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Rationale: Alveolar and endothelial injury may be differentially associated with coronavirus disease (COVID-19) severity over time. Objectives: To describe alveolar and endothelial injury dynamics and associations with COVID-19 severity, cardiorenovascular injury, and outcomes. Methods: This single-center observational study enrolled patients with COVID-19 requiring respiratory support at emergency department presentation. More than 40 markers of alveolar (including receptor for advanced glycation endproducts [RAGE]), endothelial (including angiopoietin-2), and cardiorenovascular injury (including renin, kidney injury molecule-1, and troponin-I) were serially compared between invasively and spontaneously ventilated patients using mixed-effects repeated-measures models. Ventilatory ratios were calculated for intubated patients. Associations of biomarkers with modified World Health Organization scale at Day 28 were determined with multivariable proportional-odds regression. Measurements and Main Results: Of 225 patients, 74 (33%) received invasive ventilation at Day 0. RAGE was 1.80-fold higher in invasive ventilation patients at Day 0 (95% confidence interval [CI], 1.50-2.17) versus spontaneous ventilation, but decreased over time in all patients. Changes in alveolar markers did not correlate with changes in endothelial, cardiac, or renal injury markers. In contrast, endothelial markers were similar to lower at Day 0 for invasive ventilation versus spontaneous ventilation, but then increased over time only among intubated patients. In intubated patients, angiopoietin-2 was similar (fold difference, 1.02; 95% CI, 0.89-1.17) to nonintubated patients at Day 0 but 1.80-fold higher (95% CI, 1.56-2.06) at Day 3; cardiorenovascular injury markers showed similar patterns. Endothelial markers were not consistently associated with ventilatory ratios. Endothelial markers were more often significantly associated with 28-day outcomes than alveolar markers. Conclusions: Alveolar injury markers increase early. Endothelial injury markers increase later and are associated with cardiorenovascular injury and 28-day outcome. Alveolar and endothelial injury likely contribute at different times to disease progression in severe COVID-19.
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Células Epiteliais Alveolares , COVID-19/fisiopatologia , Endotélio/lesões , Gravidade do Paciente , Alvéolos Pulmonares/lesões , Síndrome do Desconforto Respiratório/fisiopatologia , Adulto , Idoso , Biomarcadores/análise , Resultados de Cuidados Críticos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema Renina-Angiotensina , Respiração Artificial , SARS-CoV-2RESUMO
BACKGROUND: Three-dimensional (3D) preoperative planning software for reverse total shoulder arthroplasty (rTSA) has been implemented in recent years in order to increase accuracy, improve efficiency, and add value to the outcome. A comprehensive literature review is required to determine the utility of preoperative 3D planning software in guiding orthopedic surgeons for implant placement in rTSA. We hypothesize that implementation of 3D preoperative planning software in the setting of rTSA leads to high concordance with minimal deviation from the preoperative plan. METHODS: A comprehensive and iterative literature review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) using the PubMed, Embase, OVID Medline, Scopus, Cinahl, Web of Science, and Cochrane databases for original English-language studies evaluating the impact of preoperative planning software usage on rTSA outcomes published from January 1, 2000, to present. Blinded reviewers conducted multiple screens. All included studies were graded based on level of evidence, and data concerning patient demographics and postoperative outcomes were extracted. RESULTS: Nine articles met inclusion criteria (1 level II, 3 level III, and 5 level IV articles), including 415 patients and 422 shoulders. Of the patients who underwent rTSA, 235 were female and 140 were male, although 3 studies (n = 40) did not report sex breakdowns for rTSA patients. The average age was 72.7 years. Four studies (79 shoulders) reported implant final position as mean deviation from planned version and planned inclination. Six studies (n = 236) reported screw angle deviation, fixation, length, and concordance. Concordance with the preoperative plan was measured in 3 studies (n = 178), resulting in complete concordance of 90% (n = 100), arthroplasty type concordance (rTSA vs. TSA) of 100% (n = 100), and glenosphere size concordance between 93% (n = 100) and 88% (n = 76). For screw length concordance, baseplate screw matched by 81% (n = 76) and 100% (n = 2), and upper (n = 35) and lower (n = 35) screw length concordance was observed as 74% and 69%, respectively. The use of preoperative planning (n = 178) was associated with low deviation from preoperative plan, more 2-screw fixations, and longer average screw length in comparison with an unplanned cohort. CONCLUSION: The use of preoperative planning software in the setting of rTSA results in minimal deviation from preoperative plan. High levels of concordance in screw angle, screw length, and glenosphere size were observed. Further prospective studies should be conducted to further substantiate these results.
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Artroplastia do Ombro , Articulação do Ombro , Prótese de Ombro , Idoso , Artroplastia , Artroplastia do Ombro/métodos , Feminino , Humanos , Masculino , Estudos Prospectivos , Articulação do Ombro/diagnóstico por imagem , Articulação do Ombro/cirurgia , SoftwareRESUMO
BACKGROUND: Fractures are a common pediatric injury. The coronavirus disease 2019 (COVID-19) pandemic resulted in significant changes in daily life that could impact the incidence of pediatric fractures. The purpose of this study was to compare the incidence of pediatric fractures in the United States during the COVID-19 pandemic to previous seasonally adjusted fracture incidence rates using the National Electronic Injury Surveillance System (NEISS) database and the American Community Survey (ACS). METHODS: The NEISS database was queried from 2016 to 2020 for fractures occurring in pediatric (0 to 17 y) patients. ACS population data allowed for the estimation of fracture incidence per 1000 person-years. Using a quasiexperimental interrupted time series design, Poisson regression models were constructed to test the overall and differential impact of COVID-19 on monthly fracture rate by age, sex, fracture site, injury location, and disposition. RESULTS: Our sample consisted of 121,803 cases (mean age 9.6±4.6 y, 36.1% female) representing 2,959,421±372,337 fractures nationally. We identified a stable 27% decrease in fractures per month after February 2020 [risk difference (RD) per 1000 youth years=-2.3; 95% confidence interval: -2.98, -1.57]). We found significant effect modification by age, fracture site and injury location ( P <0.05). The fracture incidence among children 5 years or older significantly decreased, as well as the incidence of fractures at school [RD=-0.96 (-1.09, -0.84)] and during sports [risk difference=-1.55 (-1.77, -1.32)]. There was also a trend toward a reduction in upper extremity fractures and fractures requiring admission. CONCLUSION: A nationally representative injury database demonstrated a 27% decline in monthly pediatric fractures during the COVID-19 pandemic that persisted into the latter half of 2020. These trends appeared most attributable to a reduction in fractures discharged home and upper extremity fractures among older children sustained at school and in sports. Our findings provide unique insight into the epidemiology of pediatric fractures and demonstrate a baseline need for musculoskeletal care among young children even in the setting of a national shutdown. LEVEL OF EVIDENCE: Level II-retrospective prognostic study.
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COVID-19 , Fraturas Ósseas , Adolescente , COVID-19/epidemiologia , Criança , Pré-Escolar , Serviço Hospitalar de Emergência , Feminino , Fraturas Ósseas/epidemiologia , Humanos , Incidência , Masculino , Pandemias , Estudos Retrospectivos , Estados Unidos/epidemiologiaRESUMO
Background: Glenohumeral osteophytes (OPs) can adversely influence postoperative range of motion (ROM) following shoulder arthroplasty due to mechanical impingement. Though commercial three-dimensional preoperative planning software (3D PPS) is available to simulate ROM before and after OP resection, little is known about the magnitude of effect OPs and their subsequent removal have on simulated glenohumeral ROM. Methods: Included patients were 1) indicated for reverse total shoulder arthroplasty (rTSA) using 3D PPS and 2) presented with glenoid and/or humeral head OPs on preoperative two-dimensional computed tomography (2D-CT) imaging. Thirty patients met the inclusion criteria (9 females, 21 males; mean age 70.45 ± 4.99 years, range 63-80 years). All subjects (n = 30) presented with humeral OPs (mean volume: 2905.16 mm3, range 109.1-11,246 mm3), while 11 subjects also presented with glenoid OPs (mean volume 108.06 mm3, range 37.59-791.4 mm3). Preoperative CTs were used to calculate OP volume (mm3) and OP circumferential extent (clockface). Mean clockface position for circumferential humeral OPs originated at 6:09 (range 4:30-7:15) and extended to 8:51 (range 8:15-10:15). Mean clockface position for glenoid OPs originated at 3:00 (range 2:00-5:00) and extended to 6:16 (range 3:00-7:30). 3D implants on PPS were standardized to achieve 0° of version, 0° of inclination and 4 mm of net lateralization. Thirty-nine and thirty-six mm glenospheres were used for males and females, respectively. 3D PPS was used to evaluate simulated ROM differences before and after OP removal in the planes of adduction (ADD), abduction, internal rotation (IR), external rotation (ER), extension, and flexion. Impact of OP volume and circumferential extent on pre and postop removal ROM were also analyzed. Results: Humeral OP removal significantly increased impingement-free ADD, IR, ER, extension, and flexion. Removal of larger (mm3) humeral OPs positively correlated with improvement in IR (R = 0.452, P = .011), ER (R = 0.394, P = .033), and flexion (R = 0.500, P < .01). Greater circumferential extent of humeral OPs correlated with worse preremoval ROM in the planes of ADD (R = 0.364, P = .02) and extension (R = 0.403, P = .04), and improvements in ER postop removal (R = 0.431, P = .03). Conclusion: Humeral OP removal significantly increases impingement-free ADD, IR, ER, extension, and flexion in simulated 3D PPS models following rTSA. Magnitude of simulated ROM improvement is influenced by initial humeral OP volume and circumferential clockface extent. Surgeons should consider these effects when using 3D PPS for rTSA planning to optimize postoperative ROM prognostics.
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Anterior cruciate ligament (ACL) injuries rarely occur as an isolated event and often include associated meniscal, subchondral bone, and collateral ligament injuries. Concomitant pathology frequently complicates primary and revision ACL reconstruction and must be addressed to ensure comprehensive diagnosis and treatment. In this Technical Note, we describe our method for treatment of complex knee instability following multiple failed ACL reconstruction using a multiligament reconstruction technique with an osteochondral allograft transplantation to the lateral femoral condyle. This comprehensive repair technique restores the anatomic load bearing forces of the cruciate and collateral ligaments and promotes biological repair through incorporation of cartilage resurfacing to ultimately achieve optimal kinematics of the knee joint.
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Traditionally, total shoulder arthroplasty is performed using a deltopectoral approach through which the glenohumeral joint is accessed by mobilization of the subscapularis. Despite several variations on the subscapularis management techniques, postoperative complications, including subscapularis deficiency and lower functional outcomes, remain an area for improvement. The purpose of this Technical Note is to describe in detail our technique for management of the subscapularis in the setting of a stemless humeral implant through which the repair is planned and almost entirely performed at the beginning of the case, prior to the subscapularis peel. This technique aims to improve outcomes after total shoulder arthroplasty by 1) avoiding the anatomic implant with anchor drilling, 2) improving procedure efficiency, and 3) anatomically "repairing" the subscapularis prior to takedown by placing anchors exactly at the repair-tension site.
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Background and hypothesis: The impact of preoperative fatty infiltration of specific rotator cuff muscles on the outcomes of reverse total shoulder arthroplasty (rTSA) has not been well defined. Preoperative fatty infiltration of the shoulder musculature will negatively affect rTSA outcomes. Methods: A comprehensive literature review was conducted as per the Preferred Reporting Items for Systematic Reviews and Meta-analyses using PubMed, Embase, OVID Medline, Scopus, Cinahl, Web of Science, and Cochrane databases for original, English-language studies evaluating effect of fatty infiltration of shoulder musculature on rTSA outcomes published from January 1, 2000 to present. Blinded reviewers conducted multiple screens. All included studies were graded based on the level of evidence, and data concerning patient demographics and postoperative outcomes were extracted. Results: A total of 11 articles were included, including one level I article, three level III articles, and seven level IV articles. The review consisted of 720 patients and 731 shoulders (320 women and 157 men), with a mean age of 72.4 years. A single deltopectoral approach was performed for a majority of studies (627/731 shoulders), followed by a superolateral approach (70/731 shoulders) and a single transdeltoid approach (4/731 patients). Eleven studies reported data specifically about preoperative fatty infiltration of the rotator cuff musculature; the teres minor was studied most widely (298/731 shoulders), followed by the subscapularis (256/731 shoulders) and infraspinatus (232/731 shoulders). The Constant score (562/731 shoulders) and American Shoulder and Elbow Surgeons score (284/731 shoulders) were the most common recorded outcome scores. Fatty infiltration of the teres minor, supraspinatus, and infraspinatus was associated with worse range of motion after rTSA. Conclusion: Preoperative fatty infiltration of the rotator cuff, particularly of the teres minor and infraspinatus, has a negative impact on subjective patient outcomes and restoration of range of motion, especially external rotation, after rTSA. The impact of fatty infiltration of the other rotator cuff muscles remains unclear, which may be due to intersurgeon differences in the handling of the remaining rotator cuff muscles or differences in implant design. The evaluated literature provides information on which patients can be educated about probable outcomes and restoration of function after rTSA.
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BACKGROUNDSARS-CoV-2 plasma viremia has been associated with severe disease and death in COVID-19 in small-scale cohort studies. The mechanisms behind this association remain elusive.METHODSWe evaluated the relationship between SARS-CoV-2 viremia, disease outcome, and inflammatory and proteomic profiles in a cohort of COVID-19 emergency department participants. SARS-CoV-2 viral load was measured using a quantitative reverse transcription PCR-based platform. Proteomic data were generated with Proximity Extension Assay using the Olink platform.RESULTSThis study included 300 participants with nucleic acid test-confirmed COVID-19. Plasma SARS-CoV-2 viremia levels at the time of presentation predicted adverse disease outcomes, with an adjusted OR of 10.6 (95% CI 4.4-25.5, P < 0.001) for severe disease (mechanical ventilation and/or 28-day mortality) and 3.9 (95% CI 1.5-10.1, P = 0.006) for 28-day mortality. Proteomic analyses revealed prominent proteomic pathways associated with SARS-CoV-2 viremia, including upregulation of SARS-CoV-2 entry factors (ACE2, CTSL, FURIN), heightened markers of tissue damage to the lungs, gastrointestinal tract, and endothelium/vasculature, and alterations in coagulation pathways.CONCLUSIONThese results highlight the cascade of vascular and tissue damage associated with SARS-CoV-2 plasma viremia that underlies its ability to predict COVID-19 disease outcomes.FUNDINGMark and Lisa Schwartz; the National Institutes of Health (U19AI082630); the American Lung Association; the Executive Committee on Research at Massachusetts General Hospital; the Chan Zuckerberg Initiative; Arthur, Sandra, and Sarah Irving for the David P. Ryan, MD, Endowed Chair in Cancer Research; an EMBO Long-Term Fellowship (ALTF 486-2018); a Cancer Research Institute/Bristol Myers Squibb Fellowship (CRI2993); the Harvard Catalyst/Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, NIH awards UL1TR001102 and UL1TR002541-01); and by the Harvard University Center for AIDS Research (National Institute of Allergy and Infectious Diseases, 5P30AI060354).
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COVID-19/sangue , COVID-19/virologia , SARS-CoV-2 , Viremia/sangue , Viremia/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Coortes , Feminino , Interações entre Hospedeiro e Microrganismos , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Pandemias , Prognóstico , Proteoma/metabolismo , Proteômica , SARS-CoV-2/patogenicidade , SARS-CoV-2/fisiologia , Índice de Gravidade de Doença , Internalização do VírusRESUMO
The introduction of vaccines has inspired hope in the battle against SARS-CoV-2. However, the emergence of viral variants, in the absence of potent antivirals, has left the world struggling with the uncertain nature of this disease. Antibodies currently represent the strongest correlate of immunity against SARS-CoV-2, thus we profiled the earliest humoral signatures in a large cohort of acutely ill (survivors and nonsurvivors) and mild or asymptomatic individuals with COVID-19. Although a SARS-CoV-2specific immune response evolved rapidly in survivors of COVID-19, nonsurvivors exhibited blunted and delayed humoral immune evolution, particularly with respect to S2-specific antibodies. Given the conservation of S2 across ß-coronaviruses, we found that the early development of SARS-CoV-2specific immunity occurred in tandem with preexisting common ß-coronavirus OC43 humoral immunity in survivors, which was also selectively expanded in individuals that develop a paucisymptomatic infection. These data point to the importance of cross-coronavirus immunity as a correlate of protection against COVID-19.
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COVID-19/imunologia , Reações Cruzadas , Imunidade Humoral , SARS-CoV-2/imunologia , Adolescente , Estudos de Coortes , Coronavirus Humano OC43/imunologia , Progressão da Doença , Humanos , Switching de Imunoglobulina , Receptores Fc/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Sobreviventes , Adulto JovemRESUMO
Mechanisms underlying severe coronavirus disease 2019 (COVID-19) disease remain poorly understood. We analyze several thousand plasma proteins longitudinally in 306 COVID-19 patients and 78 symptomatic controls, uncovering immune and non-immune proteins linked to COVID-19. Deconvolution of our plasma proteome data using published scRNA-seq datasets reveals contributions from circulating immune and tissue cells. Sixteen percent of patients display reduced inflammation yet comparably poor outcomes. Comparison of patients who died to severely ill survivors identifies dynamic immune-cell-derived and tissue-associated proteins associated with survival, including exocrine pancreatic proteases. Using derived tissue-specific and cell-type-specific intracellular death signatures, cellular angiotensin-converting enzyme 2 (ACE2) expression, and our data, we infer whether organ damage resulted from direct or indirect effects of infection. We propose a model in which interactions among myeloid, epithelial, and T cells drive tissue damage. These datasets provide important insights and a rich resource for analysis of mechanisms of severe COVID-19 disease.