Introduction: Primary aldosteronism (PA) is a common yet underdiagnosed cause of secondary hypertension, associated with increased cardiovascular and renal morbidity. Early detection and subtype-directed management significantly improve outcomes. However, adherence to recommended diagnostic pathways in real-world practice remains variable. Case: We conducted a retrospective audit of patients diagnosed with PA in a Malaysian tertiary centre from January 2018 to December 2025. Data collected included demographics, clinical presentation, biochemical parameters, diagnostic workup (aldosterone-renin ratio [ARR], confirmatory testing, adrenal imaging, and adrenal venous sampling [AVS]), treatment modality, and outcomes. Audit standards were based on established international guidelines. A total of 14 patients were included, with equal gender distribution. The cohort comprised 57% Malay and 43% Chinese. Most patients presented with hypertension (mean ~170/100 mmHg), and hypokalemia was present in approximately 70% of the patients. ARR and adrenal imaging were performed in all patients (100%), while confirmatory testing was conducted in 85% of the patients. However, AVS utilization remained limited (50%). Contributing factors included failed cannulation, technical challenges in overweight patients, preference for medical therapy, refusal of surgery, and limited access to AVS services. The majority had unilateral adrenal adenoma (~75%). Treatment was divided between surgical (55%) and medical (45%) approaches. Post-treatment, hypokalemia resolved in 90% of patients, with a significant reduction in antihypertensive burden and complete hypertension resolution in approximately 35% of the patients. Quality of life improved in most patients. Conclusion This audit demonstrates good adherence to initial screening and imaging in PA but highlights suboptimal utilization of AVS. Barriers to AVS utilization are multifactorial, encompassing technical, patient-related, and system level limitations. Addressing these barriers is essential to optimize subtype-directed management and improve longterm cardiovascular outcomes in patients with PA. Despite this, clinical outcomes were favorable. Strengthening adherence to diagnostic pathways, particularly subtype confirmation, may further improve patient outcomes.
Hyperaldosteronism ; Treatment Outcome ; Retrospective Studies

Introduction: Diabetic ketoacidosis (DKA) is a life-threatening complication associated with significant morbidity and healthcare burden. Despite advances in diabetes care, recurrent DKA remains common, often reflecting gaps in treatment adherence and patient education. Identifying predictors of recurrence is crucial for risk stratification and targeted intervention. Methodology: We conducted a retrospective observational study of all adult DKA admissions to a tertiary centre between 2001 and 2025. Electronic medical records were reviewed for demographic data, biochemical parameters, precipitating factors, and clinical outcomes. DKA was defined using standard biochemical criteria. Recurrent DKA was defined as ≥2 admissions during the study period. Factors associated with recurrent DKA admissions were analyzed. Patients under the age of 18 years and those with missing vital information were excluded. Results: A total of 667 DKA admissions, comprising 566 patients, were identified, of which 101 admissions (15.1%) were recurrent, involving 65 patients. Among recurrent DKA episodes, the most common precipitating factors were infection (64.4%) and insulin omission (62.4%). After multivariate analyses, patients with type 1 diabetes mellitus (T1DM) were more likely to develop recurrent DKA compared to those with type 2 diabetes mellitus (aOR 4.16; 95% confidence interval [CI] 2.58–6.70; p <0.001). Insulin omission was strongly associated with recurrent DKA (aOR 2.29; 95% CI 1.46–3.60; p <0.001). In contrast, baseline glycated hemoglobin and chronic kidney disease were not significantly associated with recurrence. Diabetic counseling during the first DKA admission did not reduce recurrent DKA. There were no significant differences in mortality (3.9% vs 6.2%, p = 0.524) or critical care admission rates (40.6% vs 38.7%, p = 0.718) between recurrent and first DKA episodes. Conclusion Recurrent DKA accounts for a substantial proportion of DKA admissions and is strongly associated with insulin omission and T1DM. Our findings suggest that recurrent DKA is driven predominantly by behavioral and adherencerelated factors, indicating the need for multidisciplinary interventions beyond standard inpatient counseling.
Diabetic Ketoacidosis ; Retrospective Studies

Introduction: Tuberculosis patients with comorbid diabetes face a substantially higher risk of mortal outcomes. The “metainflammation” loop between hyperglycemia and tuberculosis (TB) infection exacerbates systemic severity and increases hazard rates for death. This study aims to quantify the association between baseline hemoglobin A1c (HbA1c) levels and all-cause mortality within a Malaysian cohort. Methodology: This was a retrospective cross-sectional audit analyzing 131 adult TB-DM (diabetes mellitus) patients during their treatment course (2022–2025) in the TB Clinic, Hospital Sungai Buloh. Primary outcomes were all-cause mortality and clinical severity, stratified by baseline HbA1c and diabetes mellitus DM treatment modality (OHA vs. insulin). Results: The overall mortality rate was 17% (22/131). A stark disparity in glycemic control was observed between survivors and deceased patients: those who died presented with extreme mean HbA1c levels of 16.0%, compared to 10.5% in survivors. High HbA1c was also associated with a higher prevalence of pulmonary involvement compared to extrapulmonary disease (10.9% vs 8.9%). Patients requiring insulin therapy experienced significantly higher mortality rates compared to those managed on OHAs, with 25% (12 out of 47) patients requiring insulin therapy having died during TB treatment, compared to only 8.2% (7 out of 84) patients in the OHA-only group. Conclusion Baseline HbA1c is a critical prognostic marker that identifies a high-risk “lethal threshold” at extreme glycemic levels (HbA1c ≥16). Furthermore, the nearly fourfold increase in death risk among insulin-treated patients likely reflects a high-risk phenotype of advanced metabolic failure, which corresponds with a study done in Kelantan (Siti Rohana et al., 2020). The study shows that TB patients with DM had three times higher risk of developing unsuccessful TB treatment outcomes compared to TB patients without DM. Collectively, these data necessitate mandatory early HbA1c screening and aggressive metabolic management to reduce the staggering mortality of this dual epidemic.
Retrospective Studies

Introduction: Diabetes mellitus (DM) is a significant comorbidity associated with adverse tuberculosis (TB) treatment outcomes and remains an ongoing clinical challenge. Chronic hyperglycemia impairs host immune responses, particularly macrophage function, leading to delayed bacillary clearance. This contributes to poorer outcomes, including delayed sputum conversion, prolonged treatment duration, relapse, and increased mortality. Poor glycemic control is a key modifiable factor influencing these outcomes. This study aimed to evaluate the impact of glycemic control at diagnosis on TB treatment outcomes in a Malaysian cohort. Methodology: A retrospective cross-sectional audit was conducted using the TB clinic registry at Hospital Sungai Buloh from 2022 to 2025. Adult patients (≥18 years) with confirmed TB (any form) and DM (Type 1 or Type 2) with complete records were included. Of 241 patients screened, 131 were included after exclusions due to incomplete records (29.9%), transfer (29.9%), loss to follow-up (19.9%), and drug-resistant TB (2.9%). Data collected included demographics, hemoglobin A1c (HbA1c) at diagnosis, sputum conversion duration, treatment duration, type of DM therapy, and clinical outcomes. Results: The cohort had a mean age of 53 years, with 97% having Type 2 DM. Mean HbA1c at diagnosis was 10.5%. Poorer glycemic control was associated with delayed sputum conversion. Patients who achieved sputum conversion by 8 weeks had an average HbA1c of 9.6%, compared to 11.8% in those with delayed conversion. Longer treatment duration was associated with higher HbA1c (mean 10.5, 8.6, and 11.8% for 6-, 12-, and 18-month regimens, respectively). Relapse analysis demonstrated a trend towards higher HbA1c with increasing relapse episodes (11.2, 13.75, and 14.5% for one, two, and three relapses, respectively). Overall mortality was 17% (22/131), with markedly higher mean HbA1c in deceased patients compared to survivors (16.0% vs 10.5%). Conclusion Poor glycemic control at TB diagnosis is associated with delayed sputum conversion, prolonged treatment duration, and increased mortality. These findings are consistent with regional evidence, including a South Asian systematic review (Gautam et al., 2021), demonstrating higher mortality and treatment failure in patients with TB and DM. Early and aggressive optimization of glycemic control, alongside standard anti-TB therapy, is essential to improve outcomes.
Humans ; Glycemic Control ; Retrospective Studies ; Diabetes Mellitus ; Treatment Outcome ; Tuberculosis

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: Improving glycemic control while minimizing unnecessary insulin exposure is an important goal in diabetes management. The Rapid Optimization Clinic (ROC) was established as a structured multidisciplinary service to support therapy individualization, close follow-up, and timely insulin deintensification. This audit evaluated early changes in glycated hemoglobin A1c (HbA1c) and insulin treatment burden following ROC care over 3 months. Methodology: We conducted a retrospective audit of routine clinical data from patients with diabetes managed in the ROC at a district hospital. Baseline and 3-month HbA1c and insulin data were extracted from non-electronic clinic records. Insulin dose was standardized as total daily dose (TDD) in units/kg/day. Insulin deintensification was evaluated primarily by change in TDD from baseline to 3 months and by the proportion of patients who discontinued insulin during follow-up. Paired analyses were performed for patients with complete baseline and follow-up data for each outcome. Continuous variables are presented as mean ± standard deviation or median with interquartile range, as appropriate. Exploratory analyses were undertaken to assess whether available patient factors were associated with HbA1c improvement. Results: Twenty-three patients were included. Paired HbA1c data were available for 12 patients, whereas paired TDD data were available for 21 patients. Mean HbA1c decreased from 10.78 ± 2.59% at baseline to 8.42 ± 2.29% at 3 months, representing a mean reduction of 2.36 percentage points (95% confidence interval [CI] 0.09–4.62; p = 0.043). Mean TDD decreased from 0.434 ± 0.248 to 0.286 ± 0.313 units/kg/day, corresponding to a mean reduction of 0.148 units/kg/day (95% CI 0.077–0.219; p <0.001). Insulin was discontinued in 9 of 21 patients (42.9%). No clear association was observed between HbA1c improvement and age, sex, or number of visits. Interpretation is limited by the small sample size, reflecting the early phase of a newly established clinic. Conclusion In this early audit, ROC care was associated with clinically meaningful improvement in glycemic control and significant insulin deintensification over 3 months. These findings support the potential role of a structured multidisciplinary optimization clinic in delivering individualized diabetes care and facilitating safe reduction of insulin burden.
Humans ; Glycemic Control ; Retrospective Studies ; Diabetes Mellitus ; Insulins

OBJECTIVE: To analyze the clinical characteristics, treatment, and prognosis of seven pediatric patients with Acute myeloid leukemia (AML) positive for the t(16;21)(p11;q22) FUS::ERG fusion gene. METHODS: A retrospective analysis was carried out on the clinical data, treatment, and prognosis of seven AML patients with t(16;21)(p11;q22) FUS::ERG fusion gene admitted to Henan Children's Hospital between June 2015 and November 2024. Relevant literature was also reviewed. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: 2024-102-001). RESULTS: Among 297 pediatric patients with AML, 7 cases (2.36%) were positive for the t(16;21)(p11;q22) FUS::ERG fusion gene, including 3 males and 4 females, with a median age of 11 years (range: 3 ~ 12 years). According to the FAB classification, these included 1 case of M2, 3 cases of M5, and 3 cases of AML-not otherwise specified (non-M3). All 7 patients were found to harbor the t(16;21)(p11;q22) translocation, with 3 cases showing additional chromosomal abnormalities. Immunophenotyping revealed universal expression of CD13, CD33, CD34, and CD117, with partial expression of CD56, CD4, CD64, CD123, CD15, CD38, CD11b, HLA-DR, cMPO, and CD16. One patient achieved complete remission (CR) after the first course of DAE (cytarabine + daunorubicin + etoposide) induction chemotherapy but relapsed and discontinued the treatment. Six patients received DAH (cytarabine + daunorubicin + homoharringtonine) induction therapy, of whom 2 achieved CR after two courses and underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), resulting in an overall CR rate of 42.86%. Five children did not receive allo-HSCT and had a median overall survival of 9 months (range: 6 ~ 18 months). Two children who underwent transplantation achieved bone marrow morphological and molecular biological relapse at 6 and 9 months post-transplantation, respectively. After receiving combined chemotherapy and donor lymphocyte infusion, one child failed to achieve remission and died at 22 months post-transplantation, while the other has been followed up to date with positive fusion gene status. Their overall survival was 25 months and 30 months, respectively. CONCLUSION The t(16;21)(p11;q22) FUS::ERG fusion gene is rare in pediatric AML and associated with poor prognosis. Allo-HSCT may mitigate the adverse prognostic impact of the FUS::ERG fusion gene and contribute to prolonged survival.
Humans ; Male ; Child ; Female ; Leukemia, Myeloid, Acute/drug therapy* ; Oncogene Proteins, Fusion/genetics* ; Translocation, Genetic ; Retrospective Studies ; RNA-Binding Protein FUS/genetics* ; Chromosomes, Human, Pair 16/genetics* ; Adolescent ; Child, Preschool ; Chromosomes, Human, Pair 21/genetics* ; Prognosis ; Treatment Outcome

OBJECTIVE: To summarize the clinical features and management of two brothers affected with X-linked inhibitor of apoptosis protein (XIAP) deficiency. METHODS: This study retrospectively analyzed the clinical presentations, treatment, and follow-up of two brothers with XIAP deficiency diagnosed at Shanghai Children's Hospital in 2020, and summarized similar cases recorded in databases such as PubMed, Wanfang, Chinese Medical Association Journals, and WIP from January 2006 to November 2024. This study was approved by the Medical Ethics Committee of our hospital (Ethics No.: 2025R128-E01). RESULTS: Patient 1 was the younger brother, who presented at 8 years of age with growth retardation, folliculitis, erythema nodosum, and perineal abscess. Sequencing revealed that he has carried a hemizygous c.566T>C (p.Leu189Pro) variant of the XIAP gene, which was inherited from his mother. He was allergic to infliximab treatment and underwent allogeneic stem cell transplantation (HSCT) in January 2021. During a follow-up of 3 years and 10 months post-transplantation, he showed no gastrointestinal symptoms and had a good outcome. Patient 2 was the elder brother, who presented at 10 years and 6 months of age with growth retardation, rash, and anal fistula. Genetic testing revealed the same variant. He was treated with oral azathioprine but did not have regular follow-ups. At 14-years-and-6-months of age, he had developed severe gastrointestinal infection and hemophagocytic lymphohistiocytosis, which was alleviated after treatment with antibiotics, glucocorticoids, immunoglobulin, and rituximab. He is currently being prepared for HSCT. A total of 13 publications were retrieved, which involved 64 patients from 23 families, with 23 different variants identified. The main clinical manifestations included splenomegaly (34 cases, 53.1%), hemophagocytic lymphohistiocytosis (27 cases, 42.2%), and inflammatory bowel disease or colitis (20 cases, 31.8%). There were significant phenotypic differences among patients from the same family. Thirteen patients (20.3%) underwent HSCT, with a survival rate of 61.5%. CONCLUSION For male children with early onset, poor treatment response, especially those with unexplained splenomegaly and IBD-like symptoms, early genetic testing is recommended. HSCT is a safe and effective treatment for XIAP deficiency. For patients with developmental delay, early onset, and severe IBD phenotype, early transplantation is recommended.
Humans ; Male ; X-Linked Inhibitor of Apoptosis Protein/deficiency* ; Child ; Genetic Diseases, X-Linked/therapy* ; Phenotype ; Siblings ; Retrospective Studies ; Hematopoietic Stem Cell Transplantation

OBJECTIVE: To explore the application value of artificial intelligence (AI)-assisted chromosomal karyotype analysis in the diagnosis of prenatal chromosomal mosaicism. METHODS: A retrospective analysis was conducted on 172 pregnant women who underwent amniocentesis at the Department of Medical Genetics and Prenatal Diagnosis, the Third Affiliated Hospital of Zhengzhou University between January 2019 and December 2024. All cases whose fetuses were diagnosed with chromosomal mosaicism via karyotype analysis and stratified into two groups based on the analytical software employed: the conventional analysis group (n = 70), which utilized Leica analysis software for karyotype image recognition and cell counting; and the AI-assisted analysis group (n = 102), which utilized AI-assisted software for the same procedures. The clinical performance of AI-assisted karyotype analysis in diagnosing chromosomal mosaicism was comprehensively evaluated by comparing the types of mosaic karyotypes, distribution of mosaic ratios, and verification outcomes of different detection modalities between the two groups. This study was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethics No.: 2024-406-01). RESULTS: No statistically significant difference was observed in baseline characteristics (maternal age, gestational week, and indications for prenatal diagnosis) between the two groups. Regarding the detection efficacy for numerical and structural mosaicisms, no significant difference was found in the detection of numerical mosaicism. However, the conventional analysis group exhibited a significantly higher detection rate of autosomal structural mosaicism compared to the AI-assisted group (11.43% vs. 0.98%, P < 0.05). Numerical mosaicism cases were further verified using copy number variation sequencing (CNV-seq) and/or fluorescence in situ hybridization (FISH). The AI-assisted group demonstrated a significantly lower inconsistency rate (5.56% vs. 20.41%, P < 0.05) compared to the conventional group. For low-proportion (< 10%) chromosomal mosaicism, the AI-assisted group had a significantly lower detection rate (13.25% vs. 29.69%, P < 0.05). Subsequent validation of low-proportion mosaicism by CNV-seq and/or FISH showed a higher consistency rate in the AI-assisted group (81.82% vs. 54.55%), though the difference did not reach statistical significance (P = 0.360). CONCLUSION For the karyotyping analysis of prenatal chromosomal mosaicism, AI-assisted karyotype analysis shows high accuracy and consistency in identifying numerical chromosomal mosaicism, particularly in reducing the detection of low-proportion (< 10%) mosaicism while improving verification accuracy. AI-assisted analysis can significantly improve the detection accuracy of numerical mosaicism and mitigate the risk of misclassification for low-proportion (< 10%) mosaicism, thereby providing more precise clinical evidence for the prenatal diagnosis of chromosomal mosaicisms.
Humans ; Female ; Mosaicism ; Pregnancy ; Karyotyping/methods* ; Artificial Intelligence ; Prenatal Diagnosis/methods* ; Adult ; Retrospective Studies ; Chromosome Disorders/genetics* ; Amniocentesis

OBJECTIVE: To investigate the detection patterns, clinical phenotypic characteristics, and differences in diagnostic timeliness of Klinefelter syndrome (KS) across prenatal and postnatal stages, with an aim to provide a basis for optimizing strategies for early screening, diagnosis, and intervention. METHODS: A retrospective study was conducted to analyze data from two phases. The prenatal diagnosis group included 33,302 pregnant women who underwent amniocytic karyotyping due to advanced maternal age, abnormal ultrasound findings, or high-risk non-invasive prenatal testing (NIPT). The postnatal diagnosis group included 52,101 patients who underwent peripheral blood karyotyping due to primary infertility, abnormal external genitalia, or growth and developmental abnormalities. Additionally, medical histories of adult diagnosed patients were reviewed retrospectively to identify early occult symptoms. This study was approved by the Medical Ethics Committee of Chengdu Women's and Children's Central Hospital (Ethics No.: LCYJ-2025-030). RESULTS: In the prenatal group, 96 cases of KS were detected (detection rate 0.29%). The primary indications for referral were NIPT indicating sex chromosome abnormalities (45.83%), advanced maternal age (16.66%), and ultrasound abnormalities (17.70%). In the postnatal group, 128 cases of KS were detected (detection rate 0.25%). Clinical presentations were primarily primary infertility/azoospermia (77.34%), and the patients were predominantly adults (84.40%). Retrospective analysis revealed that adult patients presented with specific physical signs that had been overlooked during childhood. CONCLUSION As KS lacks typical early clinical manifestations, diagnosis is often delayed until adulthood when reproductive needs arise, showing a pattern of "passive detection" and resulting in missed opportunities for optimal intervention. By conducting a comparative analysis of prenatal diagnostic data and postnatal retrospective data, a risk association model linking prenatal screening indications with childhood-specific signs was developed. This study has provided empirical evidence for establishing a multidisciplinary, full life-cycle management system of "screening ~ diagnosis ~ monitoring ~ intervention" helping to shift from "passive detection in adulthood" to "proactive management across the entire life course," and laid a foundation for improving early diagnosis rate and long-term quality of life for patients.
Humans ; Klinefelter Syndrome/genetics* ; Female ; Adult ; Pregnancy ; Retrospective Studies ; Prenatal Diagnosis/methods* ; Male ; Phenotype ; Karyotyping ; Young Adult ; Adolescent ; Middle Aged