The prognosis of early breast cancer (BC) relies on cell autonomous and immune parameters. The impact of the intestinal microbiome on clinical outcome has not yet been evaluated. Shotgun metagenomics ...was used to determine the composition of the fecal microbiota in 121 specimens from 76 early BC patients, 45 of whom were paired before and after chemotherapy. These patients were enrolled in the CANTO prospective study designed to record the side effects associated with the clinical management of BC. We analyzed associations between baseline or post-chemotherapy fecal microbiota and plasma metabolomics with BC prognosis, as well as with therapy-induced side effects. We examined the clinical relevance of these findings in immunocompetent mice colonized with BC patient microbiota that were subsequently challenged with histo-compatible mouse BC and chemotherapy. We conclude that specific gut commensals that are overabundant in BC patients compared with healthy individuals negatively impact BC prognosis, are modulated by chemotherapy, and may influence weight gain and neurological side effects of BC therapies. These findings obtained in adjuvant and neoadjuvant settings warrant prospective validation.
Treatment of metastatic non-small cell lung cancer (mNSCLC) has been modified due to the development of immunotherapy. We assessed survival outcomes (overall OS and progression-free rwPFS survivals, ...time-to-next-treatment TNT) in mNSCLC patients after first-line immunotherapy and chemotherapy in real-life settings. Association between rwPFS and TNT, two candidate surrogate endpoints (SE), with OS was assessed. This retrospective multi-center study uses data from patients included in the Epidemio-Strategy Medico-Economic program with mNSCLC over 2015-2019. The impact of treatment on rwPFS/OS was evaluated with Cox models. Individual-level associations between SE and OS were estimated with an iterative multiple imputation approach and joint survival models. The population included 5294 patients (63 years median age). Median OS in immunotherapy group was 16.4 months (95%CI 14.1-NR) and was higher than in chemotherapy group (11.6 months; 95%CI 11.0-12.2). Improved OS was observed for the immunotherapy group after 3 months for subjects with performance status 0-1 (HR = 0.59; 95%CI 0.42-0.83, p < 0.01). The associations between rwPFS and TNT with OS were close (Formula: see text=0.57). Results emphasized a survival improvement with immunotherapy for patients in good health condition. There was moderate evidence of individual-level association between candidate SE and OS.
The recent thriving development of biobanks and associated high-throughput phenotyping studies requires the elaboration of large-scale approaches for monitoring biological sample quality and ...compliance with standard protocols. We present a metabolomic investigation of human blood samples that delineates pitfalls and guidelines for the collection, storage and handling procedures for serum and plasma. A series of eight pre-processing technical parameters is systematically investigated along variable ranges commonly encountered across clinical studies. While metabolic fingerprints, as assessed by nuclear magnetic resonance, are not significantly affected by altered centrifugation parameters or delays between sample pre-processing (blood centrifugation) and storage, our metabolomic investigation highlights that both the delay and storage temperature between blood draw and centrifugation are the primary parameters impacting serum and plasma metabolic profiles. Storing the blood drawn at 4 °C is shown to be a reliable routine to confine variability associated with idle time prior to sample pre-processing. Based on their fine sensitivity to pre-analytical parameters and protocol variations, metabolic fingerprints could be exploited as valuable ways to determine compliance with standard procedures and quality assessment of blood samples within large multi-omic clinical and translational cohort studies.
Purpose
Severely ill patients affected by coronavirus disease 2019 (COVID-19) develop circulatory failure. We aimed to report patterns of left and right ventricular dysfunction in the first ...echocardiography following admission to intensive care unit (ICU).
Methods
Retrospective, descriptive study that collected echocardiographic and clinical information from severely ill COVID-19 patients admitted to 14 ICUs in 8 countries. Patients admitted to ICU who received at least one echocardiography between 1st February 2020 and 30th June 2021 were included. Clinical and echocardiographic data were uploaded using a secured web-based electronic database (REDCap).
Results
Six hundred and seventy-seven patients were included and the first echo was performed 2 1, 4 days after ICU admission. The median age was 65 56, 73 years, and 71% were male. Left ventricle (LV) and/or right ventricle (RV) systolic dysfunction were found in 234 (34.5%) patients. 149 (22%) patients had LV systolic dysfunction (with or without RV dysfunction) without LV dilatation and no elevation in filling pressure. 152 (22.5%) had RV systolic dysfunction. In 517 patients with information on both paradoxical septal motion and quantitative RV size, 90 (17.4%) had acute cor pulmonale (ACP). ACP was associated with mechanical ventilation (OR > 4), pulmonary embolism (OR > 5) and increased PaCO
2
. Exploratory analyses showed that patients with ACP and older age were more likely to die in hospital (including ICU).
Conclusion
Almost one-third of this cohort of critically ill COVID-19 patients exhibited abnormal LV and/or RV systolic function in their first echocardiography assessment. While LV systolic dysfunction appears similar to septic cardiomyopathy, RV systolic dysfunction was related to pressure overload due to positive pressure ventilation, hypercapnia and pulmonary embolism. ACP and age seemed to be associated with mortality in this cohort.
Background
To describe the clinical, pathological, and molecular characteristics of late‐onset (LO) dysferlinopathy patients.
Methods
Retrospective series of patients with LO dysferlinopathy, defined ...by an age at onset of symptoms ≥30 years, from neuromuscular centers in France and the International Clinical Outcome Study for dysferlinopathy (COS). Patients with early‐onset (EO) dysferlinopathy (<30 years) were randomly selected from the COS study as a control group, and the North Star Assessment for Dysferlinopathy (NSAD) and Activity Limitation (ACTIVLIM) scores were used to assess functionality. Muscle biopsies obtained from 11 LO and 11 EO patients were revisited.
Results
Forty‐eight patients with LO dysferlinopathy were included (28 females). Median age at onset of symptoms was 37 (range 30–57) years and most patients showed a limb‐girdle (n = 26) or distal (n = 10) phenotype. However, compared with EO dysferlinopathy patients (n = 48), LO patients more frequently showed atypical phenotypes (7 vs. 1; p = 0.014), including camptocormia, lower creatine kinase levels (2855 vs. 4394 U/L; p = 0.01), and higher NSAD (p = 0.008) and ACTIVLIM scores (p = 0.016). Loss of ambulation in LO patients tended to occur later (23 ± 4.4 years after disease onset vs. 16.3 ± 6.8 years; p = 0.064). Muscle biopsy of LO patients more frequently showed an atypical pattern (unspecific myopathic changes) as well as significantly less necrosis regeneration and inflammation. Although LO patients more frequently showed missense variants (39.8% vs. 23.9%; p = 0.021), no differences in dysferlin protein expression were found on Western blot.
Conclusions
Late‐onset dysferlinopathy patients show a higher frequency of atypical presentations, are less severely affected, and show milder dystrophic changes in muscle biopsy.
Late‐onset dysferlinopathy patients show a higher frequency of atypical presentations, including camptocormia, and are less severely affected compared with early‐onset patients. Furthermore, they present less necrosis and inflammation in muscle biopsy.
Background
Higher consumption of coffee and tea has been associated with improved health outcomes in the general population and improved breast cancer (BC) prognosis. This study investigated patterns ...of coffee and tea consumption and association with patient‐reported outcomes (PROs) and clinical outcomes among survivors of BC.
Methods
The authors included survivors of stage I–III BC enrolled in the CANTO cohort (NCT01993498) that provided post‐treatment assessment of coffee and tea consumption from years 1 to 4 after diagnosis. Group‐based trajectory modeling clustered patients according to daily consumption of coffee and tea. Multivariable mixed models and Cox models examined associations between consumption, PROs and clinical outcomes.
Results
Among 3788 patients, the authors identified four stable patterns of consumption: “Low” (25.8%), “Moderate” (37.6%), “High” (25.3%), and “Very high” (11.3%), corresponding to <1, 2, 3, and ≥ 4 cups of coffee and/or tea per day. Patients in the “Very high” group (vs. “Low”), were more likely to be younger, smokers, with higher monthly income and education. PROs and survival outcomes were similar across the four groups.
Conclusions
Over one in three survivors of BC reported high or very high consumption of coffee and/or tea. The authors found no association between higher consumption of coffee and/or tea, worse PROs and clinical outcomes.
More than 30% of survivors of breast cancer report high post‐diagnostic consumption of coffee and tea. In this study, the authors did not find any detrimental association between higher consumption of coffee and tea and patient‐reported or clinical outcomes.
Border studies at 45 Walther, Olivier J.; Amilhat Szary, Anne-Laure; Brambilla, Chiara ...
Political geography,
June 2023, 2023-06-00, Letnik:
104
Journal Article
Recenzirano
This essay takes stock of the work conducted in border studies so far and discusses some of the challenges ahead. It argues that, nearly half a century after border studies emerged in the social ...sciences, much remains to be done to turn our field into an academic discipline. As we approach a metaphorical middle age, it is high time for border studies scholars to invest a substantial part of our energies into developing common theoretical and methodological frameworks to better understand how borders, borderlands and borderlanders evolve. Doing so holds promise to make our work more relevant to the numerous academic and civil society stakeholders for whom borders and borderlands remain a crucially important though often underexamined issue.
The PACS 01 trial compared six cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC) with a sequential regimen of three cycles of FEC followed by three cycles of docetaxel (FEC-D) as ...adjuvant treatment for women with node-positive early breast cancer.
Between June 1997 and March 2000, 1,999 patients with operable node-positive breast cancer were randomly assigned to either FEC every 21 days for six cycles, or three cycles of FEC followed by three cycles of docetaxel, both given every 21 days. Hormone-receptor-positive patients received tamoxifen for 5 years after chemotherapy. The primary end point was 5-year disease-free survival (DFS).
Median follow-up was 60 months. Five-year DFS rates were 73.2% with FEC and 78.4% with FEC-D (unadjusted P = .011; adjusted P = .012). Multivariate analysis adjusted for prognostic factors showed an 18% reduction in the relative risk of relapse with FEC-D. Five-year overall survival rates were 86.7% with FEC and 90.7% with FEC-D, demonstrating a 27% reduction in the relative risk of death (unadjusted P = .014; adjusted P = .017). The incidence of grade 3 to 4 neutropenia, the need for hematopoietic growth factor, and incidence of nausea/vomiting were higher with FEC. Docetaxel was associated with more febrile neutropenia in the fourth cycle, stomatitis, edema, and nail disorders. Though rare overall, there were fewer cardiac events after FEC-D (P = .03), attributable mainly to the lower anthracycline cumulative dose.
Sequential adjuvant chemotherapy with FEC followed by docetaxel significantly improves disease-free and overall survival in node-positive breast cancer patients and has a favorable safety profile.
PURPOSE The indications of adjuvant chemotherapy for patients with estrogen receptor (ER) -positive breast cancer are controversial. We analyzed the predictive value of Ki67, HER2, and progesterone ...receptor (PR) expression for the efficacy of docetaxel in patients with ER-positive, node-positive breast cancer. PATIENTS AND METHODS Expression of Ki67, HER2, and PR was measured by immunohistochemistry in tumor samples from 798 patients with ER-positive breast cancer who participated in PACS01, a randomized trial that evaluated the efficacy of docetaxel. Risk reduction was evaluated using a Cox model adjusted for age, tumor size, nodal involvement, treatment arm, and biomarkers. The predictive value of biomarkers was assessed by an interaction test. Disease-free survival (DFS) was the primary end point. Results Ki67, HER2, and PR were expressed in 21%, 9%, and 62% of samples, respectively. Hazard ratios for relapse associated with docetaxel were 0.51 (95% CI, 0.26 to 1.01) in ER-positive/Ki67-positive tumors and 1.03 (95% CI, 0.69 to 1.55) in ER-positive/Ki67-negative tumors (ratio for interaction: 0.53; 95% CI, 0.24 to 1.16; P = .11). Five-year DFS rates were 81% (95% CI, 76% to 86%) and 84% (95% CI, 75% to 93%) in patients with ER-positive/Ki67-negative and ER-positive/Ki67-positive tumors treated with docetaxel and 81% (95% CI, 76% to 86%) and 62% (95% CI, 52% to 72%) in patients with ER-positive/Ki67-negative and ER-positive/Ki67-positive tumors treated with fluorouracil, epirubicin, and cisplatin. No trend for interaction was observed between docetaxel and HER2 (ratio for interaction: 0.83; 95% CI, 0.35 to 1.94; P = .66), nor between docetaxel and PR (ratio for interaction: 0.89; 95% CI, 0.47 to 1.66; P = .71). CONCLUSION Ki67 expression identifies a subset of patients with ER-positive breast cancer who could be sensitive to docetaxel treatment in the adjuvant setting.
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