Infliximab therapy in refractory sarcoidosis: a multicenter real-world analysis.

BACKGROUND: Infliximab is a monoclonal antibody that binds and neutralizes circulating tumor necrosis factor-alpha, a key inflammatory cytokine in the pathophysiology of sarcoidosis. Despite the paucity of randomized clinical trials, infliximab is often considered a therapeutic option for refractory disease. Our study aimed to investigate the effectiveness of infliximab in patients with refractory sarcoidosis. METHODS: Sarcoidosis patients from three tertiary centres were retrospectively identified by pharmacy records based on treatment with infliximab. Treatment with Infliximab was initiated in patients who failed first and second line immunomodulators as determined by a multidisciplinary team of Respirologists, Dermatologists, ENT specialists, Rheumatologists, and Neurologists. Participants were characterized by the primary organ for which infliximab was initiated and the total number of organs involved. Clinical outcomes were categorized as treatment success versus failure. We defined treatment success as (A) improvement of cutaneous, upper airway, lymph node, gastrointestinal, eye, or joint manifestations; or (B) improvement or no change in central nervous system (CNS) or pulmonary manifestations. RESULTS: 33 patients with refractory sarcoidosis were identified. The proportion of treatment success was 100% (95% CI 54.1-100) in CNS, 91.7% (95% CI 61.5-99.8) in cutaneous, 78.6% (95% CI 49.2-95.3) in pulmonary and 71.5% (95% CI 29.0-96.3) in upper airway disease. The use of infliximab was associated with a reduction prednisone dose by 50%. CONCLUSION: Infliximab is possibly an effective therapy for refractory sarcoidosis, with the greatest value in neurologic and cutaneous manifestations. Across all disease presentations, infliximab facilitated a clinically relevant reduction in corticosteroid dose. Relapse is common after discontinuation of infliximab.

Blood Eosinophils and Pulmonary Rehabilitation in COPD.

Background: Blood eosinophils predict the response to therapy, risk of exacerbation, and readmission in COPD. This study investigates whether blood eosinophils predict pulmonary rehabilitation (PR) outcomes in COPD. Methods: We categorized patients into eosinophilic (blood eosinophils ≥300 cells/ml) or noneosinophilic (<300 cells/ml). In a retrospective design, we compared changes within and between the two groups on BODE index, 6-minute walk test (6MWT), FEV1, and mMRC dyspnea scale. Results: Of 206 patients enrolled, 176 were included for analysis; 90 were eosinophilic. BODE index improved in both groups: (MD -1.25; 95% CI (-0.45, -4.25), P ≤ 0.001) in the eosinophilic and (MD -1.33; 95% CI (-1.72, -0.94), P ≤ 0.001) in the noneosinophilic, but a higher BODE index remained in the eosinophilic (4.98); adjusted mean change (ß): 0.7 (95% CI (0.15, 1.26), P=0.01). 6MWT improved by 29.3 m in the eosinophilic (95% CI (14.2, 44.4), P ≤ 0.001) vs. 115.1 m in the noneosinophilic (95% CI (-30.4, 260.6), P=0.12). FEV1 did not change in the eosinophilic (MD -0.6; 95% CI (-2.64, 1.48), P=0.58), but improved by 2.5% in the noneosinophilic (MD 2.5; 95% CI (0.77, 4.17), P=0.005). There were no significant between-group differences in 6MWT and FEV1; adjusted mean changes (ß) were -9.69 m (95% CI (-39.51, 20.14), P=0.52) and -2.31% (95% CI (-5.69, 1.08), P=0.18), respectively. There were no significant within- or between-group changes in the mMRC scale. Conclusion: Although PR improves the BODE index in both eosinophilic and noneosinophilic COPD, a higher eosinophil count (≥300 cells/ml) is associated with a higher (worse) BODE index. Blood eosinophils may predict PR outcomes.

Temperature control in critically ill patients with fever: A meta-analysis of randomized controlled trials.

PURPOSE: Fever is frequently encountered in ICU. It is unclear if targeted temperature control is beneficial in critically ill patients with suspected or confirmed infection. We conducted a systemic review and meta-analysis to answer this question. METHODS: We systematically reviewed major databases before January 2020 to identify randomized controlled trials (RCTs) that compared antipyretic with placebo for temperature control in non-neurocritical ill adult patients with suspected or confirmed infection. Outcomes of interest were 28-day mortality, temperature level, hospital mortality, length of stay, shock reversal, and patient comfort. RESULT: 13 RCTs enrolling 1963 patients were included. No difference in 28-day mortality between antipyretic compared with placebo (risk ratio [RR] 1.03; 95% CI 0.79-1.35). Lower temperature levels were achieved in the antipyretic group (MD [mean difference] -0.41; 95% CI -0.66 to -0.16). Antipyretic use did not affect the risk of hospital mortality (RR 0.97; 95% CI 0.73-1.30), ICU length of stay (MD -0.07; 95% CI -0.70 to 0.56), or shock reversal (RR 1.11; 95% CI 0.76-1.62). CONCLUSION: Antipyretic therapy effectively reduces temperature in non-neurocritical ill patients but does not reduce mortality or impact other outcomes.