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Two large randomized controlled trials have shown mortality benefit from lung cancer screening (LCS) in high-risk groups. Updated guidelines by the United State Preventative Service Task Force in 2020 will allow for inclusion of more patients who are at high risk of developing lung cancer and benefit from screening. As medical clinics and lung cancer screening programs around the country continue to work on perfecting the LCS workflow, it is important to understand some controversial issues surrounding LCS that should be addressed. In this article, we identify some of these issues, including false positive rates of low-dose CT, over-diagnosis, cost expenditure, LCS disparities in minorities, and utility of biomarkers. We hope to provide clarity, potential solutions, and future directions on how to address these controversies., (Published by Elsevier Inc.)

Importance: SARS-CoV-2 entry requires the TMPRSS2 cell surface protease. Antiandrogen therapies reduce expression of TMPRSS2., Objective: To determine if temporary androgen suppression induced by degarelix improves clinical outcomes of inpatients hospitalized with COVID-19., Design, Setting, and Participants: The Hormonal Intervention for the Treatment in Veterans With COVID-19 Requiring Hospitalization (HITCH) phase 2, placebo-controlled, double-blind, randomized clinical trial compared efficacy of degarelix plus standard care vs placebo plus standard care on clinical outcomes in men hospitalized with COVID-19 but not requiring invasive mechanical ventilation. Inpatients were enrolled at 14 Department of Veterans Affairs hospitals from July 22, 2020, to April 8, 2021. Data were analyzed from August 9 to October 15, 2021., Interventions: Patients stratified by age, history of hypertension, and disease severity were centrally randomized 2:1 to degarelix, (1-time subcutaneous dose of 240 mg) or a saline placebo. Standard care included but was not limited to supplemental oxygen, antibiotics, vasopressor support, peritoneal dialysis or hemodialysis, intravenous fluids, remdesivir, convalescent plasma, and dexamethasone., Main Outcomes and Measures: The composite primary end point was mortality, ongoing need for hospitalization, or requirement for mechanical ventilation at day 15 after randomization. Secondary end points were time to clinical improvement, inpatient mortality, length of hospitalization, duration of mechanical ventilation, time to achieve a temperature within reference range, maximum severity of COVID-19, and the composite end point at 30 days., Results: The trial was stopped for futility after the planned interim analysis, at which time there were 96 evaluable patients, including 62 patients randomized to the degarelix group and 34 patients in the placebo group, out of 198 initially planned. The median (range) age was 70.5 (48-85) years. Common comorbidities included chronic obstructive pulmonary disorder (15 patients [15.6%]), hypertension (75 patients [78.1%]), cardiovascular disease (27 patients [28.1%]), asthma (12 patients [12.5%]), diabetes (49 patients [51.0%]), and chronic respiratory failure requiring supplemental oxygen at baseline prior to COVID-19 (9 patients [9.4%]). For the primary end point, there was no significant difference between the degarelix and placebo groups (19 patients [30.6%] vs 9 patients [26.5%]; P = .67). Similarly, no differences were observed between degarelix and placebo groups in any secondary end points, including inpatient mortality (11 patients [17.7%] vs 6 patients [17.6%]) or all-cause mortality (11 patients [17.7%] vs 7 patents [20.6%]). There were no differences between degarelix and placebo groups in the overall rates of adverse events (13 patients [21.0%] vs 8 patients [23.5%) and serious adverse events (19 patients [30.6%] vs 13 patients [32.4%]), nor unexpected safety concerns., Conclusions and Relevance: In this randomized clinical trial of androgen suppression vs placebo and usual care for men hospitalized with COVID-19, degarelix did not result in amelioration of COVID-19 severity., Trial Registration: ClinicalTrials.gov Identifier: NCT04397718.

Background: This meta-analysis assessed the relationship between obstructive sleep apnea (OSA) and echocardiographic parameters of diastolic dysfunction (DD), which are used in the assessment of heart failure with preserved ejection fraction., Methods: We searched the databases including Ovid MEDLINE, Ovid Embase, Scopus, Web of Science, Google Scholar, and EBSCO CINAHL from inception up to December 26, 2020. The search was not restricted to time, publication status, or language. Two independent investigators screened the identified studies and extracted the data in duplicate. We conducted a meta-analysis using RevMan v.5. The risk of bias was assessed using Cochrane collaboration tools. Comparisons were made between patients with OSA, diagnosed in-laboratory polysomnography or home sleep apnea testing, and patients without OSA in relation to established markers of DD., Results: Primary search identified 2,512 studies. A total of 18 studies including 2,509 participants were included. The two groups were free of conventional cardiovascular risk factors. Significant structural changes were observed between the two groups. Patients with OSA exhibited greater left atrial volume index (LAVI) (3.94 95% CI [0.8, 7.07]; p = 0.000) and left ventricular mass index (11.10 95% CI [2.56, 19.65]; p = 0.000) as compared to control group. The presence of OSA was also associated with more prolonged deceleration time (10.44 ms 95% CI [0.71, 20.16]; p = 0.04), isovolumic relaxation time (IVRT) (7.85 ms 95% CI [4.48, 11.22]; p = 0.000), and a lower ratio of early to late mitral inflow velocities (E/A) ratio (-0.62 95% CI [-1, -0.24]; p = 0.001) suggestive of early DD. The early mitral inflow velocity to mitral annular early diastolic velocity (E/e') ratio (0.94 95% CI [0.44, 1.45]; p = 0.000) was increased. Linear correlation between severity of OSA and LAVI and IVRT parameters was observed but this association did not sustain for the E/A and E/e'. The ejection fraction was not significantly different between patients with OSA and healthy controls (-0.48 95% CI [-1.18, 0.23]; p = 0.18)., Conclusion: An association between OSA and echocardiographic parameters of DD was detected that was independent of conventional cardiovascular risk factors. OSA may be independently associated with DD perhaps due to higher LV mass. Investigating the role of continuous positive airway pressure therapy in reversing or ameliorating DD is recommended., (© 2022 S. Karger AG, Basel.)

Background: This meta-analysis assessed the effect of long-term (>6 weeks) noninvasive positive airway pressure (PAP) on diastolic function in patients with obstructive sleep apnea (OSA)., Methods: We searched the databases for randomized clinical trials including Ovid MEDLINE, Ovid Embase Scopus, Web of Science, Google Scholar, and EBSCO CINAHL from inception up to December 20, 2019. The search was not restricted to time, publication status, or language. Two independent investigators screened the studies and extracted the data, in duplicate. Risk of bias was assessed using Cochrane collaboration tools., Results: A total of 2,753 abstracts were resulted from literature search. A total of 9 randomized clinical trials assessing the effect of long-term (>6 weeks) PAP on diastolic function in patients with OSA including 833 participants were included. The following echo parameters were found in treated patients: a decrease in deceleration time (-39.49 ms CI [-57.24, -21.74]; p = 0.000), isovolumic relaxation time (-9.32 ms CI [-17.08, -1.57]; p = 0.02), and the ratio of early mitral inflow velocity to mitral annular early diastolic velocity (-1.38 CI [-2.6, -0.16]; p = 0.03). However, changes in left-atrial volume index and the ratio of early to late mitral inflow velocities were not statistically different. The risk of bias was mild to moderate among the studies., Conclusion: Our results suggest that chronic treatment of moderate to severe OSA with noninvasive PAP is associated with improvement in echocardiographic findings of diastolic dysfunction., (© 2021 S. Karger AG, Basel.)

Background: During the COVID-19 pandemic, the need for judicious use of diagnostic tests and to limit personnel exposure has led to increased use and dependence on point-of-care ultrasound (POCUS) examinations. We reviewed POCUS findings in patients admitted to the intensive care unit (ICU) for acute respiratory failure with COVID-19 and correlated the findings to severity of illness and 30-day outcomes., Methods: Patients admitted to the ICU in March and April 2020 were reviewed for inclusion (acute hypoxemic respiratory failure secondary to COVID-19 pneumonia; documentation of POCUS findings)., Results: Forty-three patients met inclusion criteria. B lines and pleural thickening were associated with a lower PaO 2 /FiO 2 by 71 ( P = .005; adjusted R 2 = 0.24). Right ventricle (RV) dilation was more common in patients with 30-day mortality ( P = .02) and was a predictor of mortality when adjusted for hypertension, diabetes mellitus, and age (odds ratio, 12.0; P = .048). All patients with RV dilation had bilateral B lines with pleural irregularities., Conclusions: Although lung ultrasound abnormalities are prevalent in patients with severe disease, RV involvement seems to be predictive of outcomes. Further studies are needed to discern the etiology and pathophysiology of RV dilation in COVID-19., Competing Interests: Author disclosures The authors report no actual or potential conflicts of interest with regard to this article., (Copyright © 2021 Frontline Medical Communications Inc., Parsippany, NJ, USA.)

Background: Therapeutic targeting of host-cell factors required for SARS-CoV-2 entry is an alternative strategy to ameliorate COVID-19 severity. SARS-CoV-2 entry into lung epithelium requires the TMPRSS2 cell surface protease. Pre-clinical and correlative data in humans suggest that anti-androgenic therapies can reduce the expression of TMPRSS2 on lung epithelium. Accordingly, we hypothesize that therapeutic targeting of androgen receptor signaling via degarelix, a luteinizing hormone-releasing hormone (LHRH) antagonist, will suppress COVID-19 infection and ameliorate symptom severity., Methods: This is a randomized phase 2, placebo-controlled, double-blind clinical trial in 198 patients to compare efficacy of degarelix plus best supportive care versus placebo plus best supportive care on improving the clinical outcomes of male Veterans who have been hospitalized due to COVID-19. Enrolled patients must have documented infection with SARS-CoV-2 based on a positive reverse transcriptase polymerase chain reaction result performed on a nasopharyngeal swab and have a severity of illness of level 3-5 (hospitalized but not requiring invasive mechanical ventilation). Patients stratified by age, history of hypertension, and severity are centrally randomized 2:1 (degarelix: placebo). The composite primary endpoint is mortality, ongoing need for hospitalization, or requirement for mechanical ventilation at 15 after randomization. Important secondary endpoints include time to clinical improvement, inpatient mortality, length of hospitalization, duration of mechanical ventilation, time to achieve a normal temperature, and the maximum severity of COVID-19 illness. Exploratory analyses aim to assess the association of cytokines, viral load, and various comorbidities with outcome. In addition, TMPRSS2 expression in target tissue and development of anti-viral antibodies will also be investigated., Discussion: In this trial, we repurpose the FDA approved LHRH antagonist degarelix, commonly used for prostate cancer, to suppress TMPRSS2, a host cell surface protease required for SARS-CoV-2 cell entry. The objective is to determine if temporary androgen suppression with a single dose of degarelix improves the clinical outcomes of patients hospitalized due to COVID-19., Trial Registration: ClinicalTrials.gov NCT04397718. Registered on May 21, 2020.

The coronavirus disease 2019 pandemic has impacted millions of people worldwide. This novel virus has a variety of presentations and complications. Notably, patients with this infection have an associated coagulopathy, presenting with symptoms such as gastrointestinal bleeds, deep vein thrombosis, ischemic cerebrovascular events, and pulmonary embolism. Although there are documented cases of venous thromboembolism in patients with coronavirus disease 2019, the authors present an interesting case of upper extremity arterial thromboembolism in a 75-year-old patient surgically treated for arterial thrombus removal. We also discuss diagnosis, medical management, and surgical approach to an upper extremity arterial thromboembolism in a patient with coronavirus disease 2019, to highlight the challenges of hypercoagulability in such patients., Competing Interests: Conflict of InterestNot applicable., (© The Author(s), under exclusive licence to Springer Nature Switzerland AG part of Springer Nature 2021.)

Study Objectives: Obstructive sleep apnea (OSA) is associated with chronic inflammation likely triggered by nocturnal, intermittent hypoxemia and increased adrenergic tone. The neutrophil-to-lymphocyte ratio (NLR) was recently described as a measure of subclinical systemic inflammation. Studies on the effect of continuous positive airway pressure (CPAP) therapy in OSA on subclinical inflammation measured by NLR are lacking. We hypothesize that NLR levels would improve as chronic inflammation diminishes in patients with OSA treated with CPAP., Methods: We retrospectively reviewed patients in whom OSA was diagnosed and who were treated with CPAP therapy. Complete blood count (CBC) were obtained pretreatment and posttreatment for calculation of NLR, which was calculated by dividing the number of neutrophils by the number of lymphocytes. Patients with conditions known to affect NLR such as chronic infections, inflammatory diseases, active cardiovascular disease, and malignancies were excluded from the study. CPAP adherence downloads were obtained for all patients., Results: Out of 184 patients in whom OSA was diagnosed and who were treated with CPAP, 109 met our study criteria, including baseline polysomnogram, baseline and posttreatment CBC, and available adherence download. We compared the NLR before and after treatment with CPAP. There was a significant difference in NLR before and after treatment with CPAP (P < .0001). There was also a significant difference in apnea-hypopnea index before and after treatment (P < .0001). We also assessed the relationship between CPAP adherence (percentage of days used for > 4 hours) and the change in NLR. NLR decreased significantly in both the adherent (CPAP use ≥ 70% of days; P = .014) and nonadherent groups (CPAP use < 70% of days; P = .0003). Finally, we noticed a significant direct correlation between CPAP adherence beyond 70% and the change in NLR (ΔNLR) (P = .046) in patients who had ≥ 70% adherence with CPAP, which was not observed in patients with < 70% adherence., Conclusions: The NLR may be a useful marker for monitoring improvement, as CPAP had a desirable effect on the chronic inflammation induced by OSA when measured by NLR in this study. Our results specifically suggest that the NLR values decrease significantly in patients using CPAP regardless of adherence, but with a more direct relationship in those who use it beyond 70% of days, at least 4 hours a day., (© 2020 American Academy of Sleep Medicine.)

Cocaine is a commonly abused recreational drug in the United States. An adult man developed non-specific pleuritic chest pain, pharyngitis and odynophagia after inhaling cocaine. Initial laboratory results revealed eosinophilia. Bronchoalveolar lavage also showed eosinophilia in the lavage fluid. These findings suggested the diagnosis of eosinophilic pneumonia. Chest imaging revealed scattered bilateral opacities and interstitial infiltrates. After initiation of systemic corticosteroids, the patient reported symptomatic resolution and radiographic clearance was achieved at 2 months follow up.

For patients with acute fulminant liver failure, imaging and histopathologic studies are indicated to reveal the underlying etiology, and metastatic small cell carcinoma should be included in the clinical differential diagnosis when appropriate., Competing Interests: Author disclosures The authors report no actual or potential conflicts of interest with regard to this article.

Hepatitis A virus is rarely associated with extrahepatic complications. A child presented with a history suggesting Raynaud's phenomenon and severe digital gangrene, as a complication of hepatitis A infection. Coagulation study results (protein C, protein S, antithrombin III, and activated protein C resistance) were all normal except for anticardiolipin antibodies, which were present on initial presentation and resolved later. Antinuclear antibodies, rheumatoid factor, lupus anticoagulant, antineutrophilic cytoplasmic antibodies, and Venereal Disease Research Laboratory test were all negative. Cryoglobulins were not detected. C3 and C4 levels were normal. Blood urea nitrogen and creatinine levels were normal as well. The patient was treated with aspirin and diclofenac, and improved slowly with complete resolution of gangrene and symptoms after 3 months. She remains asymptomatic 4 years later. Transient antiphospholipid syndrome or isolated Raynaud's phenomenon may be added to the list of extrahepatic complications of hepatitis A.