Background: Periorificial dermatitis (POD) is a common inflammatory skin condition primarily affecting infants, children, and young women. Novel therapies such as phosphodiesterase 4 (PDE4) inhibitors provide promising non-steroidal anti-inflammatory treatment options. Objective: This study evaluated the efficacy and safety of topical crisaborole 2% ointment, a PDE4 inhibitor, for treating pediatric patients with POD. Methods: A randomized, double-blind, vehicle-controlled trial included 23 participants aged 3 months to 18 years. Patients were treated with crisaborole 2% ointment or placebo for 4 weeks, followed by a 4-week treatment-free observational period. Primary endpoints were a 50% reduction in the Perioral Dermatitis Severity Index (PODSI) and an Investigator’s Global Assessment (IGA) score of 0 or 1 by day 14. Assessments were also conducted on days 29 and 58. Secondary measures included changes in Quality-of-Life Index scores over time and safety evaluations. Results: Both groups demonstrated improvement in PODSI and IGA scores during treatment.Although a small, non-significant numerical trend favored the crisaborole group across primary and secondary endpoints, no statistically significant differences between crisaborole and placebo were observed at any time point. Mild burning or stinging were reported more frequently in the crisaborole group, but they were generally tolerable. Conclusion While there was a modest numerical trend favoring crisaborole, its efficacy was not statistically superior to placebo in this small pilot study. Larger studies are needed to further validate the efficacy of crisaborole for the treatment for POD.

Objective: Cisplatin, a widely used chemotherapy agent, is known to induce testopathy and degeneration of the germinal epithelium (GE). Origanum vulgare L. (OV) leaf extract, due to its antioxidative properties, may alleviate such cellular damage. This experimental study was conducted to evaluate the protective and therapeutic effects of OV against cisplatin-induced testopathy. Methods: Forty-eight male Naval Medical Research Institute mice were assigned to six groups. Testopathy was induced via intraperitoneal injection of cisplatin (single dose, 1 mg/kg on day 0). OV was administered as treatment (400 mg/kg orally, 5 days per week, for 5 weeks). Phytochemical screening of OV was also performed. After the experimental period, the animals were euthanized, and both blood serum and testicular samples were collected. Total body weight and total testicular weight were measured. Histopathological examination using hematoxylin and eosin staining (to assess the gonadosomatic index [GSI]) and immunohistochemical (IHC) detection of 3β-hydroxysteroid dehydrogenase (3β-HSD) protein were conducted. Expression levels of the p53 and B-cell lymphoma 2 (Bcl-2) genes, as well as serum testosterone levels, were evaluated. Statistical analysis was performed with SPSS ver.16, and significance was set at p<0.05. Results: A phytochemical analysis of OV confirmed the presence of antioxidant compounds. Cisplatin administration resulted in significant detrimental alterations in testicular tissue (p<0.05). In animals receiving OV following cisplatin exposure, the GSI, testosterone levels, histological parameters, and total testicular weight improved toward physiological values (p<0.05). Additionally, IHC staining for 3β-HSD protein indicated regeneration of Leydig cells. Gene expression analysis showed down-regulation of p53 and up-regulation of Bcl-2 (p<0.05). Conclusion OV administration, owing to its antioxidative characteristics, shows promise as a protective phytomedicine against cisplatin-induced testopathy. OV promotes GE proliferation, enhances testosterone secretion, and modulates the expression of apoptotic genes.

Introduction: Histoplasmosis is a rare opportunistic, inhalation-acquired systemic mycosis caused by Histoplasma capsulatum, endemic to Southeast Asia, including Malaysia. Although classically seen in immunocompromised hosts, it is increasingly reported in immunocompetent individuals. Infection is associated with environmental exposures such as bat or bird droppings and soil disruption. Histoplasmosis is a progressive granulomatous disease that can closely mimic tuberculosis and malignancy, making diagnosis challenging. Case: An 87-year-old Malay male with a history of treated pulmonary tuberculosis presented with a 6-month history of intermittent fever, anorexia, weight loss, and hypotension. Initial computed tomography imaging demonstrated bilateral heterogeneous adrenal masses (right: 2.2 × 3.7 × 5.0 cm; left: 2.0 × 3.7 × 5.2 cm) with indeterminate washout characteristics. Biochemical adrenal evaluation, including a short Synacthen test, confirmed primary adrenal insufficiency. Extensive microbiological and malignancy workup, including bronchoscopy, cultures, and tumor markers, was non-diagnostic. In view of clinical deterioration and epidemiological risk, empirical antituberculous therapy was initiated; however, no clinical improvement was observed after 2 months. PET-FDG revealed intensely hypermetabolic bilateral adrenal masses (SUVmax right 16.7, left 13.2) with no other abnormal foci. Non-invasive fungal investigations were negative. Definitive diagnosis was established via computed tomography-guided adrenal biopsy, which demonstrated necrotizing granulomatous inflammation with intracellular yeasts, subsequently identified as H. capsulatum. The patient was treated with oral itraconazole and corticosteroid replacement, resulting in significant clinical improvement and planned interval radiological reassessment. Conclusion Disseminated histoplasmosis is a diagnostic challenge, particularly in frail elderly patients, where invasive procedures may be delayed. It can mimic tuberculosis and malignancy and may lack an identifiable exposure history. Non-invasive tests may be inconclusive, making tissue biopsy essential. Adrenal involvement may result in primary adrenal insufficiency, further complicating the clinical picture. Early consideration and timely confirmation are crucial for appropriate management.
Adrenal incidentaloma ; Lung Neoplasms

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

Introduction: Paragangliomas are rare neuroendocrine tumors arising from extra-adrenal chromaffin cells, with an estimated incidence of 2–8 cases per million per year. These tumors originate from neural crest–derived cells of the sympathetic and parasympathetic paraganglia and may secrete catecholamines, resulting in malignant hypertension or symptoms such as headache, palpitations, and diaphoresis. They can occur anywhere along the paravertebral and para-aortic regions from the skull base to the pelvic floor. Case: We report a case of a 14-year-old male with no known premorbid conditions who presented with presyncope and a 1-month history of headache. On examination, he had severe hypertension (242/167 mmHg), tachycardia (127 bpm), and grade IV hypertensive retinopathy. Investigations showed preserved renal function with markedly elevated 24-hour urinary metanephrines (normetanephrine 90.75 µmol/L). Computed tomography revealed a lobulated, heterogeneously enhancing mass measuring 5.0 × 6.1 × 5.4 cm along the left margin of the abdominal aorta at the infrarenal level, suggestive of an extra-adrenal lesion. Gallium-68 PET scan demonstrated a somatostatin receptor–avid left peritoneal mass. The patient underwent exploratory laparotomy and tumor excision, complicated intraoperatively by blood pressure lability requiring nitroprusside and inotropic support. Postoperatively, he improved significantly and was able to wean off all antihypertensive medications. Histopathology confirmed left retroperitoneal paraganglioma. Conclusion Primary peritoneal paraganglioma is a rare but important cause of secondary hypertension, especially in young patients presenting with hypertensive emergency. High index of suspicion is essential for early diagnosis. Management requires a multidisciplinary approach with careful preoperative optimization to minimize perioperative complications. Surgical resection remains the definitive treatment and, as demonstrated in this case, can result in marked clinical improvement with resolution of hypertension.
Paraganglioma

Introduction: Isolated hypothyroxinemia (IH) in pregnancy, characterized by low free thyroxine 4 (FT4) with normal thyroidstimulating hormone (TSH), has a reported prevalence of 1.3–8%. We present a diagnostically challenging case that initially mimicked central hypothyroidism before evolving into classic IH. Case: A 37-year-old G4P3 female at 22 + 3 weeks gestation with β-thalassemia trait presented with palpitations and tachycardia (150–184 bpm). A bedside echocardiogram showed volume depletion. Her heart rate improved to 108– 116 bpm following a 1.5 L normal saline bolus. Incidentally, thyroid function tests (TFTs) revealed both low FT4 6.04 pmol/L (7.86–14.41) and low TSH 0.009 mIU/L (0.38–5.33). Anti-thyroid peroxidase antibody was markedly elevated at 360 IU/mL (<35). At 24 + 4 weeks, TFTs showed persistently low FT4 (5.84 pmol/L) and TSH (0.022 mIU/L). Differential diagnoses included central hypothyroidism or assay interference. Tests were repeated using different platforms. Both the Beckman system (FT4: 5.73 pmol/L, TSH: 0.086 mIU/L) and Roche system (FT4: 8.83 pmol/L [12.0–22.0], TSH: 0.11 mIU/L [0.27–4.20]) confirmed low values, ruling out assay interference. Following endocrinology consultation and given her asymptomatic status, IH was considered most likely, and a plan for close monitoring was initiated. Serial follow-up demonstrated biochemical evolution. By 31 + 6 weeks, TFTs showed a low TSH (0.753 mIU/L) with an FT4 level (5.86 pmol/L) within the normal reference range, a pattern typical of IH in pregnancy. Repeat TFTs 6 weeks postpartum showed both TSH and FT4 within normal range. Conclusion This case illustrates a rare and unexpected biochemical progression of IH in pregnancy, initially presenting with a pattern indistinguishable from central hypothyroidism. It underscores that in an asymptomatic, fertile patient, IH can manifest with an atypical pattern early in gestation. The findings suggest that vigilant serial monitoring, rather than immediate extensive pituitary workup, may be a prudent initial approach in such scenarios, as the biochemical profile can normalize toward the classic IH pattern as pregnancy advances.
Female ; Pregnancy ; Thyrotropin

Objective: The clinical presentation of depressive disorders might be influenced by age, and its diagnosis and treatment can be affected by ageism-related bias. A network analysis can reveal symptom patterns unrecognized by the reductionistic approach. Therefore, this study explores the network structure of depression and anxiety symptoms in older Asian patients with depressive disorders and examines age-related differences in the context of ageism. Methods: We used data from the Research on Asian Psychotropic Prescription Patterns for Antidepressants, Phase 3 study and included 2,785 psychiatric patients from 11 Asian countries. Depression and anxiety symptoms were assessed using the Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7. Network analyses were conducted to identify symptom interconnections and centrality among older (>65 years), middle-aged (35–64 years), and young (18–34 years) adult groups. The network structures were also compared using a network comparison test. Results: Depressed mood was the most central symptom across all age groups. Network comparisons revealed no significant structural differences among the three age groups, despite several variations in terms of global strength. The network structure of the older group was characterized by strong interconnections between somatic symptoms (insomnia-energy) and core depressive symptoms (little interest or pleasure-feelings of hopelessness). Conclusion This study reveals that the network structures of depression and anxiety symptoms have relatively consistent interconnections across age groups, despite subtle age-based differences. Specifically, older adults tend to present anxiety and depression symptoms as physical complaints. These findings challenge ageist stereotypes and advocate for inclusive, age-neutral approaches to treatment.

The effects of smoking on human health have long been documented. However, only a few studies have highlighted the direct effects of nicotine on sperm function. Nicotine, as a chemical compound found in tobacco, has been shown to modulate different aspects of spermatogenesis and sperm functions. Nicotine can lead to a reduction in the number of sperm, their motility and functionality. It can change the molecular expressions involved in sperm function, including genes encoding sperm nuclear proteins. The most important nuclear proteins that play a critical role in sperm function are known as H2B histone family, member W, testis-specific (H2BFWT), transition protein 1 (TNP1), transition protein 2 (TNP2), protamine-1 (PRM1), and protamine-2 (PRM2). These proteins are involved in sperm chromatin condensation, which in turn affects fertilization and embryonic development. Any alteration in the expression of these genes due to nicotine exposure/usage may lead to adverse implications in couples’ fertility and the health of future generations. Since research in this area is still relatively new, it underscores the importance of understanding the potential side effects of environmental factors such as nicotine on reproductive health.

Purpose: This study aimed to evaluate our institution's experience in using artificial intelligence (AI) decision support (DS) as part of the clinical workflow to triage patients with Breast Imaging Reporting and Data System (BI-RADS) 3 sonographic lesions whose follow-up was delayed during the coronavirus disease 2019 (COVID-19) pandemic, against subsequent imaging and/or pathologic follow-up results. Methods: This retrospective study included patients with a BI-RADS category 3 (i.e., probably benign) breast ultrasound assessment from August 2019–December 2019 whose follow-up was delayed during the COVID-19 pandemic and whose breast ultrasounds were re-reviewed using Koios DS Breast AI as part of the clinical workflow for triaging these patients. The output of Koios DS was compared with the true outcome of a presence or absence of breast cancer defined by resolution/stability on imaging follow-up for at least 2 years or pathology results. Results: The study included 161 women (mean age, 52 years) with 221 BI-RADS category 3 sonographic lesions. Of the 221 lesions, there were two confirmed cancers (0.9% malignancy rate). Koios DS assessed 112/221 lesions (50.7%) as benign, 42/221 lesions (19.0%) as probably benign, 64/221 lesions (29.0%) as suspicious, and 3/221 lesions (1.4%) as probably malignant. Koios DS had a sensitivity of 100% (2/2; 95% confidence interval [CI], 16% to 100%), specificity of 70% (154/219; 95% CI, 64% to 76%), negative predictive value of 100% (154/154; 95% CI, 98% to 100%), and false-positive rate of 30% (65/219; 95% CI, 24% to 36%). Conclusion When many follow-up appointments are delayed, e.g., natural disaster, or scenarios where resources are limited, breast ultrasound AI DS can help triage patients with probably benign breast ultrasounds.

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.