Researching COVID to enhance recovery (RECOVER) tissue pathology study protocol: Rationale, objectives, and design.

IMPORTANCE: SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or organ dysfunction after the acute phase of infection, termed Post-Acute Sequelae of SARS-CoV-2 (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are poorly understood. The objectives of the Researching COVID to Enhance Recovery (RECOVER) tissue pathology study (RECOVER-Pathology) are to: (1) characterize prevalence and types of organ injury/disease and pathology occurring with PASC; (2) characterize the association of pathologic findings with clinical and other characteristics; (3) define the pathophysiology and mechanisms of PASC, and possible mediation via viral persistence; and (4) establish a post-mortem tissue biobank and post-mortem brain imaging biorepository. METHODS: RECOVER-Pathology is a cross-sectional study of decedents dying at least 15 days following initial SARS-CoV-2 infection. Eligible decedents must meet WHO criteria for suspected, probable, or confirmed infection and must be aged 18 years or more at the time of death. Enrollment occurs at 7 sites in four U.S. states and Washington, DC. Comprehensive autopsies are conducted according to a standardized protocol within 24 hours of death; tissue samples are sent to the PASC Biorepository for later analyses. Data on clinical history are collected from the medical records and/or next of kin. The primary study outcomes include an array of pathologic features organized by organ system. Causal inference methods will be employed to investigate associations between risk factors and pathologic outcomes. DISCUSSION: RECOVER-Pathology is the largest autopsy study addressing PASC among US adults. Results of this study are intended to elucidate mechanisms of organ injury and disease and enhance our understanding of the pathophysiology of PASC.

Vascular disorders in athletes.

Athletes rarely present with symptoms or clinical findings suggestive of vascular disease. However, vascular etiologies should be considered when an athlete complains of persistent symptoms which are refractory to conservative therapies commonly used for presumed musculoskeletal injuries. A comprehensive history should be performed, with special consideration to the postures the athlete assumes repeatedly during their chosen sport. Musculoskeletal anatomy surrounding the vascular bed of interest should be thoroughly reviewed. Physical examination should include provocative maneuvers specific to the suspected vascular disorder. The proper use of noninvasive diagnostic studies, including duplex ultrasonography, computerized tomography (CT), and magnetic resonance imaging (MRI), along with catheter-based angiography, when indicated, can ensure prompt diagnosis. Appropriate, multifaceted treatment of an athlete affected by a vascular disorder can facilitate an expeditious return to previous levels of activity.

Mechanical stress analysis of a rigid inclusion in distensible material: a model of atherosclerotic calcification and plaque vulnerability.

The role of atherosclerotic calcification in plaque rupture remains controversial. In previous analyses using finite element model analysis, circumferential stress was reduced by the inclusion of a calcium deposit in a representative human anatomical configuration. However, a recent report, also using finite element analysis, suggests that microscopic calcium deposits increase plaque stress. We used mathematical models to predict the effects of rigid and liquid inclusions (modeling a calcium deposit and a lipid necrotic core, respectively) in a distensible material (artery wall) on mechanical failure under uniaxial and biaxial loading in a range of configurations. Without inclusions, stress levels were low and uniform. In the analytical model, peak stresses were elevated at the edges of a rigid inclusion. In the finite element model, peak stresses were elevated at the edges of both inclusions, with minimal sensitivity to the wall distensibility and the size and shape of the inclusion. Presence of both a rigid and a soft inclusion enlarged the region of increased wall stress compared with either alone. In some configurations, the rigid inclusion reduced peak stress at the edge of the soft inclusion but simultaneously increased peak stress at the edge of the rigid inclusion and increased the size of the region affected. These findings suggest that the presence of a calcium deposit creates local increases in failure stress, and, depending on relative position to any neighboring lipid pools, it may increase peak stress and the plaque area at risk of mechanical failure.

Relation of brain natriuretic peptide to myocardial performance index in adults with congenital heart disease.

Myocardial performance index (MPI) is an echocardiographic Doppler-derived measure of ventricular function previously validated in patients with congenital heart disease. It may be preferred over conventional noninvasive measures of ventricular function in patients with complex anatomy because it is dependent on neither geometric shape nor heart rate. Brain natriuretic peptide (BNP) is a predictor of systolic and diastolic dysfunction in anatomically correct hearts. The correlation of BNP to MPI in patients with congenital heart disease was determined. Fifty-four adults with congenital heart disease were evaluated. BNP was measured using standardized assays. Doppler echocardiography was performed within 6 months of BNP assay. There were no changes in clinical status during this interval. An experienced observer was blinded and evaluated all echocardiographic images, and MPI and ejection fraction (EF) were determined. Left ventricular (LV) or univentricular MPI was calculated in 34 patients and right ventricular (RV) MPI was calculated in 23 patients. Pearson's correlation coefficient test showed that BNP significantly correlated with LV/univentricular MPI (r = 0.461, p = 0.006) and RV MPI (r = 0.748, p <0.0001), whereas LV/univentricular EF and RVEF had no significant correlation with BNP (r = -0.189, p = 0.172; r = 0.066, p = 0.729, respectively). In patients with congenital heart disease, BNP correlated significantly with MPI, but not with LV, RV, or univentricular EF. This is particularly true in patients with geometrically variable right ventricles in which EF may be more difficult to assess. In conclusion, these findings emphasize the unique ability of both BNP and MPI to assess global ventricular function in geometrically complex hearts.

Do patients understand their physician's level of training? a survey of emergency department patients.

PURPOSE: To assess patients' understanding of levels of training and responsibilities for residents, medical students, and attendings in the emergency department as well as their degree of comfort in being cared for by a physician-in-training. METHOD: In 1999, a questionnaire was administered to a convenience sample of 430 adult patients and family members in a university emergency department. The questionnaire asked for demographic information and contained 17 questions addressing the different levels of medical training and seven opinion-based questions on patients' willingness to have physicians-in-training care for them. RESULTS: Respondents answered 65% of the knowledge-based questions about physicians' training correctly. Only 43% understood that residents are always supervised when caring for patients, and 30% thought attendings required supervision by a resident. Respondents with education greater than a high school diploma answered more questions correctly (71% versus 59%; p <.05). A total of 80% felt it was very important to know their physician's level of training, but only 58% reported actually knowing the level of training. Only 62% felt comfortable knowing that their physician might be a supervised physician-in-training. In addition, despite the fact that this survey took place at a teaching hospital, 22% of respondents prefer not to be treated in a teaching hospital. CONCLUSIONS: Patients and their families do not fully understand the roles and responsibilities of the physicians-in-training that may be caring for them despite feeling it is important to know their physicians' level of training.