Objectives: This study aimed to examine the temporal dynamics of dengue cases in Malaysia from 2022 to 2024 using seasonal-trend decomposition and time-series modeling. Methods: Weekly dengue case counts from the national registry were analyzed across all states using seasonal-trend decomposition using LOESS (STL) to separate trend, seasonal, and irregular components. Autoregressive integrated moving average (ARIMA) and seasonal ARIMA(SARIMA) models were fitted to validate temporal structures, with model selection based onthe Akaike information criterion (AIC), corrected AIC, and Bayesian information criterion.Diagnostic checks, including residual analysis and Ljung-Box testing, were performed to ensure model adequacy. Results: Dengue incidence showed marked heterogeneity across states. STL decompositionindicated that long-term trends contributed more strongly to case dynamics than seasonality in most states, although seasonal influences were significant in the states of Kedah and Kelantan. Seasonal peak timing varied between states, highlighting differences in epidemic cycles. ARIMA and SARIMA modeling confirmed that no single temporal structure could adequately represent all states; while some series were well fitted by simple ARIMA models,others required seasonal adjustments. Residual diagnostics demonstrated that the selected models were statistically adequate. Conclusion Dengue dynamics in Malaysia are shaped by both trend and seasonal components, with considerable variation across states. Combining STL decomposition with ARIMA/SARIMA modeling strengthens the evidence base for state-specific forecasting and proactive vectorcontrol. Tailoring surveillance systems and interventions to local temporal patterns may improve early warning capacity and optimize resource allocation for dengue prevention.

Introduction: Functioning gonadotroph adenomas, also known as follicle-stimulating hormone (FSH)-secreting pituitary adenomas (FSH-omas), are rare pituitary tumors characterized by the secretion of biologically active FSH. Unlike the more common clinically nonfunctioning gonadotroph adenomas, these tumors produce endocrine manifestations due to excessive FSH secretion. Clinical presentation may result from local mass effects such as headache, visual disturbances due to optic chiasmal compression, or from hormonal activity affecting reproductive function. The endocrine manifestations vary between males and females and can lead to diagnostic challenges. Cases: We report two patients with functioning gonadotroph adenomas presenting with distinct clinical manifestations. The first case involved a 23-year-old female who presented with secondary amenorrhea for 4 years, accompanied by personality changes. Abdominal ultrasound demonstrated bilaterally enlarged multicystic ovaries suggestive of ovarian hyperstimulation, which subsequently regressed postoperatively. Biochemical evaluation revealed inappropriately elevated FSH levels (3.5-fold increase), with suppressed luteinizing hormone (LH) and markedly elevated estradiol levels (11-fold increase). Pituitary magnetic resonance imaging (MRI) identified a large sellar–suprasellar mass with mass effect, consistent with a pituitary macroadenoma. The second case involved a 68-year-old male who presented with progressively worsening vision over 2 years. Hormonal evaluation demonstrated elevated FSH levels (4.5-fold increase), with relatively normal LH and low testosterone levels. Pituitary MRI revealed a sellar mass consistent with a pituitary adenoma. Both patients subsequently underwent pterional craniotomy with tumor debulking. Histopathological examination confirmed gonadotroph adenomas, with positive immunohistochemical staining for FSH. Conclusion Functioning gonadotroph adenomas are rare and may present with diverse clinical features related to gonadal hyperstimulation or mass effects. Early recognition of the characteristic hormonal profile and radiological findings is crucial for diagnosis and appropriate management. These cases highlight the importance of considering functioning gonadotroph adenoma in patients presenting with unexplained gonadal hyperstimulation or atypical reproductive hormonal profiles.
Gonadotrophs ; Adenoma

Introduction: Normotensive pheochromocytomas in Von Hippel-Lindau (VHL) syndrome present unique perioperative challenges. Standard alpha-blockade may induce intolerable orthostatic hypotension, making calcium channel blockers (CCB) a practical alternative. Furthermore, the primary intraoperative danger in these specific phenotypes may not be a hypertensive crisis, but profound vasoplegia. We report a VHL patient undergoing synchronous robotic surgery exhibiting this paradoxical hemodynamic response. Case: A 37-year-old female with VHL syndrome presented with an incidental 3.5-cm left adrenal mass and bilateral renal masses. Biochemistry confirmed a normotensive, noradrenergic pheochromocytoma (24-hour urine normetanephrines 4.2x upper limit of normal). Renal biopsy revealed a clear cell papillary renal cell tumor. Due to prior severe intolerance to Prazosin (hypotension/dizziness with low-dose Prazosin 0.5 mg ON), we utilized amlodipine for preoperative optimization. She was only able to tolerate low-dose 2.5 mg OD alongside oral sodium chloride and ample oral fluid loading. She underwent a synchronous robotic-assisted left adrenalectomy and left midpole renal tumor excision. Strikingly, tumor manipulation did not precipitate a hypertensive crisis. Instead, she developed hypotension requiring an intravenous noradrenaline infusion prior to adrenal vein ligation and tumor removal. Vasopressor support was successfully weaned 12 hours postoperatively, and she was discharged well. Conclusion Normotensive, noradrenergic pheochromocytomas in VHL are hemodynamically fragile. Chronic catecholamine excess induces homologous desensitization and downregulation of alpha-1 adrenergic receptors. This physiological adaptation explains the normotensive presentation and highlights the intraoperative vasoplegia experienced once sympathetic tone is altered by anesthesia. While CCB monotherapy with volume expansion safely facilitates prolonged, synchronous robotic surgeries, clinicians must anticipate and combat refractory hypotension rather than classical hypertensive spikes.

Introduction: Sodium-glucose cotransporter-2 (SGLT2) inhibitors are cornerstone therapies for heart failure and diabetes, offering proven cardiorenal benefits. However, expanded use necessitates vigilance regarding adverse effects, particularly genitourinary infections. While mild cystitis is common, serious upper urinary tract infections remain rare and potentially life-threatening. We describe a case of renal abscess presenting as recurrent urinary tract infections (UTI) following SGLT2 inhibitor initiation, emphasizing the need for clinical vigilance. Case: A 69-year-old male with a significant cardiovascular history, including heart failure with reduced ejection fraction (HFrEF), hypertrophic cardiomyopathy with an implantable cardioverter-defibrillator for non-sustained ventricular tachycardia, diabetes mellitus, hypertension, and hyperlipidemia, presented with a 1-week history of right flank pain, dysuria, urinary frequency, and fever. Initial labs confirmed infection: leukocytosis (22.6 × 10³/ µL), markedly elevated CRP (200 mg/L), and bacteriuria. He was diagnosed with a UTI and started on IV Cefuroxime. This marked his third UTI admission in 5 months, following discharge just 3 weeks prior for septic shock secondary to UTI, establishing a relapsing pattern. Subsequent urine and blood cultures were unremarkable. Medication review revealed Dapagliflozin had been initiated for HFrEF 8 months ago. Following clinical improvement from each prior UTI episode, Dapagliflozin was consistently restarted. Despite an initial antibiotic response, symptoms recurred after discharge each time. The recurrent nature of his infections prompted a renal ultrasound revealing a large (5.3 × 7.5 × 7.4 cm), non-drainable, heterogeneously hypoechoic collection at the left kidney’s mid-lower pole, diagnostic of an early renal abscess. Conclusion This report highlights renal abscess as a rare and severe complication of SGLT2 inhibitor therapy. It serves as a critical reminder that recurrent or relapsing UTIs in patients on these agents should prompt immediate investigation with renal imaging to rule out deep-seated pathology rather than simple cystitis. While these drugs offer proven cardiorenal benefits, their role in promoting urological infections necessitates a cautious approach.
Abscess ; Sodium-Glucose Transporter 2 Inhibitors

Entamoeba histolytica (E. histolytica) is a protozoan parasite that causes amoebiasis in humans. It is prevalent in developing countries, particularly in areas with inadequate sanitation and limited access to clean water. While some data on the infection in the Malaysian population is available, comprehensive data on the overall prevalence is lacking. Our study aimed to determine the prevalence of E. histolytica in Malaysia through systematic review and meta-analysis using data published up to 2025. Fourteen studies covering diverse population groups from various states in Malaysia, including rural and urban residents, schoolchildren, indigenous communities, and high-risk populations were reviewed. We found an overall pooled prevalence of 7% with high heterogeneity (I² = 92.5%). Prevalence varied widely by state and population subgroup, with higher rates in Pahang (18%) and among aboriginal schoolchildren (16%). Lower prevalence was found among urban residents (2%) and patients with gastrointestinal disorders (2%). There was only a slight difference in prevalence between individuals with co-infections (8%) and those without (7%). Studies using microscopy showed higher prevalence (7%) than molecular methods (4%). This is likely due to the misidentification of non-pathogenic Entamoeba species as E. histolytica when using microscopy. These findings contribute to a better understanding of the epidemiology of E. histolytica intestinal infection in Malaysia. Although the overall prevalence is relatively low, the results highlight the need for continued surveillance and more accurate diagnostic approaches to support targeted control.

Introduction: Pituitary apoplexy is a rare but potentially life-threatening endocrine emergency caused by hemorrhage or infarction of the pituitary gland. Its presentation often mimics other acute neurological conditions, posing diagnostic and management challenges. We report a case series of three patients presenting with similar neuro-ophthalmic complaints but differing in symptom onset and radiological features. Cases: The first case was a 25-year-old obese female who presented with acute headache, fever, and right eye ptosis with complete ophthalmoplegia for 2 days. Imaging demonstrated a heterogeneous pituitary macroadenoma with superimposed hemorrhage. Cortisol, prolactin, and insulin-like growth factor-1 levels were low. She received hydrocortisone replacement and underwent left pterional craniotomy with tumor debulking, resulting in marked visual improvement. The second case involved a 59-year-old male who presented with headache and bilateral blurred vision for 1 week, followed by acute right-sided ptosis. Imaging showed a heterogeneous sellar-suprasellar mass compressing the optic chiasm. He had central hypocortisolism, hypothyroidism, and hyponatremia. Surgical intervention was declined, and outpatient follow-up showed stable neuro-ophthalmic findings. The third case was a 30-year-old female who presented with a 2-week history of headache and right-sided blurred vision with temporal hemianopia. Imaging revealed a sellar-suprasellar mass with fluid-fluid levels compressing the optic chiasm. She had central hypocortisolism, hypothyroidism, and hypogonadism. Hydrocortisone replacement was initiated, followed by transsphenoidal surgery with tumor debulking. Her vision improved after the surgery. Conclusion Pituitary apoplexy may present with similar clinical features despite differing onset and radiological characteristics. Early corticosteroid therapy is essential, while surgical intervention should be reserved for patients with severe or progressive neuro-ophthalmic deficits. This case series highlights the importance of individualized, multidisciplinary management to achieve favorable outcomes.
Pituitary Apoplexy

Introduction: Graves’ disease is typically managed with antithyroid drugs (ATDs) and beta-blockers like propranolol. While allergic reactions to ATDs are common, beta-blockers are rarely identified as allergens. Case: A 42-year-old female with Graves’ disease was started on carbimazole 5 mg daily and propranolol 40 mg daily. She developed mild itchiness, which was tolerable. One month later, liver enzyme derangement led to the discontinuation of carbimazole. Propylthiouracil (PTU) 300 mg daily was initiated while continuing propranolol, but caused generalized urticaria, necessitating its cessation. Prednisolone was started, but her thyroid function worsened. Alternative therapies were proposed but declined by the patient. Upon resolution of urticaria, PTU was reintroduced at 50 mg daily without adverse effects, and propranolol was discontinued. Her cutaneous symptoms did not recur, implicating propranolol as the allergen. Conclusion In hyperthyroidism, increased hepatic clearance reduces plasma propranolol levels, minimizing the risk of adverse effects. However, as thyroid function normalizes, propranolol clearance slows, leading to drug accumulation and increased susceptibility to side effects. Clinicians should consider all medications as potential allergens and understand how thyroid states affect drug metabolism to optimize treatment.
Graves Disease ; Allergens

Multiple morphological abnormalities of the flagella (MMAF) represent a severe form of sperm defects leading to asthenozoospermia and male infertility. In this study, we identified a novel homozygous splicing mutation (c.871-4 ACA>A) in the adenylate kinase 7 (AK7) gene by whole-exome sequencing in infertile individuals. Spermatozoa from affected individuals exhibited typical MMAF characteristics, including coiled, bent, short, absent, and irregular flagella. Transmission electron microscopy analysis showed disorganized axonemal structure and abnormal mitochondrial sheets in sperm flagella. Immunofluorescence staining confirmed the absence of AK7 protein from the patients' spermatozoa, validating the pathogenic nature of the mutation. This study provides direct evidence linking the AK7 gene to MMAF-associated asthenozoospermia in humans, expanding the mutational spectrum of AK7 and enhancing our understanding of the genetic basis of male infertility.
Humans ; Male ; Sperm Tail/ultrastructure* ; Homozygote ; Consanguinity ; Asthenozoospermia/pathology* ; Infertility, Male/genetics* ; Mutation ; Pakistan ; Adenylate Kinase/genetics* ; Adult ; Pedigree ; RNA Splicing ; Exome Sequencing ; Spermatozoa

Male infertility can result from impaired sperm motility caused by multiple morphological abnormalities of the flagella (MMAF). Distinct projections encircling the central microtubules of the spermatozoal axoneme play pivotal roles in flagellar bending and spermatozoal movement. Mammalian sperm-associated antigen 17 ( SPAG17 ) encodes a conserved axonemal protein of cilia and flagella, forming part of the C1a projection of the central apparatus, with functions related to ciliary/flagellar motility, skeletal growth, and male fertility. This study investigated two novel homozygous SPAG17 mutations (M1: NM_206996.2, c.829+1G>T, p.Asp212_Glu276del; and M2: c.2120del, p.Leu707*) identified in four infertile patients from two consanguineous Pakistani families. These patients displayed the MMAF phenotype confirmed by Papanicolaou staining and scanning electron microscopy assays of spermatozoa. Quantitative real-time polymerase chain reaction (PCR) of patients' spermatozoa also revealed a significant decrease in SPAG17 mRNA expression, and immunofluorescence staining showed the absence of SPAG17 protein signals along the flagella. However, no apparent ciliary-related symptoms or skeletal malformations were observed in the chest X-rays of any of the patients. Transmission electron microscopy of axoneme cross-sections from the patients showed incomplete C1a projection and a higher frequency of missing microtubule doublets 1 and 9 compared with those from fertile controls. Immunofluorescence staining and Western blot analyses of spermatogenesis-associated protein 17 (SPATA17), a component of the C1a projection, and sperm-associated antigen 6 (SPAG6), a marker of the spring layer, revealed disrupted expression of both proteins in the patients' spermatozoa. Altogether, these findings demonstrated that SPAG17 maintains the integrity of spermatozoal flagellar axoneme, expanding the phenotypic spectrum of SPAG17 mutations in humans.
Humans ; Male ; Infertility, Male/pathology* ; Sperm Tail/ultrastructure* ; Homozygote ; Microtubule-Associated Proteins/genetics* ; Axoneme/genetics* ; Spermatozoa/ultrastructure* ; Adult ; Mutation ; Sperm Motility/genetics* ; Pedigree ; Microtubules ; Microtubule Proteins/genetics*