Healthcare utilization 9 months pre- and post- COVID-19 hospitalization among patients discharged alive.

BACKGROUND: Emerging evidence suggests that there is an increase in healthcare utilization (HCU) in patients due to Coronavirus Disease 2019 (COVID-19). We investigated the change in HCU pre and post hospitalization among patients discharged home from COVID-19 hospitalization for up to 9 months of follow up. STUDY DESIGN AND METHODS: This retrospective study from a United States cohort used Optum® de-identified Clinformatics Data Mart; it included adults discharged home post hospitalization with primary diagnosis of COVID-19 between April 2020 and March 2021. We evaluated HCU of patients 9 months pre and post -discharge from index hospitalization. We defined HCU as emergency department (ED), inpatient, outpatient (office), rehabilitation/skilled nursing facility (SNF), telemedicine visits, and length of stay, expressed as number of visits per 10,000 person-days. RESULTS: We identified 63,161 patients discharged home after COVID-19 hospitalization. The cohort of patients was mostly white (58.8%) and women (53.7%), with mean age 72.4 (SD± 12) years. These patients were significantly more likely to have increased HCU in the 9 months post hospitalization compared to the 9 months prior. Patients had a 47%, 67%, 65%, and 51% increased risk of ED (rate ratio 1.47; 95% CI 1.45-1.49; p < .0001), rehabilitation (rate ratio 1.67; 95% CI 1.61-1.73; p < .0001), office (rate ratio1.65; 95% CI 1.64-1.65; p < .0001), and telemedicine visits (rate ratio 1.5; 95% CI 1.48-1.54; p < .0001), respectively. We also found significantly different rates of HCU for women compared to men (women have higher risk of ED, rehabilitation, and telemedicine visits but a lower risk of inpatient visits, length of stay, and office visits than men) and for patients who received care in the intensive care unit (ICU) vs those who did not (ICU patients had increased risk of ED, inpatient, office, and telemedicine visits and longer length of stay but a lower risk of rehabilitation visits). Outpatient (office) visits were the highest healthcare service utilized post discharge (64.5% increase). Finally, the risk of having an outpatient visit to any of the specialties studied significantly increased post discharge. Interestingly, the risk of requiring a visit to pulmonary medicine was the highest amongst the specialties studied (rate ratio 3.35, 95% CI 3.26-3.45, p < .0001). CONCLUSION: HCU was higher after index hospitalization compared to 9 months prior among patients discharged home post-COVID-19 hospitalization. The increases in HCU may be driven by those patients who received care in the ICU.

Site-specific acetylation of polynucleotide kinase 3'-phosphatase regulates its distinct role in DNA repair pathways.

Mammalian polynucleotide kinase 3'-phosphatase (PNKP), a DNA end-processing enzyme with 3'-phosphatase and 5'-kinase activities, is involved in multiple DNA repair pathways, including base excision (BER), single-strand break (SSBR), and double-strand break repair (DSBR). However, little is known as to how PNKP functions in such diverse repair processes. Here we report that PNKP is acetylated at K142 (AcK142) by p300 constitutively but at K226 (AcK226) by CBP, only after DSB induction. Co-immunoprecipitation analysis using AcK142 or AcK226 PNKP-specific antibodies showed that AcK142-PNKP associates only with BER/SSBR, and AcK226 PNKP with DSBR proteins. Despite the modest effect of acetylation on PNKP's enzymatic activity in vitro, cells expressing non-acetylable PNKP (K142R or K226R) accumulated DNA damage in transcribed genes. Intriguingly, in striatal neuronal cells of a Huntington's Disease (HD)-based mouse model, K142, but not K226, was acetylated. This is consistent with the reported degradation of CBP, but not p300, in HD cells. Moreover, transcribed genomes of HD cells progressively accumulated DSBs. Chromatin-immunoprecipitation analysis demonstrated the association of Ac-PNKP with the transcribed genes, consistent with PNKP's role in transcription-coupled repair. Thus, our findings demonstrate that acetylation at two lysine residues, located in different domains of PNKP, regulates its distinct role in BER/SSBR versus DSBR.

Pulmonary Rehabilitation Utilization in Older Adults with Chronic Obstructive Pulmonary Disease, 2013-2019.

Rationale: Pulmonary rehabilitation (PR) is very effective in patients with chronic obstructive pulmonary disease (COPD) for improving exercise tolerance and functional capacity, alleviating dyspnea, and improving respiratory quality of life. Access to and use of PR remain poor. Objectives: To assess the trends in PR use and factors associated with PR use in adults with COPD. Methods: We retrospectively analyzed the use of PR in adults with COPD using a 20% Medicare beneficiary population from January 1, 2013, to December 31, 2019. Adults with COPD were identified by 1) two or more outpatient visits >30 days apart within 1 year with an encounter diagnosis of COPD or 2) hospitalization with COPD as the primary diagnosis or a primary diagnosis of acute respiratory failure with a secondary discharge diagnosis of COPD. PR use in each calendar year was identified using Current Procedural Terminology and Healthcare Common Procedure Coding System codes. Factors associated with PR use were tested in bivariate and multivariable logistic regression models. Results: There was a gradual but modest increase in the percentage of patients with COPD using PR; the proportion increased from 2.5% in 2013 to 4.0% in 2019. Overall, the percentage of patients using PR remained low. Factors associated with higher odds of using PR included younger age (66-74 yr), White race, higher socioeconomic status, lower comorbidity score, residence in a metropolitan urban area, and sole or comanagement by a pulmonologist. Conclusions: The use of PR by Medicare beneficiaries with COPD has not changed meaningfully in the past decade and remains low.

The DNA glycosylase NEIL2 is protective during SARS-CoV-2 infection.

SARS-CoV-2 infection-induced aggravation of host innate immune response not only causes tissue damage and multiorgan failure in COVID-19 patients but also induces host genome damage and activates DNA damage response pathways. To test whether the compromised DNA repair capacity of individuals modulates the severity of COVID-19 infection, we analyze DNA repair gene expression in publicly available patient datasets and observe a lower level of the DNA glycosylase NEIL2 in the lungs of severely infected COVID-19 patients. This observation of lower NEIL2 levels is further validated in infected patients, hamsters and ACE2 receptor-expressing human A549 (A549-ACE2) cells. Furthermore, delivery of recombinant NEIL2 in A549-ACE2 cells shows decreased expression of proinflammatory genes and viral E-gene, as well as lowers the yield of viral progeny compared to mock-treated cells. Mechanistically, NEIL2 cooperatively binds to the 5'-UTR of SARS-CoV-2 genomic RNA to block viral protein synthesis. Collectively, these data strongly suggest that the maintenance of basal NEIL2 levels is critical for the protective response of hosts to viral infection and disease.

Factors that impact initiation of pain management agreements for patients on chronic opioid therapy.

OBJECTIVE: This analysis seeks to understand variables within our institution that impact pain management agreement (PMA) utilization for chronic noncancer pain (CNCP). DESIGN: Retrospective chart review. SETTING: Public academic medical center. PATIENTS: Adults prescribed an opioid for CNCP between July 2020 and October 2020. MAIN OUTCOME MEASURE: We assessed the association between patient demographics, prescription factors, and prescriber factors with the presence of a PMA. Unadjusted rates and chi-square tests were generated for each predictor. Additionally, we performed two multivariable logistic regressions: one including all variables and another utilizing a stepwise forward variable selection process to further understand the relationships between predictors and the presence of a PMA. RESULTS: 49.7 percent of patients who received an opioid for CNCP had a PMA on file. One significant predictor of the presence of PMA was prescriber specialty with anesthesia/pain medicine, demonstrating 88 percent compliance. Compared to anesthesia/pain medicine, patients receiving opioids from internal medicine had an odds ratio (OR) of 0.155 (95 percent confidence interval (CI), 0.109-0.220), while patients receiving opioids from family medicine had an OR of 0.122 (95 percent CI, 0.090-0.167). Additionally, patients who received schedule II opioids (as opposed to schedule III/IV opioids), patients with multiple opioid fills in 3 months, middle aged patients, and Black patients were more likely to have a PMA. CONCLUSIONS: Compliance with PMA within our institution was only 49 percent despite an existing state law mandating use. Our analysis suggests quality improvement interventions should target patients on schedule III/IV opioids who receive their prescriptions from primary care providers.

Healthcare Utilization in Patients with Chronic Obstructive Pulmonary Disease Discharged from Coronavirus 2019 Hospitalization.

Rationale: There is concern that patients with chronic obstructive pulmonary disease (COPD) are at greater risk of increased healthcare utilization (HCU) following Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-COV-2) infection. Objective: To assess whether COPD is an independent risk factor for increased post-discharge HCU. Methods: We conducted a retrospective cohort study of patients with COPD discharged home from a hospitalization due to Coronavirus Disease 2019 (COVID-19) between April 1, 2020, and March 31, 2021, using Optum's de-identified Clinformatics® Data Mart Database (CDM). COVID-19 was identified by an International Classification of Diseases, tenth revision, clinical modification (ICD-10-CM) diagnosis code of U07.1. The primary outcome was HCU (ie, emergency department (ED) visits, readmissions, rehabilitation/skilled nursing facility (SNF) visits, outpatient office visits, and telemedicine visits) nine months post-discharge after COVID-19 hospitalization (from here on "post-discharge") in patients with COPD compared to HCU of patients without COPD. Poisson regression modeling was used to calculate relative risk (RR) and confidence interval (CI) for COPD, adjusted for the other covariates. Results: We identified a cohort of 160,913 patients hospitalized with COVID-19, with 57,756 discharged home and 14,622 (25.3%) diagnosed with COPD. Patients with COPD had a mean age of 75.48 years (±9.49); 55.5% were female and 70.9% were White. Patients with COPD had an increased risk of HCU in the nine months post-discharge after adjusting for the other covariates. Risk of ED visits, readmissions, length of stay during readmission, rehabilitation/SNF visits, outpatient office visits, and telemedicine visits were increased by 57% (RR 1.57; 95% CI 1.53-1.60), 50% (RR 1.50; 95% CI 1.46-1.54), 55% (RR 1.55; 95% CI 1.53-1.56), 18% (RR 1.18; 95% CI 1.14-1.22), 16% (RR 1.16; 95% CI 1.16-1.17), and 28% (RR 1.28; 95% CI 1.24-1.31), respectively. Younger patients (ages 18 to 65 years), women, and Hispanic patients with COPD showed an increased risk for post-discharge HCU. Conclusion: Patients with COPD hospitalized with COVID-19 experienced increased HCU post-discharge compared to patients without COPD.

Site-specific acetylation of polynucleotide kinase 3'-phosphatase (PNKP) regulates its distinct role in DNA repair pathways.

Mammalian polynucleotide kinase 3'-phosphatase (PNKP) is a dual-function DNA end-processing enzyme with 3'-phosphatase and 5'-kinase activities, which generate 3'-OH and 5'-phosphate termini respectively, as substrates for DNA polymerase and DNA ligase to complete DNA repair. PNKP is thus involved in multiple DNA repair pathways, including base excision (BER), single-strand break (SSBR), and double-strand break repair (DSBR). However, little is known as to how PNKP functions in such diverse repair processes, which involve distinct sets of proteins. In this study, we report that PNKP is acetylated at two lysine (K142 and K226) residues. While K142 (AcK142) is constitutively acetylated by p300, CBP acetylates K226 (AcK226) only after DSB induction. Co-immunoprecipitation analysis using antibodies specific for PNKP peptides containing AcK142 or AcK226 of PNKP showed that AcK142-PNKP associates only with BER/SSBR, and AcK226 PNKP only with DSBR proteins. Although acetylation at these residues did not significantly affect the enzymatic activity of PNKP in vitro, cells expressing nonacetylable PNKP (K142R or K226R) accumulated DNA damage, specifically in transcribed genes. Intriguingly, in striatal neuronal cells of a Huntington's Disease (HD)-based mouse model, K142, but not K226, was acetylated. This observation is consistent with the reported degradation of CBP but not p300 in HD cells. Moreover, genomes of HD cells progressively accumulated DSBs specifically in the transcribed genes. Chromatin-immunoprecipitation analysis using anti-AcK142 or anti-AcK226 antibodies demonstrated an association of Ac-PNKP with the transcribed genes, consistent with PNKP's role in transcription-coupled repair. Thus, our findings collectively demonstrate that acetylation at two lysine residues located in different domains of PNKP regulates its functionally distinct role in BER/SSBR vs. DSBR.

Structured Evaluation and Management of Patients with COPD in an Accredited Program.

Background: Chronic obstructive pulmonary disease (COPD) is an ambulatory care-sensitive condition. Methods: We compared the impact of care received by patients with COPD at Joint Commission-accredited, disease-specific clinics and primary care clinics at an academic health care systemfrom April 2014 to March 2018. Patients with COPD ≥ 40 years old with ≥ 2 outpatient visits 30 days apart were identified. Baseline demographics, disease-specific performance measures, and health care utilization were compared between groups. Propensity matching was conducted and time to the first emergency department (ED) visit and hospitalization was performed using Cox regression analysis. Results: Of 4646 unique patients with COPD, 1114 were treated at disease-specific clinics and 3532 at primary care clinics. The entire group was predominantly female (58.8 %), non-Hispanic White (74.2 %) with a mean age of 65.4 ± 11.4 years consisting of current (47.6 %) or former smokers (38.4 %). In the disease-specific group, performance measures were performed more frequently, and lower rates of ED visits (hazard ratio [HR]=0.31, 95% confidence interval [CI] 0.18-0.54) and hospitalizations (HR 0.41, 95% CI 0.21-0.79) noted in comparison to the primary care group. Conclusions: In this observational study, the implementation of achronic disease management program through accredited disease-specific clinics for patients with COPD was associated with reduced all-cause ED visits and hospitalizations.

A Closer Look-Who Are We Screening for Lung Cancer?

Objective: To evaluate the characteristics of individuals receiving lung cancer screening (LCS) and identify those with potentially limited benefit owing to coexisting chronic illnesses and/or comorbidities. Patients and Methods: In this retrospective study in the United States, patients were selected from a large clinical database who received LCS from January 1, 2019, through December 31, 2019, with at least 1 year of continuous enrollment. We assessed for potentially limited benefit in LCS defined strictly as not meeting the traditional risk factor inclusion criteria (age <55 years or >80 years, previous computed tomography scan within 11 months before an LCS examination, or a history of nonskin cancer) or liberally as having the potential exclusion criteria related to comorbid life-limiting conditions, such as cardiac and/or respiratory disease. Results: A total of 51,551 patients were analyzed. Overall, 8391 (16.3%) individuals experienced a potentially limited benefit from LCS. Among those who did not meet the strict traditional inclusion criteria, 317 (3.8%) were because of age, 2350 (28%) reported a history of nonskin malignancy, and 2211 (26.3%) underwent a previous computed tomography thorax within 11 months before an LCS examination. Of those with potentially limited benefit owing to comorbidity, 3680 (43.9%) were because of severe respiratory comorbidity (937 [25.5%] with any hospitalization for coronary obstructive pulmonary disease, interstitial lung disease, or respiratory failure; 131 [3.6%] with hospitalization for respiratory failure requiring mechanical ventilation; or 3197 [86.9%] with chronic obstructive disease/interstitial lung disease requiring outpatient oxygen) and 721 (8.59%) with cardiac comorbidity. Conclusion: Up to 1 of 6 low-dose computed tomography examinations may have limited benefit from LCS.

Corticosteroids and Outcomes in Solid Organ Transplant Recipients Infected With Severe Acute Respiratory Syndrome Coronavirus 2.

Objective: To examine outcomes in organ transplant and nontransplant patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the initial 22 months of the pandemic. Patients and Methods: We used Optum electronic health records to compare outcomes between an adult transplant group and a propensity-matched nontransplant group that tested positive for SARS-CoV-2 from February 1, 2020, to December 15, 2021. Baseline characteristics, hospitalization, intensive care unit admission, mechanical ventilation, renal replacement therapy, inpatient, and 90-day mortality were compared between the transplant and nontransplant groups and among specific transplant recipients. Cox proportional analysis was used to examine hospitalization and mortality by organ transplant, medical therapy, sex, and the period of the pandemic. Results: We identified 876,959 patients with SARS-CoV-2 infection, of whom 3548 were organ transplant recipients. The transplant recipients had a higher risk of hospitalization (30.6% vs 25%, respectively; P<.001), greater use of mechanical ventilation (7.8% vs 5.6%, respectively; P<.001), and increased inpatient mortality (6.7% vs 4.7%, respectively; P<.001) compared with the nontransplant patients. The initiation of mechanical ventilation was significantly more frequent in the transplant group. After adjustment for baseline characteristics and comorbidities, the transplant group had a higher risk of hospitalization (odds ratio, 1.38; 95% confidence interval, 1.19-1.59), without a difference in mortality. In the transplant group, lung transplant recipients had the highest inpatient mortality (11.6%). Conclusion: Among patients with SARS-CoV-2 infection, the transplant recipients were at a higher risk of hospitalization and inpatient mortality; however, mortality was mainly driven by advanced age and comorbidities rather than by transplant status or immunosuppressive medications. Lung transplant recipients had the greatest inpatient and 90-day mortality.

SARS-CoV-2 infection-induced immunity reduces rates of reinfection and hospitalization caused by the Delta or Omicron variants.

During a pandemic, effective vaccines are typically in short supply, particularly at onset intervals when the wave is accelerating. We conducted an observational, retrospective analysis of aggregated data from all patients who tested positive for SARS-CoV-2 during the waves caused by the Delta and Omicron variants, stratified based on their known previous infection and vaccination status, throughout the University of Texas Medical Branch (UTMB) network. Next, the immunity statuses within each medical parameter were compared to naïve individuals for the effective decrease of occurrence. Lastly, we conducted studies using mice and pre-pandemic human samples for IgG responses to viral nucleocapsid compared to spike protein toward showing a functional component supportive of the medical data results in relation to the immunity types. During the Delta and Omicron waves, both infection-induced and hybrid immunities were associated with a trend of equal or greater decrease of occurrence than vaccine-induced immunity in hospitalizations, intensive care unit admissions, and deaths in comparison to those without pre-existing immunity, with hybrid immunity often trending with the greatest decrease. Compared to individuals without pre-existing immunity, those vaccinated against SARS-CoV-2 had a significantly reduced incidence of COVID-19, as well as all subsequent medical parameters. Though vaccination best reduces health risks associated with initial infection toward acquiring immunity, our findings suggest infection-induced immunity is as or more effective than vaccination in reducing the severity of reinfection from the Delta or Omicron variants, which should inform public health response at pandemic onset, particularly when triaging towards the allotment of in-demand vaccinations.

Access to Pulmonary Rehabilitation among Medicare Beneficiaries with Chronic Obstructive Pulmonary Disease.

Rationale: Pulmonary rehabilitation (PR) remains substantially underused as a treatment modality for chronic obstructive pulmonary disease (COPD). A major barrier to the uptake of PR is the poor availability of and access to PR. Objectives: To quantify patients' access to PR centers in the United States. Methods: Using the 100% Medicare population with coverage for 2018, four geodesic distance-based buffers of 10-, 15-, 25-, and 50-mi radii around the geographic centroid of each ZIP code with at least one beneficiary with COPD were created. Street addresses of PR centers across the continental United States were geocoded. We calculated the distance between the residential ZIP code centroid and the closest PR center. The proportions of individuals with at least one PR center available within the four distance buffers were calculated overall as well as in metropolitan, micropolitan, small-town, and rural areas. Results: Of 62,930,784 Medicare beneficiaries, 10,376,949 (16.5%) had COPD. There were 1,696 PR centers across the United States, with one PR center for every 6,030 individuals with COPD. Mean distance to the nearest PR center was 12.4 (standard deviation, 16.6) mi. Overall, the proportions of individuals with COPD who had PR centers available within 10-, 15-, 25-, and 50-mi radii were 61.5%, 73.2%, 86.6%, and 97.1%, respectively. Proportions for rural areas were 11.3%, 24.3%, 53.4%, and 88.6%, respectively. Compared with those living in metropolitan areas, those living in rural areas were 95% less likely to have PR centers within 10 mi of their residences (odds ratio, 0.048 [95% confidence interval, 0.039-0.057]). Conclusions: In a nationally representative sample of Medicare beneficiaries, we found that two-fifths of adults with COPD overall, and eight in nine of those in rural areas, have poor access to PR.

Co-prescribing of Central Nervous System-Active Medications for COPD Patients: Impact on Emergency Room Visits and Hospitalization.

BACKGROUND: Anxiety and chronic pain are common comorbidities in patients with chronic obstructive pulmonary disease (COPD), which are frequently managed with benzodiazepines (BZDs) and opioids, respectively. OBJECTIVE: The purpose of this study was to determine whether different combinations of opioids, BZD, and their substitutes-gabapentinoids (GABA) and selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors (SSRIs/SNRIs)-are associated with lower risk of acute respiratory events in COPD patients with co-occurring chronic pain and anxiety. METHODS: This retrospective cohort study used a nationally representative sample of Medicare beneficiaries with COPD, chronic pain, and anxiety. Patients were grouped based on drug combination (opioid + BZD/Z-hypnotics, opioid + GABA, opioid + SSRI/SNRI, BZD/Z-hypnotics + GABA, BZD/Z-hypnotics + SSRI/SNRI, GABA + SSRI/SNRI, or ≥3 drugs). The primary outcome was emergency room (ER) visit or hospitalization due to acute respiratory events assessed up to 180 days following initiation of drug combination. Overdose secondary to central nervous system (CNS)-related drugs was also assessed up to 180 days following initiation of drug combination. RESULTS: The drug combination opioid + GABA was associated with decreased risk for ER visit (hazard ratio [HR] = 0.73; 95% CI = 0.61-0.87) and hospitalization (HR = 0.69; 95% CI = 0.55-0.85). Opioid + SSRI/SNRI also showed decreased risk for ER visit (HR = 0.84; 95% CI = 0.71-0.99). There was no significant difference in risk for CNS-related drug overdose among different drug combinations compared with opioid + BZD/Z-hypnotics. CONCLUSION AND RELEVANCE: Opioids in combination with GABA and SSRI/SNRI demonstrate relatively lower risk for acute respiratory events among patients with COPD and comorbid chronic pain and anxiety. The findings emphasize the need for multimodal management in this vulnerable population.

ABV-CoViD: An Ensemble Forecasting Model to Predict Availability of Beds and Ventilators for COVID-19 Like Pandemics.

Recently, healthcare stakeholders have orchestrated steps to strengthen and curb the COVID-19 wave. There has been a surge in vaccinations to curb the virus wave, but it is crucial to strengthen our healthcare resources to fight COVID-19 and like pandemics. Recent researchers have suggested effective forecasting models for COVID-19 transmission rate, spread, and the number of positive cases, but the focus on healthcare resources to meet the current spread is not discussed. Motivated from the gap, in this paper, we propose a scheme, ABV-CoViD (Availibility of Beds and Ventilators for COVID-19 patients), that forms an ensemble forecasting model to predict the availability of beds and ventilators (ABV) for the COVID-19 patients. The scheme considers a region-wise demarcation for the allotment of beds and ventilators (BV), termed resources, based on region-wise ABV and COVID-19 positive patients (inside the hospitals occupying the BV resource). We consider an integration of artificial neural network (ANN) and auto-regressive integrated neural network (ARIMA) model to address both the linear and non-linear dependencies. We also consider the effective wave spread of COVID-19 on external patients (not occupying the BV resources) through a [Formula: see text]- ARNN model, which gives us long-term complex dependencies of BV resources in the future time window. We have considered the COVID-19 healthcare dataset on 3 USA regions (Illinois, Michigan, and Indiana) for testing our ensemble forecasting scheme from January 2021 to May 2022. We evaluated our scheme in terms of statistical performance metrics and validated that ensemble methods have higher accuracy. In simulation, for linear modelling, we considered the [Formula: see text] model, and [Formula: see text] model for ANN modelling. We considered the [Formula: see text](12,6) forecasting. On a population of 2,93,90,897, the obtained mean absolute error (MAE) on average for 3 regions is 170.5514. The average root means square error (RMSE) of [Formula: see text]-ARNN is 333.18, with an accuracy of 98.876%, which shows the scheme's efficacy in ABV measurement over conventional and manual resource allocation schemes.

The DNA glycosylase NEIL2 plays a vital role in combating SARS-CoV-2 infection.

Compromised DNA repair capacity of individuals could play a critical role in the severity of SARS-CoV-2 infection-induced COVID-19. We therefore analyzed the expression of DNA repair genes in publicly available transcriptomic datasets of COVID-19 patients and found that the level of NEIL2, an oxidized base specific mammalian DNA glycosylase, is particularly low in the lungs of COVID-19 patients displaying severe symptoms. Downregulation of pulmonary NEIL2 in CoV-2-permissive animals and postmortem COVID-19 patients validated these results. To investigate the potential roles of NEIL2 in CoV-2 pathogenesis, we infected Neil2-null (Neil2-/-) mice with a mouse-adapted CoV-2 strain and found that Neil2-/- mice suffered more severe viral infection concomitant with increased expression of proinflammatory genes, which resulted in an enhanced mortality rate of 80%, up from 20% for the age matched Neil2+/+ cohorts. We also found that infected animals accumulated a significant amount of damage in their lung DNA. Surprisingly, recombinant NEIL2 delivered into permissive A549-ACE2 cells significantly decreased viral replication. Toward better understanding the mechanistic basis of how NEIL2 plays such a protective role against CoV-2 infection, we determined that NEIL2 specifically binds to the 5'-UTR of SARS-CoV-2 genomic RNA and blocks protein synthesis. Together, our data suggest that NEIL2 plays a previously unidentified role in regulating CoV-2-induced pathogenesis, via inhibiting viral replication and preventing exacerbated proinflammatory responses, and also via its well-established role of repairing host genome damage.

Glenoid Version Assessment When the CT Field of View Does Not Permit the Friedman Method: The Robertson Method.

Background: To improve spatial resolution, current clinical shoulder cross-sectional imaging studies reduce the field of view of the shoulder, excluding the medial scapula border and preventing glenoid version measurement according to the Friedman method. Purpose: To evaluate a method to accurately and reliably measure glenoid version on cross-sectional shoulder images when the medial scapula border is not included in the field of view, and to establish measurements equivalent to the Friedman method. Study Design: Controlled laboratory study. Methods: Sixty-five scapulae underwent computed tomography (CT) scanning with an optimal shoulder CT-positioning protocol. Glenoid version was measured on CT images of the full scapula using the Friedman method. We developed a measurement method (named the Robertson method) based on the glenoid vault version from partial scapula images, with a correction angle subtracted from the articular-surface-glenoid vault measurement. Comparison with the Friedman method defined the accuracy of the Robertson method. Three observers tested inter- and intraobserver reliability of the Robertson method. Accuracy was statistically evaluated with t tests and reliability with the intraclass correlation coefficient (ICC). Results: The statistical distribution of glenoid version was similar to published data,-0.5° ± 3° [mean ± SD]. The initial measurement using the Robertson method resulted in a more retroverted angle compared with the Friedman method, and a correction angle of 7° was then applied. After this adjustment, the difference between the 2 methods was nonsignificant (0.1° ± 4°; P > .65). Reliability of the Robertson method was excellent, as the interrater ICC was 0.77, the standard error of measurement (SEM) was 1.1° with P < .001. The intrarater ICC ranged between 0.84 and 0.92, the SEM ranged between 0.9° and 1.2° with P < .01. Conclusion: A validated glenoid version measurement method is now available for current clinical shoulder CT protocols that reliably create Friedman-equivalent values. Clinical Relevance: Friedman-equivalent values may be made from common clinical CTs of the shoulder and compared with prior and future Friedman measurements of the scapula.

Characteristics and Factors Associated With Mortality in Patients With Coronavirus Disease 2019 and Pneumothorax.

Objective: To describe the incidence, clinical characteristics, and factors associated with mortality in patients hospitalized for coronavirus disease 2019 (COVID-19) in whom pneumothorax developed. Patients and Methods: This study was a retrospective analysis conducted using a large administrative database of adult patients hospitalized for COVID-19 in the United States from February 1, 2020, to June 10, 2021. We characterized the clinical features of patients in whom pneumothorax developed and the factors associated with mortality and stratified pneumothorax by the timing of the initiation of invasive mechanical ventilation (IMV) and by the time of hospital admission (early versus late). Results: A total of 811,065 adult patients had a positive test result for severe acute respiratory syndrome coronavirus 2, of whom 103,858 (12.8%) were hospitalized. Pneumothorax occurred in 1915 patients (0.24% overall and 1.84% among hospitalized patients). Over time, the use of steroids and remdesivir increased, whereas the use of IMV, pneumothorax rates, and mortality decreased. The clinical characteristics associated with pneumothorax were male sex; the receipt of IMV; and treatment with steroids, remdesivir, or convalescent plasma. Most patients with pneumothorax received IMV, but pneumothorax developed before the initiation of IMV and/or early during hospitalization in majority. Multivariable analysis revealed that pneumothorax increased the risk of death (adjusted hazard ratio [aHR], 1.15; 95% CI, 1.06-1.24). In patients who did not receive IMV, pneumothorax led to nearly twice the mortality (aHR, 1.99; 95% CI, 1.56-2.54). Increased mortality was also noted when pneumothorax occurred before IMV (aHR, 1.37; 95% CI, 1.11-1.69) and within 7 days of hospital admission (aHR, 1.60; 95% CI, 1.29-1.98). Conclusion: The overall incidence of pneumothorax in patients hospitalized for COVID-19 was low. Pneumothorax is an independent risk factor for death.

Outcomes of Patients with COPD Hospitalized for Coronavirus Disease 2019.

RATIONALE: There is controversy concerning the association of chronic obstructive pulmonary disease (COPD) as an independent risk factor for mortality in patients hospitalized with Coronavirus Disease 2019 (COVID-19). We hypothesize that patients with COPD hospitalized for COVID-19 have increased mortality risk. OBJECTIVE: To assess whether COPD increased the risk of mortality among patients hospitalized for COVID-19. METHODS: We conducted a retrospective cohort analysis of patients with COVID-19 between February 10, 2020, and November 10, 2020, and hospitalized within 14 days of diagnosis. Electronic health records from U.S. facilities (Optum COVID-19 data) were used. RESULTS: In our cohort of 31,526 patients, 3030 (9.6%) died during hospitalization. Mortality in patients with COPD was higher than that of patients without COPD, 14.02% and 8.8%, respectively. Univariate (odds ratio [OR] 1.68; 95% confidence interval [CI] 1.54 to 1.84) and multivariate (OR 1.33; 95% CI 1.18 to 1.50) analysis showed that patients with COPD had greater odds of death due to COVID-19 than patients without COPD. We found significant interactions between COPD and sex and COPD and age. Specifically, the increased mortality risk associated with COPD was observed among female (OR 1.62; 95% CI 1.36 to 1.95) but not male patients (OR 1.14; 95% CI 0.97 to 1.34); and in patients aged 40 to 64 (OR 1.42; 95% CI 1.07 to 1.90) and 65 to 79 (OR 1.48; 95% CI 1.23 to 1.78) years. CONCLUSIONS: COPD is an independent risk factor for death in adults aged 40 to 79 years hospitalized with COVID-19 infection.