Prostate cancer is the most prevalent malignant tumor among men, ranking first in incidence and second in mortality globally. Novel hormone therapies (NHT) targeting the androgen receptor (AR) pathway have become the standard of care for metastatic prostate cancer. This review offers a comprehensive overview of NHT, including abiraterone, enzalutamide, apalutamide, darolutamide, and rezvilutamide, which have demonstrated efficacy in delaying disease progression and improving patient survival and quality of life. Nevertheless, resistance to NHT remains a critical challenge. The mechanisms underlying resistance are complex, involving AR gene amplification, mutations, splice variants, increased intratumoral androgens, and AR-independent pathways such as the glucocorticoid receptor, neuroendocrine differentiation, DNA repair defects, autophagy, immune evasion, and activation of alternative signaling pathways. This review discusses these resistance mechanisms and examines strategies to counteract them, including sequential treatment with novel AR-targeted drugs, chemotherapy, poly ADP-ribose polymerase inhibitors, radionuclide therapy, bipolar androgen therapy, and approaches targeting specific resistance pathways. Future research should prioritize elucidating the molecular basis of NHT resistance, optimizing existing therapeutic strategies, and developing more effective combination regimens. Additionally, advanced sequencing technologies and resistance research models should be leveraged to identify novel therapeutic targets and improve drug delivery efficiencies. These advancements hold the potential to overcome NHT resistance and significantly enhance the management and prognosis of patients with advanced prostate cancer.

BACKGROUND:Exercise has been widely recognized in the prevention and treatment of diabetes.Aerobic exercise has become an important part of the treatment of type 1 diabetes.However,the effect of treadmill exercise on the metabolism and chronic neuroinflammation of type 1 diabetes in different sexes needs further discussion. OBJECTIVE:To study the effects of treadmill exercise on metabolism and chronic neuroinflammation in type 1 diabetes mice of different sexes. METHODS:Forty C57BL/6 mice were divided into male group and female group,with 20 mice in each group.Then,a diabetes model was established by continuous injection of streptozotocin at 80 mg/kg for 3 days.Ten rats from each group were randomly selected to perform 6-week treadmill exercise as the diabetes+exercise group and another 10 rats from each group were selected as the diabetes group.Serum sex hormones,liver tissue oxidative stress,brain tissue inflammatory factors,and liver pathology were detected,and Morris water maze was performed for the observation of behavioral changes in mice. RESULTS AND CONCLUSION:Compared with the diabetes group,the diabetes+exercise group delayed the rise of blood sugar in type 1 diabetes mice(P＜0.05)and showed a significant reduction in serum follicle-stimulating hormone,luteinizing hormone,liver superoxide dismutase,malondialdehyde,brain tumor necrosis factor α,interleukin-6 and interleukin-1β levels(P＜0.01),while serum estradiol,progesterone,estrogen,and liver glutathione peroxidase protein levels were significantly increased(P＜0.01,P＜0.05).Compared with male type 1 diabetes mice,female type 1 diabetes mice had significantly higher estradiol levels and lower luteinizing hormone levels(P＜0.05).Compared with the male diabetes+exercise group,the female diabetes+exercise group had lower liver glutathione peroxidase levels(P＜0.05).Compared with type 1 diabetes mice,the escape latency of exercise training mice was shorter(P＜0.01).In male mice,exercises significantly increased the time and platform crossing times of type 1 diabetes mice in the target quadrant(P＜0.01 or P＜0.05),while in female mice,exercises significantly increased the time of type 1 diabetes mice in the target quadrant(P＜0.05).Correlation analysis results showed that the levels of follicle-stimulating hormone,luteinizing hormone,progesterone,superoxide dismutase,malondialdehyde,tumor necrosis factor α,and interleukin-6 were positively correlated with the level of interleukin-1β(P＜0.05 or P＜0.01),whereas the levels of estradiol and progesterone were negatively correlated with the levels of superoxide dismutase,malondialdehyde,tumor necrosis factor α,interleukin-6 and interleukin-1β(P＜0.05 or P＜0.01).Overall,there are sex differences in the effects of treadmill exercise on metabolic indicators and chronic neuroinflammatory regulation in diabetes mice.Sex hormones are an important variable of treadmill exercise in the metabolic,inflammatory and cognitive responses in diabetes mice.

Less invasive transcatheter tricuspid therapies are optimal alternative for surgery in high-risk individuals with severe symptomatic tricuspid regurgitation on medical therapy. Various techniques are available with Transcatheter Edge-to-Edge Repair (TEER) having the greatest experience worldwide. When the coaptation gap becomes too large for TEER, caval valve implantation (CAVI) emerge as a better option. We described a series of 4 patients who underwent CAVI with the TricValve system and periprocedural computed tomography angiography imaging for the purpose of TricValve sizing. There were few procedural complications, with significant improvements in New York Heart Association functional class and right ventricular function post-procedure.

Humans ; Aged ; Psychotic Disorders/therapy* ; Acute Disease

INTRODUCTION: H. pylori eradication reduces the risk of gastric malignancies and peptic ulcer disease. First-line therapies include 14-day PAC (proton pump inhibitor [PPI], amoxicillin, clarithromycin) and PBMT (PPI, bismuth, metronidazole, tetracycline). Second-line therapies include 14-day PBMT and PAL (PPI, amoxicillin, levofloxacin). This clinical audit examined current treatment outcomes in Singapore. METHODS: Clinical data of H. pylori-positive patientswho underwent empirical first- and second-line eradication therapies from 1 January 2017 to 31 December 2018 were reviewed. Treatment success was determined by ¹³C urea breath test performed at least 4 weeks after treatment and 2 weeks off PPI. RESULTS: A total of 963 patients (862 PAC, 36 PMC [PPI, metronidazole, clarithromycin], 18 PBMT, 13 PBAC [PAC with bismuth], 34 others) and 98 patients (62 PMBT, 15 PAL, 21 others) received first-and second-line therapies respectively. A 14-day treatment duration was appropriately prescribed for first- and second-line therapies in 65.2% and 82.7% of patients, respectively. First-line treatment success rates were noted for PAC (seven-day: 76.9%, ten-day: 88.3%, 14-day: 92.0%), PMC (seven-day: 0, ten-day: 75.0%, 14-day: 69.8%), PBMT (ten-day: 100%, 14-day: 87.5%) and PBAC (14-day: 100%). 14-day treatment was superior to seven-day treatment (90.8% vs. 71.4%; P = 0.028). PAC was superior to PMC (P < 0.001) but similar to PBMT (P = 0.518) and PBAC (P = 0.288) in 14-day therapies. 14-day second-line PAL and PBMT had similar efficacy (90.9% vs. 82.4%; P = 0.674). CONCLUSION First-line empirical treatment using PAC, PBMT and PBAC for 14 days had similar efficacy. Success rates for second-line PBMT and PAL were similar.
Humans ; Helicobacter pylori ; Clarithromycin/therapeutic use* ; Helicobacter Infections/drug therapy* ; Metronidazole/therapeutic use* ; Bismuth/therapeutic use* ; Singapore ; Drug Therapy, Combination ; Amoxicillin/therapeutic use* ; Proton Pump Inhibitors/therapeutic use* ; Anti-Bacterial Agents/therapeutic use* ; Treatment Outcome ; Clinical Audit

In this paper, we aim to provide professional guidance to clinicians who are managing patients with chronic liver disease during the current coronavirus disease 2019 (COVID-19) pandemic in Singapore. We reviewed and summarised the available relevant published data on liver disease in COVID-19 and the advisory statements that were issued by major professional bodies, such as the American Association for the Study of Liver Diseases and European Association for the Study of the Liver, contextualising the recommendations to our local situation.
COVID-19/epidemiology* ; Carcinoma, Hepatocellular/therapy* ; Chronic Disease ; Hepatitis B, Chronic/therapy* ; Hepatitis C, Chronic/therapy* ; Humans ; Liver Cirrhosis/therapy* ; Liver Diseases/therapy* ; Liver Neoplasms/therapy* ; Liver Transplantation ; Singapore/epidemiology*

BACKGROUND AND PURPOSE: Recombinant tissue plasminogen activator (rtPA) is one of the proven therapies that improve the outcome of patients with acute ischemic stroke (AIS). In 2009, the Ministry of Health and Welfare, Executive Yuan, Republic of China, launched the project “Hospital Emergent Capability Accreditation by Level-Stroke (HECAL-Stroke)” to improve AIS treatment in Taiwan. The current study was performed to determine whether the project launched by the government was effective in promoting rtPA therapy among AIS patients. METHODS: All participating hospitals were verified and designated as “heavy duty (HD),”“moderate duty (MoD),” or “medium duty (MeD)” according to the stroke center criteria. Four annual indices (rates of treatment, protocol adherence, in-time treatment, and complications) were recorded from 2009 to 2014 as outcome measures. The data were analyzed using the χ² test for significance. RESULTS: The number of certified hospitals progressively increased from 74 to 112 during the 6-year period and finally consisted of 33 HD, 9 MoD and 70 MeD hospitals in 2014. The annual intravenous rtPA treatment rate increased significantly from 3.0% in 2009 to 4.5% in 2014. The protocol adherence rates were 95.7% in the HD group, 92.4% in the MoD group and 72.8% in the MeD group. The annual in-time treatment rate significantly improved from 26.0% in 2009 to 60.1% in 2014. The overall symptomatic intracranial hemorrhagic rate after rtPA treatment was 8.6%. CONCLUSIONS: Initiation of the HECAL-Stroke project by the government significantly improved rtPA treatment in Taiwan.
Accreditation* ; Humans ; Outcome Assessment (Health Care) ; Stroke* ; Taiwan* ; Tissue Plasminogen Activator

Obstructive sleep apnoea (OSA), a sleep-related breathing condition, is diagnosed based on a patient's apnoea-hypopnea index from a sleep study, and the presence or absence of symptoms. Diabetes mellitus (DM) and OSA share a significant common risk factor, obesity, with all three conditions contributing to the risk of developing cardiovascular diseases. The pathophysiological links between OSA and DM are still unclear, but intermittent hypoxia may be an important mechanism. More awareness of the possible link between OSA and DM is needed, given their increasing prevalence locally and worldwide. Continuous positive airway pressure is the standard treatment for OSA, while weight loss through dietary and lifestyle modifications is important to holistically manage patients with either condition. There is currently insufficient evidence to support the benefits of screening every diabetic patient for OSA. However, diabetic patients with symptoms suggestive of OSA should be referred to a sleep specialist for further evaluation.

INTRODUCTIONThe prevalence of hiatal hernias and para-oesophageal hernias (PEHs) is lower in Asian populations than in Western populations. Progressive herniation can result in giant PEHs, which are associated with significant morbidity. This article presents the experience of an Asian acute care tertiary hospital in the management of giant PEH and parahiatal hernia.

METHODSSurgical records dated between January 2003 and January 2013 from the Department of Surgery, Changi General Hospital, Singapore, were retrospectively reviewed.

RESULTSTen patients underwent surgical repair for giant PEH or parahiatal hernia during the study period. Open surgery was performed for four patients with giant PEH who presented emergently, while elective laparoscopic repair was performed for six patients with either giant PEH or parahiatal hernia (which were preoperatively diagnosed as PEH). Anterior 180° partial fundoplication was performed in eight patients, and mesh reinforcement was used in six patients. The electively repaired patients had minimal or no symptoms during presentation. Gastric volvulus was observed in five patients. There were no cases of mortality. The median follow-up duration was 16.3 months. There were no cases of mesh erosion, complaints of dysphagia or recurrence of PEH in all patients.

CONCLUSIONGiant PEH and parahiatal hernia are underdiagnosed in Asia. Most patients with giant PEH or parahiatal hernia are asymptomatic; they often present emergently or are incidentally diagnosed. Although surgical outcomes are favourable even with a delayed diagnosis, there should be greater emphasis on early diagnosis and elective repair of these hernias.

Adult ; Aged ; Digestive System Surgical Procedures ; methods ; Elective Surgical Procedures ; Female ; Hernia, Hiatal ; diagnostic imaging ; surgery ; Humans ; Laparoscopy ; Male ; Middle Aged ; Retrospective Studies ; Singapore ; Surgical Mesh ; Tertiary Care Centers ; Treatment Outcome