INTRODUCTION: Trastuzumab deruxtecan (T-DXd) has revolutionised treatment for metastatic breast cancer (MBC). While effective, its high cost and toxicities, such as fatigue and nausea, pose challenges. METHOD: Medical records from the Joint Breast Cancer Registry in Singapore were used to study MBC patients treated with T-DXd (February 2021-June 2024). This study was conducted to address whether reducing dose intensity and density may have an adverse effect on treatment outcomes. RESULTS: Eighty-seven MBC patients were treated with T-DXd, with a median age of 59 years. At the time of data cutoff, 32.1% of patients were still receiving T-DXd. Over half (54%) of the patients received treatment with an initial relative dose intensity (RDI) of <;85%. Overall median real-world progression-free survival (rwPFS) was 8.1 months. rwPFS was similar between RDI groups (<85%: 8.7 months, <85%: 8.1 months, P=0.62). However, human epidermal growth receptor 2 (HER2)-positive patients showed significantly better rwPFS outcomes compared to HER2-low patients (8.8 versus 2.5 months, P<0.001). Only 16% with central nervous system (CNS) involvement had CNS progressive disease on treatment. No significant progression-free survival (PFS) differences were found between patients with or without CNS disease, regardless of RDI groups. Five patients (5.7%) developed interstitial lung disease (ILD), with 3 (3.4%) having grade 3 events. Two required high-dose steroids and none were rechallenged after ILD. There were no fatalities. CONCLUSION Our study demonstrated that reduced dose intensity and density had no significant impact on rwPFS or treatment-related toxicities. Furthermore, only 5.7% of patients developed ILD. T-Dxd provided good control of CNS disease, with 82% of patients achieving CNS disease control.
Humans ; Female ; Breast Neoplasms/mortality* ; Middle Aged ; Trastuzumab/adverse effects* ; Aged ; Adult ; Singapore/epidemiology* ; Antineoplastic Agents, Immunological/adverse effects* ; Camptothecin/adverse effects* ; Immunoconjugates/adverse effects* ; Retrospective Studies ; Progression-Free Survival ; Receptor, ErbB-2/metabolism* ; Neoplasm Metastasis ; Dose-Response Relationship, Drug ; Treatment Outcome ; Registries

Reverse transcription-polymerase chain reaction (RT-PCR) cycle threshold (Ct) value in detecting the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is inversely proportionate to the virus load in the patient’s specimen. These values could be beneficial in the epidemic trajectory at the population level. The SARS-CoV-2 B.1.617.2 (Delta) variant which emerged in late 2020, caused an unprecedented exponential increase in SARS-CoV-2 infection cases worldwide. In Malaysia, the surge in coronavirus disease 2019 (COVID-19) cases and the inclining positivity rate contributed to the epidemic waves in late May 2021. Sudden surge in cases was suggested to be associated with increased transmission caused by the emergence of the B.1.617.2 variant. In the present study, Ct value distribution of the positive COVID-19 samples from 2020 and 2021 was tabulated against SARS-CoV-2 genomic variants determined from genomic sequencing. A significant decreasing pattern of median Ct values from overall 2020 and 2021 samples was evident (p<0.01). However, notable variability was observed in the Ct values between 2020 and 2021, which samples showing lower median Ct values in 2021. The percentages of SARS-CoV-2 genomic variants B.1.36 and B.1.524 were 31.6% and 68.4%, respectively, for samples obtained in October and December 2020. Whereas samples obtained in June and July 2021 were 100% of the B.1.617.2 variant. The population neutralizing antibody against SARS-CoV-2 during the initial peak of B.1.617.2 was low, however, increased during the B.1.617.2 wave. A decreasing trend in the Ct value distribution from samples tested in our laboratory correlated well with the increasing weekly COVID-19 cases reported by the Malaysia national data, which was subsequently attributed to the emergence of B.1.617.2 variant. This study proposes that analyzing Ct value distribution in screened SARS-CoV-2 samples could reveal population-level transmission dynamics and emerging variants. Coupled with genomic sequencing, it supports early control strategies against new SARS-CoV-2 strains.

Biliary fibrosis (BF) is the result of pathological repair of bile tract injury, characterized by thickening and sclerosis of the bile duct wall and progressive stricture of the lumen, which may ultimately lead to serious adverse outcomes such as biliary obstruction, biliary cirrhosis, liver failure, and hepatobiliary malignancies. Current research describes BF as a pathological feature of certain bile tract diseases, lacking a systematic summary of its etiology, pathophysiology, molecular mechanisms, and treatment. BF is a common but easily neglected disease state in biliary system, which may promote the development and progression of hepatobiliary diseases through abnormal repair mechanism after pathological biliary tract injury. Based on the latest research progress from both domestic and international perspectives, the authors review the concept, clinical manifestation, etiology, pathogenesis, and therapeutic strategies of BF to provide a reference for clinical physicians.

Using prostate-specific antigen (PSA) for prostate cancer (PCa) screening led to overinvestigation and overdiagnosis of indolent PCa. We aimed to investigate the value of prostate health index (PHI) and magnetic resonance imaging (MRI) prostate in an Asian PCa screening program. Men aged 50-75 years were prospectively recruited from a community-based PSA screening program. Men with PSA 4.0-10.0 ng ml -1 had PHI result analyzed. MRI prostate was offered to men with PSA 4.0-50.0 ng ml -1 . A systematic prostate biopsy was offered to men with PSA 4.0-9.9 ng ml -1 and PHI ≥35, or PSA 10.0-50.0 ng ml -1 . Additional targeted prostate biopsy was offered if they had PI-RADS score ≥3. Clinically significant PCa (csPCa) was defined as the International Society of Urological Pathology (ISUP) grade group (GG) ≥2 or ISUP GG 1 with involvement of ≥30% of total systematic cores. In total, 12.8% (196/1536) men had PSA ≥4.0 ng ml -1 . Among 194 men with PSA 4.0-50.0 ng ml -1 , 187 (96.4%) received MRI prostate. Among them, 28.3% (53/187) had PI-RADS ≥3 lesions. Moreover, 7.0% (107/1536) men were indicated for biopsy and 94.4% (101/107) men received biopsy. Among the men received biopsy, PCa, ISUP GG ≥2 PCa, and csPCa was diagnosed in 42 (41.6%), 24 (23.8%), and 34 (33.7%) men, respectively. Compared with PSA/PHI pathway in men with PSA 4.0-50.0 ng ml -1 , additional MRI increased diagnoses of PCa, ISUP GG ≥2 PCa, and csPCa by 21.2% (from 33 to 40), 22.2% (from 18 to 22), and 18.5% (from 27 to 32), respectively. The benefit of additional MRI was only observed in PSA 4.0-10.0 ng ml -1 , and the number of MRI needed to diagnose one additional ISUP GG ≥2 PCa was 20 in PHI ≥35 and 94 in PHI <35. Among them, 45.4% (89/196) men with PSA ≥4.0 ng ml -1 avoided unnecessary biopsy with the use of PHI and MRI. A screening algorithm with PSA, PHI, and MRI could effectively diagnose csPCa while reducing unnecessary biopsies. The benefit of MRI prostate was mainly observed in PSA 4.0-9.9 ng ml -1 and PHI ≥35 group. PHI was an important risk stratification step for PCa screening.
Humans ; Male ; Early Detection of Cancer/methods* ; East Asian People ; Image-Guided Biopsy/methods* ; Magnetic Resonance Imaging/methods* ; Prostate/pathology* ; Prostate-Specific Antigen ; Prostatic Neoplasms/pathology* ; Retrospective Studies ; Middle Aged ; Aged

Various methods have been developed for rapid and high throughput full genome sequencing of SARS-CoV-2. Here, we described a protocol for targeted multiplex full genome sequencing of SARS-CoV-2 genomic RNA directly extracted from human nasopharyngeal swabs using the Ion Personal Genome Machine (PGM). This protocol involves concomitant amplification of 237 gene fragments encompassing the SARS-CoV-2 genome to increase the abundance and yield of viral specific sequencing reads. Five complete and one near-complete genome sequences of SARS-CoV-2 were generated with a single Ion PGM sequencing run. The sequence coverage analysis revealed two amplicons (positions 13 751-13 965 and 23 941-24 106), which consistently gave low sequencing read coverage in all isolates except 4Apr20-64Hu. We analyzed the potential primer binding sites within these low covered regions and noted that the 4Apr20-64-Hu possess C at positions 13 730 and 23 929, whereas the other isolates possess T at these positions. The genome nucleotide variations observed suggest that the naturally occurring variations present in the actively circulating SARS-CoV-2 strains affected the performance of the target enrichment panel of the Ion AmpliSeq™ SARS CoV 2 Research Panel. The possible impact of other genome nucleotide variations warrants further investigation, and an improved version of the Ion AmpliSeq™ SARS CoV 2 Research Panel, hence, should be considered.

Traditional Chinese medicine (TCM) was the primary source of medical treatment for the people inhabiting East Asia for thousands of years. These ancient practices have incorporated a wide variety of materia medica including plants, animals and minerals. As modern sciences, including natural products chemistry, emerged, there became increasing efforts to explore the chemistry of this materia medica to find molecules responsible for their traditional use. Insects, including beetles have played an important role in TCM. In our survey of texts and review articles on TCM materia medica, we found 48 species of beetles from 34 genera in 14 different families that are used in TCM. This review covers the chemistry known from the beetles used in TCM, or in cases where a species used in these practices has not been chemically studied, we discuss the chemistry of closely related beetles. We also found several documented uses of beetles in Traditional Korean Medicine (TKM), and included them where appropriate. There are 129 chemical constituents of beetles discussed.

INTRODUCTION: Frontline healthcare workers (HCWs) exposed to coronavirus disease 2019 (COVID-19) are at risk of psychological distress. This study evaluates the psychological impact of COVID-19 pandemic on HCWs in a national paediatric referral centre. METHODS: This was a survey-based study that collected demographic, work environment and mental health data from paediatric HCWs in the emergency, intensive care and infectious disease units. Psychological impact was measured using the Depression, Anxiety, Stress Scale-21. Multivariate regression analysis was performed to identify risk factors associated with psychological distress. RESULTS: The survey achieved a response rate of 93.9% (430 of 458). Of the 430 respondents, symptoms of depression, anxiety and stress were reported in 168 (39.1%), 205 (47.7%) and 106 (24.7%), respectively. Depression was reported in the mild (47, 10.9%), moderate (76, 17.7%), severe (23, 5.3%) and extremely severe (22, 5.1%) categories. Anxiety (205, 47.7%) and stress (106, 24.7%) were reported in the mild category only. Collectively, regression analysis identified female sex, a perceived lack of choice in work scope/environment, lack of protection from COVID-19, lack of access to physical activities and rest, the need to perform additional tasks, and the experience of stigma from the community as risk factors for poor psychological outcome. CONCLUSION A high prevalence of depression, anxiety and stress was reported among frontline paediatric HCWs during the COVID-19 pandemic. Personal psychoneuroimmunity and organisational prevention measures can be implemented to lessen psychiatric symptoms. At the national level, involving mental health professionals to plan and coordinate psychological intervention for the country should be considered.
Adult ; Anxiety/etiology* ; COVID-19/psychology* ; Depression/etiology* ; Female ; Health Surveys ; Hospitals, Pediatric ; Humans ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Occupational Diseases/etiology* ; Pandemics ; Personnel, Hospital/psychology* ; Prevalence ; Risk Factors ; Self Report ; Severity of Illness Index ; Singapore/epidemiology* ; Stress, Psychological/etiology*