Purpose: Adjuvant pembrolizumab improved disease-free survival (DFS) and overall survival (OS) versus placebo in participants with renal cell carcinoma (RCC) at increased risk of recurrence after nephrectomy in the global phase 3 KEYNOTE-564 study. This post hoc subgroup analysis evaluated the efficacy and safety of adjuvant pembrolizumab in East Asian (Japan, South Korea, and Taiwan) participants enrolled in KEYNOTE-564. Materials and Methods: Eligible participants were randomly assigned 1:1 to receive adjuvant pembrolizumab 200 mg or placebo intravenously every 3 weeks for ≤ 17 cycles. The primary endpoint was DFS by investigator assessment. OS was a key secondary endpoint. Safety was a secondary endpoint. Results: The East Asian subgroup included 126 participants (pembrolizumab, n=58; placebo, n=68). Median follow-up was 62.1 months (range, 49.6 to 73.0 months). Hazard ratio for DFS with pembrolizumab versus placebo was 0.70 (95% confidence interval 0.41 to 1.20). Median DFS was not reached with pembrolizumab versus 58.8 months with placebo; estimated 48-month rate was 61.3% versus 51.2%. Hazard ratio for OS was 0.47 (95% confidence interval, 0.15 to 1.49). Median OS was not reached with pembrolizumab and placebo; estimated 48-month rate was 94.8% versus 91.2%. Treatment-related adverse events occurred in 70.7% of participants (29.3% grade 3 or 4) receiving pembrolizumab and 36.8% of participants (0.0% grade 3 or 4) receiving placebo. No pembrolizumab-related deaths occurred. Conclusion In the KEYNOTE-564 East Asian subgroup, adjuvant pembrolizumab provided DFS and OS benefits versus placebo and had a safety profile consistent with the global results. These results further support pembrolizumab as adjuvant treatment for East Asian patients with RCC at increased risk of recurrence after nephrectomy.

Background: Despite the lack of official COVID-19 statistics, various workplaces and occupations have been at the center of COVID-19 outbreaks. We aimed to compare legal measures and governance established for managing COVID-19 infection risks at workplaces in nine Asia and Pacific countries and to recommend key administrative measures. Methods: We collected information on legal measures and governance from both general citizens and workers regarding infection risks such as COVID-19 from industrial hygiene professionals in nine countries (Indonesia, India, Japan, Malaysia, New Zealand, Republic of the Philippines, Republic of Korea, Taiwan, and Thailand) using a structured questionnaire. Results: A governmental body overseeing public health and welfare was in charge of containing the spread and occurrence of infectious diseases under an infectious disease control and prevention act or another special act, although the name of the pertinent organizations and legislation vary among countries. Unlike in the case of other traditional hazards, there have been no specific articles or clauses describing the means of mitigating virus risk in the workplace that are legally required of employers, making it difficult to define the responsibilities of the employer. Each country maintains own legal systems regarding access to the duration, administration, and financing of paid sick leave. Many workers may not have access to paid sick leave even if it is legally guaranteed. Conclusion Specific legal measures to manage infectious disease risks, such as providing proper personal protective equipment, education, engineering control measures, and paid sick leave are recommended to be stipulated in Industrial safety and health-related acts.

Background: While international data exists on hospitalisation and its associated mortality among endstage renal disease (ESRD) population on maintenance renal replacement therapy (RRT), local data is not known. The objective of this single centre retrospective observational study is to determine the burden of hospital admission and readmission among the ESRD population and the mortality outcome after hospitalisation. Methods: We obtained our study data from the HSNI Batu Pahat nephrology service inpatient database, patients’ medical records and Jabatan Pendaftaran Negara (JPN) registry of death. Results: There were 195 index admissions identified from January to June 2016. We found that hospital readmission rate was high at 19.5% within 30 days, 34.4% within 60 days, and 44.6% within 90 days of discharge. Commonest reason of admission was fluid overload (20.7%). Overload was also the commonest reason of readmissions within 30 and 60 days (28.9% and 23.8% respectively), whereas vascular access related issues were the commonest reason of readmission within 90 days of discharge (21.8%). The 90-day mortality rate after index admission was also high at around 18%. The commonest cause of mortality was Infection and Sepsis (42.9%), followed by Acute Coronary Syndrome (22.9%). Conclusions: This study demonstrated the heavy burden of hospitalisation and high mortality rate among ESRD populations. Further larger researches are welcomed to look into the factors associated and the problems faced, in order to improve not only individual morbidity and mortality outcomes, but also on hospitalisation cost and healthcare resources.
Patient Readmission

INTRODUCTIONThe near terminal patient with skeletal metastasis may suitably be palliated with an intramedullary nail whereas another patient with good survival potential may benefit from a more extensive resection and reconstructive procedure. In a previous study by the senior author (Nathan et al, 2005), life expectancy in patients operated on for bone metastases correlated with clinical and haematological parameters in a normogram. We performed a cross-cultural comparison to validate this normogram.

MATERIALS AND METHODSWe randomly selected 73 patients who had undergone surgery for metastatic bone disease between 28 December 2000 and 11 March 2009. The time to deaths was recorded from hospital records and telephone interviews. Multiple parameters including clinical, radiological and haematological were evaluated for significant prognostic value using Kaplan-Meier survivorship analysis. Statistically significant parameters were entered into a Cox regression model for statistically independent significance. A multi-tier prediction of survival was performed by workers from various levels of seniority.

RESULTSAt the time of analysis, there were 40 deaths (55%). Median survival was 15.8 (95% CI, 7.9 to 23.7) months. Kaplan-Meier analysis showed that low haemoglobin (P = 0.0000005), presence of lymph node metastases (P = 0.00008), multiple bone metastases (P = 0.003), presence of visceral metastases, (P = 0.007), low lymphocyte count (P = 0.02) and low serum albumin (P = 0.02) were significantly associated with poor survival. By Cox regression analysis, presence of visceral metastases (P = 0.002), presence of lymph node metastases (P = 0.0002) and low haemoglobin (P = 0.01) were shown to be independent factors in the prediction of survival. Survivorship readings were superimposed onto the previous normogram and found to be similar. Independent blinded use of the normogram allowed good prediction of survival. There was a tendency to underestimate survival when patients survived beyond 1 year of skeletal metastasis.

CONCLUSIONOur findings are similar to that of the previous study in showing a relationship between the above-mentioned parameters and survival. This is despite differences in patient demographic characteristics and management protocols. Use of the tools may allow better siting of most appropriate surgery in metastatic bony disease.

Bone Neoplasms ; mortality ; surgery ; Decision Support Systems, Clinical ; Female ; Humans ; Male ; Middle Aged ; Prognosis ; Proportional Hazards Models ; Survival Analysis ; Terminal Care

Objective: To assess the expression of retinoic acid receptor beta 2 (RAR-β2) in breast tumor and to evaluate the relationship between RAR-β2 expression and tumorigenesis of breast cancer. Methods: Immu-nohistochemistry was used to detect the expression of RAR-β2 protein in specimens from 40 cases of breast cancer, 40 cases of atypical ductal hyperplasia, 40 cases of fibroadenoma and 20 cases of normal breast tissues. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect the mRNA expression levels of RAR-β2 gene in 20 cases of breast cancer, 20 cases of atypical ductal hyperplasia, 20 cases of fibroadenoma, and 20 cases of normal breast tissues. Results: Immunohistochemical staining results revealed that the positive expression of RAR-β2 protein showed nuclear staining. The positive expression rate of RAR-β2 was 30% (12/40) in breast cancer, 17.5% (7/40) in atypical ductal hyperplasia, 87.5% (35/40)in fibroadenoma, and 95% (19/20) in normal breast tissues. The expression of RAR-β2 protein in breast cancer was significantly lower than that in normal breast tissues (X~2=26.30, P<0.001). The expression of RAR-β2 was not significantly different between atypical ductal hyperplasia and breast cancer (P>0.05). No correlation was found between the expression of RAR-β 2 protein and the tumor size, menopausal age, lymph node metastasis, clinical stage, histological grade, or protein expression of ER and PR in breast cancer tissues (P>0.05). Follow-up results showed that 3 out of 28 patients with negative RAR-β2 expression had visceral organ metastasis, but only one of the 12 RAR-β2 positive patients had osseous metastasis. RT-PCR analysis showed that the positive expression rate of RAR-β2 mRNA in breast cancer, atypical ductal hyperplasia, fibroadenoma and normal breast tissues was 25% (5/20), 35% (7/20), 85% (17/20) and 100% (20/20), respectively. The RAR-β2 mRNA expression rate in breast cancer was significantly lower than that in normal breast tissues (X~2=30.43, P<0.001). No significant difference in RAR-β2 mRNA expression was found between atypical ductal hyperplasia and breast cancer tissues (P>0.05). Conclusion: RAR-β2 gene may play a repressive role in the initiation of breast cancer, and the loss of the expression of RAR-β2 gene may be the initial step in breast carcinogenesis.

AIM:To explore whether the balance between endothelin(ET) and nitric oxide(NO) plays an important role in airway hyperresponsiveness of asthmatic rats. METHODS:The tension of isolated perfused rat tracheal rings was measured after ET-1 stimulation and incubation of JKC 302 and L-NAME. RESULTS:ET-1 constricted isolated rat tracheal ring, produced slowly developing and long-lasting contraction. The ET-1-induced contraction response of asthmatic rat tracheal ring was higher than that of normal control group (P＜0.01). JKC 302, a selective ETA receptor antagonist, partly blocked ET-1-induced contraction in asthmatic rat trachea ring. L-NAME significantly augmented the constriction caused by ET-1. CONCLUSION:The effects of ET on bronchomotor tone may be modified by NO as this is a bronchomotor, and the imbalance between ET and NO may play an important role in asthma pathogenesis.