INTRODUCTION: Chronic lymphocytic leukaemia (CLL) has a heterogeneous disease course and a variable preva-lence across populations. Appropriate management for achieving optimal outcomes requires consideration of multiple factors, including disease-related factors like genomic alterations, patient characteristics and fitness, availability and access to treatments, and logistics/cost. This review aims to provide comprehen-sive and pragmatic recommendations for the management of treatment-naïve (TN) CLL that are relevant to Singapore's clinical context. METHOD: Clinical consensus statements were developed by an expert panel of haematologists from Singapore through a 2-round modified Delphi process. Statements were drafted using recent evidence-based guidelines and published literature. Panel members reviewed draft statements, provided anonymised feedback and proposed modifications where relevant. A physical meeting was held to facilitate discussion, voting and endorsement of the final consensus statements. RESULTS: The final consensus included 15 statements covering major TN CLL patient subsets. The recommendations highlight the importance of molecular testing for key biomarkers, where available/accessible, to guide initial therapy. Due to the superior efficacy of targeted agents (Bruton's tyrosine kinase inhibitors [BTKis] and B-cell lymphoma 2 inhibitors [BCL2is]) these are favoured over standard chemotherapy or chemotherapy-immunotherapy, especially for patients with del(17p) or TP53 mutation, and less fit patients. CONCLUSION These consensus statements provide practical recommendations for the current manage-ment of TN CLL patients in Singapore and similar healthcare systems based on up-to-date evidence. Regular updates to treatment guidelines are important to ensure responsiveness to emerging evidence and evolving clinical practices and to improve patient outcomes and quality of life.
Humans ; Consensus ; Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis* ; Singapore

Background: The pathogenesis and development of autoimmune diseases are associated with alteration of hormone levels. The effects of menopausal hormone therapy (MHT) on Behcet’s disease (BD) are unclear. Objective: We hypothesized that MHT would increase the risk of BD in postmenopausal women due to the central role of immunomodulation of estrogen and other sex hormones in autoimmune diseases. Methods: We analyzed data from the Korean National Health Insurance Service database and investigated the relationship between MHT and the risk of BD in postmenopausal women with BD. The study included 220,663 patients who received MHT and 1,170,566 who did not. The hazard ratio (HR) of BD was measured in all subjects.Statistical analyses were utilized with adjustments for possible confounding factors such as age, body mass index, smoking, alcohol consumption, physical activity, income, diabetes, hypertension, dyslipidemia, age at menarche (group), age at menopause (group), parity, breastfeeding, and oral contraceptive use. Results: After adjusting for confounding factors, the participants with a history of MHT had a higher risk of BD (MHT＜2 years, HR=1.459, 95% confidence interval [95% CI]=1.29∼1.649; MHT＞2 and ＜5 years, HR=1.512, 95% CI=1.265∼1.808; MHT≥5 years, HR=2.045, 95% CI=1.708∼2.447). Conclusion The findings demonstrate that MHT is associated with an increased risk of BD in postmenopausal women, indicating that estrogen plays an important role in the disease activity of BD. However, additional studies are needed to confirm these findings.

Background: In pediatric patients, the common cold coronavirus (ccCoV) usually causes mild respiratory illness. There are reports of coronavirus causing central nervous system (CNS) infection in experimental animal models. Some immunocompromised patients have also been reported to have fatal CNS infections with ccCoV. The aim of this study was to investigate the clinical characteristics of CNS complications related to ccCoV infection. Methods: From January 2014 to December 2019, a retrospective analysis was performed of medical records from hospitalized patients under 19 years of age whose ccCoV was detected through polymerase chain reaction in respiratory specimens. The CNS complications were defined as clinically diagnosed seizure, meningitis, encephalopathy, and encephalitis. Results: A total of 436 samples from 420 patients were detected as ccCoV. Among the 420 patients, 269 patients were immunocompetent and 151 patients were immunocompromised.The most common type of ccCoV was OC43 (52% in immunocompetent, 37% in immunocompromised). CNS complications were observed in 9.4% (41/436). The most common type of CNS complication was the fever-provoked seizure under pre-existing neurologic disease (42% in immunocompetent and 60% in immunocompromised patients).Among patients with CNS complications, two immunocompetent patients required intensive care unit admission due to encephalitis. Three patients without underlying neurological disease started anti-seizure medications for the first time at this admission. There was no death related to ccCoV infection. Conclusion ccCoV infection may cause severe clinical manifestations such as CNS complications or neurologic sequelae, even in previously healthy children.

INTRODUCTION: Three doses of SARS-CoV-2 mRNA vaccines have been recommended for cancer patients to reduce the risk of severe disease. Anti-neoplastic treatment, such as chemotherapy, may affect long-term vaccine immunogenicity. METHOD: Patients with solid or haematological cancer were recruited from 2 hospitals between July 2021 and March 2022. Humoral response was evaluated using GenScript cPASS surrogate virus neutralisation assays. Clinical outcomes were obtained from medical records and national mandatory-reporting databases. RESULTS: A total of 273 patients were recruited, with 40 having haematological malignancies and the rest solid tumours. Among the participants, 204 (74.7%) were receiving active cancer therapy, including 98 (35.9%) undergoing systemic chemotherapy and the rest targeted therapy or immunotherapy. All patients were seronegative at baseline. Seroconversion rates after receiving 1, 2 and 3 doses of SARS-CoV-2 mRNA vaccination were 35.2%, 79.4% and 92.4%, respectively. After 3 doses, patients on active treatment for haematological malignancies had lower antibodies (57.3%±46.2) when compared to patients on immunotherapy (94.1%±9.56, P<0.05) and chemotherapy (92.8%±18.1, P<0.05). SARS-CoV-2 infection was reported in 77 (28.2%) patients, of which 18 were severe. No patient receiving a third dose within 90 days of the second dose experienced severe infection. CONCLUSION This study demonstrates the benefit of early administration of the third dose among cancer patients.
Humans ; SARS-CoV-2 ; COVID-19/prevention & control* ; Treatment Outcome ; Neoplasms/drug therapy* ; Hematologic Neoplasms ; Vaccination ; RNA, Messenger ; Antibodies, Viral ; Immunogenicity, Vaccine

A Case Report of 46 XY Partial Gonadal Dysgenesis with Dual Gonadal Tumours 46XY gonadal dysgenesis is known as a disorder of sex development (DSD) that occurs due to abnormality in gonadal development. There is a conflict between one’s genotype, phenotype, and gonadal development, which influences the wide range of presentation and clinical appearance of 46XY females. This was a case of a 46XY female who presented with primary amenorrhea with delayed puberty at the age of 18 years old. She had ambiguous genitalia. Her breast and pubic hair were at Tanner Stage 2. Transabdominal ultrasound found a small uterus with a vagina; however, the gonads were not seen. A magnetic resonance imaging (MRI) showed a 20mm right gonad located extra-pelvis near the right iliac vessels while the 9mm streak left gonad was at the usual location next to the sigmoid colon. All her tumour markers were normal except lactate dehydrogenase (LDH) was elevated. She was given estrogen therapy for pubertal induction and underwent laparoscopy prophylactic bilateral gonadectomy. The intraoperative findings were similar to the MRI findings, and the histopathology examination (HPE) results showed left gonadoblastoma and right dysgerminoma FIGO stage 1A. She continued taking estrogen therapy until she had withdrawal bleeding, and oral progesterone was added. 46XY-DSD has high risk of developing germ cell tumour and requires prophylactic gonadectomy as soon as the diagnosis is established. However, delay in presentation and surgery may affect the outcomes and prognosis.

Croup is a common upper airway infection characterized by a barking cough, stridor, and hoarseness. It is usually caused by viral infection. A small number of croup caused by coronavirus disease 2019 (COVID-19) has been reported in children before the omicron variant surge. Previously reported cases indicated that croup caused by COVID-19 can be treated in the same manner as those with other viral causes. We describe two cases (9-monthold girl and 11-month-old boy) of previously healthy infants who presented with a barking cough and chest retraction and required endotracheal intubation and cardiopulmonary resuscitation. Despite receiving dexamethasone and nebulized racemic epinephrine (NRE) treatment for croup in the emergency department, these patients still developed acute respiratory failure. Reverse transcription polymerase chain reaction (RT-PCR) of nasopharyngeal samples revealed severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) omicron BA.2 variant (Stealth omicron) and no other common respiratory viral pathogens. Both patients were treated with mechanical ventilation, dexamethasone, and NRE in the pediatric intensive care unit. The duration of intubation was 112 hours and 80 hours, respectively. Both patients were discharged without complications. To the best of our knowledge, this is the first report of life-threatening croup produced by the omicron BA.2 variant and confirmed by RT-PCR. We suggest that this SARS-CoV-2 variant may cause severe croup that may not improve with conventional treatment, even in children without underlying diseases.

Purpose: Intraoperative femoral condyle fracture is a significant but rarely reported complication during primary total knee arthroplasty (TKA). This is the first study to identify the incidence, risk factors, location and outcome of these fractures in an Asian population with modern posterior-stabilized (PS) TKA. Materials and methods: We reviewed 2682 consecutive primary TKAs performed between 2011 and 2017 in a single centre; 23 femoral condyle fractures were identified and analysed. Results: Fractures were managed conservatively with screw fixation or revision arthroplasty. Mean follow up was 3.0 years (range 3 months to 5.9 years). All patients achieved bone union and good functional outcome. The mean Knee Society Knee score was 89.4 (range 71–100) and the function score was 80.2 (range 60–95) at a mean of 3.0 years post-operation. Bilateral surgery was found to be a significant risk factor for femoral condyle fracture, while there was a higher trend of fracture in female patients and Stryker articular surface mounted (ASM) navigation. Conclusions Intraoperative fracture is not uncommon with modern PS TKA. Postulated risk factors for fracture were discussed. Early identification of risk factors and a rigorous surgical technique may reduce risk of fracture. A good functional result was expected after proper treatment.

Background: Forgotten Joint Score (FJS) has become a popular tool for total knee arthroplasty (TKA), but almost all studies had assessment performed 1 year after surgery. There is a need for a sensitive tool for earlier outcome assessment. The aim of this study was to investigate the usefulness of FJS within the first year after TKA. Methods: This was a cross-sectional study. Patients within the first year after primary TKA were recruited. FJS was translated into the local language with a cross-cultural adaptation and was validated by assessing the correlation with the Western Ontario and McMaster Universities Arthritis Index score (WOMAC). Ceiling and floor effects (highest or lowest 10% or 15%) of both scores were compared. Skewness of scores was assessed with a histogram. Results: One hundred sixty-three subjects were recruited: 84 (51.5%) had evaluation at 3 months after the operation, 56 (34.4%) at 6 months, and 23 (14.1%) at 12 months. FJS had fewer patients at the highest 10% (10.7% vs. 16.1%, P = 0.046) or 15% (19.6% vs. 32.1%, P = 0.027) at 6 months and within the first year overall (6.7% vs. 13.5%, P <0.001; 14.1% vs. 22.7%, P <0.001). Also, it had more patients at the lowest 10% (16.7% vs. 0%, P <0.001) or 15% (21.4% vs. 0%, P < 0.001) at 3 months, 6 months (10.7% vs. 0%,P <0.001), and overall (12.9% vs. 0%, P <0.001; 16.6% vs. 0%, P <0.001). The skewness was much less than WOMAC (0.09 vs. −0.56). Conclusions FJS has a low ceiling effect but a high floor effect in the first year after TKA. Such characteristics make it less useful for the general assessment of early patient report outcome after operation.

The habenula (Hb) is small but important brain structure, anatomically and functionally links the forebrain with the midbrain to modulate various neuropsychiatric functions associated with drug addiction and emotion-associated dysfunctions. Several reports suggested that the dysfunction of Hb-related functions affected the Hb structurally and functionally. However, the technical limitation has awaited the solid conclusion of whether Hb change due to depression is likely to occur in certain subnuclei of the Hb. To probe this possibility, we developed 3-dimensional reconstruction methods for the high-resolution volumetric analysis of Hb and the mRNA levels at the given volume in normal or lipopolysaccharide (LPS)-mediated mouse model of depression. Notably, we discovered that the volume reduction was prominent in medial Hb but not in lateral Hb after LPS treatments. On the other hand, the RNA expression levels of known Hb regional markers such as Tac1 (dorsal part of medial Hb), ChAT (ventral part of medial Hb), and Tacr1 (medial and lateral Hb) were all decreased in all Hb subnuclei in LPS-injected mice. Accordingly, accurate volumetry with marker labeling was not feasible. Collectively, these established 3D analyses of mouse Hb successfully and precisely determine the volume-based changes of small brain structure, which should be applicable in a wider range of mouse models or pathological specimens.
Animals ; Brain ; Depression ; Gene Expression ; Habenula ; Hand ; Mesencephalon ; Mice ; Prosencephalon ; RNA ; RNA, Messenger ; Substance-Related Disorders