Neoadjuvant immunotherapy with nivolumab and ipilimumab induces major pathological responses in patients with head and neck squamous cell carcinoma.

Surgery for locoregionally advanced head and neck squamous cell carcinoma (HNSCC) results in 30‒50% five-year overall survival. In IMCISION (NCT03003637), a non-randomized phase Ib/IIa trial, 32 HNSCC patients are treated with 2 doses (in weeks 1 and 3) of immune checkpoint blockade (ICB) using nivolumab (NIVO MONO, n = 6, phase Ib arm A) or nivolumab plus a single dose of ipilimumab (COMBO, n = 26, 6 in phase Ib arm B, and 20 in phase IIa) prior to surgery. Primary endpoints are feasibility to resect no later than week 6 (phase Ib) and primary tumor pathological response (phase IIa).

Infection control in the intensive care unit: expert consensus statements for SARS-CoV-2 using a Delphi method.

During the current COVID-19 pandemic, health-care workers and uninfected patients in intensive care units (ICUs) are at risk of being infected with SARS-CoV-2 as a result of transmission from infected patients and health-care workers. In the absence of high-quality evidence on the transmission of SARS-CoV-2, clinical practice of infection control and prevention in ICUs varies widely. Using a Delphi process, international experts in intensive care, infectious diseases, and infection control developed consensus statements on infection control for SARS-CoV-2 in an ICU.

Adaptive Measurement of Change: A Novel Method to Reduce Respondent Burden and Detect Significant Individual-Level Change in Patient-Reported Outcome Measures.

Objective: To describe the adaptive measurement of change (AMC) as a means to identify psychometrically significant change in reported function of hospitalized patients and to reduce respondent burden on follow-up assessments.

Design: The AMC method uses multivariate computerized adaptive testing (CAT) and psychometric hypothesis tests based in item response theory to more efficiently measure intra-individual change using the responses of a single patient over 2 or more testing occasions. Illustrations of the utility of AMC in clinical care and estimates of AMC-based item reduction are provided using the Functional Assessment in Acute Care Multidimensional Computerized Adaptive Test (FAMCAT), a newly developed functional multidimensional CAT-based measurement of basic mobility, daily activities, and applied cognition.

Sleep apnea, coronary artery calcium density, and cardiovascular events: results from the Multi-Ethnic Study of Atherosclerosis.

Study Objectives: Evaluate the association between obstructive sleep apnea (OSA), coronary artery calcium (CAC) density, and cardiovascular events in the Multi-Ethnic Study of Atherosclerosis (MESA).

Methods: We analyzed 1,041 participants with nonzero CAC scores who had polysomnography and CAC density data from the fifth examination of the Multi-Ethnic Study of Atherosclerosis. OSA was defined as apnea-hypopnea index ≥ 15 events/h.

WSES/GAIS/SIS-E/WSIS/AAST global clinical pathways for patients with intra-abdominal infections.

Intra-abdominal infections (IAIs) are common surgical emergencies and have been reported as major contributors to non-trauma deaths in hospitals worldwide. The cornerstones of effective treatment of IAIs include early recognition, adequate source control, appropriate antimicrobial therapy, and prompt physiologic stabilization using a critical care environment, combined with an optimal surgical approach. Together, the World Society of Emergency Surgery (WSES), the Global Alliance for Infections in Surgery (GAIS), the Surgical Infection Society-Europe (SIS-E), the World Surgical Infection Society (WSIS), and the American Association for the Surgery of Trauma (AAST) have jointly completed an international multi-society document in order to facilitate clinical management of patients with IAIs worldwide building evidence-based clinical pathways for the most common IAIs.

Improvement in Kansas City Cardiomyopathy Questionnaire Scores After a Self-Care Intervention in Patients With Acute Heart Failure Discharged From the Emergency Department.

Background: We conducted a secondary analysis of changes in the Kansas City Cardiomyopathy Questionnaire (KCCQ)-12 over 30 days in a randomized trial of self-care coaching versus structured usual care in patients with acute heart failure who were discharged from the emergency department.

Methods: Patients in 15 emergency departments completed the KCCQ-12 at emergency department discharge and at 30 days. We compared change in KCCQ-12 scores between the intervention and usual care arms, adjusted for enrollment KCCQ-12 and demographic characteristics.

Defining variant-resistant epitopes targeted by SARS-CoV-2 antibodies: A global consortium study.

Antibody-based therapeutics and vaccines are essential to combat COVID-19 morbidity and mortality after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Multiple mutations in SARS-CoV-2 that could impair antibody defenses propagated in human-to-human transmission and spillover or spillback events between humans and animals. To develop prevention and therapeutic strategies, we formed an international consortium to map the epitope landscape on the SARS-CoV-2 spike protein, defining and structurally illustrating seven receptor binding domain (RBD)–directed antibody communities with distinct footprints and competition profiles.

The Un-meeting approach to stimulate collaborative adult learning: an application for clinical research professionals.

We used a Zoom Un-meeting as an educational approach to provide experienced clinical research professional (CRP) adult learners a collaborative learning space to learn more about current issues for academic medical center (AMC) clinical research workforce development and collaborate on solution finding. CRPs operationalize the conduct of clinical trials and represent a significant brain trust for the Clinical and Translational Science (CTSA) consortium hubs with their vast knowledge base, extensive experience, understanding of relevant institutional policy, organizational culture, and clinical research operations. Un-meetings are an intentionally organized and coordinated group activity that encourages participants to focus on a topic and incorporate an open flow of ideas through brainstorming and an open discussion format, setting the stage for future collaborative action.

Extending human healthspan and longevity: a symposium report.

For many years, it was believed that the aging process was inevitable and that age-related diseases could not be prevented or reversed. The geroscience hypothesis, however, posits that aging is, in fact, malleable and, by targeting the hallmarks of biological aging, it is indeed possible to alleviate age-related diseases and dysfunction and extend longevity. This field of geroscience thus aims to prevent the development of multiple disorders with age, thereby extending healthspan, with the reduction of morbidity toward the end of life.

The ASAS-OMERACT core domain set for axial spondyloarthritis.

Background: The current core outcome set for ankylosing spondylitis (AS) has had only minor adaptations since its development 20 years ago. Considering the significant advances in this field during the preceding decades, an update of this core set is necessary.

Objective: To update the ASAS-OMERACT core outcome set for AS into the ASAS-OMERACT core outcome set for axial spondyloarthritis (axSpA).

Effects of Levodopa Therapy on Cerebral Arteries and Perfusion in Parkinson's Disease Patients.

Background: Levodopa is the most-commonly used therapy for Parkinson's Disease (PD). Imaging findings show increased cerebral blood flow (CBF) response to levodopa, but the artery morphological change is less studied.

Purpose: To investigate the effect of levodopa on cerebral arteries and CBF.

Safety, Efficacy, and Pharmacodynamics of Tremelimumab Plus Durvalumab for Patients With Unresectable Hepatocellular Carcinoma: Randomized Expansion of a Phase I/II Study.

Purpose: This phase I/II study evaluated tremelimumab (anticytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody) and durvalumab (antiprogrammed death ligand-1 monoclonal antibody) as monotherapies and in combination for patients with unresectable hepatocellular carcinoma (HCC), including a novel regimen featuring a single, priming dose of tremelimumab (ClinicalTrials.gov identifier: NCT02519348).

Patients And Methods: Patients with HCC who had progressed on, were intolerant to, or refused sorafenib were randomly assigned to receive T300 + D (tremelimumab 300 mg plus durvalumab 1,500 mg [one dose each during the first cycle] followed by durvalumab 1,500 mg once every 4 weeks), durvalumab monotherapy (1,500 mg once every 4 weeks), tremelimumab monotherapy (750 mg once every 4 weeks [seven doses] and then once every 12 weeks), or T75 + D (tremelimumab 75 mg once every 4 weeks plus durvalumab 1,500 mg once every 4 weeks [four doses] followed by durvalumab 1,500 mg once every 4 weeks).

Improving the Delivery of Function-Directed Care During Acute Hospitalizations: Methods to Develop and Validate the Functional Assessment in Acute Care Multidimensional Computerized Adaptive Test (FAMCAT).

Objective: To (1) develop a patient-reported, multidomain functional assessment tool focused on medically ill patients in acute care settings; (2) characterize the measure's psychometric performance; and (3) establish clinically actionable score strata that link to easily implemented mobility preservation plans.

Design: This article describes the approach that our team pursued to develop and characterize this tool, the Functional Assessment in Acute Care Multidimensional Computer Adaptive Test (FAMCAT). Development involved a multistep process that included (1) expanding and refining existing item banks to optimize their salience for hospitalized patients; (2) administering candidate items to a calibration cohort; (3) estimating multidimensional item response theory models; (4) calibrating the item banks; (5) evaluating potential multidimensional computerized adaptive testing (MCAT) enhancements; (6) parameterizing the MCAT; (7) administering it to patients in a validation cohort; and (8) estimating its predictive and psychometric characteristics.

Response shift in patient-reported outcomes: definition, theory, and a revised model.

Purpose: The extant response shift definitions and theoretical response shift models, while helpful, also introduce predicaments and theoretical debates continue. To address these predicaments and stimulate empirical research, we propose a more specific formal definition of response shift and a revised theoretical model.

Methods: This work is an international collaborative effort and involved a critical assessment of the literature.

Crowdsourcing digital health measures to predict Parkinson's disease severity: the Parkinson's Disease Digital Biomarker DREAM Challenge.

Consumer wearables and sensors are a rich source of data about patients' daily disease and symptom burden, particularly in the case of movement disorders like Parkinson's disease (PD). However, interpreting these complex data into so-called digital biomarkers requires complicated analytical approaches, and validating these biomarkers requires sufficient data and unbiased evaluation methods. Here we describe the use of crowdsourcing to specifically evaluate and benchmark features derived from accelerometer and gyroscope data in two different datasets to predict the presence of PD and severity of three PD symptoms: tremor, dyskinesia, and bradykinesia.

End-of-treatment PET/CT predicts PFS and OS in DLBCL after first-line treatment: results from GOYA.

GOYA was a randomized phase 3 study comparing obinutuzumab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) vs standard-of-care rituximab plus CHOP in patients with previously untreated diffuse large B-cell lymphoma (DLBCL). This retrospective analysis of GOYA aimed to assess the association between progression-free survival (PFS) and overall survival (OS) with positron emission tomography (PET)-based complete response (CR) status. Overall, 1418 patients were randomly assigned to receive 8 21-day cycles of obinutuzumab (n = 706) or rituximab (n = 712) plus 6 or 8 cycles of CHOP.

Pragmatic Recommendations for the Management of Acute Respiratory Failure and Mechanical Ventilation in Patients with COVID-19 in Low- and Middle-Income Countries.

Management of patients with severe or critical COVID-19 is mainly modeled after care for patients with severe pneumonia or acute respiratory distress syndrome (ARDS) from other causes, and these recommendations are based on evidence that often originates from investigations in resource-rich intensive care units located in high-income countries. Often, it is impractical to apply these recommendations to resource-restricted settings, particularly in low- and middle-income countries (LMICs). We report on a set of pragmatic recommendations for acute respiratory failure and mechanical ventilation management in patients with severe/critical COVID-19 in LMICs.

Pragmatic Recommendations for Tracheostomy, Discharge, and Rehabilitation Measures in Hospitalized Patients Recovering From Severe COVID-19 in Low- and Middle-Income Countries.

New studies of COVID-19 are constantly updating best practices in clinical care. However, research mainly originates in resource-rich settings in high-income countries. Often, it is impractical to apply recommendations based on these investigations to resource-constrained settings in low- and middle-income countries (LMICs).

Pragmatic Recommendations for the Use of Diagnostic Testing and Prognostic Models in Hospitalized Patients with Severe COVID-19 in Low- and Middle-Income Countries.

Management of patients with severe or critical COVID-19 is mainly modeled after care of patients with severe pneumonia or acute respiratory distress syndrome from other causes. These models are based on evidence that primarily originates from investigations in high-income countries, but it may be impractical to apply these recommendations to resource-restricted settings in low- and middle-income countries (LMICs). We report on a set of pragmatic recommendations for microbiology and laboratory testing, imaging, and the use of diagnostic and prognostic models in patients with severe COVID-19 in LMICs.