Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2

Abstract: Although two-dose mRNA vaccination provides excellent protection against SARS-CoV-2, there is little information about vaccine efficacy against variants of concern (VOC) in individuals above eighty years of age1. Here we analysed immune responses following vaccination with the BNT162b2 mRNA vaccine2 in elderly participants and younger healthcare workers. Serum neutralization and levels of binding IgG or IgA after the first vaccine dose were lower in older individuals, with a marked drop in participants over eighty years old. Sera from participants above eighty showed lower neutralization potency against the B.1.1.7 (Alpha), B.1.351 (Beta) and P.1. (Gamma) VOC than against the wild-type virus and were more likely to lack any neutralization against VOC following the first dose. However, following the second dose, neutralization against VOC was detectable regardless of age. The frequency of SARS-CoV-2 spike-specific memory B cells was higher in elderly responders (whose serum showed neutralization activity) than in non-responders after the first dose. Elderly participants showed a clear reduction in somatic hypermutation of class-switched cells. The production of interferon-γ and interleukin-2 by SARS-CoV-2 spike-specific T cells was lower in older participants, and both cytokines were secreted primarily by CD4 T cells. We conclude that the elderly are a high-risk population and that specific measures to boost vaccine responses in this population are warranted, particularly where variants of concern are circulating

Quality Improvement in the Preoperative Evaluation:Accuracy of an Automated Clinical Decision Support System to Calculate CHA2DS2-VASc Scores

Background and Objectives: Clinical decision support systems are advocated to improve the quality and efficiency in healthcare. However, before implementation, validation of these systems needs to be performed. In this evaluation we tested our hypothesis that a computerized clinical decision support system can calculate the CHA2DS2-VASc score just as well compared to manual calculation, or even better and more efficiently than manual calculation in patients with atrial rhythm disturbances. Materials and Methods: In n = 224 patents, we calculated the total CHA2DS2-VASc score manually and by an automated clinical decision support system. We compared the automated clinical decision support system with manually calculation by physicians. Results: The interclass correlation between the automated clinical decision support system and manual calculation showed was 0.859 (0.611 and 0.931 95%-CI). Bland-Altman plot and linear regression analysis shows us a bias of −0.79 with limit of agreement (95%-CI) between 1.37 and −2.95 of the mean between our 2 measurements. The Cohen’s kappa was 0.42. Retrospective analysis showed more human errors than algorithmic errors. Time it took to calculate the CHA2DS2-VASc score was 11 s per patient in the automated clinical decision support system compared to 48 s per patient with the physician. Conclusions: Our automated clinical decision support system is at least as good as manual calculation, may be more accurate and is more time efficient

Fully automated postoperative ventilation in cardiac surgery patients: a randomised clinical trial

Background: Ensuring that lung-protective ventilation is achieved at scale is challenging in perioperative practice. Fully automated ventilation may be more effective in delivering lung-protective ventilation. Here, we compared automated lung-protective ventilation with conventional ventilation after elective cardiac surgery in haemodynamically stable patients. Methods: In this single-centre investigator-led study, patients were randomly assigned at the end of cardiac surgery to receive either automated (adaptive support ventilation) or conventional ventilation. The primary endpoint was the proportion of postoperative ventilation time characterised by exposure to predefined optimal, acceptable, and critical (injurious) ventilatory parameters in the first three postoperative hours. Secondary outcomes included severe hypoxaemia (SpO 2 <85%) and resumption of spontaneous breathing. Data are presented as mean (95% confidence intervals [CIs]). Results: We randomised 220 patients (30.4% females; age: 62–76 yr). Subjects randomised to automated ventilation (n=109) spent a 29.7% (95% CI: 22.1–37.4) higher mean proportion of postoperative ventilation time receiving optimal postoperative ventilation after surgery (P<0.001) compared with subjects receiving conventional postoperative ventilation (n=111). Automated ventilation also reduced the proportion of postoperative ventilation time that subjects were exposed to injurious ventilatory settings by 2.5% (95% CI: 1–4; P=0.003). Severe hypoxaemia was less likely in subjects randomised to automated ventilation (risk ratio: 0.26 [0.22–0.31]; P<0.01). Subjects resumed spontaneous breathing more rapidly when randomised to automated ventilation (hazard ratio: 1.38 [1.05–1.83]; P=0.03). Conclusions: Fully automated ventilation in haemodynamically stable patients after cardiac surgery optimised lung-protective ventilation during postoperative ventilation, with fewer episodes of severe hypoxaemia and an accelerated resumption of spontaneous breathing. Clinical trial registration: NCT03180203

Fully automated postoperative ventilation in cardiac surgery patients: a randomised clinical trial

Background: Ensuring that lung-protective ventilation is achieved at scale is challenging in perioperative practice. Fully automated ventilation may be more effective in delivering lung-protective ventilation. Here, we compared automated lung-protective ventilation with conventional ventilation after elective cardiac surgery in haemodynamically stable patients. Methods: In this single-centre investigator-led study, patients were randomly assigned at the end of cardiac surgery to receive either automated (adaptive support ventilation) or conventional ventilation. The primary endpoint was the proportion of postoperative ventilation time characterised by exposure to predefined optimal, acceptable, and critical (injurious) ventilatory parameters in the first three postoperative hours. Secondary outcomes included severe hypoxaemia (SpO2 <85%) and resumption of spontaneous breathing. Data are presented as mean (95% confidence intervals [CIs]). Results: We randomised 220 patients (30.4% females; age: 62–76 yr). Subjects randomised to automated ventilation (n=109) spent a 29.7% (95% CI: 22.1–37.4) higher mean proportion of postoperative ventilation time receiving optimal postoperative ventilation after surgery (P<0.001) compared with subjects receiving conventional postoperative ventilation (n=111). Automated ventilation also reduced the proportion of postoperative ventilation time that subjects were exposed to injurious ventilatory settings by 2.5% (95% CI: 1–4; P=0.003). Severe hypoxaemia was less likely in subjects randomised to automated ventilation (risk ratio: 0.26 [0.22–0.31]; P<0.01). Subjects resumed spontaneous breathing more rapidly when randomised to automated ventilation (hazard ratio: 1.38 [1.05–1.83]; P=0.03). Conclusions: Fully automated ventilation in haemodynamically stable patients after cardiac surgery optimised lung-protective ventilation during postoperative ventilation, with fewer episodes of severe hypoxaemia and an accelerated resumption of spontaneous breathing. Clinical trial registration: NCT03180203

The correlation of age with chemotherapy-induced ovarian function failure in breast cancer patients

PURPOSE: To assess the incidence of chemotherapy-induced ovarian function failure (COFF) based on estradiol and follicle stimulating hormone (FSH) monitoring in premenopausal women with hormone-receptor positive breast cancer treated with second and third generation (neo-)adjuvant chemotherapy. RESULTS: We identified 115 eligible women. Two years after start of chemotherapy, COFF was significantly more often present in women ≥ 40 years (85.6%) as compared to women < 40 years (8.7%). Only age was significantly associated with COFF two years after start of chemotherapy (HR 12.26; 95% CI 5.21–28.86). In 50% of the patients, premenopausal hormone levels were the first or only evidence of ovarian function recovery (OFR). MATERIALS AND METHODS: We included all premenopausal women with hormone-receptor positive breast cancer treated with anthracycline-based chemotherapy, with or without taxanes, in our university hospital in the Netherlands in the years 2005-2013. Patients were 3-monthly monitored for ovarian function. Cox proportional hazards model was used to determine the predictive impact of various parameters on the occurrence of COFF. CONCLUSIONS: After second- or third generation (neo-)adjuvant chemotherapy, COFF was still present in 8.7% of patients < 40 years after two years. FSH and estradiol monitoring may be relevant for those in whom ovarian function suppression is considered an additional effective endocrine treatment

The impact of high versus standard enteral protein provision on functional recovery following intensive care admission (PRECISE trial): study protocol for a randomized controlled, quadruple blinded, multicenter, parallel group trial in mechanically ventilated patients

Abstract Background Critically ill patients are subject to severe skeletal muscle wasting during intensive care unit (ICU) stay, resulting in impaired short- and long-term functional outcomes and health-related quality of life. Increased protein provision may improve functional outcomes in ICU patients by attenuating skeletal muscle breakdown. Supporting evidence is limited however and results in great variety in recommended protein targets. Methods The PRECISe trial is an investigator-initiated, bi-national, multi-center, quadruple-blinded randomized controlled trial with a parallel group design. In 935 patients, we will compare provision of isocaloric enteral nutrition with either a standard or high protein content, providing 1.3 or 2.0 g of protein/kg/day, respectively, when fed on target. All unplanned ICU admissions with initiation of invasive mechanical ventilation within 24 h of admission and an expected stay on ventilator support of at least 3 days are eligible. The study is designed to assess the effect of the intervention on functional recovery at 1, 3, and 6 months following ICU admission, including health-related quality of life, measures of muscle strength, physical function, and mental health. The primary endpoint of the trial is health-related quality of life as measured by the Euro-QoL-5D-5-level questionnaire Health Utility Score. Overall between-group differences will be assessed over the three time points using linear mixed-effects models. Discussion The PRECISe trial will evaluate the effect of protein on functional recovery including both patient-centered and muscle-related outcomes. Trial registration ClinicalTrials.gov Identifier: NCT04633421 . Registered on November 18, 2020. First patient in (FPI) on November 19, 2020. Expected last patient last visit (LPLV) in October 2023

Erratum to: Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) (Autophagy, 12, 1, 1-222, 10.1080/15548627.2015.1100356

non present