Summary Background The ESPAC-3 trial showed that adjuvant gemcitabine is the standard of care based on similar survival to and less toxicity than adjuvant 5-fluorouracil/folinic acid in patients with ...resected pancreatic cancer. Other clinical trials have shown better survival and tumour response with gemcitabine and capecitabine than with gemcitabine alone in advanced or metastatic pancreatic cancer. We aimed to determine the efficacy and safety of gemcitabine and capecitabine compared with gemcitabine monotherapy for resected pancreatic cancer. Methods We did a phase 3, two-group, open-label, multicentre, randomised clinical trial at 92 hospitals in England, Scotland, Wales, Germany, France, and Sweden. Eligible patients were aged 18 years or older and had undergone complete macroscopic resection for ductal adenocarcinoma of the pancreas (R0 or R1 resection). We randomly assigned patients (1:1) within 12 weeks of surgery to receive six cycles of either 1000 mg/m2 gemcitabine alone administered once a week for three of every 4 weeks (one cycle) or with 1660 mg/m2 oral capecitabine administered for 21 days followed by 7 days' rest (one cycle). Randomisation was based on a minimisation routine, and country was used as a stratification factor. The primary endpoint was overall survival, measured as the time from randomisation until death from any cause, and assessed in the intention-to-treat population. Toxicity was analysed in all patients who received trial treatment. This trial was registered with the EudraCT, number 2007-004299-38, and ISRCTN, number ISRCTN96397434. Findings Of 732 patients enrolled, 730 were included in the final analysis. Of these, 366 were randomly assigned to receive gemcitabine and 364 to gemcitabine plus capecitabine. The Independent Data and Safety Monitoring Committee requested reporting of the results after there were 458 (95%) of a target of 480 deaths. The median overall survival for patients in the gemcitabine plus capecitabine group was 28·0 months (95% CI 23·5–31·5) compared with 25·5 months (22·7–27·9) in the gemcitabine group (hazard ratio 0·82 95% CI 0·68–0·98, p=0·032). 608 grade 3–4 adverse events were reported by 226 of 359 patients in the gemcitabine plus capecitabine group compared with 481 grade 3–4 adverse events in 196 of 366 patients in the gemcitabine group. Interpretation The adjuvant combination of gemcitabine and capecitabine should be the new standard of care following resection for pancreatic ductal adenocarcinoma. Funding Cancer Research UK.
Summary Background Bivalirudin, with selective use of glycoprotein (GP) IIb/IIIa inhibitor agents, is an accepted standard of care in primary percutaneous coronary intervention (PPCI). We aimed to ...compare antithrombotic therapy with bivalirudin or unfractionated heparin during this procedure. Methods In our open-label, randomised controlled trial, we enrolled consecutive adults scheduled for angiography in the context of a PPCI presentation at Liverpool Heart and Chest Hospital (Liverpool, UK) with a strategy of delayed consent. Before angiography, we randomly allocated patients (1:1; stratified by age <75 years vs ≥75 years and presence of cardiogenic shock yes vs no) to heparin (70 U/kg) or bivalirudin (bolus 0·75 mg/kg; infusion 1·75 mg/kg per h). Patients were followed up for 28 days. The primary efficacy outcome was a composite of all-cause mortality, cerebrovascular accident, reinfarction, or unplanned target lesion revascularisation. The primary safety outcome was incidence of major bleeding (type 3–5 as per Bleeding Academic Research Consortium definitions). This study is registered with ClinicalTrials.gov , number NCT01519518. Findings Between Feb 7, 2012, and Nov 20, 2013, 1829 of 1917 patients undergoing emergency angiography at our centre (representing 97% of trial-naive presentations) were randomly allocated treatment, with 1812 included in the final analyses. 751 (83%) of 905 patients in the bivalirudin group and 740 (82%) of 907 patients in the heparin group had a percutaneous coronary intervention. The rate of GP IIb/IIIa inhibitor use was much the same between groups (122 patients 13% in the bivalirudin group and 140 patients 15% in the heparin group). The primary efficacy outcome occurred in 79 (8·7%) of 905 patients in the bivalirudin group and 52 (5·7%) of 907 patients in the heparin group (absolute risk difference 3·0%; relative risk RR 1·52, 95% CI 1·09–2·13, p=0·01). The primary safety outcome occurred in 32 (3·5%) of 905 patients in the bivalirudin group and 28 (3·1%) of 907 patients in the heparin group (0·4%; 1·15, 0·70–1·89, p=0·59). Interpretation Compared with bivalirudin, heparin reduces the incidence of major adverse ischaemic events in the setting of PPCI, with no increase in bleeding complications. Systematic use of heparin rather than bivalirudin would reduce drug costs substantially. Funding Liverpool Heart and Chest Hospital, UK National Institute of Health Research, The Medicines Company, AstraZeneca, The Bentley Drivers Club (UK).
Objective The purpose of this study was to determine the diagnostic performance of magnetic resonance imaging (MRI) in the diagnosis of acute appendicitis during pregnancy in a multiinstitutional ...study. Study Design In this multicenter retrospective study, the cases of pregnant women who underwent MRI evaluation of abdominal or pelvic pain and who had clinical suspicion of acute appendicitis between June 1, 2009, and July 31, 2014, were reviewed. All MRI examinations with positive findings for acute appendicitis were confirmed with surgical pathologic information. Sensitivity, specificity, negative predictive values, and positive predictive values were calculated. Receiver operating characteristic curves were generated, and area under the curve analysis was performed for each participating institution. Results Of the cases that were evaluated, 9.3% (66/709) had MRI findings of acute appendicitis. Sensitivity, specificity, accuracy, positive predictive value, and negative predictive values were 96.8%, 99.2%, 99.0%, 92.4%, and 99.7%, respectively. There was no statistically significant difference between centers that were included in the study (pair-wise probability values ranged from 0.12–0.99). Conclusion MRI is useful and reproducible in the diagnosis of suspected acute appendicitis during pregnancy.
Donor smoking history and higher fraction of inspired oxygen (FIO2) at reperfusion are associated with primary graft dysfunction (PGD) after lung transplantation. We hypothesized that oxidative ...injury biomarkers would be elevated in PGD, with higher levels associated with donor exposure to cigarette smoke and recipient hyperoxia at reperfusion.
We performed a nested case-control study of 72 lung transplant recipients from the Lung Transplant Outcomes Group cohort. Using mass spectroscopy, F2-isoprostanes and isofurans were measured in plasma collected after transplantation. Cases were defined in 2 ways: grade 3 PGD present at day 2 or day 3 after reperfusion (severe PGD) or any grade 3 PGD (any PGD).
There were 31 severe PGD cases with 41 controls and 35 any PGD cases with 37 controls. Plasma F2-isoprostane levels were higher in severe PGD cases compared with controls (28.6 pg/ml vs 19.8 pg/ml, p = 0.03). Plasma F2-isoprostane levels were higher in severe PGD cases compared with controls (29.6 pg/ml vs 19.0 pg/ml, p = 0.03) among patients reperfused with FIO2 >40%. Among recipients of lungs from donors with smoke exposure, plasma F2-isoprostane (38.2 pg/ml vs 22.5 pg/ml, p = 0.046) and isofuran (66.9 pg/ml vs 34.6 pg/ml, p = 0.046) levels were higher in severe PGD compared with control subjects.
Plasma levels of lipid peroxidation products are higher in patients with severe PGD, in recipients of lungs from donors with smoke exposure, and in recipients exposed to higher Fio2 at reperfusion. Oxidative injury is an important mechanism of PGD and may be magnified by donor exposure to cigarette smoke and hyperoxia at reperfusion.
The General Surgery Residency Experience Anya L. Greenberg, MBA; Jenny R. Cevallos, BS; Feyisayo M. Ojute, BS ...
Annals of surgery open,
09/2022, Letnik:
3, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Objectives:. We explored differences by race/ethnicity in regard to several factors that reflect or impact wellbeing. Background:. Physician wellbeing has critical ramifications for the US healthcare ...system, affecting clinical outcomes, patient experience, and healthcare economics. Within surgery, literature examining the association between race/ethnicity and wellbeing has been limited and inconclusive. Methods:. Residents at 16 academic General Surgery training programs completed an online questionnaire. Racial/ethnic identity, gender identity, post-graduate year (PGY) level, and gap years were self-reported. Differences by race/ethnicity in flourishing (global wellbeing) as well as factors reflecting resilience (mindfulness, personal accomplishment, workplace support, workplace control) and risk (depression, emotional exhaustion, depersonalization, stress, anxiety, workplace demand) were assessed. Results:. Of 300 respondents (response rate 34%), 179 (60%) were non-male, 123 (41%) were residents of color (ROC), and 53 (18%) were from racial/ethnic groups that are underrepresented in medicine (UIM). Relative to White residents, ROC have significantly lower flourishing and higher anxiety, and these remain significant when adjusting for gender, PGY level, and gap years. Relative to residents overrepresented in medicine (OIM), UIM residents have significantly lower emotional exhaustion and depersonalization after adjusting for gender, PGY level and gap years. Conclusions:. Disparities in resident wellbeing based on race/ethnicity and UIM/OIM status exist. However, the experience of ROC is not homogeneous. As part of the transformative process to address systemic racism, eliminate disparities in surgical training, and reconceptualize wellbeing as a fundamental asset for optimal surgeon performance, further understanding the specific contributors and detractors of wellbeing among different individuals and groups is critical.
Abstract Background Chronic total occlusion (CTO) is common, being reported in 18% to 30% of patients undergoing coronary angiography. Percutaneous coronary intervention (PCI) is usually performed to ...relieve anginal symptoms, but data are emerging to suggest that there may also be a mortality benefit. Objectives This study aimed to compare outcomes of patients with successful versus unsuccessful PCI to a CTO. Methods We analyzed the U.K. Central Cardiac Audit Database for all CTO PCI cases carried out in England and Wales between January 1, 2005, and December 31, 2009. Vital status in September 2010 was obtained from the Medical Research Information Service. Results A total of 13,443 patients (78.8% male) had a mean age of 63.5 years and underwent 14,439 CTO procedures. CTO PCI was successful in 10,199 cases (70.6%). During follow-up of 2.65 years (interquartile range: 1.59 to 3.83 years), successful PCI of at least 1 CTO was associated with improved survival (hazard ratio HR: 0.72; 95% CI: 0.62 to 0.83; p < 0.001). Complete revascularization was associated with improved survival compared with partial revascularization (HR: 0.70; 95% CI: 0.56 to 0.87; p = 0.002) or failed revascularization (HR: 0.61; 95% CI: 0.50 to 0.74; p < 0.001). Conclusions Successful CTO PCI was associated with improved long-term survival. The improvement was greatest in patients when complete revascularization was achieved. The identity of the successfully treated occluded vessel was not associated with differences in outcome.
Background IgE-mediated peanut allergy is a complex trait with strong heritability, but its genetic basis is currently unknown. Loss-of-function mutations within the filaggrin gene are associated ...with atopic dermatitis and other atopic diseases; therefore, filaggrin is a candidate gene in the etiology of peanut allergy. Objective To investigate the association between filaggrin loss-of-function mutations and peanut allergy. Methods Case-control study of 71 English, Dutch, and Irish oral food challenge–positive patients with peanut allergy and 1000 non peanut-sensitized English population controls. Replication was tested in 390 white Canadian patients with peanut allergy (defined by food challenge, or clinical history and skin prick test wheal to peanut ≥8 mm and/or peanut-specific IgE ≥15 kUL−1 ) and 891 white Canadian population controls. The most prevalent filaggrin loss-of-function mutations were assayed in each population: R501X and 2282del4 in the Europeans, and R501X, 2282del4, R2447X, and S3247X in the Canadians. The Fisher exact test and logistic regression were used to test for association; covariate analysis controlled for coexistent atopic dermatitis. Results Filaggrin loss-of-function mutations showed a strong and significant association with peanut allergy in the food challenge–positive patients ( P = 3.0 × 10−6 ; odds ratio, 5.3; 95% CI, 2.8-10.2), and this association was replicated in the Canadian study ( P = 5.4 × 10−5 ; odds ratio, 1.9; 95% CI, 1.4-2.6). The association of filaggrin mutations with peanut allergy remains significant ( P = .0008) after controlling for coexistent atopic dermatitis. Conclusion Filaggrin mutations represent a significant risk factor for IgE-mediated peanut allergy, indicating a role for epithelial barrier dysfunction in the pathogenesis of this disease.
We aimed to identify combinations of biomarkers to enhance the definition of primary graft dysfunction (PGD) for translational research.
Biomarkers reflecting lung epithelial injury (soluble receptor ...for advance glycation end products sRAGE and surfactant protein-D SP-D), coagulation cascade (plasminogen activator inhibitor-1 PAI-1 and protein C), and cell adhesion (intracellular adhesion molecule-1 ICAM-1) were measured in the plasma of 315 individuals derived from the Lung Transplant Outcomes Group cohort at 6 and 24 hours after transplantation. We assessed biomarker utility in 2 ways: first, we tested the discrimination of grade 3 PGD within 72 hours; second, we tested the predictive utility of plasma biomarkers for 90-day mortality.
PGD developed in 86 of 315 individuals (27%). Twenty-patients (8%) died within 90 days of transplantation, of which 16 (70%) had PGD. Biomarkers measured at 24 hours had greater discrimination than at 6 hours. Individually, sRAGE (area under the curve AUC, 0.71) and PAI-1 (AUC, 0.73) had the best discrimination of PGD. The combinations of sRAGE with PAI-1 (AUC, 0.75), PAI-1 with ICAM-1 (AUC, 0.75), and PAI-1 with SP-D (AUC, 0.76) had the best discrimination. Combinations of greater than 2 biomarkers did not significantly enhance discrimination of PGD. ICAM-1 with PAI-1 (AUC, 0.72) and ICAM-1 with sRAGE (AUC, 0.72) had the best prediction for 90-day mortality. The addition of ICAM-1, PAI-1, or sRAGE to the concurrent clinical PGD grade significantly improved the prediction of 90-day mortality (p < 0.001 each).
Measurement of the combination of a marker of impaired fibrinolysis with an epithelial injury or cell adhesion marker had the best discrimination for PGD and prediction for early death and may provide an alternative outcome useful in future research.
Abstract Background Sedentary aging has deleterious effects on the cardiovascular system, including decreased left ventricular compliance and distensibility (LVCD). Conversely, Masters level ...athletes, who train intensively throughout adulthood, retain youthful LVCD. Objectives The purpose of this study was to test the hypothesis that preservation of LVCD may be possible with moderate lifelong exercise training. Methods Healthy seniors (n = 102) were recruited from predefined populations, screened for lifelong patterns of exercise training, and stratified into 4 groups: “sedentary” (<2 sessions/week); “casual” (2 to 3 sessions/week); “committed” (4 to 5 sessions/week); and “competitive” Masters level athletes (6 to 7 sessions/week). Right heart catheterization and echocardiography were performed while preload was manipulated using lower body negative pressure and rapid saline infusion to define LV pressure–volume relationships and Frank-Starling curves. Results Peak oxygen uptake and LV mass increased with escalating doses of lifelong exercise, with little change in systolic function. At baseline, LV distensibility was greater in committed (21%) and competitive (36%) exercisers than in sedentary subjects. Group LV stiffness constants (sedentary: 0.062 ± 0.039; casual: 0.079 ± 0.052; committed: 0.055 ± 0.033; and competitive: 0.035 ± 0.033) revealed: 1) increased stiffness in sedentary subjects compared to competitive athletes, whereas lifelong casual exercise had no effect; and 2) greater compliance in committed exercisers than in sedentary or casual exercisers. Conclusions Low doses of casual, lifelong exercise do not prevent the decreased compliance and distensibility observed with healthy, sedentary aging. In contrast, 4 to 5 exercise sessions/week throughout adulthood prevent most of these age-related changes. As LV stiffening has been implicated in the pathophysiology of many cardiovascular conditions affecting the elderly, this “dose” of exercise training may have important implications for prevention of cardiovascular disease.
AbstractBackgroundMultiple studies have shown favorable outcomes for stereotactic radiosurgery (SRS) in the treatment of limited brain metastases. An obstacle of SRS in the management of numerous ...metastases is the longer treatment time using traditional radiosurgery. Single-isocenter multitarget (SIMT) SRS is a novel technique that permits rapid therapy delivery to multiple metastases. There is a lack of clinical evidence regarding its efficacy and safety. We report the outcomes of patients treated with this technique. MethodsWe reviewed the records of patients with intact or resected brain metastases treated with SRS in 1 to 5 fractions using SIMT technique at our institution, with at least one available follow-up brain MRI. Survival, disease control, and toxicity were evaluated using Cox regression, logistic regression, and Kaplan-Meier analysis. ResultsWe identified 173 patients with 1014 brain metastases. Median follow up was 12.7 months. Median beam-on time was 4.1 minutes. The median dose to the brain was 219.4 cGy. Median overall survival and freedom from intracranial progression were 13.2 and 6.3 months, respectively. Overall survival did not differ between patients treated to < vs >4 lesions (HR = 1.03; 95% CI 0.66 to 1.61; p = 0.91). Actuarial 1- and 2-year local control were 99.0% and 95.1%, respectively. Rates of grade 2 and grade 3 or higher radionecrosis were 1.4% and 0.9%, respectively. ConclusionsSIMT radiosurgery delivered in 1 to 5 fractions offers excellent local control and acceptable toxicity in the treatment of multiple intact and postoperative brain metastases. This technique should be evaluated prospectively.
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