Development of Potent Cellular and Humoral Immune Responses in Long-Term Hemodialysis Patients After 1273-mRNA SARS-CoV-2 Vaccination

Long-term hemodialysis (HD) patients are considered vulnerable and at high-risk of developing severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection due to their immunocompromised condition. Since COVID-19 associated mortality rates are higher in HD patients, vaccination is critical to protect them. The response towards vaccination against COVID-19 in HD patients is still uncertain and, in particular the cellular immune response is not fully understood. We monitored the humoral and cellular immune responses by analysis of the serological responses and Spike-specific cellular immunity in COVID-19-recovered and naïve HD patients in a longitudinal study shortly after vaccination to determine the protective effects of 1273-mRNA vaccination against SARS-CoV-2 in these high-risk patients. In naïve HD patients, the cellular immune response measured by IL-2 and IFN-ɣ secretion needed a second vaccine dose to significantly increase, with a similar pattern for the humoral response. In contrast, COVID-19 recovered HD patients developed a potent and rapid cellular and humoral immune response after the first vaccine dose. Interestingly, when comparing COVID-19 recovered healthy volunteers (HV), previously vaccinated with BNT162b2 vaccine to HD patients vaccinated with 1273-mRNA, these exhibited a more robust immune response that is maintained longitudinally. Our results indicate that HD patients develop strong cellular and humoral immune responses to 1273-mRNA vaccination and argue in favor of personalized immune monitoring studies in HD patients, especially if COVID-19 pre-exposed, to adapt COVID-19 vaccination protocols for this immunocompromised population.Funding was obtained from Instituto de Salud Carlos III (ISCIII) RICORS program to RICORS2040 (RD21/0005/0001), FEDER funds; Acción Estratégica en Salud Intramural (AESI), Instituto de Salud Carlos III, grant number AESI PI21CIII_00022 to PP and Healthstar-plus -REACT-UE Grant through Segovia Arana Research Institute Puerta de Hierro Majadahonda-IDIPHIM. JO is a member of VACCELERATE (European Corona Vaccine Trial Accelerator Platform) Network, which aims to facilitate and accelerate the design and implementation of COVID-19 phase 2 and 3 vaccine trials. JO is a member of the INsTRuCT under the MSC grant agreement Nº860003 (Innovative Training in Myeloid Regulatory Cell Therapy) Consortium, a network of European scientists from academia and industry focused on developing innovative immunotherapies.S

Use of Different Food Classification Systems to Assess the Association between Ultra-Processed Food Consumption and Cardiometabolic Health in an Elderly Population with Metabolic Syndrome (PREDIMED-Plus Cohort)

The PREDIMED-Plus trial was supported by the European Research Council (Advanced Research grant 2014–2019; agreement #340918; granted to M.Á.M.-G.); the official Spanish institutions for funding scientific biomedical research, CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN) and Instituto de Salud Carlos III (ISCIII) through the Fondo de Investigación para la Salud (FIS) which is co-funded by the European Regional Development Fund (coordinated FIS projects led by J.S-S. and J.V., including the following projects: PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI14/00972, PI14/00728, PI14/01471, PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441, PI17/00508, PI17/01732, PI17/00926, PI19/00957, PI19/00386, PI19/00309, PI19/01032, PI19/00576, PI19/00017, PI19/01226, PI19/00781, PI19/01560, PI19/01332), and the Especial Action Project “Implementación y evaluación de una intervención intensiva sobre la actividad física Cohorte PREDIMED-Plus” (J.S.-S.); the Recercaixa (grant number 2013ACUP00194) (J.S.-S.). Moreover, J.S-S. gratefully acknowledges the financial support by ICREA under the ICREA Academia program; the SEMERGEN grant; Department of Health of the Government of Navarra (61/2015), the Fundació La Marató de TV (Ref. 201630.10); the AstraZeneca Young Investigators Award in Category of Obesity and T2D 2017 (D.R.); grants from the Consejería de Salud de la Junta de Andalucía (PI0458/2013; PS0358/2016; PI0137/2018), the PROMETEO/2017/017 grant from the Generalitat Valenciana, the SEMERGEN grant; grant of support to research groups 35/2011 (Balearic Islands Government; FEDER funds) (J.A.T.). R.S.-C. acknowledges financial support from the Juan de la Cierva Program Training Grants of the Spanish State Research Agency of the Spanish Ministerio de Ciencia e Innovación y Ministerio de Universidades (FJC2018-038168- I). N.B.-T. acknowledges financial support from the Juan de la Cierva Formación Program Training Grants of the Spanish State Research Agency of the Spanish Ministerio de Ciencia e Innovación y Ministerio de Universidades (FJC2018-036016-I). M.R.B.-L. was supported by “Miguel Servet Type I” program (CP15/00028) from the ISCIII-Madrid (Spain), cofinanced by the Fondo Europeo de Desarrollo Regional-FEDER. S.K.N. acknowledges financial support from the Canadian Institute for Health Research, CIHR Fellowship. J.K. was supported by the ‘FOLIUM’ programme within the FUTURMed project from the Fundación Instituto de Investigación Sanitaria Illes Balears (financed by 2017 annual plan of the sustainable tourism tax and at 50% with charge to the ESF Operational Program 2014–2020 of the Balearic Islands. C.M.-P. was financially supported by a joint grant from the Community of Madrid and the European Social Fund (grant PEJD-2019- POST/SAL-15892). The METHYL-UP project was supported by the Spanish Ministry of Science and Innovation (RTI2018-095569-B-I00, Programa de Proyectos Orientados a los Retos de la Sociedad “Projects Toward Society Challenges Program”).The association between ultra-processed food (UPF) and risk of cardiometabolic disorders is an ongoing concern. Different food processing-based classification systems have originated discrepancies in the conclusions among studies. To test whether the association between UPF consumption and cardiometabolic markers changes with the classification system, we used baseline data from 5636 participants (48.5% female and 51.5% male, mean age 65.1 4.9) of the PREDIMEDPlus (“PREvention with MEDiterranean DIet”) trial. Subjects presented with overweight or obesity and met at least three metabolic syndrome (MetS) criteria. Food consumption was classified using a 143-item food frequency questionnaire according to four food processing-based classifications: NOVA, International Agency for Research on Cancer (IARC), International Food Information Council (IFIC) and University of North Carolina (UNC). Mean changes in nutritional and cardiometabolic markers were assessed according to quintiles of UPF consumption for each system. The association between UPF consumption and cardiometabolic markers was assessed using linear regression analysis. The concordance of the different classifications was assessed with intra-class correlation coefficients (ICC3, overall = 0.51). The highest UPF consumption was obtained with the IARC classification (45.9%) and the lowest with NOVA (7.9%). Subjects with high UPF consumption showed a poor dietary profile. We detected a direct association between UPF consumption and BMI (p = 0.001) when using the NOVA system, and with systolic (p = 0.018) and diastolic (p = 0.042) blood pressure when using the UNC system. Food classification methodologies markedly influenced the association between UPF consumption and cardiometabolic risk markers.European Research Council (ERC) European Commission #340918Centro de Investigacion Biomedica en Red-Fisiopatologia de la Obesidad y Nutricion PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441 PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI14/00972, PI14/00728, PI14/01471 PI17/00508, PI17/01732, PI17/00926, PI19/00957, PI19/00386, PI19/00309, PI19/01032, PI19/00576, PI19/00017, PI19/01226, PI19/00781, PI19/01560, PI19/0133

Development and validation of a score to predict postoperative respiratory failure in a multicentre European cohort : A prospective, observational study

BACKGROUND Postoperative respiratory failure (PRF) is the most frequent respiratory complication following surgery. OBJECTIVE The objective of this study was to build a clinically useful predictive model for the development of PRF. DESIGN A prospective observational study of a multicentre cohort. SETTING Sixty-three hospitals across Europe. PATIENTS Patients undergoing any surgical procedure under general or regional anaesthesia during 7-day recruitment periods. MAIN OUTCOME MEASURES Development of PRF within 5 days of surgery. PRF was defined by a partial pressure of oxygen in arterial blood (PaO2) less than 8 kPa or new onset oxyhaemoglobin saturation measured by pulse oximetry (SpO(2)) less than 90% whilst breathing room air that required conventional oxygen therapy, noninvasive or invasive mechanical ventilation. RESULTS PRF developed in 224 patients (4.2% of the 5384 patients studied). In-hospital mortality [95% confidence interval (95% CI)] was higher in patients who developed PRF [10.3% (6.3 to 14.3) vs. 0.4% (0.2 to 0.6)]. Regression modelling identified a predictive PRF score that includes seven independent risk factors: low preoperative SpO(2); at least one preoperative respiratory symptom; preoperative chronic liver disease; history of congestive heart failure; open intrathoracic or upper abdominal surgery; surgical procedure lasting at least 2 h; and emergency surgery. The area under the receiver operating characteristic curve (c-statistic) was 0.82 (95% CI 0.79 to 0.85) and the Hosmer-Lemeshow goodness-of-fit statistic was 7.08 (P = 0.253). CONCLUSION A risk score based on seven objective, easily assessed factors was able to predict which patients would develop PRF. The score could potentially facilitate preoperative risk assessment and management and provide a basis for testing interventions to improve outcomes. The study was registered at ClinicalTrials.gov (identifier NCT01346709)

BJS commission on surgery and perioperative care post-COVID-19

Coronavirus disease 2019 (COVID-19) was declared a pandemic by the WHO on 11 March 2020 and global surgical practice was compromised. This Commission aimed to document and reflect on the changes seen in the surgical environment during the pandemic, by reviewing colleagues' experiences and published evidence

BJS commission on surgery and perioperative care post-COVID-19

Background: Coronavirus disease 2019 (COVID-19) was declared a pandemic by the WHO on 11 March 2020 and global surgical practice was compromised. This Commission aimed to document and reflect on the changes seen in the surgical environment during the pandemic, by reviewing colleagues experiences and published evidence. Methods: In late 2020, BJS contacted colleagues across the global surgical community and asked them to describe how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had affected their practice. In addition to this, the Commission undertook a literature review on the impact of COVID-19 on surgery and perioperative care. A thematic analysis was performed to identify the issues most frequently encountered by the correspondents, as well as the solutions and ideas suggested to address them. Results: BJS received communications for this Commission from leading clinicians and academics across a variety of surgical specialties in every inhabited continent. The responses from all over the world provided insights into multiple facets of surgical practice from a governmental level to individual clinical practice and training. Conclusion: The COVID-19 pandemic has uncovered a variety of problems in healthcare systems, including negative impacts on surgical practice. Global surgical multidisciplinary teams are working collaboratively to address research questions about the future of surgery in the post-COVID-19 era. The COVID-19 pandemic is severely damaging surgical training. The establishment of a multidisciplinary ethics committee should be encouraged at all surgical oncology centres. Innovative leadership and collaboration is vital in the post-COVID-19 era

Kidney and Cardiovascular Effects of Canagliflozin According to Age and Sex: A Post Hoc Analysis of the CREDENCE Randomized Clinical Trial

Rationale & Objective: It is unclear whether the effect of canagliflozin on adverse kidney and cardiovascular events in those with diabetic kid-ney disease varies by age and sex. We assessed the effects of canagliflozin among age group categories and between sexes in the Canagli-flozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study.Study Design: Secondary analysis of a random-ized controlled trial. Setting & Participants: Participants in the CREDENCE trial. Intervention: Participants were randomly assigned to receive canagliflozin 100 mg/d or placebo.Outcomes: Primary composite outcome of kid-ney failure, doubling of serum creatinine con-centration, or death due to kidney or cardiovascular disease. Prespecified secondary and safety outcomes were also analyzed. Out-comes were evaluated by age at baseline (<60, 60-69, and >_70 years) and sex in the intention-to-treat population using Cox regression models.Results: The mean age of the cohort was 63.0 & PLUSMN; 9.2 years, and 34% were female. Older age and female sex were independently associ-ated with a lower risk of the composite of adverse kidney outcomes. There was no evidence that the effect of canagliflozin on the primary outcome (acomposite of kidney failure, a doubling of serum creatinine concentration, or death from kidney or cardiovascular causes) differed between age groups (HRs, 0.67 [95% CI, 0.52-0.87], 0.63 [0.4 8-0.82], and 0.89 [0.61-1.29] for ages <60, 60-69, and >_70 years, respectively; P = 0.3 for interaction) or sexes (HRs, 0.71 [95% CI, 0.5 4-0.95] and 0.69 [0.56-0.8 4] in women and men, respectively; P = 0.8 for interaction). No differences in safety outcomes by age group or sex were observed.Limitations: This was a post hoc analysis with multiple comparisons.Conclusions: Canagliflozin consistently reduced the relative risk of kidney events in people with diabetic kidney disease in both sexes and across age subgroups. As a result of greater background risk, the absolute reduction in adverse kidney outcomes was greater in younger participants.Funding: This post hoc analysis of the CREDENCE trial was not funded. The CREDENCE study was sponsored by Janssen Research and Development and was conducted collaboratively by the sponsor, an academic-led steering committee, and an academic research organization, George Clinical.Trial Registration: The original CREDENCE trial was registered at ClinicalTrials.gov with study number NCT02065791

Effect of SGLT2 Inhibitors on Stroke and Atrial Fibrillation in Diabetic Kidney Disease: Results From the CREDENCE Trial and Meta-Analysis

BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus.METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-analysis.RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (<45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]).CONCLUSIONS: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02065791