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

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.

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*

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.

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.

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: At the beginning of the coronavirus disease (COVID-19) pandemic in Singapore, the strategy initially involved aggressive ring-fencing of infections, before pivoting towards managing recurrent local interspersed outbreaks of COVID-19. A key feature of Singapore’s efforts to preserve health-care capacity was the implementation of the nationwide Home Recovery Programme (HRP), whereby patients were allowed to recover at home as long as they met certain criteria. The programme was centrally coordinated by Singapore’s Ministry of Health and was supported by telemedicine providers, primary care physicians and government agencies. This report aims to highlight Singapore’s experience in coordinating and implementing the HRP, the challenges faced and the outcomes. Methods: Published and internal data from the Ministry of Health in Singapore, along with policy documents, were reviewed together with a brief literature review of similar programmes conducted globally. Results: Implementation of the HRP led to the majority of patients (98%) recovering from COVID-19 in the outpatient setting, with similar mortality rates to inpatient settings. Hospitalization rates for COVID-19 cases were reduced as compared to previously, alleviating strain on the health-care system. Discussion: The HRP was largely successful at preventing health-care capacities from being overwhelmed, while keeping fatalities to a minimum. Nonetheless, the risks of emergent variants of concern remain present, and heightened vigilance and potential modification of existing protocols based on fluctuations in virulence and infectivity are still needed.

Arteries ; Female ; Head ; Humans ; Middle Aged