Effects of the Sodium-Glucose Cotransporter Inhibitors on Cardiovascular Death and All-Cause Mortality: A Systematic Review and Meta-analysis of Randomized Placebo-Controlled Clinical Trials.

BACKGROUND: Patients with diabetes mellitus are at an increased risk of cardiovascular morbidity and all-cause mortality. Heart failure and type 2 diabetes often occur concomitantly, and each disease independently increases the risk for the other. OBJECTIVE: Emerging data have revealed that some sodium-glucose cotransporter inhibitors (SGLTi) improve cardiovascular and renal outcomes, particularly in patients with type 2 diabetes. The magnitude of this effect in patients without any underlying condition remains unclear. As a result, we conducted a meta-analysis of the mortality outcomes of available SGLTi in patients with or without cardiovascular diseases, type 2 diabetes, cardiovascular risk factors, and heart failure. METHODS: We performed a systematic review and meta-analysis of randomized, placebo-controlled major cardiovascular outcome trials of SGLTi in patients regardless of their cardiovascular disease or risk status. PubMed, Cochrane, Google Scholar, MEDLINE, and EMBASE were searched for the relevant studies. Three reviewers extracted study data and three reviewers summarized the strength of the evidence. Efficacy outcomes included all-cause mortality, major adverse cardiovascular events (myocardial infarction, stroke, or cardiovascular death), the composite of all-cause mortality, cardiovascular death, or hospitalization for heart failure. Odds ratios with 95% confidence intervals were pooled across trials to calculate the overall effect size. RESULTS: A total of 5043 all-cause mortality events were observed in the study groups. In 42,050 patients who received SGLTi, 2581 events were reported, and 2462 events were reported in 35,491 patients who received placebo (odds ratio = 0.86, 95% confidence interval 0.80-0.93, p = 0.0003). The use of SGLTi significantly reduced cardiovascular mortality compared with control across the patients' population (odds ratio = 0.86, 95% confidence interval 0.79-0.93, p = 0.0001). There was a consistent pattern of mortality beneficial estimates for all patients with different co-morbid conditions in the SGLTi-treated arm compared with the placebo-treated group. The presence or absence of significant cardiovascular disease risk factors (including a family history of premature coronary artery disease, baseline estimated glomerular filtration rate, dyslipidemia, hypertension, smoking, history of cardiovascular disease, and older age) did not affect the estimated mortality benefits. CONCLUSIONS: Sodium-glucose cotransporter inhibitors significantly reduced major adverse cardiovascular events, including hospitalization and all-cause mortality in patients with or without established atherosclerotic cardiovascular disease. We observed a beneficial trend in patients with heart failure with preserved ejection fraction, and no benefits in patients with stroke or myocardial infarction.

Patients with diabetes are at increased risk of cardiac illness and mortality. Heart failure (HF) and type II diabetes mellitus (DM II) often occur concurrently, and each disease independently increases the risk for the other. Evolving data have revealed that medications utilized for diabetes management, specifically, sodium-glucose cotransporter inhibitors (SGLTi) improve cardiac and renal health, particularly in patients with DM II. The impact of this effect in other patients remains unclear. Therefore, we conducted a comprehensive review of the mortality and other benefits of available SGLTi in patients with or without cardiac diseases, DM II, cardiac risk factors, and HF. A total of 5043 mortality events were observed in the study groups. The use of SGLTi significantly reduced cardiac death compared with placebo. There was a reduction in the number of deaths for patients with different conditions in the SGLTi treated arm compared with the placebo group. The presence or absence of cardiac disease, or risk factors did not affect mortality benefits. SGLTi significantly reduced major adverse cardiac events, including hospitalization and mortality in patients with or without cardiac disease.

Prostate cancer management in the era of COVID-19: Recommendations from the Hong Kong Urological Association and Hong Kong Society of Uro-oncology.

AIM: In response to the fast-developing coronavirus disease 2019 (COVID-19) pandemic, special arrangement and coordination are urgently required in the interdisciplinary care of patients across different medical specialties. This article provides recommendations on the management of different stages of localized or metastatic prostate cancer (PC) amid this pandemic. METHODS: The Hong Kong Urological Association and Hong Kong Society of Uro-oncology formed a joint discussion panel, which consisted of six urologists and six clinical oncologists with extensive experience in the public and private sectors. Following an evidence-based approach, the latest relevant publications were searched and reviewed, before proceeding to a structured discussion of relevant clinical issues. RESULTS: The joint panel provided recommendations for PC management during the pandemic, in terms of general considerations, diagnostic procedures, different disease stages, treatment modules, patient support, and interdisciplinary collaboration. The overall goal was to minimize the risk of infection while avoiding unnecessary delays and compromises in management outcomes. Practical issues during the pandemic were addressed such as the use of invasive diagnostic procedures, robotic-assisted laparoscopic prostatectomy, hypofractionated radiotherapy, and prolonged androgen deprivation therapy. The recommendations were explicated in the context of Hong Kong, a highly populated international city, in relation to the latest international guidelines and evidence. CONCLUSION: A range of recommendations on the management of PC patients during the COVID-19 pandemic was developed. Urologists, oncologists, and physicians treating PC patients may refer to them as practical guidance.

Hong Kong Urological Association-Hong Kong Society of Uro-Oncology consensus statements on the management of advanced prostate cancer-2019 Updates.

BACKGROUND: To update the Hong Kong Urological Association-Hong Kong Society of Uro-Oncology consensus statements on the management of advanced prostate cancer, the same panelists as in the previous consensus panel held a series of meetings to discuss updated clinical evidence and experiences. METHODS: The previous consensus statements were retained, deleted, or revised, and new statements were added. At the final meeting, all statements were reviewed and amended as appropriate, followed by panel voting. RESULTS: There were significant changes and additions to the previous consensus statements, primarily driven by the advances in androgen receptor signaling inhibitors, treatment sequencing in metastatic castration-resistant prostate cancer, and increasing recognition of oligometastatic prostate cancer since the introduction of prostate-specific membrane antigen positron emission tomography. In this update, a total of 59 consensus statements were accepted and established. CONCLUSIONS: The consensus panel updated consensus statements on the management of advanced prostate cancer, aiming to allow physicians in the region to keep abreast of the recent evidence on optimal clinical practices.

Management of advanced prostate cancer in Hong Kong: Insights from an APCCC-Derived survey.

AIM: The 2017 Advanced Prostate Cancer Consensus Conference (APCCC) convened an international multidisciplinary panel to vote on controversial issues in the management of advanced prostate cancer (APC). We aimed to compare their conclusions with the opinions of local specialists and explore the practicability of international recommendations in the healthcare setting in Hong Kong. METHODS: Urologists and clinical oncologists practicing in Hong Kong were invited to complete a survey based on the original APCCC 2017 questionnaire and recently published trials in APC. A joint committee of expert key opinion leaders was convened to discuss and analyze the voting differences between local specialists and the APCCC 2017 panel. RESULTS: The respondents constituted 21% (28/132) of registered urologists and 21% (31/146) of clinical oncologists in Hong Kong. Discrepancies in three key areas were identified as being the most timely for this analysis: (a) management of metastatic hormone-sensitive/naïve prostate cancer; (b) management of metastatic castration-resistant prostate cancer; and (c) treatment monitoring and initiation of androgen-deprivation therapy. Fears of toxicity and intolerance among patients and physicians (especially urologists) may be driving the relative underuse of chemotherapy in multiple APC patient groups in Hong Kong. Local patients can face long wait times and limited access to contemporary imaging modalities compared with other developed countries. CONCLUSION: Increased collaborative efforts by urologists and clinical oncologists could ensure that patients gain wider access to the latest diagnostic, treatment and monitoring modalities for APC in Hong Kong.

Consensus statements on the management of clinically localized prostate cancer from the Hong Kong Urological Association and the Hong Kong Society of Uro-Oncology.

OBJECTIVE: To formulate consensus statements to facilitate physician management strategies for patients with clinically localized prostate cancer (PCa) in Hong Kong by jointly convening a panel of 12 experts from the two local professional organizations representing PCa specialists, who had previously established consensus statements on the management of metastatic PCa for the locality. METHODS: Through a series of meetings, the panellists discussed their clinical experience and the published evidence regarding various areas of the management of localized PCa, then drafted consensus statements. At the final meeting, each drafted statement was voted on by every panellist based on its practicability of recommendation in the locality. RESULTS: A total of 76 consensus statements were ultimately accepted and established by panel voting. CONCLUSION: Derived from the recent evidence and major overseas guidelines, along with local clinical experience and practicability, the consensus statements were aimed to serve as a practical reference for physicians in Hong Kong for the management of localized PCa.

Treatment of gastrointestinal bleeding with idarucizumab in a patient receiving dabigatran.

PURPOSE: A case report describing use of idarucizumab for dabigatran reversal without the use of hemostatic agents in a patient who developed acute upper gastrointestinal (GI) bleeding while receiving triple antithrombotic therapy is presented. SUMMARY: A 77-year-old man with a complex cardiac history presented to the emergency room with chief complaints of black tarry stools and low blood pressures for 4 days. His past medical history included recent percutaneous coronary intervention (PCI) and drug-eluting stent (DES) placement, atrial fibrillation, hypertension, hyperlipidemia, coronary artery disease, coronary artery bypass graft surgery, stage 3 chronic kidney disease, and cholecystectomy. His triple antithrombotic therapy consisted of aspirin, clopidogrel, and dabigatran. The patient stated that his last dose of dabigatran was taken the night before. Serum dabigatran levels were not measured. Due to suspicion of acute upper GI bleeding, all antithrombotic agents were withheld. Treatment with idarucizumab, i.v. pantoprazole, and blood transfusion was ordered. An upper endoscopy was safely performed 24 hours later and revealed a minor Mallory-Weiss tear. The patient was discharged 48 hours later with prescriptions for acid suppressant and triple antithrombotic therapy; his melena had resolved before discharge. At 14-week follow-up, the patient reported that his cardiologist had deleted aspirin from his antithrombotic regimen. CONCLUSION: A patient who had recently undergone PCI and DES placement and was receiving aspirin, clopidogrel, and dabigatran for atrial fibrillation was successfully treated for acute GI bleeding with idarucizumab without the use of a hemostatic agent.

Consensus statements on the management of metastatic prostate cancer from the Hong Kong Urological Association and Hong Kong Society of Uro-Oncology.

To establish a set of consensus statements to facilitate physician management strategies for patients with metastatic prostate cancer (mPCa) in Hong Kong. A local expert consensus was organized jointly by the two main professional organizations representing prostate cancer specialists in Hong Kong. A total of 12 experts were included in the consensus panel. Six of the most crucial and relevant areas of debate regarding the management of mPCa were identified. With the use of a modified Delphi method, several panel meetings were held for the members to discuss their clinical experience and the published literature relevant to the areas of debate. At the final meeting, each drafted statement was voted on by every member based on its practicability of recommendation in the locality. After the panel voting, a total of 45 consensus statements regarding the management of mPCa were ultimately accepted and established. The consensus statements were primarily derived from the latest clinical evidence and major overseas guidelines, with the consideration of local clinical experience and practicability. These are considered applicable recommendations for Hong Kong physicians for the management of mPCa patients.

Rare ligamentum flavum cyst causing incapacitating lumbar spinal stenosis: Experience with 3 Chinese patients.

Three Chinese patients suffered from severe lumbar spinal stenosis with debilitating symptoms due to a rare condition of ligamentum flavum cysts in the midline of the lumbar spine. This disease is distinct from synovial cyst of the facet joints or ganglion cysts, both intraoperatively and histopathologically. Magnetic Resonance imaging features of the ligamentum flavum cyst are also demonstrated. We share our surgical experiences of identification of the ligamentum flavum cysts, decompression and excision for two of the patients with demonstrably good recovery. This disease should be considered in the differential diagnosis of an extradural instraspinal mass in patients with lumbar spinal stenosis.

Choice of spirometric reference values for compensation assessment.

BACKGROUND AND OBJECTIVE: Two sets of local reference values are available for spirometry in Hong Kong, but it is uncertain how well they work in the assessment of occupational lung diseases. This study examined their relative performance in the compensational assessment of silicosis. METHODS: Local reference values published in 1982 and 2006 were compared in two different populations comprising normal construction/quarry workers and silicosis patients. Only men aged 20-74 years were included. RESULTS: The FVC results of 93 normal workers were significantly higher than those predicted by either the 1982 or the 2006 reference values. Compared with the 1982 reference values, the mean FEV(1)% or FVC% was age-dependent and 5.2% higher in the normal workers. Smoking decreased the forced expiratory ratio, but did not show a major effect on FEV(1) or FVC among asymptomatic subjects. Despite their derivation largely from never-smokers, the 2006 reference values better predicted FEV(1) and FVC among all smoking categories. Among the 357 silicosis patients, the 1982 reference values also gave 8.8% higher FEV(1)% and 7.4% higher FVC%. These spirometric values differed by more than 10% in patients aged 60 years or more. Despite the presence of disease, the mean FVC% was still significantly above 100%. CONCLUSIONS: Both the 1982 and 2006 local reference values underestimated the FVC of normal construction and quarry workers, reflecting possible occupational selection factors. The 2006 reference values outperformed the 1982 ones, especially among older subjects. Careful calibration with similar occupational groups in the same laboratory is highly desirable in the choice of spirometric reference values for compensation assessment. Smoking does not appear to affect this choice.

Assay of pleural fluid interleukin-6, tumour necrosis factor-alpha and interferon-gamma in the diagnosis and outcome correlation of tuberculous effusion.

OBJECTIVE: To assess the usefulness of interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) in the diagnosis and prediction of outcome of pleural tuberculosis. PATIENTS AND METHODS: Pleural fluid from 32 TB and 34 non-TB patients was sent for assay of IL-6, TNF-alpha and IFN-gamma. Clinical parameters at presentation and residual pleural scarring at completion of treatment were assessed for pleural TB cases. RESULTS: The pleural fluid Levels of IL-6, TNF-alpha and IFN-gamma in TB patients were significantly higher than those with non-TB effusions (P values of <0.001, 0.018 and <0.001, respectively by independent t-test). Utility of these cytokines for diagnosis of pleural TB was evaluated using receiver operating characteristic (ROC) curve analysis. The cut-off values for IL-6, TNF-alpha and IFN-gamma determined in this analysis were 4000, 4 and 60 pg/ml respectively, and their sensitivity and specificity were 90.6% and 76.5%, 90.6% and 79.4%, 100% and 100%, respectively. The pretreatment pleural fluid IL-6 levels had a positive correlation with the number of febrile days after treatment (Pearson correlation test: r=0.60, P=0.009). A negative correlation was found between the percentage reduction in pleural fluid cytokines after 2 weeks treatment and the extent of residual pleural scarring (IL-6: r=-0.62, P=0.041; TNF-alpha: r=-0.65, P=0.030; IFN-gamma: r=0.83, P=0.002). CONCLUSION: Pleural fluid IL-6, TNF-alpha and IFN-gamma assays are useful in the diagnosis of pleural TB. The initial IL-6 level correlates with the number of febrile days. The percentage change of cytokines after 2 weeks of treatment also helps to predict residual pleural scarring.

Targeting anti-apoptotic genes upregulated by androgen withdrawal using antisense oligonucleotides to enhance androgen- and chemo-sensitivity in prostate cancer.

The main obstacle to improved survival of advanced prostate cancer is our failure to prevent its progression to its lethal and untreatable stage of androgen independence. New therapeutic strategies designed to prevent androgen-independent (AI) progression must be developed before significant impact on survival can be achieved. Characterization of changes in gene expression profiles after androgen ablation and during progression to androgen-independence suggest that the various therapies used to kill neoplastic cells may precipitate changes in gene expression that lead to the resistant phenotype. Castration-induced increases in antiapoptosis genes, Bcl-2 and clusterin, help create a resistant phenotype, while antisense oligonucleotides can inhibit these adaptive cell survival mechanisms and enhance both hormone and chemotherapy. Ongoing efforts are necessary to identify additional molecular pathways mediating AI progression and chemoresistance, since complexities of tumor heterogeneity and adaptability dictate that optimal control over tumor progression will require multi-target systemic therapies.