Background Dexamethasone 6 mg daily for 10 days is the recommended treatment for patients with severe or critical coronavirus disease 2019 (COVID-19). The evidence on the benefit of high-dose dexamethasone is limited. The goal of this study was to assess the effects of 6 mg daily vs. 20 mg daily of dexamethasone in hospitalized patients with COVID-19 pneumonia. Methods We conducted a single-center, randomized, clinical trial involving hospitalized patients with COVID-19 pneumonia. Participants were randomized 1:1 to dexamethasone 6 mg daily or dexamethasone 20 mg daily, and were stratified by the WHO-Ordinal Scale for Clinical Improvement (OSCI). The primary outcome was clinical improvement equal to or greater than 2 points by OSCI on day 28. Secondary outcomes were 28-day mortality, intensive care unit-free days, and ventilator-free days on day 28. Results Of the 107 patients who enrolled and completed the follow up, 55 patients enrolled in the low-dose group and 52 patients enrolled in the high-dose group. Treatment with dexamethasone 20 mg daily compared with dexamethasone 6 mg daily did not result in better clinical improvement based on OSCI on day 28 (71.2% vs. 78.2%; odds ratio, 1.45 [0.55–3.86]; p = 0.403). For participants who required high-flow oxygen or noninvasive ventilation at randomization, the 6-mg group had better survival than the 20-mg group on day 28 (100% vs. 57.1%; p = 0.025). Although more participants in the 6-mg group received immune modulators (40% vs. 21.2%; p = 0.035), 50% of death cases in the 20-mg group who required high-flow oxygen or noninvasive ventilation at randomization received immune modulators. Conclusions Dexamethasone 20 mg daily did not result in better clinical outcome improvement, and was probably associated with higher 28-day mortality in patients on high-flow oxygen or noninvasive ventilation, compared with dexamethasone 6 mg daily. Trial registration Clinialtrials.gov number, NCT04707534, registered January 13, 2021

Tocilizumab is an interleukin receptor inhibitor that has been used in patients with COVID-19 pneumonia. There are recent randomized controlled trials (RCTs) that evaluated the efficacy and safety of tocilizumab in hospitalized patients with COVID-19 pneumonia. We performed a systematic review and meta-analysis of RCTs that evaluated the effectiveness of tocilizumab in hospitalized patients with COVID-19 not requiring mechanical ventilation. RCTs comparing tocilizumab with the standard of care treatment in hospitalized patients with COVID-19 pneumonia not requiring mechanical ventilation at the time of administration were included for analysis. The primary outcome was a composite of mechanical ventilation or 28-day mortality and the secondary outcomes were 28-day mortality and major adverse events. A total of 6 RCTs were included for the analysis. Tocilizumab was associated with a statistically significant reduction in the primary composite outcome of mechanical ventilation or 28-day mortality (risk ratio (RR): 0.83 (95% CI: 0.74 to 0.92, I2=0, tau2=0). Treatment with tocilizumab did not show a statistically significant reduction in 28-day mortality (RR: 0.90 (95% CI: 0.76 to 1.07), I2=0, tau2=0) and rate of serious adverse events (RR: 0.82 (95% CI: 0.62 to 1.10), I2=0, tau2=0). Tocilizumab was associated with a decrease in the incidence of primary outcome, that is, mechanical ventilation or death at 28 days in hospitalized patients with COVID-19 pneumonia.

Sarcoidosis is a systemic inflammatory disease characterized by infiltration of immune cells into granulomas. Previous gene expression studies using heterogeneous cell mixtures lack insight into cell-type-specific immune dysregulation. We performed the first single-cell RNA-sequencing study of sarcoidosis in peripheral immune cells in 48 patients and controls. Following unbiased clustering, differentially expressed genes were identified for 18 cell types and bioinformatically assessed for function and pathway enrichment. Our results reveal persistent activation of circulating classical monocytes with subsequent upregulation of trafficking molecules. Specifically, classical monocytes upregulated distinct markers of activation including adhesion molecules, pattern recognition receptors, and chemokine receptors, as well as enrichment of immunoregulatory pathways HMGB1, mTOR, and ephrin receptor signaling. Predictive modeling implicated TGFβ and mTOR signaling as drivers of persistent monocyte activation. Additionally, sarcoidosis T cell subsets displayed patterns of dysregulation. CD4 naïve T cells were enriched for markers of apoptosis and Th17/Treg differentiation, while effector T cells showed enrichment of anergy-related pathways. Differentially expressed genes in regulatory T cells suggested dysfunctional p53, cell death, and TNFR2 signaling. Using more sensitive technology and more precise units of measure, we identify cell-type specific, novel inflammatory and regulatory pathways. Based on our findings, we suggest a novel model involving four convergent arms of dysregulation: persistent hyperactivation of innate and adaptive immunity via classical monocytes and CD4 naïve T cells, regulatory T cell dysfunction, and effector T cell anergy. We further our understanding of the immunopathology of sarcoidosis and point to novel therapeutic targets.

A 62-year-old female presented to the emergency room with one-month history of epigastric abdominal pain, nausea and vomiting. She endorsed progressive dyspnea over two weeks. CT of the abdomen demonstrated bilateral pleural effusions and pancreatic inflammation, so the working diagnosis was pancreatitis. A diagnostic thoracentesis was performed and the pleural fluid analysis was classified as transudate by Light's criteria. Given the atypical features in history and concern for malignancy, fluid was sent for cytological examination and immunohistochemistry which suggested a mucinous malignancy. EGD revealed poorly differentiated signet ring cell adenocarcinoma of stomach. Patient underwent placement of indwelling pleural catheters for symptomatic improvement and was discharged to hospice. The decision whether to routinely send transudative effusions for cytological evaluation remains controversial. This case demonstrates the importance of using clinical judgement to guide that decision.

Despite recent developments, evaluation of peripheral pulmonary lesions (PPL) remains clinically challenging, and the diagnostic yield of many image-guided and bronchoscopy methods is still poor. Furthermore, complications from such procedures, such as pneumothorax and airway hemorrhage, are a major concern. Recently launched robotic-assisted bronchoscopy (RAB) platforms are still in the early exploration stage and may provide another tool for achieving PPL evaluation. We present our experience here as a retrospective cohort study describing the 12-month diagnostic yield with the shape-sensing Ion™ platform for minimally invasive peripheral lung biopsy. The study describes forty-two patients undergoing shape sensing robotic-assisted bronchoscopy (ssRAB) at our institute. The early performance trend reveals a lesion localization of 100% and an overall 12-month diagnostic yield of 88.10%. The diagnostic yield for lesions less than 20 mm was 76% and for lesions greater than 20 mm was 100%. We also report our complication profile; we noted no pneumothoraces, excessive bleeding, or post-operative complications. In comparison to traditional bronchoscopy and image-guided modalities, our experience shows that ssRAB can be utilized successfully to travel to extremely small peripheral lesions with a higher diagnostic yield and better safety profile.

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IntroductionSerum Soluble Interleukin-2 Receptor (sIL-2R) levels are used clinically as a disease activity marker for systemic sarcoidosis. Studies have investigated the diagnostic role of serum soluble interleukin-2 receptor (sIL-2R) level for sarcoidosis relative to biopsy. We performed a systematic review and meta-analysis of studies evaluating the diagnostic utility of sIL-2R.MethodsWe carried out an electronic search in Medline, Embase, Google Scholar, and Cochrane databases using keyword and Medical Subject Heading (MeSH) terms: sarcoidosis and sIL-2R. Studies evaluating the sIL-2R levels as a diagnostic tool in clinically diagnosed or biopsy-proven sarcoidosis patients compared to control groups with non-sarcoidosis patients were included. Forest plots were constructed using a random effect model depicting pooled sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy.ResultsWe selected ten studies comprising 1477 patients, with 592 in the sarcoidosis group and 885 in the non-sarcoidosis group. Pooled sensitivity and specificity of sIL-2R levels were 0.88 (95% CI: 0.75-0.95) and 0.87 (95% CI 0.73-0.94) respectively. Pooled negative predictive value and positive predictive value were 0.91 (95% CI 0.77-0.97) and 0.85 (95% CI 0.59-0.96) respectively with diagnostic accuracy of 0.86 (95% CI 0.71-0.93).ConclusionIn addition to its utility as a marker of sarcoidosis disease activity, sIL-2R has high diagnostic accuracy. Despite the limitations of the heterogenous sarcoidosis population and different sIL-2R cutoffs, our results suggest that sIL-2R is an important biomarker that can be used to confirm sarcoidosis diagnosis in unconfirmed or unclear cases.

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