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AbstractBackgroundThe role of microbes in chronic rhinosinusitis (CRS) is poorly understood. We hypothesize that analyzing prior microbial exposures via assessing microbial protein serological reactivity in CRS versus controls may offer insights for CRS etiopathogenesis.MethodsWe profiled IgG and IgA antibodies to individual microbial proteins in serum samples of CRS patients and controls using a novel high‐throughput microarray protein technology, Nucleic Acid Programmable Protein Array (NAPPA). The study was conducted on 118 subjects (39 CRS, 79 controls). A CRS‐focused NAPPA array, with 1557 potentially sero‐reactive microbial proteins elected from a pre‐screening of 6500 genes of interest was constructed. It included membrane‐associated proteins from 47 bacterial species and all proteins from 43 viral strains. Differences between CRS and controls were compared across individual antimicrobial antibodies and the species.ResultsChronic rhinosinusitis patients had significantly elevated antimicrobial antibodies compared with controls. One bacterium (Staphylococcus aureus) and three viral strains (human metapneumovirus, human herpesvirus 5, and human herpesvirus 4) were identified as sources of the proteins that showed significantly elevated sero‐reactivity in CRS patients. Within CRS, patients with polyps had elevated antibodies against S. aureus, influenza A virus (H1N1, H3N2), and rhinovirus B14. CRS patients without polyps showed more antibodies against human herpesvirus 1 and vaccinia virus WR.ConclusionsCompared with healthy controls, CRS patients’ serum samples showed significantly increased sero‐reactivity to both bacterial and viral proteins, reflecting recent or current infection or active colonization. Significantly higher antibodies against S. aureus, human metapneumovirus, human herpesvirus 5, and human herpesvirus 4 in CRS need further study.

Abstract Objective This work aims to guide clinicians practicing endocrinology in the use of telehealth (synchronous patient-clinician visits conducted over video or telephone) for outpatient care. Participants The Endocrine Society convened a 9-member panel of US endocrinologists with expertise in telehealth clinical care, telehealth operations, patient-centered care, health care delivery research, and/or evidence-based medicine. Evidence The panel conducted a literature search to identify studies published since 2000 about telehealth in endocrinology. One member extracted a list of factors affecting the quality of endocrine care via telehealth from the extant literature. The panel grouped these factors into 5 domains: clinical, patient, patient-clinician relationship, clinician, and health care setting and technology. Consensus Process For each domain, 2 or 3 members drew on existing literature and their expert opinions to draft a section examining the effect of the domain’s component factors on the appropriateness of telehealth use within endocrine practice. Appropriateness was evaluated in the context of the 6 Institute of Medicine aims for health care quality: patient-centeredness, equity, safety, effectiveness, timeliness, and efficiency. The panel held monthly virtual meetings to discuss and revise each domain. Two members wrote the remaining sections and integrated them with the domains to create the full policy perspective, which was reviewed and revised by all members. Conclusions Telehealth has become a common care modality within endocrinology. This policy perspective summarizes the factors determining telehealth appropriateness in various patient care scenarios. Strategies to increase the quality of telehealth care are offered. More research is needed to develop a robust evidence base for future guideline development.

ImportanceThere is limited evidence for therapeutic options for pediatric COVID-19 outside of multisystem inflammatory syndrome in children (MIS-C).ObjectiveTo determine whether the use of steroids within 2 days of admission for non–MIS-C COVID-19 in children is associated with hospital length of stay (LOS). The secondary objective was to determine their association with intensive care unit (ICU) LOS, inflammation, and fever defervescence.Design, Setting, and ParticipantsThis cohort study analyzed data retrospectively for children (<18 years) who required hospitalization for non–MIS-C COVID-19. Data from March 2020 through September 2021 were provided by 58 hospitals in 7 countries who participate in the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS) COVID-19 registry.ExposureAdministration of steroids within 2 days of admission.Main Outcomes and MeasuresLength of stay in the hospital and ICU. Adjustment for confounders was done by mixed linear regression and propensity score matching.ResultsA total of 1163 patients met inclusion criteria and had a median (IQR) age of 7 years (0.9-14.3). Almost half of all patients (601/1163, 51.7%) were male, 33.8% (392/1163) were non-Hispanic White, and 27.9% (324/1163) were Hispanic. Of the study population, 184 patients (15.8%) received steroids within 2 days of admission, and 979 (84.2%) did not receive steroids within the first 2 days. Among 1163 patients, 658 (56.5%) required respiratory support during hospitalization. Overall, patients in the steroids group were older and had greater severity of illness, and a larger proportion required respiratory and vasoactive support. On multivariable linear regression, after controlling for treatment with remdesivir within 2 days, country, race and ethnicity, obesity and comorbidity, number of abnormal inflammatory mediators, age, bacterial or viral coinfection, and disease severity according to ICU admission within first 2 days or World Health Organization ordinal scale of 4 or higher on admission, with a random intercept for the site, early steroid treatment was not significantly associated with hospital LOS (exponentiated coefficient, 0.94; 95% CI, 0.81-1.09; P = .42). Separate analyses for patients with an LOS of 2 days or longer (n = 729), those receiving respiratory support at admission (n = 286), and propensity score–matched patients also showed no significant association between steroids and LOS. Early steroid treatment was not associated with ICU LOS, fever defervescence by day 3, or normalization of inflammatory mediators.Conclusions and RelevanceSteroid treatment within 2 days of hospital admission in a heterogeneous cohort of pediatric patients hospitalized for COVID-19 without MIS-C did not have a statistically significant association with hospital LOS.

Nosocomial infections pose an imminent challenge to hospitalized Coronavirus disease-19 (COVID-19) patients due to complex interplay of dysregulated immune response combined with immunomodulator therapy. In the pre-pandemic era, immunomodulatory therapy has shown benefit in certain autoimmune conditions with untamed inflammatory response. Efforts to recapitulate these immunomodulatory effects in COVID-19 patients has gained impetus and were followed by NIH COVID-19 expert panel recommendations. The current NIH guideline recommends interleukin-6 inhibitors (tocilizumab and sarilumab) and Janus kinase inhibitors (baricitinib and tofacitinib). Several landmark research trials like COVAVTA, EMPACTA, REMDACTA, STOP-COVID and COV BARRIER have detailed the various effects associated with administration of immunomodulators. The historical evidence of increased infection among patients receiving immunomodulators for autoimmune conditions, raised concerns regarding administration of immunomodulators in COVID-19 patients. The aim of this review article is to provide a comprehensive update on the currently available literature surrounding this issue. We reviewed 40 studies out of which 37 investigated IL-6 inhibitors and 3 investigated JAK inhibitors. Among the studies reviewed, the reported rates of nosocomial infections among the COVID-19 patients treated with immunomodulators were similar to patients receiving standard of care for COVID-19. However, these studies were not powered to assess the side effect profile of these medications. Immunomodulators, by dampening the pyrogenic response and inflammatory markers may delay detection of infections among the patients. This underscores the importance of long-term surveillance which are necessary to discover the potential risks associated with these agents.

Takotsubo cardiomyopathy or Takotsubo Syndrome (TTS) is a reversible left ventricular dysfunction syndrome that is increasingly being recognized. Recent advances in nuclear imaging have allowed us to study TTS in greater detail. We searched the PubMed and Medline databases and identified 53 publications with 221 patients reporting nuclear imaging findings in TTS. The age of the patients ranged from 17 to 87 years and were predominantly women (88.2%). The TTS variant was apical (typical) in 170 (76.9%), mid-ventricular in 23 (10.4%), and basal (reverse TTS) in 2 (0.9%). Cardiac perfusion was assessed using 99mTc sestamibi (MIBI) SPECT, 99mTc tetrofosmin SPECT, 201Tl SPECT, 82Rb PET, 201Tl SPECT, and 13N ammonia PET. Additional studies used were 123I MIBG SPECT, 123I BMIPP SPECT, 18F FDG PET, 67Ga citrate, and 11C hydroxy-ephedrine. A perfusion defect was seen in 69 (31.2%), and an inverse perfusion–metabolism mismatch (normal or near-normal perfusion with absent myocardial metabolic activity) was seen in 183 (82.8%) patients. Nuclear imaging has a significant role in evaluating, diagnosing, and prognosticating patients with TTS. As nuclear imaging technology evolves, we will surely gain more insights into this fascinating disorder.