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101.
ObjectiveThe aim of this study was to explore the relationship between fasting glucose levels and all-cause and cause-specific mortality in Chinese population.MethodsThe role of fasting blood glucose levels as a predictor of all-cause and cause-specific mortality was estimated in 9930 participants from four Chinese general populations with a 20-year follow-up. Multivariate Cox proportional hazard models were used to identify the relationship between fasting glucose and mortality.ResultsThere were 1471 deaths after a median follow-up of 20.2 years (a total of 187,374 person-years), including 310 cardiovascular deaths, 581 cancer deaths, and 580 other-cause deaths. After adjustment for age, sex, urban or rural, northern or southern of China, types of work, education level, physical exercise, smoking status, drinking status, body mass index, systolic blood pressure, and serum total cholesterol at baseline, the hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality in the fasting blood glucose categories of <60, 60–69, 70–79, 90–99, 100–109, 110–125, and ≥126 mg/dl were 1.38 (1.04–1.84), 1.20 (1.01–1.43), 1.18 (1.03–1.36), 1.18 (0.99–1.41), 1.48 (1.16–1.88), 1.17 (0.84–1.62), and 2.23 (1.72–2.90), respectively, in contrast to the reference group (80–89 mg/dl). The HRs and 95% CIs for cardiovascular disease mortality in these groups were 2.58 (1.44–4.61), 1.41 (0.95–2.10), 1.56 (1.15–2.11), 1.29 (0.88–1.89), 1.36 (0.78–2.37), 1.05 (0.52–2.11), and 2.73 (1.64–4.56), respectively.ConclusionsBoth low and high fasting glucose were significantly associated with increased risk of all-cause and cardiovascular mortality in Chinese general population.  相似文献   
102.

Objective

Comparative survival between neoadjuvant chemotherapy and adjuvant chemotherapy for patients with cT2-4N0-1M0 non–small cell lung cancer has not been extensively studied.

Methods

Patients with cT2-4N0-1M0 non–small cell lung cancer who received platinum-based chemotherapy were retrospectively identified. Exclusion criteria included stage IV disease, induction radiotherapy, and targeted therapy. The primary end point was disease-free survival. Secondary end points were overall survival, chemotherapy tolerance, and ability of Response Evaluation Criteria In Solid Tumors response to predict survival. Survival was estimated using the Kaplan–Meier method, compared using the log-rank test and Cox proportional hazards models, and stratified using matched pairs after propensity score matching.

Results

In total, 330 patients met the inclusion criteria (n = 92/group after propensity-score matching; median follow-up, 42 months). Five-year disease-free survival was 49% (95% confidence interval, 39-61) for neoadjuvant chemotherapy versus 48% (95% confidence interval, 38-61) for adjuvant chemotherapy (P = .70). On multivariable analysis, disease-free survival was not associated with neoadjuvant chemotherapy or adjuvant chemotherapy (hazard ratio, 1.1; 95% confidence interval, 0.64-1.90; P = .737), nor was overall survival (hazard ratio, 1.21; 95% confidence interval, 0.63-2.30; P = .572). The neoadjuvant chemotherapy group was more likely to receive full doses and cycles of chemotherapy (P = .014/0.005) and had fewer grade 3 or greater toxicities (P = .001). Response Evaluation Criteria In Solid Tumors response to neoadjuvant chemotherapy was associated with disease-free survival (P = .035); 15% of patients receiving neoadjuvant chemotherapy (14/92) had a major pathologic response.

Conclusions

Timing of chemotherapy, before or after surgery, is not associated with an improvement in overall or disease-free survival among patients with cT2-4N0-1M0 non–small cell lung cancer who undergo complete surgical resection.  相似文献   
103.
Background and aimEffects of whole egg consumption on cardiovascular diseases (CVD) risk in the middle-aged and older population remain unclear due to inconsistent findings from observational and randomized controlled trials (RCTs). This meta-analysis aimed to assess the impacts of whole egg and egg category (whole eggs versus egg substitutes) intake quantity on CVD risk factors from systematically searched RCTs. Egg substitutes were hypothesized to have minimal effects of the blood lipid and lipoprotein profile as they are void of dietary cholesterol.Methods and resultsAs many as 434 studies identified from PubMed, Cochrane Library, CINAHL and Medline (Ovid) databases were screened and data were extracted from 8 selected RCTs. Quality of the selected studies were assessed and the overall effect sizes of weighted mean differences (WMD) were calculated using a random effects model. Non-differential effects in blood pressures, lipids and lipoproteins were observed when >4 whole eggs/week compared to ≤4 whole eggs/week were consumed. Intake of >4 whole eggs/week compared to equivalent amounts of egg substitutes caused greater elevations in blood total cholesterol (WMD: 0.198 mmol/L; 95% CIs: 0.056, 0.339), HDL cholesterol (WMD: 0.068 mmol/L; 95% CIs: 0.006, 0.130) and LDL cholesterol (WMD: 0.171 mmol/L; 95% CIs: 0.028, 0.315) but did not differentially affect triglycerides concentration.ConclusionOverall, the results support the notion that quantity of whole egg intake does not affect CVD risk factors and consuming egg substitutes may also be beneficial compared to whole eggs on lowering CVD risk in the middle-aged and older population.  相似文献   
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Background

In colorectal cancer liver metastases (CRCLM), bevacizumab-based neoadjuvant strategies provide increased pathologic response. We aimed at assessing the activity of perioperative capecitabine, oxaliplatin, irinotecan, and bevacizumab (COI-B regimen) in patients with potentially resectable CRCLM, and investigating biomarkers for early prediction of pathologic response.

Patients and Methods

This was a single-center phase II study enrolling patients with liver-limited, borderline resectable disease and/or high-risk features. Patients received 5 preoperative and 4 postoperative cycles of biweekly COI-B (irinotecan 180 mg/m2 and bevacizumab 5 mg/Kg on day 1, oxaliplatin 85 mg/m2 on day 2, and capecitabine 1000 mg/m2 twice a day on days 2 to 6). The primary endpoint was pathologic response rate in the intention-to-treat population. A Simon 2-stage design was adopted to detect an increase from 30% to 50% with a power of 90%. Dynamic imaging biomarkers (early tumor shrinkage [ETS], deepness of response, maximum standardized uptake volume [SUVmax]/regression index) and next generation sequencing data were explored as surrogates.

Results

From June 2013 to March 2017, 46 patients were enrolled. Pathologic response was achieved in 63% patients (endpoint met), and responders achieved significantly better survival outcomes with respect to non-responders. The most frequent grade 3/4 adverse events were diarrhea and neutropenia (8.7%) in the preoperative phase and thromboembolic events (5.9%) in the postoperative phase. ETS and lower SUV-2 were significantly associated with pathologic response.

Conclusion

The COI-B regimen is a feasible and highly active perioperative strategy in patients with molecularly unselected, potentially resectable CRCLM. ETS and SUV-2 have a promising role as imaging-based biomarkers for pathologic response.  相似文献   
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BackgroundThe improved overall survival (OS) after short course preoperative radiotherapy (SCPRT) using 5 × 5 Gy reported in the early rectal cancer trials could not be replicated in subsequent phase III trials. This original survival advantage is attributed to poor quality of surgery and the large differential in local recurrence rates, with and without SCPRT. Immuno-modulation during and after SCPRT and its clinical implications have been poorly investigated. We propose an alternative explanation for this survival benefit in terms of immunological mechanisms induced by SCPRT and the timing of surgery, which may validate the concept of consolidation chemotherapy.Material and methodsWe reviewed randomized controlled trials (RCTs) and studies of SCPRT from 1985 to 2019. We aimed to examine the precise timing of surgery in days following SCPRT and identify evidence for immune modulation, neo-antigens and memory cell induction by radiation.ResultsConsiderable variability is reported in randomised trials for median overall treatment time (OTT) from start of SCPRT to surgery (8–14 days). Only three early trials showed a benefit in terms of OS from SCPRT, although the level of benefit in preventing local recurrence was consistent across all trials. Different patterns of immune effects are observed within days after SCPRT depending on the OTT, but human leukocyte antigen (HLA)-1 expression was not upregulated.ConclusionsSCPRT has a substantial immune-stimulatory potential. The importance of the timing of surgery after SCPRT may have been underestimated. An optimal interval for surgery after 5 × 5 Gy may lead to better outcomes, which is possibly exploited in total neoadjuvant therapy schedules using consolidation chemotherapy. Individual patient meta-analyses from appropriate SCPRT trials examining outcomes for each day and prospective trials are needed to clarify the validity of this hypothesis. The interaction of SCPRT with tumour adaptive immunology, in particular the kinetics and timing, should be examined further.  相似文献   
108.
《Clinical breast cancer》2020,20(2):e173-e180
BackgroundIn PALOMA-2, palbociclib + letrozole significantly prolonged progression-free survival (PFS) versus placebo + letrozole in patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2) advanced breast cancer (ABC). We investigated clinical outcomes of patients who achieved or did not achieve a confirmed objective response (OR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (data cutoff: May 31, 2017).Patients and MethodsPostmenopausal patients untreated for ER+/HER2 ABC were randomized 2:1 to palbociclib + letrozole or placebo + letrozole. Median PFS, median duration of OR, baseline characteristics, and palbociclib exposure were compared in patients with or without OR by treatment arm.ResultsIn the intent-to-treat population, OR was achieved by 194 (44%) of 444 and 77 (35%) of 222 patients in the palbociclib and placebo arms, respectively (odds ratio, 1.5; 95% confidence interval [CI], 1.0-2.1; P = .0156). Regardless of treatment, more OR than non-OR patients had de novo metastatic disease (47%-50% and 28%-31%, respectively) and no prior endocrine therapy (55% and 35%-37%, respectively). Rates of palbociclib dose reduction owing to adverse events were similar regardless of OR (41% and 38%, respectively). Among the patients with OR during the study, approximately 50% achieved OR within the first 3 months regardless of treatment. The median PFS was significantly prolonged with palbociclib + letrozole versus placebo + letrozole in patients with measurable disease in both OR (37.2 months; 95% CI, 28.1 months to not estimable vs. 27.4 months; 95% CI, 22.2-31.1 months; hazard ratio, 0.66; 95% CI, 0.47-0.94; P = .009) and non-OR groups (10.9 months; 95% CI, 8.2-11.2 months vs. 5.6 months; 95% CI, 5.3-8.3 months; hazard ratio, 0.72; 95% CI, 0.54-0.97; P = .016).ConclusionsPalbociclib + letrozole provided significant clinical benefit versus placebo + letrozole to patients with ER+/HER2 ABC regardless of achieving RECIST-defined OR.Pfizer; ClinicalTrials.gov: NCT01740427  相似文献   
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