Loss-of-function (LOF) variants of cytochrome P450 2C19 (CYP2C19) have been hypothesized to be associated with lesser degrees of platelet inhibition and increased risk for recurrent ischemic events ...in patients with coronary artery disease on clopidogrel therapy; however, studies from Western countries have yielded mixed results. We aimed to assess the impact of CYP2C19 LOF variants on clinical outcomes from different ethnic groups. Sixteen prospective cohort studies including 7,035 patients carrying ≥1 CYP2C19 LOF allele and 13,750 patients with the wild-type genotype were included in this meta-analysis. Carriers of ≥1 CYP2C19 LOF allele were at significantly higher risk for adverse clinical events compared to noncarriers during clopidogrel therapy (odds ratio OR 1.42, 95% confidence interval CI 1.13 to 1.78). The summary OR showed a significant association between CYP2C19 LOF variants and an increased risk of cardiac death (OR 2.18, 95% CI 1.37 to 3.47), myocardial infarction (OR 1.42, 95% CI 1.12 to 1.81), and stent thrombosis (OR 2.41, 95% CI 1.76 to 3.30). Stratified analysis by ethnicity of study population suggested higher odds of adverse clinical events in the Asian population with LOF variants of CYP2C19 (OR 1.89, 95% CI 1.32 to 2.72) compared to Western populations (OR 1.28, 95% CI 1.00 to 1.64). In conclusion, carrier status for LOF CYP2C19 is associated with an increased risk of adverse clinical events in patients with coronary artery disease on clopidogrel therapy despite differences in clinical significance according to ethnicity.
Background Tumor location is a prognostic factor for survival in patients with T2 gallbladder cancer. However, the optimal extent of resection according to tumor location remains unclear. Methods We ...reviewed the records of 192 patients with T2 gallbladder cancer who underwent R0 or R1 resection at 6 institutions. Perioperative and oncologic outcomes were compared according to the extent of resection between hepatic-sided ( n = 93) and peritoneal-sided ( n = 99) tumors. Results After a median follow-up of 30 months, the 5-year overall survival (84.9% vs 71.8%, P = .048) and recurrence-free survival (74.6% vs 62.2%, P = .060) were greater in T2P patients than in hepatic-sided T2 patients. Among hepatic-sided T2 patients, the 5-year overall survival was greater in patients who underwent radical cholecystectomy including lymph node dissection with liver resection than in patients who underwent lymph node dissection without liver resection (80.3% vs 30.0%, P = .032), and the extent of liver resection was not associated with overall survival ( P = .526). Lymph node dissection without liver resection was an independent prognostic factor for overall survival in hepatic-sided T2 gallbladder cancer (hazard ratio 5.009, 95% confidence interval 1.512–16.596, P = .008). In peritoneal-sided T2 patients, the 5-year overall survival was not significantly different between the lymph node dissection with liver resection and the lymph node dissection without LR subgroups (70.5% vs 54.8%, P = .111) and the extent of lymph node dissection was not associated with overall survival ( P = .395). Conclusion In peritoneal-sided T2 gallbladder cancer, radical cholecystectomy including lymph node dissection without liver resection is a reasonable operative option. Radical cholecystectomy including lymph node dissection with liver resection is suitable for hepatic-sided T2 gallbladder cancer.
Objectives The aim of this study was to test the hypothesis that angiotensin (Ang)-converting enzyme-2 (ACE2) overexpression may inhibit myocardial collagen accumulation and improve left ventricular ...(LV) remodeling and function in diabetic cardiomyopathy. Background Hyperglycemia activates the renin-Ang system, which promotes the accumulation of extracellular matrix and progression of cardiac remodeling and dysfunction. Methods Ninety male Wistar rats were divided randomly into treatment (n = 80) and control (n = 10) groups. Diabetes was induced in the treatment group by a single intraperitoneal injection of streptozotocin. Twelve weeks after streptozotocin injection, rats in the treatment group were further divided into adenovirus-ACE2, adenovirus–enhanced green fluorescent protein, losartan, and mock groups (n = 20 each). LV volume; LV systolic and diastolic function; extent of myocardial fibrosis; protein expression levels of ACE2, Ang-converting enzyme, and Ang-(1-7); and matrix metalloproteinase–2 activity were evaluated. Cardiac myocyte and fibroblast culture was performed to assess Ang-II and collagen protein expression before and after ACE2 gene transfection. Results Four weeks after ACE2 gene transfer, the adenovirus-ACE2 group showed increased ACE2 expression, matrix metalloproteinase–2 activity, and LV ejection fractions and decreased LV volumes, myocardial fibrosis, and ACE, Ang-II, and collagen expression in comparison with the adenovirus–enhanced green fluorescent protein and control groups. ACE2 was superior to losartan in improving LV remodeling and function and reducing collagen expression. The putative mechanisms may involve a shift in balance toward an inhibited fibroblast-myocyte cross-talk for collagen and transforming growth factor–beta production and enhanced collagen degradation by matrix metalloproteinase–2. Conclusions ACE2 inhibits myocardial collagen accumulation and improves LV remodeling and function in a rat model of diabetic cardiomyopathy. Thus, ACE2 provides a promising approach to the treatment of patients with diabetic cardiomyopathy.
Background No reported prospective, randomized study has evaluated the impact of an endoscopy nurse participating as a second observer during colonoscopy. Objective To determine whether the ...participation of an endoscopy nurse enhanced the polyp detection rate (PDR) and adenoma detection rate (ADR) during screening colonoscopy. Design Multicenter, prospective, randomized study. Setting Academic hospitals. Patients A total of 844 consecutive patients undergoing screening colonoscopy. Interventions Single observation by colonoscopist or dual observation by colonoscopist and endoscopy nurse during colonoscope withdrawal. Main Outcome Measurements PDR and ADR. Results No significant difference in patient demographic data, adequacy of bowel preparation, or mean withdrawal time was observed between the 2 groups. In total, 1153 polyps, including 762 adenomas, were detected in 791 patients. Seven nonpolypoid, depressed neoplastic lesions (0-IIc or combined types) were only detected in the dual observation group. A multivariate analysis revealed that experienced (≥2 years) endoscopy nurse participation significantly increased the PDR and ADR compared with those in the single observation group by a colonoscopist alone (adjusted odds ratio OR 1.58 95% CI, 1.07-2.32; adjusted OR 1.47 95% CI, 1.01-2.12, respectively). Additionally, the PDR was significantly higher in the dual-observation group with fellows (<500 colonoscopies) and an experienced endoscopy nurse versus that in the single observation group (adjusted OR 2.07 95% CI, 1.15-3.74). There was no significant benefit of experienced nurse participation in the subgroup with experienced colonoscopists. Limitations Absence of colonoscopist blinding. Conclusions Experienced endoscopy nurse participation increased the PDR and ADR during screening colonoscopy. However, the benefit of participation by experienced nurses appears to be exclusively with inexperienced colonoscopists. (Clinical trial registration number: NCT01124266 .)
Background α-Klotho is reported to have protective effects against kidney injury, and its renal expression is decreased in many experimental models of kidney disease. However, circulating α-klotho ...levels in human chronic kidney disease (CKD) and the relationship to progression are unknown. Study Design Post hoc analysis of a prospective cohort study. Setting & Participants 243 of 301 participants from a CKD cohort at our institution between January 2006 and December 2011 were eligible for the study. Predictor Baseline α-klotho levels. Outcomes Primary outcome was the composite of doubling of baseline serum creatinine concentration, end-stage renal disease, or death. End-stage renal disease was defined as onset of treatment by renal replacement therapy. Measurements Serum α-klotho and fibroblast growth factor 23 (FGF-23) were measured using enzyme-linked immunosorbent assay. Results Lower serum α-klotho levels were associated with more severe CKD stage in the cross-sectional analysis of the baseline data ( P for trend < 0.001). In the adjusted multivariable linear regression model, log(α-klotho) was associated independently with estimated glomerular filtration rate (β = 0.154; P = 0.001). Cox regression analysis showed that baseline α-klotho level independently predicted the composite outcome after adjustment for age, diabetes, blood pressure, estimated glomerular filtration rate, proteinuria, parathyroid hormone level, and FGF-23 level (HR per 10-pg/mL increase, 0.96; 95% CI, 0.94-0.98; P < 0.001). When patients were categorized into 2 groups according to baseline median α-klotho value, 43 (35.2%) patients with α-klotho levels ≤396.3 pg/mL reached the primary composite outcome compared with 19 (15.7%) with α-klotho levels >396.3 pg/mL (HR, 2.03; 95% CI, 1.07-3.85; P = 0.03). Limitations Uncontrolled dietary phosphorus intake and use of frozen samples. Conclusions This observational study showed that low circulating α-klotho levels were associated with adverse kidney disease outcome, suggesting that α-klotho is a novel biomarker for CKD progression. More data from larger prospective longitudinal studies are required to validate our findings.
Objectives
This retrospective cohort study investigated the association of socioeconomic status with survival outcomes among patients with nasopharyngeal carcinoma in an endemic area of China.
...Methods
The primary endpoint was overall survival. Survival outcomes were estimated by the Kaplan-Meier method and compared by the log-rank test, and the multivariate Cox proportional hazards model was used to estimate hazard ratios, 95% CIs, and independent prognostic factors.
Results
A total of 11 069 adult patients with NPC were enrolled and included in the analysis. Kaplan-Meier survival analysis revealed that overall survival was significantly different among socioeconomic status. Compared with high socioeconomic status patients, low socioeconomic status patients (HR, 1.190; 95% CI, 1.063-1.333) and medium socioeconomic status patients (HR, 1.111; 95% CI, 1.006-1.226) were associated with increased hazard ratio (HR) of overall survival.
Conclusion
This analysis highlights patients with nasopharyngeal carcinoma who had high socioeconomic status had better overall survival compared with those who had low and medium socioeconomic status.
Abstract Purpose Gastrectomy results in a significant loss of body composition in the long term, but the acute skeletal muscle wasting after gastrectomy has been rarely investigated. Moreover, the ...association between postoperative muscle wasting and quality of life (QOL) has never been reported. In the present study, we aimed to investigate the risk factors for acute muscle wasting after gastric cancer surgery and its effect on QOL and short-term postoperative outcomes. Methods We conducted a prospective study of patients who underwent curative gastrectomy for gastric cancer between June 2015 and December 2015. Skeletal muscle mass was measured by computed tomography within 1 month before and 1 week after surgery. QOL was assessed 1, 3, and 6 months postoperatively. Univariate and multivariate analyses were performed to identify the risk factors for clinically relevant muscle wasting (muscle wasting ≥10%). Results A total of 110 patients were included, in which 35 patients had muscle wasting ≥10% within 1 week after surgery. Age ≥65 years and diabetes were independent risk factors for muscle wasting ≥10%. Patients with muscle wasting ≥10% had a poorer QOL in terms of fatigue and physical functioning at 1 and 3 months postoperatively, as well as a higher incidence of postoperative complications, a higher incidence of handgrip strength reduction ≥10%, longer hospital stays, and higher costs. Conclusions Age ≥65 years and diabetes were independently associated with clinically relevant muscle wasting within 1 week after gastric cancer surgery. Clinically relevant muscle wasting was associated with a poorer QOL and short-term outcomes after surgery.
Background Some studies have proposed that subclinical hypothyroidism (SCH) has adverse effects on the cardiovascular system, but little is known about the effect on patients undergoing ...cardiovascular operations. We examined the influence of preoperative SCH on postoperative outcome in patients undergoing coronary artery bypass grafting (CABG). Methods Among patients who underwent CABG between July 2005 and June 2007 at Seoul National University Bundang Hospital, 224 with normal thyroid function and 36 with SCH were enrolled. Preoperative risks and postoperative outcomes were evaluated prospectively without thyroid hormone replacement. Results There were no significant differences in primary outcomes (major adverse cardiovascular events) and secondary outcomes such as wound problems, mediastinitis, leg infection, respiratory complications, delirium, or reoperation during the same hospitalization. However, patients with SCH had a higher incidence of postoperative atrial fibrillation than those with normal thyroid function after adjustment for age, gender, body mass index, and other independent variables such as emergency operation, the use of cardiopulmonary bypass, combined valvular operation, preoperative creatinine levels, left ventricular systolic dysfunction, and nonuse of β-blockers (45.5% vs 29%; odds ratio, 2.552; 95% confidence interval, 1.117 to 5.830; p = 0.026). Conclusions SCH appears to influence the postoperative outcome for patients by increasing the development of postoperative atrial fibrillation. However, it is still unproven whether preoperative thyroxine replacement therapy for patients with SCH might prevent postoperative atrial fibrillation after CABG.
Background Various platelet function tests are currently used to measure responsiveness to antiplatelet therapy. We sought to compare 2 point-of-care platelet function tests, VerifyNow Assay ...(Accumetrics, San Diego, CA) and Multiple Electrode Platelet Aggregometry (MEA) (Dynabyte, Munich, Germany), for predicting early clinical outcomes after percutaneous coronary intervention. Methods Platelet reactivity in the arachidonic acid–induced and adenosine diphosphate (ADP)–induced platelet aggregation was measured simultaneously with the VerifyNow Assay and MEA in 222 patients undergoing percutaneous coronary intervention between August and October 2009. We investigated the correlations between the 2 tests and performed receiver operating characteristic curve analysis for major adverse cardiovascular events (MACE), a composite of death, myocardial infarction (MI), stroke, and target vessel revascularization, at 30 days. Results Major adverse cardiovascular events occurred in 19 patients (8.6%), including 14 patients with periprocedural MI and 5 patients with stroke. Correlations were weak between the 2 tests in the arachidonic acid–induced (Spearman r = 0.189, P = .006) and ADP-induced platelet reactivity (Spearman r = 0.390, P < .001). Although the VerifyNow P2Y12 Assay (Accumetrics) was able to predict periprocedural MI (area under the aggregation curve 0.680, P = .024) and 30-day MACE (area under the aggregation curve 0.649, P = .032), VerifyNow Aspirin Assay (Accumetrics), MEA ASPI test, and MEA ADP test failed to predict such clinical events. Hyporesponsiveness to clopidogrel based on the VerifyNow Assay was associated with about a 6-fold increased risk of MACE at 30 days. Conclusions Hyporesponsiveness to clopidogrel measured by VerifyNow Assay was able to identify patients with dual antiplatelet therapy who were at higher risk for periprocedural MI and MACE at 30 days. Further randomized studies are required to validate the effectiveness of different platelet function tests for predicting long-term clinical outcomes.
Even in the era of contemporary drug-eluting stents, it is not clear whether percutaneous coronary intervention (PCI) for nonculprit lesions can improve long-term outcomes in patients with ...non–ST-segment elevation acute coronary syndrome (NSTE-ACS) with multivessel coronary disease. Relevant studies published through August 2014 were searched and identified in the electronic databases. Summary estimates were obtained using a random-effects model. From 368 initial citations, 8 observational studies with 8,425 patients (3,227 multivessel and 5,198 culprit-only PCI) were included. Mean follow-up duration was 18 months. There were no significant differences in all-cause mortality (odds ratios ORs 0.85, 95% confidence interval CI 0.70 to 1.04) and myocardial infarction (OR 0.86, 95% CI 0.55 to 1.35). However, multivessel PCI was associated with a significantly lower rate of repeat revascularization (OR 0.75, 95% CI 0.56 to 1.00). Comparison of multivessel versus culprit-only PCI disclosed OR for major adverse cardiac events of 0.74 (95% CI 0.57 to 0.97). In conclusion, multivessel PCI reduced repeat revascularization without significant benefits in terms of mortality or myocardial infarction at the long-term follow-up in patients with NSTE-ACS and multivessel coronary disease. Future randomized studies that examine the safety and efficacy of multivessel PCI in NSTE-ACS are warranted.
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