Baqir, Misbah

AbstractInflammatory processes, such as an infection or drug reaction, can cause antineutrophil cytoplasmic autoantibody (ANCA)‐associated vasculitis (AAV). Although quite rare, AAV may occur with SARS‐coronavirus disease 2019 (COVID‐19) antigenic exposure, either from infection or immunization. We present two cases of AAV: one that developed after COVID‐19 infection presenting as diffuse alveolar haemorrhage and another that developed shortly after vaccination, presenting as granulomatous pulmonary nodules. Both patients improved with supportive care and immunosuppressive therapies. This adverse event appears to be a very rare complication of COVID‐19 infection or vaccination. Early diagnosis of AAV is important because immunosuppressive therapy may improve patient outcomes.

Abstract ObjectiveThe objective of this study was to identify the predictors of in-hospital mortality among patients with diffuse alveolar hemorrhage (DAH).Patients and MethodsWe conducted a retrospective review of 89 patients hospitalized for DAH at our institution between 2001 and 2017: 49 patients who died during hospitalization and 40 patients who survived were compared. We reviewed their presenting signs and symptoms, clinical course, radiologic and pathologic findings, along with medical management. We then performed univariate and multivariate analyses to identify the risk factors associated with in-hospital mortality.ResultsWe identified 12 factors to be associated with mortality when comparing survivor vs non-survivor cohorts: smoking (27 [67%] vs 21 [42%], p = 0.02), malignancy (7 [17%] vs 24 [49%], p = 0.002), interstitial lung disease (0 vs 7 [14%], p = 0.01), liver failure (1 [2%] vs 14 [28%], p = 0.001), autoimmune diseases (16 [40%] vs 4 [8%], p =0.0006), thrombocytopenia (3 [7%] vs 35 [71%], p <0.0001), ICU admission (23 [57%] vs 40 [85%], p=0.004), mean duration of ICU stay (3.5 days [± 6.7] vs 5.5 days [± 5.5], p = 0.4), steroid use (36 [90%] vs 31 [63%], p = 0.003), use of plasma exchange (6 [15%] vs 0, p = 0.005), use of mechanical ventilation (15 [37%] vs 36 [75%], p value = 0.0007) and development of acute respiratory distress syndrome (ARDS) (9 [22%] vs 37 [77%], p <0.0001), respectively. On multivariate analysis, thrombocytopenia (OR 52.08: 95% CI, 8.59-315.71; p <0.0001) and ARDS (OR 11.71: 95% CI, 2.60-52.67; p = 0.0013) were associated with higher odds of mortality in DAH while steroid use (OR 0.05: 95% CI, 0.007-0.39; p = 0.0004) was associated with a lower risk of in-hospital mortality in patients with DAH.ConclusionIn DAH, thrombocytopenia and ARDS were predictors of in-hospital mortality whereas the use of steroid was associated with a more favorable prognosis.

Significance Statement Efficacy of rituximab (RTX) in ANCA-associated vasculitis (AAV) in patients with severe renal involvement (eGFR<30 ml/min per 1.73 m 2 ) has not been addressed in clinical trials. This observational study did not find statistically significant differences between RTX and cyclophosphamide (CYC) for remission-induction therapy or any apparent benefit from the addition of plasma exchange (PLEX) to standard remission-induction therapy for patients with AAV and severe renal involvement. Although our analyses suggest that the benefits and risks of these therapeutic choices (RTX versus CYC with and without PLEX) are balanced, a randomized, controlled trial is needed to confirm these findings. Background Treatment of patients with ANCA-associated vasculitis (AAV) and severe renal involvement is not established. We describe outcomes in response to rituximab (RTX) versus cyclophosphamide (CYC) and plasma exchange (PLEX). Methods A retrospective cohort study of MPO- or PR3-ANCA–positive patients with AAV (MPA and GPA) and severe kidney disease (eGFR <30 ml/min per 1.73 m 2 ). Remission, relapse, ESKD and death after remission-induction with CYC or RTX, with or without the use of PLEX, were compared. Results Of 467 patients with active renal involvement, 251 had severe kidney disease. Patients received CYC ( n =161) or RTX ( n =64) for remission-induction, and 51 were also treated with PLEX. Predictors for ESKD and/or death at 18 months were eGFR <15 ml/min per 1.73 m 2 at diagnosis (IRR 3.09 [95% CI 1.49 to 6.40], P =0.002), renal recovery (IRR 0.27 [95% CI 0.12 to 0.64], P =0.003) and renal remission at 6 months (IRR 0.40 [95% CI 0.18 to 0.90], P =0.027). RTX was comparable to CYC in remission-induction (BVAS/WG=0) at 6 months (IRR 1.37 [95% CI 0.91 to 2.08], P =0.132). Addition of PLEX showed no benefit on remission-induction at 6 months (IRR 0.73 [95% CI 0.44 to 1.22], P =0.230), the rate of ESKD and/or death at 18 months (IRR 1.05 [95% CI 0.51 to 2.18], P =0.891), progression to ESKD (IRR 1.06 [95% CI 0.50 to 2.25], P =0.887), and survival at 24 months (IRR 0.54 [95% CI 0.16 to 1.85], P =0.330). Conclusions The apparent benefits and risks of using CYC or RTX for the treatment of patients with AAV and severe kidney disease are balanced. The addition of PLEX to standard remission-induction therapy showed no benefit in our cohort. A randomized controlled trial is the only satisfactory means to evaluate efficacy of remission-induction treatments in AAV with severe renal involvement.

AbstractBackgroundNo consensus exists regarding optimal strategy for antifungal prophylaxis following lung transplant.ObjectiveTo review data regarding antifungal prophylaxis on the development of fungal infections.Study selection/AppraisalWe searched MEDLINE, Embase, and Scopus for eligible articles through December 10, 2019. Observational or controlled trials published after January 1, 2001, that pertained to the prevention of fungal infections in adult lung recipients were reviewed independently by two reviewers for inclusion.MethodsOf 1702 articles screened, 24 were included. Data were pooled using random effects model to evaluate for the primary outcome of fungal infection. Studies were stratified by prophylactic strategy, medication, and duration (short term < 6 months and long term ≥ 6 months).ResultsWe found no difference in the odds of fungal infection with universal prophylaxis (49/101) compared to no prophylaxis (36/93) (OR 0.76, CI: 0.03‐17.98; I2 = 93%) and preemptive therapy (25/195) compared to universal prophylaxis (35/222) (OR 0.91, CI: 0.06‐13.80; I2 = 93%). The cumulative incidence of fungal infections within 12 months was not different with nebulized amphotericin (0.08, CI: 0.04‐0.13; I2 = 87%) compared to systemic triazoles (0.07, CI: 0.03‐0.11; I2 = 21%) (P = .65). Likewise, duration of prophylaxis did not impact the incidence of fungal infections (short term: 0.11, CI: 0.05‐0.17; I2 = 89%; long term: 0.06, CI: 0.03‐0.08; I2 = 51%; P = .39).ConclusionsWe have insufficient evidence to support or exclude a benefit of antifungal prophylaxis.