Inhaled Pulmonary Vasodilators in COVID-19 Infection: A Systematic Review and Meta-Analysis.

Introduction: Inhaled pulmonary vasodilators (IPVD) have been previously studied in patients with non-coronavirus disease-19 (COVID-19) related acute respiratory distress syndrome (ARDS). The use of IPVD has been shown to improve the partial pressure of oxygen in arterial blood (PaO2), reduce fraction of inspired oxygen (FiO2) requirements, and ultimately increase PaO2/FiO2 (P/F) ratios in ARDS patients. However, the role of IPVD in COVID-19 ARDS is still unclear. Therefore, we performed this meta-analysis to evaluate the role of IPVD in COVID-19 patients. Methods: Comprehensive literature search of PubMed, Embase, Web of Science and Cochrane Library databases from inception through April 22, 2022 was performed for all published studies that utilized IPVD in COVID-19 ARDS patients. The single arm studies and case series were combined for a 1-arm meta-analysis, and the 2-arm studies were combined for a 2-arm meta-analysis. Primary outcomes for the 1-arm and 2-arm meta-analyzes were change in pre- and post-IPVD P/F ratios and mortality, respectively. Secondary outcomes for the 1-arm meta-analysis were change in pre- and post-IPVD positive end-expiratory pressure (PEEP) and lung compliance, and for the 2-arm meta-analysis the secondary outcomes were need for endotracheal intubation and hospital length of stay (LOS). Results: 13 single arm retrospective studies and 5 case series involving 613 patients were included in the 1-arm meta-analysis. 3 studies involving 640 patients were included in the 2-arm meta-analysis. The pre-IPVD P/F ratios were significantly lower compared to post-IPVD, but there was no significant difference between pre- and post-IPVD PEEP and lung compliance. The mortality rates, need for endotracheal intubation, and hospital LOS were similar between the IPVD and standard therapy groups. Conclusion: Although IPVD may improve oxygenation, our investigation showed no benefits in terms of mortality compared to standard therapy alone. However, randomized controlled trials are warranted to validate our findings.

Pulse versus nonpulse steroid regimens in patients with coronavirus disease 2019: A systematic review and meta-analysis.

Systemic steroids are associated with reduced mortality in hypoxic patients with coronavirus disease 2019 (COVID-19). However, there is no consensus on the doses of steroid therapy in these patients. Several studies showed that pulse dose steroids (PDS) could reduce the progression of COVID-19 pneumonia. However, data regarding the role of PDS in COVID-19 is still unclear. Therefore, we performed this meta-analysis to evaluate the role of PDS in COVID-19 patients compared to nonpulse steroids (NPDS). Comprehensive literature search of PubMed, Embase, Cochrane Library, and Web of Science databases from inception through February 10, 2022 was performed for all published studies comparing PDS to NPDS therapy to manage hypoxic patients with COVID-19. Primary outcome was mortality. Secondary outcomes were the need for endotracheal intubation, hospital length of stay (LOS), and adverse events in the form of superimposed infections. A total of 10 observational studies involving 3065 patients (1289 patients received PDS and 1776 received NPDS) were included. The mortality rate was similar between PDS and NPDS groups (risk ratio [RR]: 1.23, 95% confidence interval [CI]: 0.92-1.65, p = 0.16). There were no differences in the need for endotracheal intubation (RR: 0.71, 95%: CI 0.37-1.137, p = 0.31), LOS (mean difference: 1.93 days; 95% CI: -1.46-5.33; p = 0.26), or adverse events (RR: 0.93, 95% CI: 0.56-1.57, p = 0.80) between the two groups. Compared to NPDS, PDS was associated with similar mortality rates, need for endotracheal intubation, LOS, and adverse events. Given the observational nature of the included studies, randomized controlled trials are warranted to validate our findings.

Fluvoxamine in Nonhospitalized Patients With Acute COVID-19 Infection and the Lack of Efficacy in Reducing Rates of Hospitalization, Mechanical Ventilation, and Mortality in Placebo-Controlled Trials: A Systematic Review and Meta-Analysis.

BACKGROUND: Recent clinical trials have investigated the use of fluvoxamine in preventing clinical deterioration in nonhospitalized patients with acute COVID-19 infection via stimulation of sigma-1 receptors, which regulates cytokine production and functional inhibition of acid sphingomyelinase activity, which may prevent infection of epithelial cells with SARS-CoV-2. However, the role of fluvoxamine is currently unclear because of a paucity of studies, particularly because the drug is being repurposed as an immunomodulatory and antiviral agent. STUDY QUESTION: Aim of our meta-analysis was to investigate the efficacy of fluvoxamine in nonhospitalized patients with acute COVID-19 infection. DATA SOURCE: Comprehensive literature search of PubMed, Embase, Cochrane Library databases, and Web of Science was performed from inception to February 10, 2022, for studies comparing fluvoxamine versus placebo for outpatient management of COVID-19. STUDY DESIGN: The primary outcome of interest was rate of hospitalization. The secondary outcomes were rates of patients requiring mechanical ventilation and mortality. The random-effects model was used to calculate the risk ratios (RR) and confidence intervals (CI). A P value <0.05 was considered statistically significant. Heterogeneity was assessed using the Higgins I2 index. RESULTS: Three studies (2 randomized controlled trials and one prospective cohort trial) involving 1762 patients were included in the meta-analysis. In patients who received fluvoxamine compared with placebo, there was no significant difference in rates of hospitalization (RR 0.26, 95% CI, 0.04-1.73, P = 0.16, I2 = 62%), mechanical ventilation (RR 0.73, 95% CI, 0.45-1.19, P = 0.21, I2 = 0%), and mortality (RR 0.67, 95% CI, 0.37-1.22, P = 0.19, I2 = 0%). CONCLUSION: Current evidence does not indicate a significant effect of fluvoxamine on the rates of hospitalization, mechanical ventilation, and mortality of patients with COVID-19 infection.

Subacute Cutaneous Lupus as a Paraneoplastic Manifestation of Non-Hodgkin Lymphoma.

Malignancies have been associated with paraneoplastic syndromes, such as dermatomyositis. Subacute cutaneous lupus erythematosus (SCLE) can occur due to a wide array of cancers. Paraneoplastic SCLE obeys McLean's criteria and often regresses after the underlying malignancy has been treated appropriately. Anti-Ro/SSA antibodies are often present in patients with paraneoplastic SCLE; however, there have been many instances where anti-Ro may not be present. We report a case of non-Hodgkin lymphoma causing SCLE, a malignancy not previously known to be associated with paraneoplastic SCLE. We also highlight the importance of perhaps prompt chemotherapy to treat the underlying malignancy, as a failure to do so may lead to worse patient outcomes.

Does a Starting Positive End-Expiratory Pressure of 8 cmH2O Decrease the Probability of a Ventilator-Associated Event?

Introduction: Ventilator-associated events (VAEs) are objective measures as defined by the Centers for Disease Control and Prevention (CDC). To reduce VAEs, some hospitals have started patients on higher baseline positive end-expiratory pressure (PEEP) to avoid triggering VAE criteria due to respiratory fluctuations. Methods: At our institution, VAEs were gathered from January 2014 through December 2019. Using the CDC-defined classifications, VAEs were split into two groups to separate patients with hypoxemia only (VAC) and those with hypoxemia and evidence of inflammation or infection (IVAC-plus). We used the geometric distribution to calculate the daily event probability before and after the protocol implementation. A probability threshold was used to determine if the days between events was exceeded during the post-protocol period. Results: A total of 306 VAEs were collected over the study period. Of those, 155 were VACs and 107 were IVAC-plus events during the pre-protocol period. After implementing the protocol, 24 VACs and 20 IVAC-plus events were reported. There was a non-significant decrease in daily event probabilities in both the VAC and IVAC-plus groups (0.083 vs. 0.068 and 0.057 vs. 0.039, respectively). Conclusion: We concluded a starting PEEP of 8 cmH2O is unlikely to be an effective intervention at reducing the probability of a VAE. Until specific guidelines by the CDC are established, hospitals should consider alternative methods to reduce VAEs.

Rituxan-Induced Tumor Lysis Syndrome in a Patient With Diffuse Large B-Cell Lymphoma.

Rituximab or Rituxan is a common drug used in the treatment of lymphomas. It is almost always used in conjunction with other chemotherapy regimens. Mechanism of action involves killing of the CD 20+ cells. Rituximab is implicated in precipitating tumor lysis syndrome (TLS) in patients with diffused large B cell lymphoma (DLBCL). The precise pathophysiological mechanism is not well known. Here, we present a case where the patient only received Rituxan for her newly diagnosed B-cell lymphoma which triggered a tumor lysis cascade. This in turn resulted in multiple electrolyte disturbances, multi-organ failure, and mortality. This report discusses the case presentation in addition to the different types of TLS and how this knowledge can be applied in the clinical setting for the future.

Legionella pneumophila as a cause of cavitary lung disease in systemic lupus erythematous.

Legionnaire's disease (LD) is most commonly caused by Legionella pneumophila (L. pneumophila). In immunocompromised patients LD can cause necrosis of the lung parenchyma with abscess formation and cavitation. Systemic lupus erythematosus (SLE) is an autoimmune disorder with features of both primary and secondary immunodeficiency. SLE patients often develop pulmonary abnormalities, but rarely develop lung cavitations. We report a case of cavitary pneumonia caused by L. pneumophila in a 64-year-old female patient with SLE. We also highlight reasons why SLE patients are more prone to L. pneumophila infections. The importance of using correct diagnostic methods for recognizing and treating such infections is also discussed, as mistreatment of cavitary lesions in SLE patients with steroid therapy can have fatal outcomes as the infectious process can significantly worsen.

Current treatment of congenital pseudarthrosis of the tibia: a systematic review and meta-analysis.

To compare the current treatments for congenital pseudarthrosis of tibia, a total of 33 studies were reviewed. Vascularized fibular graft with external fixation or combined fixation had the fastest time till initial union (P<0.05). Bone morphogenetic protein had no advantage in terms of initial union, time till union, and refracture rates. This meta-analysis supports that fixation methods with corticocancellous bone autograft utilizing the combined technique of Ilizarov external fixation and intramedullary rod stabilization ensure a statistically significant reduction in the number of refractures compared with standalone fixation methods and would be the preferred method for preventing long-term complications in patients with congenital pseudarthrosis of tibia.