Sarcoidosis and burn pit exposure in military deployers to Iraq, Afghanistan, and Southwest Asia.

BACKGROUND AND AIM: Inhalational exposures have been hypothesized to play a role in the pathogenesis of sarcoidosis. Herein, we describe a cohort of US Military personnel diagnosed with sarcoidosis during or after deployment to Southwest Asia and Afghanistan, who experienced complex inhalational exposures to burn-pits and desert dust. METHODS: Consecutive military personnel at four sub-specialty clinics across the United States were screened for deployment to Southwest Asia and Afghanistan and diagnosis of sarcoidosis based on 1999 ATS/ERS/WASOG Statement on Sarcoidosis. Detailed demographic, deployment and exposure data was collected. The data combined was analyzed after de-identification and local IRB approval. RESULTS: Twenty-one patients met our case definition. Seventeen patients were male and 62% had extrapulmonary involvement, including 38% with musculoskeletal involvement.  Conclusions: Our study suggests that the sarcoidosis in military personnel to Southwest Asia can be diagnosed many years after deployment. To our knowledge, this is the first case series to describe a group of military personnel diagnosed with sarcoidosis and exposures specific to military deployment to Southwest Asia.

Role of Serum Soluble Interleukin-2 Receptor Level in the Diagnosis of Sarcoidosis: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIM: Serum 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. METHODS: We 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. RESULTS: We 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). CONCLUSION: In 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.

Low-dose versus high-dose dexamethasone for hospitalized patients with COVID-19 pneumonia: A randomized clinical trial.

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.

Navigational Bronchoscopy with Cryobiopsy for Diagnosis of ILD.

Background: Interstitial lung diseases (ILDs) are a group of parenchymal pulmonary diseases in which pathologic diagnosis is essential. Although cryobiopsy has a high diagnostic yield, the complication rate remains high. Case Presentation. We report two cases of lung cryobiopsy guided by navigational bronchoscopy (LCB) for the diagnosis of ILD. In both cases, a CT chest angiogram (CTA) using a navigational protocol was performed. Targets were premarked and reached with the navigational system. Radial ultrasound (RU) was applied in combination with fluoroscopy guidance (FG) prior to sampling. Both patients achieved a final diagnosis; they were discharged home after procedure and no complications were noted. Discussion. By using a CTA with navigational guidance, we were able to perform cryobiopsy in areas with most disease activity and least vascularization. Conclusion: LCB used with navigational guidance for the diagnosis of ILD provides may be a safe and effective procedure that provides high diagnostic yield. Limitations include cost, availability, and expertise. Larger trials are needed to confirm the additional benefit.

Tocilizumab in patients hospitalized with COVID-19 pneumonia: systematic review and meta-analysis of randomized controlled trials.

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.

Interlobular Septal Thickening in a Young Man With Dyspnea.

CASE PRESENTATION: A 30-year-old man with a history of childhood asthma, a 15-pack-year smoking history, and methamphetamine abuse was intubated and started on mechanical ventilation because of acute hypoxic respiratory failure after experiencing progressive dyspnea and a nonproductive cough over the previous year. During the previous 3 months, he had multiple clinic visits, with chest radiographs showing diffuse, bilateral, reticulonodular opacities and small bilateral pleural effusions and was treated for community-acquired pneumonia. Testing for COVID pneumonia was negative, and he failed to respond to antimicrobial therapy. Physical examination on admission showed diffuse fine crackles bilaterally on lung auscultation. Admission laboratory test results were unremarkable.

Single Cell Transcriptomics Implicate Novel Monocyte and T Cell Immune Dysregulation in Sarcoidosis.

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 TGFß 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.

Transudative pleural effusion of malignant etiology: Rare but real.

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.