Does the femoral component design modified in consideration of Asian anatomical characteristics fit better than the conventional design for Korean femora in reality?

INTRODUCTION: We aimed to investigate the anatomical and clinical advantages of an Asian-specific femoral component design with a high femoral aspect ratio, compared with the conventional femoral component design. MATERIALS AND METHODS: A retrospective analysis of the operation and outpatient clinic records of 239 knees operated on using an anatomically modified femoral component design (MFCD, Group A) and 153 knees operated on using a conventional femoral component design (CFCD, Group B) in Korean patients was performed. Three subgroups were created based on the mediolateral size of the two different femoral component designs. The geometric accommodation of each femoral component was assessed using intraoperatively measured femoral posterior condylar resection and posterior condylar trimming amounts. Clinical outcomes were assessed using a range of motion (ROM) and patient-reported outcome measurements. RESULTS: In the comparison between Groups A and B, the mean combined bilateral posterior condylar trimming (XPCT) was 2.91 [2SD: - 4.12-9.94] and 1.45 [2SD: - 5.89-8.80], and the median XPCT was 3 and 1.5. In the largest subgroup (subgroup 2), Groups A and B included 100 and 112 patients, all six posterior condylar resection and trimming parameters were significantly larger in Group A. Preoperative and postoperative ROM and Hospital for Special Surgery scores were similar between the two groups. Preoperative Western Ontario and McMaster Universities Arthritis Index (WOMAC) was higher in Group A. However, postoperative WOMAC was similar between the groups. Perioperative improvement in WOMAC index was significantly greater in Group B. CONCLUSIONS: The Asian-specific femoral component design resulted in more resection and trimming of the femoral posterior condyle than the conventional design despite it was not associated with different clinical outcomes. Surgeons should be aware of unexpected excessive posterior condylar resection and formation of large flexion gap when using femoral component design with high femoral aspect ratio.

Deep PSA response and extended time-to-nadir as robust predictors of survival in Asian patients with de novo metastatic hormone-sensitive prostate cancer receiving upfront intensified treatment.

INTRODUCTION: In de novo metastatic hormone-sensitive prostate cancer (mHSPC) treated with upfront intensification using androgen receptor signaling inhibitor or chemotherapy (Docetaxel), achieving a PSA nadir less than 0.2 ng/mL, indicative of superior survival in trials, may often be unattainable in real-world settings. We explored the predictive value of the degree of PSA decline and time to PSA nadir (TTPN) on oncological outcomes. METHODS: A prospectively maintained database of consecutive prostate cancer cases in Hong Kong was accessed. Patients diagnosed with de novo mHSPC from 2016 to 2022 and treated with upfront intensification were included in this analysis. Landmark analysis on PSA kinetics at 6-months following treatment intensification was performed. They were classified based on 1) TTPN (≥6 months vs. <6 months), and 2) a combined response (deep responders achieving both ≥95% PSA decline and TTPN ≥ 6 months vs. shallow responders). Multivariable regression analysis was employed to identify the effects of confounders. FINDINGS: A total of 131 patients were included in this analysis. Classifying patients by combined response best predicted survival outcomes. Deep responders had better progression-free survival (HR = 0.56; 95%CI = 0.34-0.91; p = 0.019), overall survival (HR = 0.50; 95%CI = 0.26-0.97; p = 0.036), and cancer-specific survival (HR = 0.43; 95%CI = 0.19-0.99; p = 0.042). Difference in overall survival remained significant after adjustment in multivariable regression analysis. CONCLUSION: Our analysis demonstrates that alternative PSA targets can predict treatment response and survival outcomes in de novo mHSPC patients in a real-world setting, providing valuable information for patient counselling and potentially guiding future trial design.

Erdafitinib in Asian patients with advanced solid tumors: an open-label, single-arm, phase IIa trial.

BACKGROUND: FGFR genomic aberrations occur in approximately 5-10% of human cancers. Erdafitinib has previously demonstrated efficacy and safety in FGFR-altered advanced solid tumors, such as gliomas, thoracic, gastrointestinal, gynecological, and other rare cancers. However, its efficacy and safety in Asian patients remain largely unknown. We conducted a multicenter, open-label, single-arm phase IIa study of erdafitinib to evaluate its efficacy in Asian patients with FGFR-altered advanced cholangiocarcinoma, non-small cell lung cancer (NSCLC), and esophageal cancer. METHODS: Patients with pathologically/cytologically confirmed, advanced, or refractory tumors who met molecular and study eligibility criteria received oral erdafitinib 8 mg once daily with an option for pharmacodynamically guided up-titration to 9 mg on a 28-day cycle, except for four NSCLC patients who received erdafitinib 10 mg (7 days on/7 days off) as they were recruited before the protocol amendment. The primary endpoint was investigator-assessed objective response rate per RECIST v1.1. Secondary endpoints included progression-free survival, duration of response, disease control rate, overall survival, safety, and pharmacokinetics. RESULTS: Thirty-five patients (cholangiocarcinoma: 22; NSCLC: 12; esophageal cancer: 1) were enrolled. At data cutoff (November 19, 2021), the objective response rate for patients with cholangiocarcinoma was 40.9% (95% CI, 20.7-63.6); the median progression-free survival was 5.6 months (95% CI, 3.6-12.7) and median overall survival was 40.2 months (95% CI, 12.4-not estimable). No patient with RET/FGFR-altered NSCLC achieved objective response and the disease control rate was 25.0% (95% CI, 5.5-57.2%), with three patients with stable disease. The single patient with esophageal cancer achieved partial response. All patients experienced treatment-emergent adverse events, and grade ≥ 3 treatment-emergent adverse events were reported in 22 (62.9%) patients. Hyperphosphatemia was the most frequently reported treatment-emergent adverse event (all-grade, 85.7%). CONCLUSIONS: Erdafitinib demonstrated efficacy in a population of Asian patients in selected advanced solid tumors, particularly in those with advanced FGFR-altered cholangiocarcinoma. Treatment was tolerable with no new safety signals. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov (NCT02699606); study registration (first posted): 04/03/2016.

Risk of gastrointestinal bleeding in Asian patients receiving oral anticoagulants for stroke prevention in atrial fibrillation.

Non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly used for stroke prevention in atrial fibrillation. At the Asia Pacific Advancing Patient care with EdoXaban 2023 meeting, experts shared insights on gastrointestinal bleeding with NOACs for stroke prevention in atrial fibrillation in Asian clinical practice, where NOACs have gained widespread acceptance due to their favourable profiles. Gastrointestinal bleeding risk varies amongst NOACs, emphasizing the importance of diligent patient assessment, dosage selection and vigilant monitoring. Edoxaban emerged as a viable option with a low gastrointestinal bleeding risk profile in Asian compared with non-Asian patients, supporting its continued clinical utilization for appropriate patients.

One-Month Dual Antiplatelet Therapy in High Bleeding Risk Asian Patients Undergoing Percutaneous Coronary Intervention　- Onyx ONE Clear 2-Year Results.

Background: One-month dual antiplatelet therapy (DAPT) in high bleeding risk (HBR) patients undergoing percutaneous coronary intervention (PCI) with the Resolute OnyxTM zotarolimus-eluting stents (ZES) is safe and effective. Asian patients have a unique ischemia/bleeding risk profile. Here, we compare the outcomes between Asian and non-Asian patients after PCI and 1-month DAPT. Methods and Results: Onyx ONE Clear was a prospective, multicenter study enrolling HBR patients undergoing PCI with the Resolute Onyx ZES (ClinicalTrials.gov identifier NCT03647475). Event-free patients after 1-month DAPT transitioned to single antiplatelet therapy. Clinical outcomes between 1 month and 2 years were compared between patients from Asian and non-Asian countries after 1 : 1 propensity score matching accounting for baseline differences. Patients from Asian countries represented 18% (n=273) of the study group (n=1,507). Non-Asian patients had greater clinical complexity; however, these differences were minimal after matching. There were no significant differences in ischemic outcomes between matched cohorts from 1 month to 2 years, including the primary composite endpoint of cardiac death or myocardial infarction (12% vs. 12%; P>0.99). However, there were significantly fewer Bleeding Academic Research Consortium types 3-5 bleeding events in the Asian vs. non-Asian cohort (4% vs. 9%; P=0.007), despite similar bleeding risk profiles after matching. Conclusions: After propensity score matching, HBR patients from Asian countries undergoing PCI treated with 1-month DAPT had similar ischemic outcomes but fewer bleeding events between 1 month and 2 years compared with patients from non-Asian countries.

Treatment of masseter muscle hypertrophy with botulinum toxin type A injection: A review of adverse events.

BACKGROUND: The popularity of noninvasive botulinum toxin type A (BTX-A) injections for masseter muscle hypertrophy is increasing among Asian individuals with a square-shaped lower face. AIMS: This study aimed to analyze the adverse events (AEs) caused by BTX-A injections into the masseter muscle. PATIENTS/METHODS: This observational study retrospectively evaluated 46 250 patients who underwent BTX-A injections into the masseter muscle in 2022. The inclusion criteria were the diagnosis of an AE by the physician at the return visit and subsequent follow-up of progress (n = 223). The patients who were lost to follow-up (n = 40) were excluded from the study. RESULTS: Among the 223 patients with AEs, the most common AE was paradoxical bulging (88.3%, n = 197/223). The average period from treatment until confirmation of improvement was 159.6 ± 113.6 days (range 13-667 days) for all AEs, all of which were temporary. The period until improvement was 166.1 days in the intervention group (n = 122) and 151.9 days in the observation group (n = 101) (p = 0.24). As the period until improvement of AEs included the period until the patients visited the clinics and the improvements were confirmed by physicians, the actual period was likely to have been shorter. CONCLUSIONS: (1) All AEs were temporary. (2) All AEs improved within 22.2 months (within 5.3 ± 3.8 months on average). (3) There was no significant difference between the intervention and observation groups in the period until the improvement of AEs.

Exploring the effectiveness of molecular subtypes, biomarkers, and genetic variations as first-line treatment predictors in Asian breast cancer patients: a systematic review and meta-analysis.

BACKGROUND: Breast cancer incidence has been on the rise significantly in the Asian population, occurring at an earlier age and a later stage. The potential predictive value of molecular subtypes, biomarkers, and genetic variations has not been deeply explored in the Asian population. This study evaluated the effect of molecular subtype classification and the presence or absence of biomarkers and genetic variations on pathological complete response (pCR) after neoadjuvant treatment in Asian breast cancer patients. METHODS: A systematic search was conducted in MEDLINE (PubMed), Science Direct, Scopus, and Cochrane Library databases. Studies were selected if they included Asian breast cancer patients treated with neoadjuvant chemotherapy and contained data for qualitative or quantitative analyses. The quality of the included studies was assessed using the Newcastle Ottawa Scale. Following the random effects model, pooled odds ratios or hazard ratios with 95% confidence intervals for pCR were analysed using Review Manager Software. Heterogeneity between studies was assessed using Cochran's Q-test and I2 test statistics. RESULTS: In total, 19,708 Asian breast cancer patients were pooled from 101 studies. In the neoadjuvant setting, taxane-anthracycline (TA) chemotherapy showed better pCR outcomes in triple-negative breast cancer (TNBC) (p<0.0001) and human epidermal growth factor receptor 2 enriched (HER2E) (p<0.0001) than luminal breast cancer patients. Similarly, taxane-platinum (TP) chemotherapy also showed better pCR outcomes in TNBC (p<0.0001) and HER2E (p<0.0001). Oestrogen receptor (ER)-negative, progesterone receptor (PR)-negative, HER2-positive and high Ki-67 were significantly associated with better pCR outcomes when treated with either TA or TP. Asian breast cancer patients harbouring wildtype PIK3CA were significantly associated with better pCR outcomes when treated with TA in the neoadjuvant setting (p=0.001). CONCLUSIONS: In the neoadjuvant setting, molecular subtypes (HER2E and TNBC), biomarkers (ER, PR, HER2, HR, Ki-67, nm23-H1, CK5/6, and Tau), and gene (PIK3CA) are associated with increased pCR rates in Asian breast cancer patients. Hence, they could be further explored for their possible role in first-line treatment response, which can be utilised to treat breast cancer more efficiently in the Asian population. However, it needs to be further validated with additional powered studies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021246295.

Post-traumatic stress disorder symptoms are frequent among inflammatory bowel disease patients of South Asian descent-A case-control study.

BACKGROUND: Post-traumatic stress (PTS) is the psycho-physiological response to a traumatic or life-threatening event and is implicated in inflammatory bowel disease (IBD). IBD-PTS is present in up to 30% of white, non-Hispanic patients. The rates of IBD in Asian populations are expanding, making the exploration of IBD-PTS in this population imperative. METHODS: Adult patients of South/Southeast (S/SE) Asian decent with IBD for more than 6 months were recruited online via social media and patient-support groups. Participants completed the post-traumatic stress disorder (PTSD) Checklist-5 (PCL-5), the United States National Institutes of Health's Patient-Reported Outcomes Measurement Information System (NIH-PROMIS) -43 profile and demographics. S/SE Asian participants were age and sex matched (1:2) with randomly selected white, non-Hispanic controls. Statistical analyses evaluated differences in IBD-PTS symptoms between groups, the relationship between disease severity and health-related quality of life (HRQoL) and predictors of IBD-PTS severity. RESULTS: Forty-seven per cent of the 51 S/SE Asian participants met the diagnostic cut-off for PTSD on the PCL-5 compared to 13.6% of 110 IBD controls. The mean global score on the PCL-5 was three times higher in S/SE Asians. Patients of S/SE Asian decent were over five times more likely to have PTSD due to their IBD experiences than controls, nearly doubling when controlling for disease activity. More severe IBD-PTS was present in S/SE Asian patients with active disease and those with extraintestinal manifestations. Higher global levels of IBD-PTS were associated with poorer HRQoL in S/SE Asians where increased hyperarousal from IBD-PTS predicted more sleep disturbance. CONCLUSIONS: S/SE Asian patients are five times more likely to experience IBD-PTS than their white, non-Hispanic counterparts. Several cultural factors lead to IBD-PTS in S/SE Asian patients that must be considered by IBD providers. Preventing, screening for and treating IBD-PTS in this population appears warranted.

A Real-World Experience of Hyperkalemia Management Using Sodium Zirconium Cyclosilicate in Chronic Hemodialysis: A Multicenter Clinical Audit.

INTRODUCTION:  Hyperkalemia, a common condition among hemodialysis (HD) patients, is associated with adverse health outcomes. Evidence of the safety and efficacy of a potassium-binder, sodium zirconium cyclosilicate (SZC), has been limited among Asian (HD) patients beyond phase 3 trials. This article demonstrates real-world evidence of SZC usage in an Asian cohort of HD patients. METHODS:  A retrospective clinical audit was conducted among 293 patients who received maintenance HD at community-based dialysis centers in Singapore. Patients received SZC for either management of hyperkalemia or hyperkalemia prevention during anticipated disruption to dialysis, such as during traveling. Among patients treated for hyperkalemia (N = 147), serum potassium (K+) prior to SZC initiation and at the endpoint was compared using a paired Student's t-test. Changes in K+ from baseline to endpoint were compared across various categories within each demographic and health-related variables using either Student's t-test or one-way ANOVA. Patients who experienced adverse events after SZC initiation or were deceased during the audit were reviewed to provide a descriptive account. RESULTS:  Among patients who received SZC for hyperkalemia treatment, SZC use was associated with a significant reduction of 0.812 mmol/L in serum potassium. Patients with ethnicities other than Chinese, Malay, or Indian had a nominal reduction in K+ of 0.7 mmol/L and this can be accounted for the small sample size of this sub-group. The three main ethnicities which represented more than 95% of the sample showed a significant reduction in K+ levels (all three p<0.001). This is consistent with other studies with SZC which showed efficacy across various ethnicities. Patients who received SZC for hyperkalemia treatment or prevention had a significant lowering of mortality rate. This mortality reduction may have inherent biases and confounders, due to the retrospective clinical audit study design.  Conclusions: Overall, SZC was safe and effective among the audited patients. The efficacy in the real-world setting was similar to previous trials. The novel use of SZC to manage serum potassium when HD sessions are missed, such as during traveling, warrants further investigation due to potentially significant life-saving implications.

Management of Acute Cancer Pain in Asia: An Expert Opinion on the Role of Tramadol/Dexketoprofen Fixed-Dose Combination.

Most patients experience acute cancer pain at some stage throughout their cancer journey. When inadequately managed, cancer pain has devastating consequences for the patient's quality of life. The suboptimal management of cancer pain in Asia is mainly driven by over-regulation and limited access to opioids. Concerns about adverse events and addiction have resulted in a negative perception of this group of drugs among physicians, as well as patients. There is a need to optimize the management of cancer pain across the region, through the provision of an alternative treatment option that is simple to prescribe, convenient to administer and well tolerated by patients, which will increase patients' compliance and good results. As recommended in many international guidelines, starting by the WHO analgesic ladder, cancer pain can be effectively managed with multimodal analgesia. Fixed-dose combinations (FDCs), in which two or more analgesic agents act synergistically to deliver a broad spectrum of pain relief, represent an effective and convenient option for delivering multimodal analgesia to patients with cancer pain. This is extremely well accepted by patients for several reasons. Any multimodal pharmacological approach to pain management should be based on the potentiality to block pain at different levels and to reduce the dosages of single analgesics, reducing their side effects. Hence, the use of NSAIDs, combined with other analgesics, is the general basis of multimodal pain management. If NSAIDs are combined with tramadol, a weak opioid that has per se a multimodal analgesic efficacy, it may be ideal. The tramadol/dexketoprofen FDC combines the centrally acting weak opioid with a peripherally acting NSAID to deliver rapid-onset, long-lasting analgesia, which has been proven efficacious and safe in the management of moderate-to-severe acute pain in the postoperative setting. This expert opinion explores the role of tramadol/dexketoprofen FDC in the management of patients with moderate-to-severe acute cancer pain. It is essentially based on the incredibly high amount of existing data on the use of the drug, and on the long-lasting experience of the experts in pain management of cancer patients participating in the advisory panel.

Whole exome sequencing and rare variant association study to identify genetic modifiers, KLF1 mutations, and a novel double mutation in Thai patients with hemoglobin E/beta-thalassemia.

OBJECTIVES: Clinical manifestations of patients with Hemoglobin E/beta-thalassemia vary from mild to severe phenotypes despite exhibiting the same genotype. Studies have partially identified genetic modifiers. We aimed to study the association between rare variants in protein-coding regions and clinical severity in Thai patients. METHODS: From April to November 2018, a case-control study was conducted based on clinical information and DNA samples collected from Thai patients with hemoglobin E/beta-thalassemia over the age of four years. Cases were patients with severe symptoms, while patients with mild symptoms acted as controls. Whole exome sequencing and rare variant association study were used to analyze the data. RESULTS: All 338 unrelated patients were classified into 165 severe and 173 mild cases. Genotypes comprised 81.4% of hemoglobin E/beta-thalassemia, 2.7% of homozygous or compound heterozygous beta-thalassemia, and 0.3% of (뫧)0 thalassemia Hb E while 15.7% of samples were not classified as beta-thalassemia. A novel cis heterozygotes of IVS I-7 (A > T) and codon 26 (G > A) was identified. Six genes (COL4A3, DLK1, FAM186A, PZP, THPO, and TRIM51) showed the strongest associations with severity (observed p-values of <0.05; significance lost after correction for multiplicity). Among known modifiers, KLF1 variants were found in four mild patients and one severe patient. CONCLUSION: No rare variants were identified as contributors to the clinical heterogeneity of hemoglobin E/beta-thalassemia. KLF1 mutations are potential genetic modifiers. Studies to identify genetic factors are still important and helpful for predicting severity and developing targeted therapy.

Factors influencing medication adherence in multi-ethnic Asian patients with chronic diseases in Singapore: A qualitative study.

Background: Poor medication adherence can lead to adverse health outcomes and increased healthcare costs. Although reasons for medication adherence have been widely studied, less is explored about factors affecting medication adherence for patients in non-Western healthcare setting and from Asian cultures. This study aimed to explore cultural perspectives on factors influencing medication adherence among patients with chronic diseases in a multi-ethnic Asian healthcare setting. Methods: We conducted a qualitative study involving in-depth interviews with patients with chronic conditions purposively recruited from a community hospital in Singapore until data saturation was achieved. A total of 25 patients participated in this study. Interviews were transcribed and thematically analyzed. Themes were subsequently mapped into the World Health Organization (WHO) Framework of Medication Adherence. Results: Participants commonly perceived that sides effects (therapy-related dimension), poor understanding of medication (patient-related dimension), limited knowledge of condition (patient-related dimension), forgetfulness (patient-related dimension) and language issues within a multi-ethnic healthcare context (healthcare team and system-related dimension) as the main factors contributing to medication adherence. Importantly, medication adherence was influenced by cultural beliefs such as the notion of modern medicines as harms and fatalistic orientations towards escalation of doses and polypharmacy (patient-related dimension). Participants made various suggestions to foster adherence, including improved patient-physician communication, enhanced care coordination across providers, use of language familiar to patients, patient education and empowerment on the benefits of medication and medication adjustment. Conclusion: A wide range of factors influenced medication adherence, with therapy- and patient-related dimensions more pronounced compared to other dimensions. Findings demonstrated the importance of cultural beliefs that may influence medication adherence. Future efforts to improve medication adherence should consider a person-centered approach to foster more positive health expectations and self-efficacy on medication adherence, supplemented with routine reviews, development of pictograms and cultural competence training for healthcare professionals.

Neoadjuvant Chemotherapy in Asian Patients With Locally Advanced Gastric Cancer.

Presently, surgery is the only treatment approach for gastric cancer and improving the prognosis of locally advanced gastric cancer is one of the key factors in promoting gastric cancer survival benefit. The MAGIC study was the first to demonstrate the efficacy of neoadjuvant chemotherapy (NAC) in European countries. In recent years, several clinical trials have provided evidence for the use of NAC in Asian patients with locally advanced gastric cancer. However, clinical practice guidelines vary between Asian and non-Asian populations. Optimal NAC regimens, proper target populations, and predictors of NAC outcomes in Asian patients are still under investigation. Herein, we summarized the current progress in the administration of NAC in Asian patients with gastric cancer.

Facial Beautification and Rejuvenation with Injectables: My Preferred Approach.

Asians are of different ethnic origins. Nevertheless, they share the common facial structural deficiencies and consequences of the aging process that create the opportunity for esthetic intervention. As a result, Injectables are widely used in young Asians to achieve an oval facial shape with increased facial height and projection. In mature Asians with lifelong structural deficiencies, the beauty treatment plan is more complex than removal of signs of aging. Therefore, apart from injectables, other treatment modalities for tissue repositioning, neocollagenesis and skin quality improvement are also required to obtain the optimal result.

Cross-cultural considerations for teleneuropsychology with Asian patients.

OBJECTIVE: Recent teleneuropsychology (TeleNP) models provide some degree of guidance in the application of telecommunication technologies toward the practice of neuropsychology. However, there remains a paucity of peer-reviewed data on TeleNP practices with culturally diverse patients, including Asian patients. This manuscript describes the challenges related to TeleNP practices with Asian patients and offers practical recommendations to complement existing TeleNP guidelines. METHOD: Based on extant literature on multicultural applications of neuropsychology, weprovide recommendations for TeleNP services with Asian patients that pertain to specific components of a TeleNP evaluation, such as a) pre-evaluation preparation, b) determining the appropriateness of the referral, c) determining language proficiency, d) working with interpreters, e) informed consent and confidentiality issues, f) conducting a culturally sensitive clinical interview, g) behavioral observations and communication, h) test selection, and i) interpreting data and writing reports. CONCLUSIONS: Our recommendations for TeleNP services with Asian patients highlight the need for flexibility to accommodate cultural differences and commitment to the complex nature of working with patients requiring interpretation services, while also recognizing the importance of preserving the validity of neuropsychological methods. Moving forward, it is imperative that the field of neuropsychology increases the training and accessibility of neuropsychologists who are knowledgeable in providing TeleNP services to Asian patients, and promotes research on the validation of TeleNP for Asian and other ethnic minority groups.

Pembrolizumab or pembrolizumab plus chemotherapy versus standard of care chemotherapy in patients with advanced gastric or gastroesophageal junction adenocarcinoma: Asian subgroup analysis of KEYNOTE-062.

OBJECTIVE: First-line pembrolizumab with/without chemotherapy versus chemotherapy was evaluated in programmed death ligand 1 combined positive score ≥1, locally advanced/unresectable or metastatic gastric cancer/gastrooesophageal junction cancer in the KEYNOTE-062 study. We present results for patients enrolled in Asia. METHODS: Eligible patients were randomly assigned 1:1:1 to pembrolizumab 200 mg, pembrolizumab plus chemotherapy (cisplatin + 5-fluorouracil or capecitabine) or placebo plus chemotherapy Q3W. End points included overall survival (primary) in combined positive score ≥1 and combined positive score ≥10 populations and safety and tolerability (secondary). RESULTS: A total of 187 patients were enrolled in Asia (pembrolizumab, n = 62; pembrolizumab plus chemotherapy, n = 64; chemotherapy, n = 61). Compared with the global population, higher proportions of patients had Eastern Cooperative Oncology Group performance status 0 and a diagnosis of stomach cancer. In the programmed death ligand 1 combined positive score ≥1 population, median overall survival was numerically longer with pembrolizumab versus chemotherapy (22.7 vs 13.8 months; hazard ratio, 0.54; 95% confidence interval, 0.35-0.82) and pembrolizumab plus chemotherapy versus chemotherapy (16.5 vs 13.8 months; hazard ratio, 0.78; 95% confidence interval, 0.53-1.16). In the programmed death ligand 1 combined positive score ≥10 population, median overall survival was also numerically longer with pembrolizumab versus chemotherapy (28.5 vs 14.8 months; hazard ratio, 0.43; 95% confidence interval, 0.21-0.89) and pembrolizumab plus chemotherapy versus chemotherapy (17.5 vs 14.8 months; hazard ratio, 0.86; 95% confidence interval, 0.45-1.64). The grade 3-5 treatment-related adverse event rate was 19.4%, 75.8% and 64.9% for patients receiving pembrolizumab, pembrolizumab plus chemotherapy and chemotherapy, respectively. CONCLUSIONS: This post hoc analysis showed pembrolizumab monotherapy was associated with numerically improved overall survival and a favourable tolerability profile versus chemotherapy in Asians with programmed death ligand 1-positive advanced gastric cancer/gastrooesophageal junction cancer.This study is registered with ClinicalTrials.gov, NCT02494583.

Effect of baseline resting heart rate on the risk of all-cause death in Chinese patients with hypertension.

The aim of this study was to investigate the association between baseline resting heart rate (RHR) and all-cause death in the China Stroke Primary Prevention Trial (CSPPT). A post hoc analysis was conducted using data from 20,648 hypertensive adults without cardiovascular disease in the CSPPT and with baseline RHR data available. Over a median follow-up duration of 4.5 years, the baseline RHR and risk for all-cause death had a nonlinear relationship. The risk of all-cause death was higher in participants with an RHR ≥85 bpm (hazard ratio 1.42; 95% confidence interval 1.03-1.96, p = .031) than in those with a baseline RHR of 75-80 bpm. The effect of RHR on all-cause death during the treatment period was modified by the folate level (p = .020) and systolic blood pressure (SBP) during treatment(p = .056). The effect of RHR on the risk of all-cause death was stronger when the folate level was low than when it was high; the risk was higher when the RHR was < 75 bpm or ≥80 bpm than when it was 75-80 bpm. RHR had a greater effect on the risk of all-cause death when SBP during treatment was well controlled than when it was not; again, the risk was higher when the RHR was < 75 bpm or ≥80 bpm than when it was 75-80 bpm. A higher baseline RHR resulted in an increased risk of all-cause mortality in Chinese adults with hypertension but no history of stroke or myocardial infarction.

N6-methyladenosine-related lncRNAs identified as potential biomarkers for predicting the overall survival of Asian gastric cancer patients.

OBJECTIVE: Gastric cancer (GC) is one of the most prevalent malignant tumors in Asian countries. Studies have proposed that lncRNAs can be used as diagnostic and prognostic indicators of GC due to the high specificity of lncRNAs expression involvement in GC. Recently, N6-methyladenosine (m6A) has also emerged as an important modulator of the expression of lncRNAs in GC. This study aimed at establishing a novel m6A-related lncRNAs prognostic signature that can be used to construct accurate models for predicting the prognosis of GC in the Asian population. METHODS: First, the levels of m6A modification and m6A methyltransferases expression in GC samples were determined using dot blot and western blot analyses. Next, we evaluated the lncRNAs expression profiles and the corresponding clinical data of 88 Asian GC patients retrieved from The Cancer Genome Atlas (TCGA) database. Differential expression of m6A-related lncRNAs between GC and normal tissues was investigated. The relationship between these target lncRNAs and potential immunotherapeutic signatures was also analyzed. Gene set enrichment analysis (GSEA) was performed to identify the malignancy-associated pathways. Univariate Cox regression, LASSO regression, and multivariate Cox regression analyses were performed to establish a novel prognostic m6A-related lncRNAs prognostic signature. Moreover, we constructed a predictive nomogram and determined the expression levels of nine m6A-related lncRNAs in 12 pairs of clinical samples. RESULTS: We found that m6A methylation levels were significantly increased in GC tumor samples compared to adjacent normal tissues, and the increase was positively correlated with tumor stage. Patients were then divided into two clusters (cluster 1 and cluster 2) based on the differential expression of the m6A-related lncRNAs. Results showed that there was a significant difference in survival probability between the two clusters (p = 0.018). Notably, the low survival rate in cluster 2 may be associated with high expression of immune cells (resting memory CD4+ T cells, p = 0.027; regulatory T cells, p = 0.0018; monocytes, p = 0.00095; and resting dendritic cells, p = 0.015), and low expression of immune cells (resting NK cells, p = 0.033; and macrophages M1, p = 0.045). Enrichment analysis indicated that malignancy-associated biological processes were more common in the cluster 2 subgroup. Finally, the risk model comprising of six m6A-related lncRNAs was identified as an independent predictor of prognoses, which could divide patients into high- or low-risk groups. Time-dependent ROC analysis suggested that the risk score could accurately predict the prognosis of GC patients. Patients in the high-risk group had worse outcomes compared to patients in the low-risk group, and the risk score showed a positive correlation with immune cells (resting memory CD4+ T cells, R = 0.31, P = 0.038; regulatory T cells, R = 0.42, P = 0.0042; monocytes, R = 0.42, P = 0.0043). However, M1 macrophages (R = -0.37, P = 0.012) and resting NK cells (R = -0.31, P = 0.043) had a negative correlation with risk scores. Furthermore, analysis of clinical samples validated the weak positive correlation between the risk score and tumor stage. CONCLUSIONS: The risk model described here, based on the six m6A-related lncRNAs signature, and may predict the clinical prognoses and immunotherapeutic response in Asian GC patients.