Introduction: Severe hypercortisolism is associated with profound impairment of both innate and adaptive immune responses, predisposing affected individuals to opportunistic infections. Excess glucocorticoids alter leukocyte trafficking, suppress pro-inflammatory cytokine production, and impair cellular immunity, increasing susceptibility to bacterial, viral, and fungal pathogens. In some cases, severe infections may precede the diagnosis of Cushing syndrome and represent the initial clinical manifestation. Early recognition is important as untreated hypercortisolism can lead to substantial morbidity and mortality. Case: A young adolescent male presented with progressive facial fullness and facial hyperpigmentation for 4 months, followed by 1 month of intermittent fever, cough, lower limb weakness, and hallucinations. On examination, he was tachypneic with cushingoid features including moon facies, pigmented acne over the face and chest, and nail bed hyperpigmentation. He was hypertensive and had severe hypokalemia with lymphopenia. Radiological imaging demonstrated multiple cavitary lung lesions and intracranial tuberculomas. Bronchoalveolar lavage identified multiple opportunistic pathogens, including Pneumocystis jirovecii, Aspergillus fumigatus, and Haemophilus influenzae, while cerebrospinal fluid testing was positive for cytomegalovirus. Given the unusual combination of infections, an underlying immunocompromised state was suspected. Endocrine evaluation revealed markedly elevated serum cortisol, with loss of diurnal rhythm and elevated adrenocorticotropic hormone (ACTH). Twenty-four-hour urinary cortisol was significantly increased, confirming severe ACTHdependent Cushing syndrome. Magnetic resonance imaging of the pituitary gland and computed tomography imaging of the thorax, abdomen, and pelvis did not identify the source of ACTH secretion. Conclusion This case highlights that overwhelming opportunistic infections may be the first manifestation of severe Cushing syndrome in children. Excess cortisol disrupts host defenses by impairing neutrophil chemotaxis and macrophage phagocytosis, suppressing T-cell-mediated immunity, and reducing cytokine signaling necessary for pathogen clearance. These mechanisms contribute to susceptibility to simultaneous bacterial, fungal, and viral infections. Clinicians should therefore consider underlying hypercortisolism in patients presenting with multiple or unusual opportunistic infections to enable earlier diagnosis and appropriate multidisciplinary management.
Cushing Syndrome ; Opportunistic Infections

Introduction: Metabolic bone disease of prematurity (MBDP) is characterized by biochemical and radiological findings related to bone demineralization in premature babies. Despite early recognition, MBDP is still a prevalent problem and is associated with significant morbidities in premature babies. This study aims to determine the prevalence and neonatal predictors of MBDP. Methodology: This retrospective cross-sectional study involved premature babies with gestational age ≤32 weeks and birth weight ≤1.5 kg, admitted to Hospital Tunku Azizah, Kuala Lumpur, between January 1, 2020, and January 31, 2024. Babies whose serum phosphate was ≤1.5 mmol/L and serum alkaline phosphatase >500 IU/L at 3–6 weeks of age fulfilled the diagnosis of MBDP. The maternal and neonatal characteristics of the study population were retrieved from the medical records. Neonatal predictors for MBDP were analyzed by simple and multiple logistic regression. Results: A total of 292 subjects were enrolled. The prevalence of MBDP was 13.4%. On simple logistic regression, male gender, low gestational age, poor APGAR score, delayed enteral feed initiation, prolonged TPN, delayed vitamin D supplementation, use of unfortified expressed breast milk, patent ductus arteriosus, and bronchopulmonary dysplasia, cholestasis, prolonged hospital stay, and prolonged ventilation were risk factors for MBDP (p <0.05). On multiple logistic regression, only cholestasis (p 0.014), prolonged TPN use (p <0.001), and prolonged hospitalization (p <0.001) were independent neonatal predictors for MBDP. Conclusion The risk of MBDP can be reduced by shortening TPN duration and hospitalization duration and preventing cholestasis. This may be achieved by early enteral feeding initiation and use of fortified EBM, thus preventing the development of MBDP.
Infant, Newborn ; Prevalence ; Bone Diseases, Metabolic ; Hospitals

Introduction: Endogenous Cushing syndrome is a rare manifestation of chronic cortisol excess. It may present with severe hypercortisolism complicated by life-threatening opportunistic infections. Surgical management of a cortisol-secreting tumor is the mainstay of therapy. However, when the source is not found or when surgery is not feasible, medical therapies may be employed for rapid control of hypercortisolism. CASE: A 13-year-old male presented with breathlessness for one day. He also had a cough associated with weight loss, weakness, and hallucinations for 1 month. On presentation, he was tachypneic and had moon facies, acne, fine moustache, limb wasting, and pigmented nail beds. He was also hypertensive and developed an episode of seizure during admission. Investigation results showed severe hypokalemia and lymphopenia. Radiological examination revealed pneumothorax with multiple lung cavitations and brain tuberculomas. Bronchoalveolar lavage (BAL) was positive for Aspergillus fumigatus. However, both BAL and CSF PCR and culture for TB were negative. Serum ACTH was 379 pg/mL (0–46), and morning serum cortisol was 2,948 nmol/L with loss of diurnal rhythm. His 24-hour urine cortisol was 14,252 nmol/24 hour (31.7–282). This is consistent with ACTH-dependent Cushing syndrome. He was started on anti-TB and anti-fungal treatment. Serum cortisol levels were persistently high while on high-dose intravenous dexamethasone treatment for TB meningitis. An MRI pituitary and a CT scan thorax, abdomen, and pelvis could not reveal an ACTH-secreting tumor source. Metyrapone was started and titrated upwards to control the hypercortisolism. Serum cortisol reduced to 200–300 nmol/L after 1 month, and 24-hour urinary cortisol was down to 22.4 nmol/24 hour after 4 months, requiring weaning of metyrapone doses. Conclusion Metyrapone is effective in the rapid control of severe hypercortisolism with life-threatening complications, as illustrated in this case. However, it warrants careful monitoring and titration.
Child ; Cushing Syndrome

INTRODUCTION: Outcomes after SARS-CoV-2 Omicron infection in patients with heart failure (HF) and ischaemic heart disease (IHD) remain poorly defined. METHOD: In a highly vaccinated cohort of adult Singapore citizens and permanent residents, we used Cox proportional hazards models (adjusted for sociodemographic variables and comorbidities) to compare the risks of Omicron infection, COVID-19- related hospitalisation, and severe COVID-19 between indivi-duals with HF or IHD and matched controls without these conditions. RESULTS: From national databases, we identified 15,426 HF patients matched 1:∼3 to 41,221 controls, and 110,442 IHD patients matched 1:∼2 to 223,843 controls. Over 80% of HF and IHD patients had received at least 3 vaccine doses. During the Omicron-predominant period, both HF and IHD cohorts demonstrated higher adjusted risks of COVID-19 hospitalisation compared with matched controls (HF: adjusted hazard ratio [aHR] 1.77, 95% confidence interval [CI] 1.65-1.90; IHD: aHR 1.21, 95% CI 1.17-1.26). Among those with at least 1 HF-or IHD-related admission in the prior year, hospitalisation risk was further elevated (HF: aHR 1.27, 95% CI 1.13-1.42; IHD: aHR 1.11, 95% CI 1.01-1.23). Receipt of ≥3 vaccine doses was associated with substantially lower risk of severe COVID-19 versus only 2 doses (HF: aHR 0.35, 95% CI 0.28-0.43; IHD: aHR 0.27, 95% CI 0.23-0.32). A fourth dose conferred additional reductions in infection and adverse outcomes, though CIs for infection overlapped with those for 3 doses. CONCLUSION During Omicron predominance, HF and IHD patients experienced greater risk of COVID-19 hospitalisation and severe COVID-19 versus matched controls. Booster vaccinations attenuated these risks. Individuals with recent HF/IHD admissions should be prioritised for receipt of booster vaccine doses.
Humans ; COVID-19/complications* ; Male ; Heart Failure/complications* ; Myocardial Ischemia/complications* ; Female ; Middle Aged ; Hospitalization/statistics & numerical data* ; Aged ; COVID-19 Vaccines/administration & dosage* ; Singapore/epidemiology* ; SARS-CoV-2 ; Proportional Hazards Models ; Adult ; Case-Control Studies ; Vaccination/statistics & numerical data*

BACKGROUND

The recent COVID-19 pandemic has led to a rise in the incidence of obesity both in children and adults. Studies on the effect of the pandemic on Type 2 diabetes mellitus (T2DM) trends in children are limited. In this study, we aim to evaluate the frequency, clinical characteristics and demographics of newly-diagnosed paediatric T2DM cases 4 years before and after the pandemic.

The frequency and clinical data of patients aged ≤18 years with newly-diagnosed T2DM in 4 tertiary centers in urban Malaysia from 18 March 2016 till 17 March 2020 (pre-pandemic) and 18 March 2020 till 17 March 2024 (postpandemic) was collected.

Seventy-five (75) patients were recorded with newly-diagnosed T2DM pre-pandemic and fifty-four (54) patients were recorded with newly-diagnosed T2DM post-pandemic. There was no significant increase in T2DM cases and diabetic ketoacidosis (DKA) during pandemic and T2DM cases fell to below pre-pandemic levels in the 3rd and 4th year postpandemic. HbA1c and serum glucose were lower post-pandemic than pre-pandemic: 10.1% vs 11.9%, p = 0.008 and 12.0 mmol/L vs 16.1 mmol/L, p = 0.038 respectively.

The incidence of T2DM and DKA did not increase during the pandemic and further declined in year 3 and 4 post-pandemic. Lower HbA1c and serum glucose in the post-pandemic group may suggest improved screening services and greater access to medical care.

Microbiome is associated with a wide range of diseases. The gut microbiome is also a dynamic reflection of health status, which can be modified, thus representing great potential to exploit the mechanisms that influence human physiology. Recent years have seen a dramatic rise in gut microbiome studies, which has been enabled by the rapidly evolving high-throughput sequencing methods (i.e. 16S rRNA sequencing and shotgun sequencing). As the emerging technologies for microbiome research continue to evolve (i.e. metatranscriptomics, metabolomics, culturomics, synthetic biology), microbiome research has moved beyond phylogenetic descriptions and towards mechanistic analyses. In this review, we highlight different approaches to study the microbiome, in particular, the current limitations and future promise of these techniques. This review aims to provide clinicians with a framework for studying the microbiome, as well as to accelerate the adoption of these techniques in clinical practice.
Humans ; Gastrointestinal Microbiome ; Phylogeny ; RNA, Ribosomal, 16S/genetics* ; Health Status

Objective: Tardive syndrome (TS) is an umbrella term used to describe a group of abnormal movement disorders caused by chronic exposure to dopamine receptor blocking agents. Few follow-up studies have been performed on the outcome of TS in patients using antipsychotics. The purpose of our study was to investigate the prevalence, incidence, remission rate, and factors associated with remission in patients using antipsychotics. Methods: This retrospective cohort study consisted of 123 patients who received continuous treatment of antipsychotics in a medical center in Taiwan, from April 1, 2011 to May 31, 2021. We assessed the demographic and clinical characteristics, prevalence, incidence, remission rate, and factors associated with remission in patients using antipsychotics.TS remission was defined as a Visual Analogue Scale score ≤ 3. Results: Of the 92 patients who completed the 10-year follow-up, 39 (42.4%) were found to have at least one episode of TS, with tardive dyskinesia (TD) being the most prevalent subtype (51.3%). With regard to concurrent physical illness, a history of extrapyramidal symptoms were significant risk factors for TS. During the 10-year follow-up period, the remission rate of TS was 74.3%. The use of antioxidants including vitamin B6 and piracetam was related to the remission of TS. Patients with tardive dystonia had a higher remission rate (87.5%) compared to TD (70%). Conclusion Our study suggests that TS may be a treatable condition, and the key to a better outcome is early detection and prompt intervention, including closely monitoring antipsychotics-related TS symptoms and using antioxidants.

Humans ; HIV Infections/prevention & control* ; Pre-Exposure Prophylaxis

Background: The PLASMIC score is a convenient tool for predicting ADAMTS13 activity of ＜10%.Lactate dehydrogenase (LDH) is widely used as a marker of haemolysis in thrombotic thrombocytopenic purpura (TTP) monitoring, and could be used as a replacement marker for lysis. We aimed to validate the PLASMIC score in a multi-centre Asia Pacific region, and to explore whether LDH could be used as a replacement marker for lysis. Methods: Records of patients with thrombotic microangiopathy (TMA) were reviewed. Patients’ ADAMTS13 activity levels were obtained, along with clinical/laboratory findings relevant to the PLASMIC score. Both PLASMIC scores and PLASMIC-LDH scores, in which LDH replaced traditional lysis markers, were calculated. We generated a receiver operator characteristics (ROC) curve and compared the area under the curve values (AUC) to determine the predictive ability of each score. Results: 46 patients fulfilled the inclusion criteria, of which 34 had ADAMTS13 activity levels of ＜10%. When the patients were divided into intermediate-to-high risk (scores 5‒7) and low risk (scores 0‒4), the PLASMIC score showed a sensitivity of 97.1% and specificity of 58.3%, with a positive predictive value (PPV) of 86.8% and negative predictive value (NPV) of 87.5%. The PLASMIC-LDH score had a sensitivity of 97.1% and specificity of 33.3%, with a PPV of 80.5% and NPV of 80.0%. Conclusion Our study validated the utility of the PLASMIC score, and demonstrated PLASMIC-LDH as a reasonable alternative in the absence of traditional lysis markers, to help identify high-risk patients for treatment via plasma exchange.