Citations

Objective Relapse following remission is common in antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV), particularly with ANCAs directed at proteinase 3 (PR3). This study was undertaken to evaluate the association of an increase in PR3‐ANCA level with subsequent relapse. Methods Data from the Rituximab versus Cyclophosphamide for ANCA‐Associated Vasculitis (RAVE) trial were used. Starting from the time of achieving complete remission, serial measurements by direct and capture enzyme‐linked immunosorbent assays (ELISAs) were analyzed in 93 patients with PR3‐ANCA, using Cox proportional hazards regression. Results An increase in PR3‐ANCA level was identified in 58 of 93 subjects (62.4%) by direct ELISA and in 59 of 93 (63.4%) by capture ELISA. Relapses occurred in 55 of 93 subjects (59.1%), with 25 and 21 occurring within 1 year after an increase by direct ELISA and capture ELISA, respectively. An increase by direct ELISA was associated with subsequent severe relapses (hazard ratio [HR] 4.57; P < 0.001), particularly in patients presenting with renal involvement (HR 7.94; P < 0.001) and alveolar hemorrhage (HR 24.19; P < 0.001). Both assays identified increased risk for severe relapse in the rituximab group (HR 5.80; P = 0.002 for direct ELISA and HR 4.54; P = 0.007 for capture ELISA) but not the cyclophosphamide/azathioprine group ( P = 0.103 and P = 0.197, respectively). Conclusion The association of an increase in PR3‐ANCA level with the risk of subsequent relapse is partially affected by the PR3‐ANCA detection methodology, disease phenotype, and remission induction treatment. An increase in PR3‐ANCA level during complete remission conveys an increased risk of relapse, particularly severe relapse, among patients with renal involvement or alveolar hemorrhage and those treated with rituximab. Serial measurements of PR3‐ANCA may be informative in this subset of patients, but the risk of relapse must be weighed carefully against the risks associated with therapy.

AbstractBackground and objectivePulmonary capillaritis is generally secondary to a systemic autoimmune process. Little is known regarding other causes of pulmonary capillaritis, particularly isolated pulmonary capillaritis (IPC). IPC is defined as pulmonary capillaritis in the absence of evidence of a systemic disease. We aim to describe the aetiology of biopsy‐proven pulmonary capillaritis to add to the existing knowledge on aetiologies of pulmonary capillaritis and provide a more detailed description of IPC cases.MethodsA retrospective cohort of biopsy‐proven pulmonary capillaritis was conducted at the Mayo Clinic, Rochester over a 17‐year period. Histologic slides were re‐reviewed by a lung pathologist. Medical records were reviewed to identify a possible aetiology of the pulmonary capillaritis. A subset analysis of patients identified with IPC was then performed.ResultsThirty‐six cases of biopsy‐proven pulmonary capillaritis were identified. The majority of cases were secondary to a systemic autoimmune disease, most commonly granulomatosis with polyangiitis. There were four cases of IPC in this cohort. Median follow‐up was 116.5 months with no evidence of systemic disease development. No risk factors for IPC were identified. All patients presented sub‐acutely with haemoptysis and diffuse alveolar haemorrhage with a delay in diagnosis. After initiation of immunosuppression, most patients obtained remission with a benign clinical course.ConclusionPulmonary capillaritis is most commonly secondary to systemic autoimmune disorders, predominantly ANCA‐associated vasculitis. IPC is a rare form of pulmonary capillaritis with very few cases described in the literature, the availability of effective treatment makes this rare disease important to recognize.

Objectives: Pulmonary complications are common following hematopoietic stem cell transplantation. Numerous idiopathic post-transplantation pulmonary syndromes have been described. Patients at the severe end of this spectrum may present with hypoxemic respiratory failure and pulmonary infiltrates, meeting criteria for acute respiratory distress syndrome. The incidence and outcomes of acute respiratory distress syndrome in this setting are poorly characterized. Design: Retrospective cohort study. Setting: Mayo Clinic, Rochester, MN. Patients: Patients undergoing autologous and allogeneic hematopoietic stem cell transplantation between January 1, 2005, and December 31, 2012. Interventions: None. Measurements and Main Results: Patients were screened for acute respiratory distress syndrome development within 1 year of hematopoietic stem cell transplantation. Acute respiratory distress syndrome adjudication was performed in accordance with the 2012 Berlin criteria. In total, 133 cases of acute respiratory distress syndrome developed in 2,635 patients undergoing hematopoietic stem cell transplantation (5.0%). Acute respiratory distress syndrome developed in 75 patients (15.6%) undergoing allogeneic hematopoietic stem cell transplantation and 58 patients (2.7%) undergoing autologous hematopoietic stem cell transplantation. Median time to acute respiratory distress syndrome development was 55.4 days (interquartile range, 15.1–139 d) in allogeneic hematopoietic stem cell transplantation and 14.2 days (interquartile range, 10.5–124 d) in autologous hematopoietic stem cell transplantation. Twenty-eight-day mortality was 46.6%. At 12 months following hematopoietic stem cell transplantation, 89 patients (66.9%) who developed acute respiratory distress syndrome had died. Only 7 of 133 acute respiratory distress syndrome cases met criteria for engraftment syndrome and 15 for diffuse alveolar hemorrhage. Conclusions: Acute respiratory distress syndrome is a frequent complication following hematopoietic stem cell transplantation, dramatically influencing patient-important outcomes. Most cases of acute respiratory distress syndrome following hematopoietic stem cell transplantation do not meet criteria for a more specific post-transplantation pulmonary syndrome. These findings highlight the need to better understand the risk factors underlying acute respiratory distress syndrome in this population, thereby facilitating the development of effective prevention strategies.

Objective To identify predictors of respiratory failure and to evaluate the therapeutic efficacy of plasma exchange (PE) and of rituximab versus cyclophosphamide in a cohort of patients with diffuse alveolar hemorrhage (DAH) secondary to antineutrophil cytoplasmic antibody–associated vasculitis (AAV) with or without respiratory failure. Methods We performed a single‐center historical cohort study of all consecutive patients with AAV‐associated DAH who were evaluated over a 16‐year period. Logistic regression models were developed to examine the predictive role of the baseline clinical characteristics for the development of respiratory failure, and for the effect of PE and remission induction therapy on the main outcome (complete remission at 6 months). Results Seventy‐three patients with DAH were identified, and 34 of them experienced respiratory failure. The degree of hypoxemia upon initial presentation, a higher percentage of neutrophils in the bronchoalveolar lavage fluid cell count, and higher C‐reactive protein levels were independently associated with the development of respiratory failure. PE was not associated with achieving complete remission at 6 months, with an odds ratio (OR) of 0.49 (95% confidence interval [95% CI] 0.12–1.95) ( P = 0.32). Rituximab treatment was independently associated with achieving complete remission at 6 months (OR 6.45 [95% CI 1.78–29], P = 0.003). Conclusion Our findings indicate that the most important predictor of respiratory failure in patients with DAH secondary to AAV is the degree of hypoxemia upon presentation. No clear benefit of the addition of PE to standard remission induction therapy was demonstrated. Complete remission by 6 months was achieved at a higher rate with rituximab than with cyclophosphamide in patients with DAH secondary to AAV, including those needing mechanical ventilation.

Background: Inconsistent results have been reported regarding mortality predictors of malignant pleural effusion (MPE). Objective: We aim to describe prognostic features of MPE in patients evaluated over 5 years in a referral center. Methods: All consecutive MPEs (confirmed by pleural cytology or biopsy) from January 2009 to July 2014 were included in this retrospective cohort study. Clinical data were collected from medical registries. Overall survival (OS) rate was calculated with Kaplan-Meier method and compared by the log-rank test. Hazard ratios (HRs) were calculated by the Cox proportional regression model. Results: A total of 110 patients were identified. Mean OS was 8.3 months (range: 25-426 days). No difference in OS was noted based on tumor type. Patients with MPE <50% had a significant better survival than those with malignant pleural effusion ≥50% (median OS: 15.7 vs 5.7 months; HR: 1.71; 95% confidence interval [CI]: 1.06-2.78; P = .0026). After adjusting for confounding variables, MPE size was independently associated with mortality (HR: 1.78; 95% CI: 1.11-2.91; P < .001). No association between glucose or pH in pleural fluid and OS was noted. Conclusion: Our study showed that MPE size, as determined by chest X-ray, is significantly associated with mortality.

Hepatopulmonary syndrome (HPS) and portopulmonary hypertension (POPH) are pulmonary vascular complications of portal hypertension with divergent clinicopathologic features and management. The presence of intrapulmonary vascular dilatations (IPVDs), detected by agitated saline contrast‐enhanced transthoracic echocardiography (cTTE), is an essential feature of HPS but is not typically characteristic of POPH. Although IPVDs have been reported rarely in POPH, the prevalence and significance of this finding have not been systematically studied. We conducted a retrospective chart review of 80 consecutive patients diagnosed with POPH from January 1, 2002 to June 30, 2014 with documentation of cTTE findings, pulmonary hemodynamics, oxygenation, and survival. A total of 34 of the 80 patients (42%) underwent cTTE during initial diagnosis of POPH. IPVDs were detected in 20/34 patients (59%); intracardiac shunting was detected in 9/34 patients (26%; 4 also had IPVDs); and 9 patients (26%) had negative cTTE with no evidence of IPVD or intracardiac shunting. Patients with IPVD had decreased survival as compared to those without IPVD (P = 0.003), a trend that persisted after exclusion of liver transplant recipients (P = 0.07). The IPVD group had a trend toward higher Model for End‐Stage Liver Disease score with and without incorporating sodium (MELD or MELD‐Na; P = 0.05 for both). The right ventricular index of myocardial performance (RIMP) was lower in the IPVD group (median, 0.4 versus 0.6; P = 0.006). Patients with moderate or large IPVDs (n = 6) had worse oxygenation parameters (partial pressure of arterial oxygen, diffusing capacity of the lung for carbon monoxide, and alveolar‐arterial oxygen gradient) as compared to the rest of the cohort. Unexpectedly, IPVDs were frequently documented in POPH and associated with decreased survival. To further understand this observation, we recommend screening for IVPD in all patients with POPH. Liver Transpl 21:1355‐1364, 2015. © 2015 AASLD.

Prior to the 1970s, severe cases of antineutrophil cytoplasmic antibody associated vasculitis (AAV) were thought to be invariably fatal. However, the use of cyclophosphamide-based treatment regimens fundamentally altered disease outcomes, transforming AAV into a manageable, chronic illness. Despite the tremendous success of cyclophosphamide in the treatment of AAV, there remained a need for alternative therapies, due to high rates of treatment failures and significant toxicities. In recent years, with the introduction of targeted biologic response modifiers into clinical practice, many have hoped that the treatment options for AAV could be expanded. Rituximab, a chimeric monoclonal antibody directed against the B-lymphocyte protein CD20, has been the most successful biologic response modifier to be used in AAV. Following the first report of its use in AAV in 2001, experience with rituximab for treatment of AAV has rapidly expanded. Rituximab, in combination with glucocorticosteroids, is now well established as a safe and effective alternative to cyclophosphamide for remission induction for severe manifestations of granulomatosis with polyangiitis and microscopic polyangiitis. In addition, initial experiences with rituximab for remission maintenance in these diseases have been favorable, as have experiences for remission induction in eosinophilic granulomatosis with polyangiitis.

Purpose. The goal of this study was to identify potential clinical predictors for the development of disseminated intravascular coagulation (DIC) in patients with septic shock. Material and Methods. We performed a retrospective analysis of a cohort of adult (>18 years of age) patients with septic shock admitted to a medical ICU in a tertiary care hospital from July 2005 until September 2007. A multivariate logistic regression model was used to determine the association of risk factors with overt DIC. Results. In this study, a total of 390 patients with septic shock were analyzed, of whom 66 (17%) developed overt DIC. Hospital mortality was significantly greater in patients who developed overt DIC (68% versus 38%, P<0.001). A delay in the timing of antibiotics was associated with an increased risk of the development of overt DIC (P<0.001). Patients on antiplatelet therapy prior to hospital admission and who that received adequate early goal-directed therapy (EGDT) were associated with a decreased risk of overt DIC (P<0.001). Conclusions. In our cohort of patients with septic shock, there was a risk reduction for overt DIC in patients on antiplatelet therapy and adequate EGDT, while there was an increased risk of DIC with antibiotic delay.