anti-cancer can be considered for nuclear medicine. Methods: First, n.c.a 177Lu (specific activity = 48 Ci/mg) was prepared using the extraction chromatography method. Then,semi-empirical quantum chemical calculations were applied to get a deeper insight into the complexation reaction between Lu+3 and curcumin ligand. UV-Vis spectrophotometry was used for the determination of the metal-to-curcumin ratio. Sub-sequently, a mixture of (111–333 MBq) n.c.a 177Lu, 50 µL curcumin solution in ethanol, and 450 µL acetate buffer at pH = 5was incubated for 1  h at 95 ºC. The Lu-curcumin complex chemical structure was characterized using IR spectroscopy.Finally, the prepared complex was analyzed by different quality control tests. Results: Complexometry using UV-Vis studies showed a 1:2 ratio for Lutetium: curcumin complex which is in agreement with theoretical calculations. The IR-spectra analysis also confirmed the complex formation. The radiochemical purity of n.c.a 177Lu -curcumin was more than 95% as determined by radio-TLC. The stability of up to 48 h was observed for theprepared complex in serum. The partition coefficient was calculated for the compound (logP = -0.31). Evaluating biodistri-bution in tumoral mice exhibited high tumor uptake (%ID/gtissue = 2.03). Conclusion The promising results showed that n.c.a 177Lu-curcumin can be considered as a possible radiopharmaceutical agent for therapeutic applications.