Neoadjuvant Trastuzumab Emtansine and Pertuzumab in Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Three-Year Outcomes From the Phase III KRISTINE Study.

PurposeThe KRISTINE study compared neoadjuvant trastuzumab emtansine plus pertuzumab (T-DM1+P) with docetaxel, carboplatin, trastuzumab plus P (TCH+P) for the treatment human epidermal growth factor receptor 2-positive stage II to III breast cancer. T-DM1+P led to a lower pathologic complete response rate (44.4% v 55.7%; P = .016), but fewer grade 3 or greater and serious adverse events (AEs). Here, we present 3-year outcomes from KRISTINE.MethodsPatients were randomly assigned to neoadjuvant T-DM1+P or TCH+P every 3 weeks for six cycles. Patients who received T-DM1+P continued adjuvant T-DM1+P, and patients who received TCH+P received adjuvant trastuzumab plus pertuzumab. Secondary end points included event-free survival (EFS), overall survival, patient-reported outcomes (measured from random assignment), and invasive disease-free survival (IDFS; measured from surgery).ResultsOf patients, 444 were randomly assigned (T-DM1+P, n = 223; TCH+P, n = 221). Median follow-up was 37 months. Risk of an EFS event was higher with TDM-1+P (hazard ratio [HR], 2.61 [95% CI, 1.36 to 4.98]) with more locoregional progression events before surgery (15 [6.7%] v 0). Risk of an IDFS event after surgery was similar between arms (HR, 1.11 [95% CI, 0.52 to 2.40]). Pathologic complete response was associated with a reduced risk of an IDFS event (HR, 0.24 [95% CI, 0.09 to 0.60]) regardless of treatment arm. Overall, grade 3 or greater AEs (31.8% v 67.7%) were less common with T-DM1+P. During adjuvant treatment, grade 3 or greater AEs (24.5% v 9.9%) and AEs leading to treatment discontinuation (18.4% v 3.8%) were more common with T-DM1+P. Patient-reported outcomes favored T-DM1+P during neoadjuvant treatment and were similar to trastuzumab plus pertuzumab during adjuvant treatment.ConclusionCompared with TCH+P, T-DM1+P resulted in a higher risk of an EFS event owing to locoregional progression events before surgery, a similar risk of an IDFS event, fewer grade 3 or greater AEs during neoadjuvant treatment, and more AEs leading to treatment discontinuation during adjuvant treatment

Characterisation of the supramolecular structure of chemically and physically modified regenerated cellulosic fibres by means of high-resolution Carbon-13 solid-state NMR

Carbon-13 high-resolution solid-state NMR techniques have been invaluable in elucidating the structure of regenerated cellulosic materials. Studies of a range of fibres have shown systematic changes in chemical shifts, which can be related to the influences of physical processing or chemical modification. A constrained curve fitting method has been applied, where the C4 spectral envelope is represented as the sum of contributions from polymer in ordered, partially-ordered and disordered environments, associated with differing conformational arrangements of the cellulose hydroxymethyl and glycocidic bonds. The empirical gamma-gauche effect seems likely to provide the best rationalization for the relationship between C4 shifts and conformational order, taking into account the increased range of bond angles in disordered environments. The quantification of proportions of polymer units within different conformational groupings will provide new insights into the development of supramolecular texture. This will allow better appreciation of the relationships between fibre processing and ultimate fibre performance

Neoadjuvant Trastuzumab Emtansine and Pertuzumab in Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Three-Year Outcomes From the Phase III KRISTINE Study

PURPOSE: The KRISTINE study compared neoadjuvant trastuzumab emtansine plus pertuzumab (T-DM1+P) with docetaxel, carboplatin, trastuzumab plus P (TCH+P) for the treatment human epidermal growth factor receptor 2-positive stage II to III breast cancer. T-DM1+P led to a lower pathologic complete response rate (44.4% v 55.7%; P = .016), but fewer grade 3 or greater and serious adverse events (AEs). Here, we present 3-year outcomes from KRISTINE. METHODS: Patients were randomly assigned to neoadjuvant T-DM1+P or TCH+P every 3 weeks for six cycles. Patients who received T-DM1+P continued adjuvant T-DM1+P, and patients who received TCH+P received adjuvant trastuzumab plus pertuzumab. Secondary end points included event-free survival (EFS), overall survival, patient-reported outcomes (measured from random assignment), and invasive disease-free survival (IDFS; measured from surgery). RESULTS: Of patients, 444 were randomly assigned (T-DM1+P, n = 223; TCH+P, n = 221). Median follow-up was 37 months. Risk of an EFS event was higher with TDM-1+P (hazard ratio [HR], 2.61 [95% CI, 1.36 to 4.98]) with more locoregional progression events before surgery (15 [6.7%] v 0). Risk of an IDFS event after surgery was similar between arms (HR, 1.11 [95% CI, 0.52 to 2.40]). Pathologic complete response was associated with a reduced risk of an IDFS event (HR, 0.24 [95% CI, 0.09 to 0.60]) regardless of treatment arm. Overall, grade 3 or greater AEs (31.8% v 67.7%) were less common with T-DM1+P. During adjuvant treatment, grade 3 or greater AEs (24.5% v 9.9%) and AEs leading to treatment discontinuation (18.4% v 3.8%) were more common with T-DM1+P. Patient-reported outcomes favored T-DM1+P during neoadjuvant treatment and were similar to trastuzumab plus pertuzumab during adjuvant treatment. CONCLUSION: Compared with TCH+P, T-DM1+P resulted in a higher risk of an EFS event owing to locoregional progression events before surgery, a similar risk of an IDFS event, fewer grade 3 or greater AEs during neoadjuvant treatment, and more AEs leading to treatment discontinuation during adjuvant treatment.status: publishe

COVID-19 In-Hospital Mortality in People with Diabetes Is Driven by Comorbidities and Age—Propensity Score-Matched Analysis of Austrian National Public Health Institute Data

Background: It is a matter of debate whether diabetes alone or its associated comorbidities are responsible for severe COVID-19 outcomes. This study assessed the impact of diabetes on intensive care unit (ICU) admission and in-hospital mortality in hospitalized COVID-19 patients. Methods: A retrospective analysis was performed on a countrywide cohort of 40,632 COVID-19 patients hospitalized between March 2020 and March 2021. Data were provided by the Austrian data platform. The association of diabetes with outcomes was assessed using unmatched and propensity-score matched (PSM) logistic regression. Results: 12.2% of patients had diabetes, 14.5% were admitted to the ICU, and 16.2% died in the hospital. Unmatched logistic regression analysis showed a significant association of diabetes (odds ratio [OR]: 1.24, 95% confidence interval [CI]: 1.15–1.34, p < 0.001) with in-hospital mortality, whereas PSM analysis showed no significant association of diabetes with in-hospital mortality (OR: 1.08, 95%CI: 0.97–1.19, p = 0.146). Diabetes was associated with higher odds of ICU admissions in both unmatched (OR: 1.36, 95%CI: 1.25–1.47, p < 0.001) and PSM analysis (OR: 1.15, 95%CI: 1.04–1.28, p = 0.009). Conclusions: People with diabetes were more likely to be admitted to ICU compared to those without diabetes. However, advanced age and comorbidities rather than diabetes itself were associated with increased in-hospital mortality in COVID-19 patients

Biomarkers Predictive for In-Hospital Mortality in Patients with Diabetes Mellitus and Prediabetes Hospitalized for COVID-19 in Austria: An Analysis of COVID-19 in Diabetes Registry

Background: This study assessed the predictive performance of inflammatory, hepatic, coagulation, and cardiac biomarkers in patients with prediabetes and diabetes mellitus hospitalized for COVID-19 in Austria. Methods: This was an analysis of a multicenter cohort study of 747 patients with diabetes mellitus or prediabetes hospitalized for COVID-19 in 11 hospitals in Austria. The primary outcome of this study was in-hospital mortality. The predictor variables included demographic characteristics, clinical parameters, comorbidities, use of medication, disease severity, and laboratory measurements of biomarkers. The association between biomarkers and in-hospital mortality was assessed using simple and multiple logistic regression analyses. The predictive performance of biomarkers was assessed using discrimination and calibration. Results: In our analysis, 70.8% had type 2 diabetes mellitus, 5.8% had type 1 diabetes mellitus, 14.9% had prediabetes, and 8.6% had other types of diabetes mellitus. The mean age was 70.3 ± 13.3 years, and 69.3% of patients were men. A total of 19.0% of patients died in the hospital. In multiple logistic regression analysis, LDH, CRP, IL-6, PCT, AST-ALT ratio, NT-proBNP, and Troponin T were significantly associated with in-hospital mortality. The discrimination of NT-proBNP was 74%, and that of Troponin T was 81%. The calibration of NT-proBNP was adequate (p = 0.302), while it was inadequate for Troponin T (p = 0.010). Conclusion: Troponin T showed excellent predictive performance, while NT-proBNP showed good predictive performance for assessing in-hospital mortality in patients with diabetes mellitus hospitalized with COVID-19. Therefore, these cardiac biomarkers may be used for prognostication of COVID-19 patients