Outcomes of Hospitalised COVID-19 Patients Arriving With Hypoxic Respiratory Failure.

BACKGROUND: Hypoxia is a common complication seen in people with COVID-19 and can often be the presenting symptom. METHODS: Using a multi-centre observational database, we analysed 3,624 hospitalised COVID-19 PCR-positive patients at Methodist Health System, Dallas, Texas, USA from March 2020 to December 2020. We compared in-hospital death or hospice referral rates and major adverse cardiovascular events (MACE) between patients with four levels of oxygen (O2) requirements (0-1 L/min, 2-10 L/min, 11-20 L/min, 21-100 L/min). MACE included congestive heart failure (CHF) exacerbations, myocardial infarctions (MI), strokes, pulmonary embolism (PE) / deep venous thrombosis (DVT), and shock. Logistic regression analysis was used to determine comorbidities and demographics associated with mortality. Multinomial regression analysis was used to find which of these variables were associated with hypoxia. RESULTS: Patients who arrived needing 0-1 L/min of O2 had reduced risk of mortality compared to those requiring 2-10 L/min (OR=1.54, 95% CI=1.207-1.976, p<0.0001), 11-20 L/min (OR=4.55, 95% CI=3.169-6.547, p<0.0001), or 21-100 L/min (OR=12.06, 95% CI=8.548-17.016, p<0.0001). In addition, patients who arrived needing 0-1 L/min of O2 showed reduced risk of MACE compared to those requiring 2-10 L/min (OR=1.20, 95% CI=1.029-1.409, p<0.0001), 11-20 L/min (OR=2.76, 95% CI 2.06-3.696, p<0.0001), or 21-100 L/min (OR=6.74, 95% CI 4.966-9.155, p<0.0001). CONCLUSION: Hypoxia on arrival is associated with a significantly increased risk of mortality and MACE among hospitalised patients with COVID-19. This data will promote better prognostication and help reduce negative outcomes in an inpatient setting.

Variation in Consult and Referral Patterns for Facial Lacerations by Emergency Department Provider Type: A Retrospective Cohort Study.

INTRODUCTION: Facial lacerations are a common reason for emergency department (ED) visits in the U.S. Proper laceration repair is imperative as poor wound management can lead to functional and aesthetic impairment and significantly impact patient quality of life. For the best outcomes and long-term scar reduction, treatment by and follow-up with a plastic surgeon or facial trauma specialist is recommended. The present study examines variations in facial trauma specialist consultation and referral by ED provider type for adult patients at hospitals within a large rural South Dakota health system. METHODS: Records for patients above the age of 18 who received treatment for facial lacerations between January 1, 2017 and January 1, 2022 were retrospectively reviewed across multiple hospitals in South Dakota, spanning a large rural catchment area. Multivariable logistic regression and Fisher's exact test were performed to examine the relationship between ED provider type and the probability of receiving specialty consult and/or referral. RESULTS: One hundred fifty-four ED visits were included in the analysis. Among these patients, 53 received specialty consult and/or follow-up referral and 101 were treated without consult or referral. ED provider type was significantly associated with the probability of having a specialty consult (OR = 5.11, 95% CI [1.05, 24.96]). When the patients had a certified nurse practitioner (CNP) as their ED provider, they had a significantly higher chance (40%) of receiving specialist consultation. CONCLUSION: For patients presenting to the ED with facial lacerations, facial trauma specialist consultation and referral for follow up varies based on provider type. CNPs placed specialist consultations more often than other ED provider types.

Impact of a Quality Improvement Initiative on Medical Management of Veterans With Peripheral Artery Disease.

Guideline-directed medical therapy (GDMT) for peripheral artery disease (PAD) remains severely underused. Prevention of Amputation in Veterans Everywhere (PAVE) is a screening program designed to prevent or delay major lower extremity amputation. This study aimed to determine whether diagnosis of PAD through the PAVE program improves the prescription of GDMT in veterans with asymptomatic PAD. Patients enrolled into the PAVE program from our institution from 2020 to 2021 were included. Patients with an abnormal ankle-brachial index (ABI), defined as ABI <0.9 or >1.2, were selected for further analysis. Primary outcome was adherence to GDMT, following class I and class IIa recommendations. Secondary outcomes included changes in low-density lipoprotein (LDL), blood pressure, and hemoglobin A1c (HbA1c). A total of 6,313 patients were enrolled into the PAVE program between 2020 and 2021. Of these, 211 had abnormal ABI and were included in our analysis. With enrollment into PAVE, there was significant increase in the prescription of aspirin (74.4% vs 64.9%, p = 0.044) and statins (91.5% vs 82%, p = 0.006). The overall adherence to GDMT significantly increased (56.9% vs 38.9%, p <0.001). The number of patients needed to enroll in PAVE to improve GDMT adherence is 5.6 (95% confidence interval 3.6 to 12.3). Patients enrolled into PAVE program saw significant decreases in HbA1c, with mean decrease of 0.3 (p = 0.012) and a decrease in LDL, with a mean decrease of 6.2 (p = 0.01). In conclusion, enrollment into an amputation prevention program secondarily increased adherence to GDMT, driven by increases in the prescription of statins and aspirin, with resulting decreases in HbA1c and LDL.

Anticoagulation Use as an Independent Predictor of Mortality and Major Adverse Cardiovascular Events in Hospitalized COVID-19 Patients: A Multicenter Retrospective Analysis.

Background: Coronavirus disease 2019 (COVID-19) is associated with increased incidence of cardiac arrhythmias and thrombotic events. The adverse cardiovascular outcomes related to ambulatory anticoagulation (AC) therapy in COVID-19 patients are unknown. The goal of this study was to identify the effects of AC use in hospitalized COVID-19 patients. Methods: This is a multicenter, retrospective study that identified 2,801 hospitalized COVID-19 polymerase chain reaction (PCR)-positive patients admitted between March 2020 and July 2021. Of these, 375 (13.4%) were ambulatory AC users. Data were collected from the electronic health records of hospitalized patients. Mortality included in-hospital death and hospice referral. Major adverse cardiovascular events (MACEs) included acute heart failure (HF), myocardial infarction (MI), myocarditis, pulmonary embolism (PE), deep venous thrombosis (DVT), pericardial effusion, pericarditis, stroke, shock, and cardiac tamponade. A Chi-square test was used to analyze categorical variables, and multivariate logistic regression analysis was performed to account for comorbidities. Results: AC non-users exhibited a higher incidence of mortality than AC users (13.9% vs. 7.7%, P = 0.001). However, MACE incidence was higher in AC users than AC non-users (44.8% vs. 26.8%, P < 0.001). The higher MACE incidence was driven by higher rates of acute HF (8.3% vs. 2.5%, P < 0.001), MI (26.9% vs. 18.2%, P < 0.001), PE/DVT (16.3% vs. 2.7%, P < 0.001), pericardial effusion (1.6% vs. 0.5%, P = 0.025), and stroke (2.9% vs. 1.2%, P = 0.018). After multivariate logistic regression, MACE incidence remained higher (odds ratio (OR) = 1.61, 95% confidence interval (CI): 1.27 - 2.05, P < 0.001) and all-cause mortality rate lower (OR = 0.34, 95% CI: 0.23 - 0.52, P < 0.001) in AC users. Conclusions: Ambulatory AC use is associated with increased MACEs but decreased all-cause mortality in patients hospitalized with COVID-19. This study will help physicians identify patients at risk of cardiovascular mortality and direct management based on the identified risk.

Mortality and Major Adverse Cardiovascular Events in Hospitalized Patients With Atrial Fibrillation With COVID-19.

COVID-19 results in increased incidence of cardiac arrhythmias, including atrial fibrillation (AF). However, little is known about the combined effect of AF and COVID-19 on patient outcomes. This study aimed to determine if AF, specifically new-onset AF (NOAF), is associated with increased risk of mortality and major adverse cardiovascular events (MACEs) in hospitalized patients with COVID-19. This multicenter retrospective analysis identified 2,732 patients with COVID-19 admitted between March and December 2020. Data points were manually reviewed in the patients' electronic health records. Multivariate logistic regression was used to assess if AF was associated with death or MACE. Patients with AF (6.4%) had an increased risk of mortality (risk ratio 2.249, 95% confidence interval [CI] 1.766 to 2.864, p <0.001) and MACE (risk ratio 1.753, 95% CI 1.473 to 2.085, p <0.001) compared with those with sinus rhythm. Patients with NOAF had an increased risk of mortality compared with those with existing AF (odds ratio 19.30, 95% CI 5.39 to 69.30, p <0.001); the risk of MACE was comparable between NOAF and patients with existing AF (p = 1). AF during hospitalization with COVID-19 is associated with a higher risk of mortality and MACE. NOAF in patients with COVID-19 is associated with a higher risk of mortality but a similar risk of MACE compared with patients with existing AF.

Coronary Artery Disease as an Independent Predictor of Cardiovascular Mortality in COVID-19 Patients.

Background: Coronavirus disease 2019 (COVID-19) is associated with increased risk of cardiovascular mortality. However, little is known about the combined effect of coronary artery disease (CAD) and COVID-19 on mortality. We aimed to investigate the incidence of cardiovascular and all-cause mortality in COVID-19 patients with CAD. Methods: This multicenter retrospective study identified 3,336 COVID-19 patients admitted between March and December 2020. Data points were manually reviewed in the patients' electronic health records. Multivariate logistic regression was used to assess whether CAD and its subtypes were associated with mortality. Results: This study shows that CAD was not an independent predictor of all-cause mortality (odds ratio (OR): 1.512, 95% confidence interval (CI): 0.1529 - 14.95, P = 0.723). However, there was a significant increase in cardiovascular mortality in patients with CAD compared to those without (OR: 6.89, 95% CI: 2.706 - 17.53, P < 0.001). There was no significant difference in all-cause mortality in patients with left main artery and left anterior descending artery disease (OR: 1.29, 95% CI: 0.80 - 2.08, P = 0.29). However, CAD patients with a history of interventions (e.g., coronary stenting or coronary artery bypass graft) showed increased mortality compared to those solely treated by medical management (OR: 1.93, 95% CI: 1.12 - 3.33, P = 0.017). Conclusions: CAD is associated with a higher incidence of cardiovascular mortality but not all-cause mortality in COVID-19 patients. Overall, this study will help clinicians identify characteristics of COVID-19 patients with increased risk of mortality in the setting of CAD.

Comparative Outcomes of Interventions for Femoropopliteal Chronic Total Occlusion Versus Non-Chronic Total Occlusion Lesions From the Multicenter XLPAD Registry.

Background Endovascular intervention of femoropopliteal chronic total occlusions (CTOs) is technically more complex. However, there is lack of comparative analysis between CTO and non-CTO femoropopliteal interventions. Methods and Results We report procedural details and outcomes of patients treated for femoropopliteal CTO and non-CTO lesions in the XLPAD (Excellence in Peripheral Artery Disease) registry (NCT01904851) between 2006 and 2019. Primary outcomes were procedural success and 1-year major adverse limb events, a composite of all-cause death, target limb revascularization, or major amputation. Analysis included 2895 patients (CTO: n=1516 patients; non-CTO: n=1379 patients) with 3658 lesions (CTO: n=1998 lesions; non-CTO: n=1660 lesions). Conventional balloon angioplasty (20.86% versus 33.48%, P<0.001) or drug-coated balloon angioplasty (1.26% versus 2.93%, P<0.001) were more frequent in the non-CTO group, whereas bare-metal stents (28.09% versus 20.22%, P<0.001) or covered stents (4.08% versus 1.83%, P<0.001) were more frequent in the CTO group. Debulking procedures were more commonly performed in the non-CTO group (41.44% versus 53.13%, P<0.001), despite a similar degree of calcification between the 2 groups. Procedural success was higher in the non-CTO group (90.12% versus 96.79%, P<0.001). Procedural complications were higher in the CTO group (7.21% versus 4.66%, P=0.002), mainly due to excess distal embolization (1.5% versus 0.6%, P=0.015). Adjusted 1-year major adverse limb events were higher in the CTO group (22.47% versus 18.77%, P=0.019), driven mainly by target limb revascularization (19.00% versus 15.34%, P=0.013). Conclusions Procedural success is lower for endovascular treatment of femoropopliteal CTO compared with non-CTO lesions. CTO lesions are associated with higher rates of periprocedural complications and reinterventions after 1 year.

Relation of interleukin-6 levels in COVID-19 patients with major adverse cardiac events.

Elevated interleukin-6 (IL-6) levels may correlate with disease severity in COVID-19. We analyzed whether there was an association between elevated IL-6 levels and major adverse cardiac events (MACE) and/or mortality in COVID-19 patients. A retrospective chart review was performed on COVID-19 patients among four hospitals in one health system from March to May 2020, extracting information on baseline characteristics, MACE (i.e., myocardial infarction, stroke, deep venous thrombosis/pulmonary embolism, or shock requiring vasopressor support), mortality, and IL-6 levels. Of the 496 patients hospitalized with COVID-19, 191 patients had an IL-6 level drawn and 68% had elevated IL-6 levels. The elevated IL-6 population had higher odds of developing a MACE compared to the normal IL-6 population (P < 0.0001, odds ratio [OR] = 5.91, 95% confidence interval [CI] = 2.65-14.11). The elevated IL-6 population also had higher mortality rates (28.2% vs 5%, P = 0.0001, OR = 7.47, 95% CI = 2.19-39.32) and an increased incidence of a MACE and/or mortality (58.78% vs 20.00%, P < 0.0001, OR = 5.7, 95% CI 2.65-12.83) compared to the normal IL-6 population. Elevated IL-6 levels in COVID-19 patients may be associated with MACE and/or mortality. Monitoring IL-6 levels in COVID-19 patients may help risk-stratify patients.

Association between treatment delays and oncologic outcome in patients treated with surgery and radiotherapy for head and neck cancer.

BACKGROUND: This study sought to determine the oncologic impact of delays to surgery, radiotherapy, and completion of therapy in patients with head and neck squamous cell carcinoma. METHODS: The impact of biopsy to surgery (BTS) time, surgery to start of radiation time (STSR), and radiation treatment time (RTT) on locoregional recurrence (LRR), distant metastases (DMs), and cancer-specific mortality (CSM) was examined. The cumulative incidences (CI) of LRR, DMs, and CSM were examined using Fine-Gray testing. RESULTS: A total of 277 patients treated with surgery and adjuvant radiotherapy were analyzed. On multivariable testing, BTS >50 days was associated with DM (P = .03), whereas RTT and STSR were not. RTT >43 days was associated with LRR (P = .02) in patients with non-p16-positive-oropharynx cancer. CONCLUSIONS: An increase in DM appears to be the mechanism by which prolonged time to treatment initiation leads to worse overall survival. Prolonged RTT has the greatest impact on patients with non-p16 positive oropharynx cancers.

Ligand binding to WW tandem domains of YAP2 transcriptional regulator is under negative cooperativity.

YES-associated protein 2 (YAP2) transcriptional regulator drives a multitude of cellular processes, including the newly discovered Hippo tumor suppressor pathway, by virtue of the ability of its WW domains to bind and recruit PPXY-containing ligands to specific subcellular compartments. Herein, we employ an array of biophysical tools to investigate allosteric communication between the WW tandem domains of YAP2. Our data show that the WW tandem domains of YAP2 negatively cooperate when binding to their cognate ligands. Moreover, the molecular origin of such negative cooperativity lies in an unfavorable entropic contribution to the overall free energy relative to ligand binding to isolated WW domains. Consistent with this notion, the WW tandem domains adopt a fixed spatial orientation such that the WW1 domain curves outwards and stacks onto the binding groove of the WW2 domain, thereby sterically hindering ligand binding to both itself and its tandem partner. Although ligand binding to both WW domains disrupts such interdomain stacking interaction, they reorient themselves and adopt an alternative fixed spatial orientation in the liganded state by virtue of their ability to engage laterally so as to allow their binding grooves to point outwards and away from each other. In short, while the ability of WW tandem domains to aid ligand binding is well documented, our demonstration that they may also be subject to negative binding cooperativity represents a paradigm shift in our understanding of the molecular action of this ubiquitous family of protein modules.