Viral infections causing asthma exacerbations in the age of biologics and the COVID-19 pandemic.

PURPOSE OF REVIEW: Asthma exacerbations are associated with substantial symptom burden and healthcare costs. Viral infections are the most common identified cause of asthma exacerbations. The epidemiology of viral respiratory infections has undergone a significant evolution during the COVID-19 pandemic. The relationship between viruses and asthmatic hosts has long been recognized but it is still incompletely understood. The use of newly approved asthma biologics has helped us understand this interaction better. RECENT FINDINGS: We review recent updates on the interaction between asthma and respiratory viruses, and we address how biologics and immunotherapies could affect this relationship by altering the respiratory mucosa cytokine milieu. By exploring the evolving epidemiological landscape of viral infections during the different phases of the COVID-19 pandemic, we emphasize the early post-pandemic stage, where a resurgence of pre-pandemic viruses with atypical seasonality patterns occurred. Finally, we discuss the newly developed RSV and SARS-CoV-2 vaccines and how they reduce respiratory infections. SUMMARY: Characterizing how respiratory viruses interact with asthmatic hosts will allow us to identify tailored therapies to reduce the burden of asthma exacerbations. New vaccination strategies are likely to shape the future viral asthma exacerbation landscape.

Majority of human circulating IgG plasmablasts stop blasting in a cell-free pro-survival culture.

Following infection or vaccination, early-minted antibody secreting cells (ASC) or plasmablasts appear in circulation transiently, and a small fraction migrates to the spleen or bone marrow (BM) to mature into long-lived plasma cells (LLPC). While LLPC, by definition, are quiescent or non-dividing, the majority of blood ASC are thought to be "blasting" or proliferative. In this study, we find > 95% nascent blood ASC in culture express Ki-67 but only 6-12% incorporate BrdU after 4 h or 24 h labeling. In contrast, < 5% BM LLPC in culture are Ki-67+ with no BrdU uptake. Due to limitations of traditional flow cytometry, we utilized a novel optofluidic technology to evaluate cell division with simultaneous functional IgG secretion. We find 11% early-minted blood ASC undergo division, and none of the terminally differentiated BM LLPC (CD19-CD38hiCD138+) divide during the 7-21 days in culture. While BM LLPC undergo complete cell cycle arrest, the process of differentiation into an ASC or plasmablasts also discourages entry into S phase. Since the majority of Ki-67+ nascent blood ASC have exited cell cycle and are no longer actively "blasting", the term "plasmablast", which traditionally refers to an ASC that still has the capacity to divide, may probably be a misnomer.

Virtual Interviews: A Cross-Sectional Quality Improvement Project Aimed to Improve the Interview Process in an Internal Medicine Residency Program.

BACKGROUND: The residency interview is a crucial step that helps the program identify potential new trainees while the trainees find out more about the program. With the onset of the COVID-19 pandemic, it became essential to hold interviews virtually. OBJECTIVE: Here, we conducted a questionnaire-based study to identify areas of improvement in the virtual interview process in our program. METHODS: The study was conducted among the residency interview applicants of the 2022 match cycle. A questionnaire was sent via email to all applicants who were invited to our residency program for an interview. Out of the 600 applicants who were interviewed in our program, 230 applicants answered the survey, an 11-point questionnaire pertaining to the various aspects of the interview process. RESULTS:  A virtual interview with an option of in-person is the most favored answer among the different groups, i.e., American Medical Graduates (AMGs), International Medical Graduates (IMGs) without need for a visa, and IMGs with a need for a visa, respectively, were, 37.5%, 42.8%, and 38.65%, respectively. An updated website with all required information was a top resource used by 95%, 84.5%, and 89.6% of the different groups of candidates. American medical graduates (32.50%) place high importance on resident interaction, while international medical graduates want the programs to focus on their website and provide more information about all aspects of the program during the virtual interview. CONCLUSIONS: In the post-COVID-19 era, Internal Medicine programs will need to improve several aspects of virtual interviews while assessing what is important to candidates.

Syndrome of Inappropriate Secretion of Antidiuretic Hormone (SIADH) With Severe Hyponatremia As the Initial and Sole Presentation of COVID-19 Infection: A Case Report and Pathophysiologic Insights.

Hyponatremia is one of the common electrolyte imbalances among hospitalized patients with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) being a common etiology for hyponatremia. There are multiple pathophysiologic considerations in the differential diagnosis of the etiologic factor for SIADH, including infections such as pneumonia and meningitis, as well as coronavirus disease 2019 (COVID-19) infection. However, SIADH, as the sole initial presentation of the infection of COVID-19, is rarely reported. In this report, we present a case of SIADH as the initial and only presentation of a COVID-19 infection, highlighting the clinical course and treatment strategy while providing the putative pathophysiologic insights into this unusual and potentially serious complication of COVID-19 infection.

Treatment of Sleep Apnea with Positive Airway Pressure and Its Association with Diastolic Dysfunction: A Systematic Review and Meta-Analysis.

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.

Novel oral anticoagulants in intracardiac thrombosis resolution: a case series.

BACKGROUND: Vitamin K antagonists (VKAs) have been regarded as the therapy of choice for intracardiac thrombosis for decades based mostly on observational data. The advent of direct oral anticoagulants (DOACs) has displaced VKAs as the first-line therapy for multiple thrombotic disorders but not for intracardiac thrombosis. Although limited, there is growing evidence that DOACs are effective for intracardiac thrombosis and some data suggest that thrombus resolution might be superior to that with warfarin. CASE SUMMARY: Here, we present a series of six patients with left atrial appendage thrombi were treated with a venous thromboembolic dose of DOACs with resolution within 2-6 months with no reported complications. DISCUSSION: This case series adds to the accumulating evidence supporting the efficacy of DOACs in the treatment of intracardiac thrombi.

A Rapidly Progressive Case of Statin-induced Necrotizing Autoimmune Myopathy.

Statins are one of the most commonly used medications to lower cholesterol and have been known to cause various side effects including myalgias, myopathies, and rhabdomyolysis. Statin-induced necrotizing autoimmune myopathy (SINAM), a subtype of inflammatory myopathy, is an exceedingly rare but severe side effect of statin use that manifests as progressive muscle weakness. We describe a rapidly progressive case of SINAM in a 66-year-old Haitian female who developed debilitating symptoms after one month of statin use. Despite aggressive treatment with steroids and immunosuppressants, she failed to regain muscle strength and functional status, and remains on therapy. Given the widespread use of statins, it is important for clinicians to be aware of this condition and its presenting symptoms in order to initiate prompt treatment.

Early Experience With Methylprednisolone on SARS-CoV-2 Infection in the African American Population, a Retrospective Analysis.

BACKGROUND: Coronavirus disease-19 (COVID-19) is associated with acute kidney injury (AKI) and acute respiratory distress syndrome (ARDS) with high mortality rates. In African American (AA) populations, COVID-19 presentations and outcomes are more severe. NIH and Interim WHO guidelines had suggested against the use of corticosteroids unless in clinical trials until the recent publication of the RECOVERY trial. Here, we analyzed the treatment effect of methylprednisolone on patients with AKI and ARDS during the initial 2 months of COVID-19 and detail the learning effect within our institution. METHODS: Between March 1 and April 30, 2020, 75 AA patients met our inclusion criteria for ARDS and AKI, of which 37 had received corticosteroids. Twenty-eight-day mortality, improvement in PaO2/FiO2 ratio, and renal function were analyzed. The impact of methylprednisolone treatment was assessed with multivariable methods. RESULTS: Survival in the methylprednisolone group reached 51% at 21 days compared to 29% in the non-corticosteroid group (P < .001). Methylprednisolone improved the likelihood of renal function improvement. PaO2/FiO2 ratio in the methylprednisolone group improved by 73% compared to 45% in the non-corticosteroid group (P = .01). Age, gender, BMI, preexisting conditions, and other treatment factors did not show any impact on renal or PaO2/FiO2 ratio improvement. The use of anticoagulants, the month of treatment, and AKI during hospitalization also influenced outcomes. CONCLUSION: In AA COVID-19 positive patients with ARDS and AKI, IV methylprednisolone lowered the incidence of mortality and improved the likelihood of renal and lung function recovery. Further investigation with a randomized control trial of corticosteroids is warranted.