ImportanceSARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals.ObjectiveTo develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections.Design, Setting, and ParticipantsProspective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, and Puerto Rico. Participants who were enrolled in the RECOVER adult cohort before April 10, 2023, completed a symptom survey 6 months or more after acute symptom onset or test date. Selection included population-based, volunteer, and convenience sampling.ExposureSARS-CoV-2 infection.Main Outcomes and MeasuresPASC and 44 participant-reported symptoms (with severity thresholds).ResultsA total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios were 1.5 or greater (infected vs uninfected participants) for 37 symptoms. Symptoms contributing to PASC score included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 (10% [95% CI, 8.8%-11%]) were PASC positive at 6 months.Conclusions and RelevanceA definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC.
Background: Atrial fibrillation (AF) has been associated with myocardial oxidative stress, and antioxidant agents have demonstrated antiarrhythmic benefit in humans. We compared serum markers of oxidation and associated inflammation in individuals with or without AF. Methods: Serum markers of oxidative stress and inflammation were compared in a cross-sectional, case-control design study of 40 male individuals, with or without persistent or permanent AF, who were matched for age, sex, diabetes, and smoking status, known confounding variables for the measurement of oxidative stress. We used derivatives of reactive oxidative metabolites (DROMs) and ratios of oxidized to reduced glutathione (E h GSH) and cysteine (E h CySH) to quantify oxidative stress. We also measured inflammatory markers, including high-sensitivity C-reactive protein, interleukins 1 and 6, and tumor necrosis factor ␣. Results: Univariate, conditional logistical regression analysis showed that oxidative stress but not inflammatory markers were statistically associated with AF (P <0.05). The increase in the odds ratios for AF for E h GSH, E h CySH, and DROMs were 6.1 (95% CI, 1.3-28.3; P ؍ 0.02), 13.6 (95% CI, 2.5-74.1; P ؍ 0.01), and 15.9 (95% CI, 1.7-153.9; P ؍ 0.02), respectively. There was a stronger correlation between E h GSH and E h CySH (r ؍ 0.66) than between E h GSH and DROMs (r ؍ 0.41). In multivariate analysis corrected for statins and other AF
The bedrock of the Shin Pond and Stacyville quadrangles, northern Penobscot County, Maine, is formed by Cambrian(?) to Lower Devonian sedimentary and igneous rocks in the chlorite zone of regional metamorphism and the nonmetamorphosed Katahdin Quartz Monzonite. Complexly deformed slate, quartzite, and related rocks of the Lower Cambrian(?) Grand Pitch Formation are unconformably overlain by tuffaceous sandstone, tuff, and flows of the Lower or Middle Ordovician Shin Brook Formation in an anticlinorium in •the central part of the area. Ordovician greenstone, largely of extrusive origin, and the Middle Ordovician Wassataquoik Chert (new) lie on the eastern and southern flanks of the anticlinorium. The Rockabema Quartz Diorite, altered and locally sheared and mylonitized, intrudes the Grand Pitch Formation and the Ordovician greenstone. Upper Ordovician and Lower Silurian conglomerate on the northwestern flank of this anticlinorium and Lower Silurian conglomerate and sandstone on its southeastern flank were probably derived from an ancestral uplift in the position of the present structure. The presence of this anticlinorium throughout the Silurian is indicated by the contrast in facies of Silurian rocks on opposite flanks. Distinctive rocks on the northwest are calcareous siltstone, limestone, and volcanic rocks, whereas on the •southeast, noncalcareous slate and siltstone (A.llsbury Formation) predominate. Lower Devonian rocks, consisting of dark slate and siltstone of the Seboomook Formation and the thick-bedded Matagamon Sandstone, overlie Silurian rocks to the northwest of the anticlinorium, but not those to the southeast. The tectonic history of the area is complex. The Grand Pitch Formation was first deformed before the deposition of the Shin Brook Formation. This folding event, here named the Penobscot disturbance, probably affected a widespread area through Maine and southeastern Quebec. The ancestral anticlinorium of the Shin Pqnd-Stacyville area probably dates from the later Ordovician Taconic orogeny, as does the intrusion of the Rockabema Quartz Diorite. Acadian (Middle Devonian) orogeny considerably modified the central anticlinorium and the adjoining basins. A. complex pattern of folds and faults, including a large right-lateral strike-slip fault system along its southeastern flank, was formed during this event, and the area was regionally metamorphosed at the same time. The posttectonic Katahdin Quartz Monzonite, which has a wide bordering breccia in this area, cuts across all these structures and represents the final phase of Acadian o:r:ogeny.
While transfusion of red blood cells (RBCs) is effective at preventing morbidity and mortality in anemic patients, studies have indicated that some RBC components have functional defects (“RBC storage lesions”) that may actually cause adverse events when transfused. For example, in some studies patients transfused with RBCs stored >14 days have had statistically worse outcomes than those receiving “fresher” RBC units. Recipient-specific factors may also contribute to the occurrence of these adverse events. Unfortunately, these events have been difficult to investigate because up to now they have existed primarily as “statistical occurrences” of increased morbidity and mortality in large data sets. There are currently no clinical or laboratory methods to detect or study them in individual transfusion recipients. Herein, we propose a unifying hypothesis, centered on Insufficient NO Bio-Availability (INOBA), to explain the increased morbidity and mortality observed in some patients following RBC transfusion. In this model, variables associated with RBC units (storage time; 2,3-DPG concentration) and transfusion recipients (endothelial dysfunction) collectively lead to changes in NO levels in vascular beds. Under certain circumstances, these variables are “aligned” such that NO concentrations are markedly reduced, leading to vasoconstriction, decreased local blood flow and insufficient O2 delivery to end organs. Under these circumstances, the likelihood of morbidity and mortality escalates. If the key tenets of the INOBA hypothesis are confirmed, it may lead to improved transfusion methodologies including altered RBC storage/processing conditions, novel transfusion recipient screening methods, and improved RBC/recipient matching.
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