Clinical Outcomes In Chinese Patients Research Articles

372 Association of tumor mutation burden (TMB) and genomic alterations (GA) with clinical outcomes in Chinese patients with advanced solid tumors treated with tislelizumab

BackgroundStudies have demonstrated correlation of GA and TMB with clinical efficacy of an anti-programmed cell death protein-1 (PD-1) therapy, but this correlation has not yet been demonstrated in Chinese patients treated with tislelizumab (anti-PD-1 antibody). We report the association between TMB, GA, and the clinical efficacy of tislelizumab in Chinese patients with different tumor types from a Phase 1/2 study (NCT04068519).MethodsChinese patients with advanced solid tumors who received tislelizumab monotherapy and had available tissues for genomic testing (BurningRock OncoScreen Plus 520 NGS panel) were eligible. Patients were classified as having hyper-amplification (HA) if their genome harbored ≥1 amplified gene with a copy number >5. Logistic regression was used to analyze the association of TMB with objective response rate (ORR) and Cox proportional hazard was used to determine the association of TMB with progression-free survival (PFS) and overall survival (OS).ResultsA total of 156 patients were evaluable. TMB was higher in responders (R) versus non-responders (NR) (median [m] TMB: 9.3 vs 6.2 mut/Mb, p=0.003). TMB-H was defined as ≥8 mut/Mb according to the receiver operating characteristic curve. Patients in the TMB-H group showed superior clinical benefit compared with the TMB-L group (table 1). Further GA analysis showed a trend toward a higher frequency of HA in NR (40.00%; 16/40) compared with R (28.78%; 5/18), in the TMB-H group. A total of 33.33% (10/30) of these amplified genes in NR belonged to the RTK-RAS-PI3K signaling pathway. When TMB-H patients with HA in this pathway were excluded, ORR reached 37.78%.Abstract 372 Table 1Median study follow-up and clinical efficacy dataNE, non-estimableConclusionsTMB-H status was associated with improved clinical efficacy of tislelizumab in Chinese patients with advanced solid tumors, consistent with other PD-1 inhibitors. These observations support TMB-H as a potential predictive biomarker for response to tislelizumab in this patient population. HA in the RTK-RAS-PI3K pathway may be associated with resistance mechanisms to anti-PD-1 therapy, even in patients with TMB-H tumors.AcknowledgementsEditorial writing support for the development of this abstract, under direction of the authors, was provided by Louise Oakes, PhD, of Ashfield MedComms, an Ashfield Health company, and was funded by BeiGene Ltd.Trial RegistrationNCT04068519Ethics ApprovalThis study was conducted according to the ethical principles of the Declaration of Helsinki, Good Clinical Practice guidelines, the principles of informed consent and the requirements of the public registration of clinical trials. Written informed consent was obtained from each patient prior to screening. The protocol was approved by the institutional ethics committee and was monitored by the investigators and study sponsor.

Outcomes after radioiodine ablation in patients with thyroid cancer: Long-term follow-up of a Chinese randomized clinicaltrial.

Two large randomized trials of patients with differentiated thyroid cancer (DTC) reported recently (HiLo and ESTIMABL1) found that the recurrence rate among patients who underwent 1.1 GBq radioactive iodine (RAI) ablation was not higher than that of patients who underwent 3.7 GBq radioactive iodine (RAI) ablation. However, no similar studies have been conducted in China. We aimed to report clinical outcomes in Chinese patients with low/intermediate risk of recurrence DTC after long-term follow-up, and evaluate the risk factors that influence the presence or absence of incomplete response at the final follow-up. A long-term follow-up of a Chinese randomized clinical trial (October 2014 and February 2021) was conducted. A total of 506 DTC patients at low/intermediate risk of recurrence who were randomized into two groups to receive 1.1(n = 251) or 3.7 GBq (n = 255) RAI ablation following thyroid hormone withdrawal were followed on levothyroxine treatment for a median of 4.5 years (range: 1.6-6.3). Suppressed serum thyroglobulin (Tg) and anti-thyroglobulin antibody (TgAb) levels were determined, and neck ultrasonography was performed. At the final follow-up, 499 (98.6%) patients showed an excellent response. The other seven patients (two patients underwent 1.1 GBq and five patients underwent 3.7 GBq RAI ablation, respectively) showed either structural incomplete response (lymph node metastasis, n = 1), biochemical incomplete response (increased serum Tg ≥ 1 ng/ml, or increased positive TgAb levels, n = 5), or indeterminate response (stable positive TgAb levels, n = 1). The risk of incomplete response at the final follow-up was significantly increased in patients with stimulated serum Tg ≥ 10 ng/ml at ablation (p = .003) and in patients with unsuccessful ablation (p = .008). Our findings indicated that there was no difference in the long-term outcomes with RAI ablation using either 1.1or 3.7 GBq in patients with low/intermediate risk of recurrence DTC, and 1.1 GBq RAI might be suitable for patients who are recommended for ablation.

Predictive models for adverse clinical outcomes in Chinese patients with atrial fibrillation undergoing percutaneous coronary intervention with stenting

Objective This study aimed to evaluate predictors for adverse cardiovascular outcomes in patients with atrial fibrillation (AF) undergoing coronary stenting. Methods We retrospectively recruited consecutive patients with previously documented non-valvular AF who underwent coronary stenting between January 2010 and June 2015 in 12 hospitals of Beijing, China. Major adverse cardiac/cerebrovascular events (MACCE) were a composite of all-cause death, non-fatal myocardial infarction, repeat revascularization, and ischaemic stroke/systemic thromboembolism (IS/STE). Major bleeding referred to grade 2 or higher of Bleeding Academic Research Consortium criteria. Results A total of 2394 patients (men: 72.3% vs. women: 27.7%, median age: 67 years) were included. The CHA2DS2-VASc and HAS-BLED were 3.6 ± 1.6 and 1.9 ± 0.7, respectively. The median follow-up duration was 36.2 months. There were 230 (9.6%) deaths, 96 (4.0%) IS/STE, 426 (17.8%) MACCE, and 72 (3.0%) major bleeding. Multivariate Cox regression yielded predictive models for (1) all-cause death: diabetes, prior myocardial infarction, chronic kidney disease (CKD), ST-segment elevation myocardial infarction (STEMI) at presentation, heart failure, no use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and statins; (2) IS/STE: advanced age, prior history of ischaemic stroke and intracranial haemorrhage; (3) MACCE: prior history of myocardial infarction and ischaemic stroke, CKD, STEMI, heart failure, and no statin use; (4) major bleeding: prior major bleeding, prior myocardial infarction, CKD and use of oral anticoagulants. Conclusion Chinese patients with AF and coronary stenting had high mortality and incidence of MACCE. We compiled separate predictive models for all-cause death, IS/STE, MACCE, and major bleeding.

Comparison of the prognostic value of SYNTAX score and clinical SYNTAX score on outcomes of Chinese patients underwent percutaneous coronary intervention

BackgroundPrevious studies have validated the capability of SYNTAX score (SS) and clinical SYNTAX score (CSS) in the prediction of clinical outcomes in patients who have undergone PCI; however, studies on comparison of these two scoring systems in Chinese population have been sparse.MethodsTo study the ability of SS and CSS in prediction of clinical outcomes of Chinese patients underwent percutaneous coronary intervention (PCI). We retrospectively calculated SS and CSS for 547 Chinese patients from a single center who underwent PCI. Patients were stratified into tertiles according to their SS and CSS. We compared the 2-year clinical outcomes in these patients stratified separately by SS and CSS tertiles.ResultsThe incidence of major adverse cardiac and cerebro-vascular events (MACCE) was the highest in patients with SSHIGH (13.5%), comparing to 6.8% in SSMED and 0% in SSLOW (p < 0.0001). The Cox multivariable analysis showed that the SS and CSS were both strong independent predictors for MACCE [1.100 (1.069–1.133), 1.017 (1.010–1.025), both p < 0.0001]. The receiver operating characteristic (ROC) curves showed the areas-under-the-curves for all-cause death by CSS was slightly larger comparing to SS but not significantly (AUC SS, 0.64; AUC CSS, 0.71; p = 0.23).ConclusionWe concluded that both the SS and CSS were capable of risk stratification of clinical outcomes in all-comers population as well as in low and moderate risk Chinese patients undergoing PCI with CSS showing slightly better advantage.

Intermittent concurrent use of clopidogrel and proton pump inhibitors did not increase risk of adverse clinical outcomes in Chinese patients with coronary artery disease

BackgroundProton pump inhibitors (PPIs) are frequently prescribed to patients with coronary heart disease (CHD) under antiplatelet therapy to prevent gastrointestinal (GI) bleeding. However, its clinical impact is still under debate, especially in Asian population. This study was undertaken to explore the effects of concurrent use of clopidogrel and PPIs on the clinical outcomes in Chinese patients with CHD in secondary prevention.MethodsA single-center retrospective study was conducted in 638 patients with CHD on consecutive clopidogrel therapy for at least 1 year. After 18-month follow-up, adverse clinical events were collected. Cox regression was used to calculate hazard ratios (HR) and 95% confidence interval (CI) for the effect of PPI use on the outcomes. A total of 638 patients were recruited from 2014 to 2015 in this study, among whom 201 were sustained PPI users, 188 were intermittent PPI users and the remaining 249 were non-PPI users.ResultsCompared with sustained PPI users, intermittent use of PPIs was associated with a lower risk of stroke, major adverse cardiac events (MACE) and net adverse clinical event (NACE) (stroke: adjusted HR: 0.109, 95% CI 0.014–0.878, p = 0.037; MACE: adjusted HR: 0.293, 95% CI 0.119–0.722; p = 0.008; NACE: adjusted HR: 0.357, 95% CI 0.162–0.786, p = 0.011). Subgroup analysis further revealed the benefit of intermittent PPI use was significant in male CHD patients over 60 years old, with hypertension or chronic kidney disease, and undergoing percutaneous coronary intervention during hospitalization.ConclusionThe current findings suggest that the intermittent concurrent use of PPIs and clopidogrel is not associated with an increased risk of 18-month adverse clinical outcomes, and intermittent use of PPIs is associated with a lower rate of MACE and NACE.

Association of renal insufficiency with treatments and outcomes in patients with acute coronary syndrome in China

BackgroundWe aimed to analyze the association of estimated glomerular filtration rate (eGFR) levels of hospitalized patients with treatment decisions and clinical outcomes in Chinese patients with acute coronary syndrome (ACS). MethodsThis was a secondary analysis study from CPACS-2 Program which was a trial of a quality improvement intervention in China and recruited 15,141 patients from 75 hospitals between October 2007 and August 2010. All patients were divided into three groups by the eGFR level on admission. The primary outcomes were several key performance indicators (KPIs) reflecting the management of ACS and the secondary outcomes were clinical outcomes. ResultsA total of 14,437 ACS patients were enrolled in this analysis. Among patients with reduced eGFR levels, fewer patients received appropriate medical therapy (p for trend <0.001) and fewer high-risk patients received coronary angiography (p for trend <0.001) compared to patients with a normal eGFR. Furthermore, 436 cases of death, 357 cases of cardiac death, 686 cases of major adverse cardiovascular events, and 198 cases of major bleeding episodes were reported. Patients with a worse eGFR level had significantly higher rates of death (p for trend <0.001), cardiac death (p for trend <0.001), major adverse cardiovascular events (p for trend <0.001) and major bleeding episodes (p for trend <0.001). ConclusionAmong Chinese ACS patients, those with renal insufficiency have a lower percentage of adherence to guideline-recommended treatments and worse clinical prognosis. Renal insufficiency is an important factor affecting guideline implementation in Chinese ACS patients. Clinical trial registrationhttp://www.anzctr.org.au/default.aspx. Unique identifier: ACTRN12609000491268.

Association between anxiety and clinical outcomes in Chinese patients with myocardial infarction in the absence of obstructive coronary artery disease

BackgroundMyocardial infarction in the absence of obstructive coronary artery disease (MINOCA) accounts for approximately 5% ‐ 6% of acute myocardial infarction (AMI) patients. Anxiety symptoms are common in patients with coronary artery disease (CAD), and are associated with a poor prognosis. However, the association between anxiety and MINOCA outcomes is less clear.HypothesisAnxiety will be associated with clinical outcomes in patients with MINOCA.Methods and ResultsBetween November 2014 and December 2016, 620 hospitalized patients with MINOCA were recruited from a single center. Within 7 days of coronary angiography, anxiety was assessed using the Zung Self‐Rating Anxiety Scale. The primary endpoint was all‐cause mortality; secondary endpoint was any major adverse cardiovascular event (MACE). After 3 years, 87 deaths and 151 MACE had occurred. Kaplan‐Meier curves indicated the unadjusted rates of all‐cause mortality (log‐rank P = .045) and MACE (log‐rank P = .023) were significantly higher in the anxiety group compared with the control group of patients without anxiety. Multivariate Cox regression analysis showed that clinically significant anxiety was an independent prognostic factor for all‐cause mortality as well as MACE (hazard ratio [HR] = 1.547; 95% confidence interval [CI], 1.006‐2.380; P = .047; HR = 1.460; 95% CI, 1.049‐2.031; P = .025; respectively).ConclusionsAnxiety is significantly and independently associated with an increased risk of all‐cause mortality and MACE in patients with MINOCA.

Health literacy and exercise interventions on clinical outcomes in Chinese patients with diabetes: a propensity score-matched comparison.

IntroductionPatients with diabetes in China have low health literacy, which likely leads to poor clinical outcomes. This study aimed to assess the effectiveness of health literacy and exercise interventions on clinical measurements in Chinese adults with type 2 diabetes mellitus (T2DM).Research design and methodsA cluster randomized controlled trial was conducted from February 2015 through April 2017 in Shanghai, China. 799 patients with T2DM aged 18 years or older recruited from eight Community Healthcare Centers were randomized into one control arm and three intervention arms receiving 1-year health literacy intervention, exercise intervention or both as the comprehensive intervention. Propensity score matching was employed to minimize potential imbalance in randomization. The intervention-attributable effects on main clinical outcomes were estimated using a difference-in-difference regression approach.ResultsAfter propensity score matching, 634 patients were included in the analysis. The three intervention groups had decreased hemoglobin A1c (A1c) level after 12 months of intervention. The largest adjusted decrease was observed in the health literacy group (−0.95%, 95% CI: −1.30 to −0.59), followed by the exercise group (−0.81%, 95% CI: −1.17 to −0.45). However, A1c was observed to increase in the health literacy and the comprehensive groups from 12 to 24 months. No obvious changes were observed for other measurements including high-density and low-density lipoprotein cholesterols, and systolic and diastolic blood pressures.ConclusionsHealth literacy and exercise-focused interventions improve glycemic control in Chinese patients with diabetes after 12 months of intervention, and the health literacy intervention shows the greatest effect. Our results suggest that the interventions may have the potential to improve diabetes self-management and reduce diabetes burden in China.Trial registration numberISRCTN76130594.

Long-term follow-up of antithrombotic management patterns in patients with acute coronary syndrome in China.

ObjectiveTo describe the long-term antithrombotic management patterns (AMPs) and clinical outcomes of Chinese patients with acute coronary syndrome (ACS).MethodsThis was an observational, multicenter, longitudinal cohort extension study of Chinese patients who had completed the EPICOR Asia 2-year follow-up study post-hospitalization for an ACS event. Changes in AMP and clinical outcomes for up to 5 years post-ACS event were evaluated.ResultsOverall, 2334 patients with ACS were enrolled at 49 sites. The mean age was 61.6 years and 76.3% were men. By study end, 2093 patients completed the 3-year follow-up. At baseline (2 years post-ACS event), 72.4% of patents received one antiplatelet (AP) medication, with aspirin being the preferred one. A small proportion of patients (21.5%) was treated with two or more APs (2+ AP), and even fewer patients (6.1%) did not receive any AP medication at baseline. Upon study completion, the proportion of patients without AP therapy increased to 13.6%, while the percentage of patients on one AP and 2+ AP decreased to 69.3% and 17.1%, respectively. Numerically, a higher incidence of clinical events (composite of all-cause mortality, myocardial infarction, stroke) was observed for the 2+ AP (13.2%) subgroup than for the no AP (10.5%) and one AP (8.6%) subgroups. Furthermore, the 2+ AP subgroup exhibited the greatest number of bleeding events, outpatient visits, and hospitalization rates. Unlike myocardial infarction or stroke, bleeding events prompted an adjustment in AMP.ConclusionMost patients in China received at least one AP medication up to 5 years after an ACS event.

Treatment patterns and long-term clinical outcomes in Chinese patients with nonmetastatic gastric cancer: Results from the non-interventional EVIDENCE registry study.

307 Background: Although gastric cancer (GC) is a leading cause of cancer-related death in China, important questions about optimal management remain unanswered. The EVIDENCE registry study evaluated data from patients with GC in China to assess the pattern of treatments and long-term clinical outcomes. Methods: Five cohorts of patients with different HER2 and metastatic (m) status were evaluated from April 2013 to June 2018 in this prospective, multicenter, non-interventional, real-world study. Data from patients with operable non-mGC are reported: Cohort III (HER2+) and Cohort V (HER2−). Outcome measures included overall survival (OS), event-free survival (EFS), and disease-free survival (DFS). Results: Cohorts III/V included 758 patients (Cohort III, 271; Cohort V, 487); 75.5% were male and the mean age was 58.8 years. The majority of Cohort III/V patients (538/758; 71.0%) received only adjuvant treatment, with 215/758 (28.4%) receiving S1+oxaliplatin. Neoadjuvant or adjuvant trastuzumab was administered to 43/758 patients (Cohort III, 42; Cohort V, 1). Radiation during neoadjuvant or adjuvant treatment was administered to 23/758 (3.0%) patients. The median duration of follow-up was 515 days, during which 72 (9.5%) patients died due to progressive disease. OS rates (95% CI) for Cohorts III and V were 94% (89–96) and 95% (92–97) at 1 year, and 76% (67–83) and 70% (64–75) at 3 years, respectively. Respective EFS rates were 82% (76–87) and 86% (83–89) at 1 year, and 62% (53–70) and 57% (51–63) at 3 years; and respective DFS rates were 88% (82–93) and 86% (81–89) at 1 year and 69% (58–78) and 62% (55–68) at 3 years. Multivariate analysis indicated that the primary tumor site (p = 0.004) and overall cancer stage (p &lt; 0.001) were associated with DFS. Regarding the primary tumor site, there was a trend towards better DFS for antrum tumors (hazard ratio 0.59; 95% CI 0.32–1.07) when evaluated against gastroesophageal junction tumors. Conclusions: This longitudinal analysis of clinicopathologic characteristics and outcomes of Chinese patients with non-mGC will provide critical information that will help to inform disease management. Clinical trial information: NCT01839500.

Persistence, effectiveness and safety of dabigatran in "real-world" Chinese patients with nonvalvular atrial fibrillation.

The purpose of this study is to provide detailed data on treatment persistence and clinical outcomes in Chinese patients with nonvalvular atrial fibrillation (NVAF). A single-center retrospective observational study was conducted. A total of 26,663 NVAF patients were enrolled from January 1, 2014 to December 31, 2017, clinical information of whom were from inpatient and outpatients data system was collected. The 1-year treatment persistence rates of 11,350 dabigatran users were 24.5% in 2014, 36.6% in 2015, 37.7% in 2016 and 51.8% in 2017. The predominant reason of non-persistence patients was the cost of treatment. Incidence rates of all-cause death, ischemic stroke and embolism were 1.99/100 person-years, 2.56/100 person-years and 0.77/100 person-years, respectively. Incidence rates of minor bleeding events, intracranial hemorrhage and gastrointestinal hemorrhage were 10.05/100 person-years, 0.51/100 person-years and 0.85/100 person-years, respectively. In conclusion, it is of importance for Chinese clinicians to know about these information because dabigatran is a relatively new drug in China. Compared with other reported data, patients of this study have (1) lower dabigatran persistence and lower incident rates of all-cause death, systemic embolism, minor bleeding events and gastrointestinal hemorrhage and (2) higher incident rates of ischemic stroke and intracranial hemorrhage.

Sex difference in clinical outcomes of Chinese patients with atrial fibrillation and coronary stenting according to age.

Sex differences in the clinical outcomes of patients with atrial fibrillation (AF) and coronary stenting should be assessed according to age. We analyzed the clinical data of all patients with nonvalvular AF who underwent coronary stenting between January 2010 and June 2015 in 12 hospitals of Beijing, China. A total of 2,146 patients (71.8% men and 28.2% women) were included in the study. The mean age of the patients was 66.6±9.4 years. Women in this study were older and had higher prevalence of hypertension, diabetes, chronic kidney disease (CKD), and anemia. Smoking history was found to be higher in men, and women were less likely to be current smokers. The mean follow-up duration was 39.7 months. Women younger than 65 years had a remarkably higher mortality (11.2% vs. 5.3%, p=0.012) and a significantly lower rate of repeat revascularization (1.6% vs. 6.3%, p=0.034) than men. Female gender remained an independent predictor for all-cause mortality [hazard ratio (HR)=2.03, 95% confidence interval (CI): 1.09-3.79, p=0.025], along with heart failure (HR=3.64, 95% CI: 2.02-6.57, p<0.001) and CKD (HR=2.46, 95% CI: 1.09-5.57, p=0.031) after multivariate regression analysis. No significant difference was noted between men and women with regard to mortality, ischemic events, and major bleeding in elderly patients. In Chinese patients younger than 65 years with AF and coronary stenting, female gender was independently associated with increased mortality; men were more likely to receive repeat revascularization possibly due to the current smoking. Whether it was a biological difference or a recognition disparity of the disease between men and women warrants further investigation.

Analysis of correlation between plasma trough level and response of generic imatinib in the treatment of Chinese patients with chronic myeloid leukemia

目的评价我国慢性髓性白血病慢性期（CML-CP）患者接受国产伊马替尼（商品名：格尼可）治疗后伊马替尼及其代谢物血浆谷浓度水平与疗效的关系。方法以2012年10月11日至2013年5月8日入组编号为YMTN1.0临床研究的21例接受国产伊马替尼治疗的CML-CP患者为研究对象，评价其血浆药物谷浓度与疗效、年龄、体重、体表面积的关系。伊马替尼及其代谢物浓度检测采用高效液相色谱-串联质谱法。结果①伊马替尼及其代谢物血浆谷浓度分别为（1 185.07±417.91）µg/L和（251.53±76.50）µg/L。②伊马替尼及其代谢物血浆谷浓度与患者年龄、体重和体表面积均无明显相关性（P值均>0.05）。③伊马替尼稳态血浆谷浓度高于1 000 µg/L的患者其完全及主要分子学反应率显著高于未达1 000 µg/L的患者（42%对0，P<0.01）。结论接受国产伊马替尼治疗的CML-CP患者中，伊马替尼及其代谢产物稳态血浆谷浓度存在较大个体差异，伊马替尼血浆谷浓度与患者获得分子学疗效有一定的相关性。

Association Between p.R4810K Variant and Long-Term Clinical Outcome in Patients With Moyamoya Disease

Objective: To estimate the association between p. R4810K variant and clinical outcomes of patients with moyamoya disease (MMD).Methods: The p.R4810K genetic variant was genotyped among 498 Chinese patients with MMD conducted from June 1, 2012, to June 31, 2017. Data was obtained by retrospective chart review, follow-up information and outcome were obtained through clinical visits and telephone.Results: Among 498 patients, 361 (72.5%) were wild-type patients (G/G), 133 (26.7%) heterozygous patients (G/A), and 4 (0.8%) homozygotes (A/A). Compared with GG group, the patients in the G/A+A/A group were younger at diagnosis and had more familial cases, more transient ischemic attack cases, more posterior cerebral artery involved hemispheres, less unilateral lesions. After the median 53 months follow-up, strokes occurred in 9 patients in the G/A+A/A group and in 52 in the G/G group. Multivariate Cox regression analysis showed that the history of hypertension (HR, 2.294; 95% CI, 1.251–4.206; p = 0.007), the presence of TIA (HR, 0.319; 95% CI, 0.120–0.846; p = 0.022), and the Suzuki stage (HR, 1.510; 95% CI, 1.129–2.018; p = 0.005) were associated with recurrent stroke. The p.R4810K (HR, 0.601; 95% CI, 0.292–1.239; p = 0.168) was not associated with recurrent stroke. Multivariate logistic regression analysis showed that recurrent stroke (OR, 5.997; 95% CI, 2.583–13.924; p = 0.000) was the only factor associated with unfavorable neurological status. And the p.R4810K (OR, 0.885; 95% CI, 0.482–1.627; p = 0.695) was not associated with neurological status.Conclusions: Compared to the patients in G/G group, patients in G/A+A/A group exhibited different clinical features, and had a lower rate of recurrent stroke and better clinical outcome after early medical and surgical interventions. Multivariate COX and logistic regression analysis showed that p.R4810Kvariant was not related to either recurrent stroke or neurological status. The p.R4810Kvariant may not be associated with long-term clinical outcome in Chinese patients with MMD.

Impact of unprotected left main percutaneous coronary intervention on long-term clinical outcomes: a large single-center study.

With the advancements of percutaneous coronary interventions (PCI), it is not clear whether unprotected left main (ULM) coronary artery disease (CAD) remains an independent predictor of adverse outcomes after PCI therapy. We have therefore carried out a large cohort study to investigate the impact of ULM disease on 2-year clinical outcomes in Chinese patients undergoing contemporary PCI treatment. From January 2013 to December 2013, 10 724 consecutive patients undergoing PCI were prospectively collected. Two-year clinical outcomes were compared for patients undergoing ULM PCI and non-ULM PCI. Among the 10 724 patients, 272 (2.5%) patients underwent ULM PCI. Overall, these patients had higher baseline clinical risks of CAD and more extensive CAD compared with non-ULM PCI patients. During the 2-year follow-up, patients who underwent ULM PCI experienced higher incidence of cardiac death (2.2 vs. 0.7%; log-rank P=0.002), myocardial infarction (7.0 vs. 1.9%; log-rank P<0.001), stroke (2.9 vs. 1.3%; log-rank P=0.02), and definite and probable stent thrombosis (3.3 vs. 0.5%; log-rank P<0.001), than patients who underwent non-ULM PCI. However, the rates of revascularization (7.4 vs. 8.7%; log-rank P=0.48), target vessel revascularization (5.5 vs. 5.0%; log-rank P=0.66), and major adverse cardiac and cerebrovascular events (15.1 vs. 12.0%; log-rank P=0.11) were not significantly different between the groups. When performing adjusted Cox regression after propensity score matching, ULM PCI was not an independent risk factor of any clinical events (all P>0.05). In this large cohort of patients who underwent modern PCI, ULM PCI patients had higher baseline clinical risks and poorer prognosis during 2-year follow-up. However, after multivariate analysis, ULM PCI was not an independent risk factor of any clinical adverse events.

The Diversity of Gut Microbiome is Associated With Favorable Responses to Anti–Programmed Death 1 Immunotherapy in Chinese Patients With NSCLC

IntroductionGut microbiome affecting the responses to immune checkpoint inhibitors against advanced NSCLC has been investigated in the Western population. However, considering pre-existing genetic and gut microbiota variation, the relevance remains unknown in the East-Asian NSCLC population. This study is designed to explore the relationship between gut microbiome and clinical outcomes in Chinese patients with NSCLC who have received treatment using an anti–programmed death 1 (PD-1) blockade. MethodsThirty-seven patients with advanced NSCLC receiving treatment with nivolumab were enrolled in CheckMate 078 (NCT02613507) and CheckMate 870 (NCT03195491). Fecal samples were collected at the starting point, when patients received nivolumab, at clinical evaluation, and when disease progression was noted. 16S ribosome RNA gene sequencing was applied to assess gut microbiota profiles. Peripheral immune signatures were determined by multicolor flow cytometry in parallel. ResultsWhen subgrouping patients into responder (R) and nonresponder according to the clinical response assessed using Response Evaluation Criteria in Solid Tumor version 1.1, R patients harbored higher diversity of gut microbiome at the starting point with stable composition during the treatment. Patients with high microbiome diversity had significantly prolonged progression-free survival when compared to those with low diversity. Compositional difference was observed between the two groups as well with the enrichment of Alistipes putredinis, Bifidobacterium longum, and Prevotella copri in R whereas Ruminococcus_unclassified enriched in nonresponding patients. Analysis of systemic immune responses using multicolor flow cytometry revealed that patients with a high abundance of microbiome diversity in the gut had a greater frequency of unique memory CD8+ T cell and natural killer cell subsets in the periphery in response to anti–PD-1 therapy. ConclusionsOur results reveal strong correlation between gut microbiome diversity and the responses to anti–PD-1 immunotherapy in Chinese patients with advanced NSCLC. Patients with favorable gut microbiome (such as those with high diversity) exhibit enhanced memory T cell and natural killer cell signatures in the periphery. These findings provide important implications for the prediction and the evaluation of anti–PD-1 immunotherapy against NSCLC in the Chinese population.

Distribution of ALK Fusion Variants and Correlation with Clinical Outcomes in Chinese Patients with Non-Small Cell Lung Cancer Treated with Crizotinib.

ALK-rearranged non-small cell lung cancer (NSCLC) represents a molecular subgroup with high sensitivity to ALK inhibitors. Crizotinib, a US Food and Drug Administration (FDA)-approved tyrosine kinase inhibitor for treating ALK-rearranged NSCLC, has shown remarkable response in ALK-positive NSCLC. However, heterogeneity of clinical responses exists among different ALK fusion partners. Several small studies have investigated the correlation between fusion partners and efficacy, but not yielded consistent results. We investigated the prevalence of ALK rearrangements in a Chinese NSCLC population, and correlated clinical outcomes of crizotinib with different ALK partners/variants. We retrospectively reviewed genomic profiling and clinical data of 110 ALK-rearranged NSCLC patients from five centers. The clinical response to crizotinib and survival data in ALK-positive patients was retrospectively analyzed. A total of 134 ALK rearrangements with 39 partners were identified in 110 patients (5.6%) among a cohort of 1971 NSCLC patients. The most frequently occurring ALK fusion partner was EML4, which was identified in 71.6% (96/134) of all of the rearrangements in 87.3% (96/110) patients, and with variant 3 (41/96, 42.7%) as the main variant type. No statistically significant differences in terms of progression-free survival (PFS) and overall survival (OS) were found between EML4-ALK and non-EML4-ALK NSCLC patients in our cohort (PFS, p = 0.207; OS, p = 0.678). Outcomes did not differ significantly between patients above and below 40years of age (PFS, p = 0.427; OS, p = 0.686), nor between patients treated with crizotinib in different lines of therapy (PFS, p = 0.171; OS, p = 0.922). For EML4-ALK-positive NSCLC (n = 96), patients harboring variant 3 or variant 5 displayed significantly lower PFS and OS than those with other variants (PFS, 8.6 vs. 11.3months, p = 0.046; OS, 31.0 vs. 37.6months, p = 0.026). In addition, patients with a single EML4-ALK rearrangement event displayed favorable PFS (10.0 vs. 7.2months, p = 0.040) and OS (36.0 vs. 20.0months, p = 0.029) compared to those harboring multiple ALK rearrangements. This study illustrates the patterns of ALK fusion variants present in Chinese NSCLC patients and might help explain heterogeneous clinical outcomes to crizotinib treatment according to different ALK fusion variants.

Primary Lymphoma of the Skull Base in the Chinese: Clinical, Radiological, Pathological, and Therapeutic Experience in a Series of 8 Patients

Primary lymphoma of the skull base (PLSB) is an extremely rare neoplasm and not much is known regarding the clinical features of, treatment strategies for, and prognoses of these lesions. We investigated the manifestations and clinical outcomes of Chinese patients with PLSB. We retrospectively reviewed the data from 8 consecutive patients with PLSB who had been treated at our center from October 2008 to December 2016 and analyzed their clinical features, treatment strategies, and prognoses. Of the 8 patients, 3 were men and 5 were women, with a male/female ratio of 0.6. The median age was 53.5 years. In most instances, the onset was characterized by headache, followed by dysfunction of the cranial nerves. The most frequently affected region was the cavernous sinus. On magnetic resonance imaging, the main characteristic was that the internal carotid artery was encased by the tumor without an obvious tendency to be deformed, dislocated, or narrowed. All patients underwent surgical biopsy via a transsphenoidal or sublabial-transmaxillary approach. The pathological diagnosis was non-Hodgkin lymphoma for all 8 patients, with diffuse large B-cell lymphoma in 7 patients. The patients underwent chemotherapy and involved-field radiotherapy. The median overall survival was 52 months, and the 1-year progression-free survival rate was 87.5%. PLSB is a rare disease and a diagnostic challenge, with most cases in the Chinese due to diffuse large B-cell lymphoma. We found that the incidence peaked in middle and old age, and the cavernous sinus was usually affected. Multidisciplinary treatment involving surgical biopsy, chemotherapy, and radiotherapy was an effective therapeutic strategy.

SURF1 mutations in Chinese patients with Leigh syndrome: Novel mutations, mutation spectrum, and the functional consequences

SURF1 is an assembly factor of mitochondrial complex IV, and its mutations are the primary cause of Leigh syndrome in infants. To date, over 100 SURF1 mutations have been reported worldwide, but the spectrum of the SURF1 mutations in China remains unclear. Here, using next-generation sequencing targeting mitochondrial protein-coding sequences, we sequenced 178 patients suspected to have mitochondrial diseases. Fifteen SURF1 mutations were identified in 12 Leigh syndrome patients, of which three, c.465_466delAA, c.532A > T, and c.826_827ins AGCATCTGCAGTACATCG, were newly described. The percentage of SURF1 frameshift mutations (6/28, 21.4%) we detected in Chinese population is higher than other studies (21/106, 19.8%) with different populations, however, the percentage of missense mutations is lower in this study than others (4/28, 14.3% VS. 25/106, 23.6%). Since complex IV can be detected in cells carrying missense mutations (3/8) but not in cells carrying null mutations (0/4) by using cell model-based complementation assay, our results indicate that SURF1 mutations may be associated with worse clinical outcome in Chinese patients than other populations. However, studies with larger sample size are needed to verify this conclusion. Additionally, we found that the frameshift mutations resulting in protein truncation closer to the C-terminus are not associated with better disease prognosis. Lastly, we found that determining the levels of complex IV assembly using cell models or lymphocyte analysis rather than invasive muscle and skin fibroblast biopsy, may help predict disease progression in Leigh syndrome patients.

Associations of common variants at ALDH2 gene and the risk of stroke in patients with coronary artery diseases undergoing percutaneous coronary intervention.

Limited data are available about the role of common variants at the aldehyde dehydrogenase 2 gene (ALDH2) on the clinical outcome in Chinese patients with coronary heart disease (CHD) undergoing percutaneous coronary intervention (PCI). In the present study, a total of 1089 patients were consecutively enrolled from January 2012 and July 2013. Six common variants at ALDH2 gene, including rs2339840, rs4648328, rs4767939, rs11066028, rs16941669, and rs671, were selected to test the associations of those polymorphisms with the cardiovascular outcome in patients with CHD after PCI. The clinical endpoints included cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. The composite of clinical endpoints was defined as the primary endpoint, and every endpoint alone was considered as the secondary endpoints. The median follow-up time was 38.27 months. Our results showed that the common variant rs2339840 was independently associated with a lower risk of stroke in patients with CHD after PCI (codominant model, HR = 0.32, 95% CI, 0.11–0.91, P = .074 for heterozygotes; HR = 0.25, 95% CI, 0.06–1.14, P = .033 for homozygotes; dominant model, HR = 0.32, 95% CI, 0.14–0.74, P = .007). However, no significant associations were found between other 5 single nucleotide polymorphisms (SNPs) and the clinical endpoints. For the first time, the common variant rs2339840 was reported to be a protective factor against stroke in CHD patients with PCI.