Susceptibility to mycobacterial infection in VEXAS syndrome.

OBJECTIVES: VEXAS is a recently described acquired auto-inflammatory and hematologic syndrome caused by somatic mutations in UBA1. To date, VEXAS is not a recognized cause of acquired immunodeficiency. PATIENTS AND METHODS: Two of our 10 VEXAS patients developed a disseminated Mycobacterium avium infection. To shed light on this observation, we retrospectively studied all patients with disseminated non-tuberculous mycobacterial infections (NTMi) seen at our institution over 13 years. Inclusion criteria were a positive blood/bone marrow culture, or 2 positive cultures from distinct sites, or one positive culture with 2 involved sites. RESULTS: patient 1 presented with fever, rash, orbital cellulitis and lung infiltrates. Patient 2 presented with fever and purpura. In both cases, Mycobacterium avium was identified on bone marrow culture. Twenty cases of disseminated NTMi were reviewed. Among 11 HIV-negative patients, three had chronic immune-mediated disease; three had untreated myeloid neoplasm; two had VEXAS; one had undergone kidney transplantation; one had GATA-2 deficiency; and one had no identified aetiology. None had lymphoid neoplasia or had undergone bone marrow transplantation. HIV-negative cases had higher CD4 counts than HIV-positive patients (median CD4: 515/mm3  vs 38/mm3, p< 0.001). Monocytopenia was present in seven cases. At 2 years, six patients had died, including both VEXAS patients. DISCUSSION: VEXAS patients have an intrinsic susceptibility to disseminated NTMi, which may result from monocytic dysfunction. NTMi can mimic VEXAS flare. Clinicians should maintain a high suspicion for opportunistic infections before escalating immunosuppressive therapy. Further studies are needed to confirm and better decipher the herein reported observations.

Does PaCO2 correction have an impact on survival of patients with chronic respiratory failure and long-term non-invasive ventilation?

Background and objective: Non-invasive ventilation (NIV) improves survival of patients with chronic respiratory failure (CRF). Most often, pressure settings are made to normalize arterial blood gases. However, this objective is not always achieved due to intolerance to increased pressure or poor compliance. Few studies have assessed the effect of persistent hypercapnia on ventilated patients' survival. Data from the Pays de la Loire Respiratory Health Research Institute cohort were analyzed to answer this question. Study design and methods: NIV-treated adults enrolled between 2009 and 2019 were divided into 5 subgroups: obesity-hypoventilation syndrome (OHS), COPD, obese COPD, neuromuscular disease (NMD) and chest wall disease (CWD). PaCO2 correction was defined as the achievement of a PaCO2 < 6 kPa or a 20% decrease in baseline PaCO2 in COPD patients. The endpoint was all-cause mortality. Follow-up was censored in case of NIV discontinuation. Results: Data from 431 patients were analyzed. Median survival was 103 months and 148 patients died. Overall, PaCO2 correction was achieved in 74% of patients. Bivariate analysis did not show any survival difference between patients who achievedPaCO2 correction and those who remained hypercapnic: overall population: p = 0.74; COPD: p = 0.97; obese COPD: p = 0.28; OHS: p = 0.93; NMD: p = 0.84; CWD: p = 0.28. Conclusion: Moderate residual hypercapnia under NIV does not negatively impact survival in CRF patients. In individuals with poor tolerance of pressure increases, residual hypercapnia can therefore be tolerated under long-term NIV. Larger studies, especially with a higher number of patients with residual PaCO2 > 7 kPa, are needed to confirm these results.

Clinical features and outcomes of patients admitted to the ICU for Cyclophosphamide-associated cardiac toxicity: a retrospective cohort.

PURPOSE: To describe the management and outcome of critically-ill patients with Cyclophosphamide (CY)-associated cardiac toxicity. METHODS: All patients admitted to the intensive care units (ICUs) of the Nantes and Rennes University Hospitals for a CY-associated cardiac toxicity between January 2015 and December 2020 were included. RESULTS: Of the thirty-four patients included in the study, twenty-four (70%) underwent allogeneic hematopoietic stem cell transplantation (HSCT), four (12%) autologous HSCT, and six (18%) chemotherapy for hematological malignancies. Acute pulmonary edema (65%), cardiac arrest (9%), and cardiac arrhythmia (6%) were the most common reasons for ICU admission. Patients were admitted to the ICU 6.5 (4-12) days after the intravenous administration of a median dose of CY of 100 [60-101] mg/Kg. Echocardiographic findings showed moderate to severe left ventricular systolic dysfunction (69%) and pericardial effusion (52%). Eighteen (53%) patients ultimately developed cardiogenic shock and required vasopressors (47%) and/or inotropes (18%). Invasive mechanical ventilation and renal replacement therapy were required in twenty (59%) and five (14%) patients, respectively. Sixteen (47%) patients died of whom 12 (35.3%) died from refractory cardiogenic shock. The left ventricular ejection fraction improved over time in most survivors with a median time until full recovery of 33 (12-62) days. Two (11%) patients had a persistent left ventricular dysfunction at 6 months. CONCLUSION: Refractory cardiogenic shock is the primary cause of death of patients with severe CY-related cardiotoxicity. Nonetheless, the cardiac function of most survivors recovered within a month.

Linking Biomedical Data Warehouse Records With the National Mortality Database in France: Large-scale Matching Algorithm.

BACKGROUND: Often missing from or uncertain in a biomedical data warehouse (BDW), vital status after discharge is central to the value of a BDW in medical research. The French National Mortality Database (FNMD) offers open-source nominative records of every death. Matching large-scale BDWs records with the FNMD combines multiple challenges: absence of unique common identifiers between the 2 databases, names changing over life, clerical errors, and the exponential growth of the number of comparisons to compute. OBJECTIVE: We aimed to develop a new algorithm for matching BDW records to the FNMD and evaluated its performance. METHODS: We developed a deterministic algorithm based on advanced data cleaning and knowledge of the naming system and the Damerau-Levenshtein distance (DLD). The algorithm's performance was independently assessed using BDW data of 3 university hospitals: Lille, Nantes, and Rennes. Specificity was evaluated with living patients on January 1, 2016 (ie, patients with at least 1 hospital encounter before and after this date). Sensitivity was evaluated with patients recorded as deceased between January 1, 2001, and December 31, 2020. The DLD-based algorithm was compared to a direct matching algorithm with minimal data cleaning as a reference. RESULTS: All centers combined, sensitivity was 11% higher for the DLD-based algorithm (93.3%, 95% CI 92.8-93.9) than for the direct algorithm (82.7%, 95% CI 81.8-83.6; P<.001). Sensitivity was superior for men at 2 centers (Nantes: 87%, 95% CI 85.1-89 vs 83.6%, 95% CI 81.4-85.8; P=.006; Rennes: 98.6%, 95% CI 98.1-99.2 vs 96%, 95% CI 94.9-97.1; P<.001) and for patients born in France at all centers (Nantes: 85.8%, 95% CI 84.3-87.3 vs 74.9%, 95% CI 72.8-77.0; P<.001). The DLD-based algorithm revealed significant differences in sensitivity among centers (Nantes, 85.3% vs Lille and Rennes, 97.3%, P<.001). Specificity was >98% in all subgroups. Our algorithm matched tens of millions of death records from BDWs, with parallel computing capabilities and low RAM requirements. We used the Inseehop open-source R script for this measurement. CONCLUSIONS: Overall, sensitivity/recall was 11% higher using the DLD-based algorithm than that using the direct algorithm. This shows the importance of advanced data cleaning and knowledge of a naming system through DLD use. Statistically significant differences in sensitivity between groups could be found and must be considered when performing an analysis to avoid differential biases. Our algorithm, originally conceived for linking a BDW with the FNMD, can be used to match any large-scale databases. While matching operations using names are considered sensitive computational operations, the Inseehop package released here is easy to run on premises, thereby facilitating compliance with cybersecurity local framework. The use of an advanced deterministic matching algorithm such as the DLD-based algorithm is an insightful example of combining open-source external data to improve the usage value of BDWs.

Seasonal effect on fatigue, pain and dryness in primary Sjögren's syndrome.

BACKGROUND: To assess the presence of a seasonal effect on fatigue, pain and dryness in primary Sjögren's syndrome (pSS). METHODS: Data (date; visual analogue scales (VAS) for pain, fatigue and dryness) were extracted from three randomised placebo-controlled trials (RCTs) evaluating infliximab (TRIPSS; n = 103 patients), hydroxychloroquine (JOQUER; n = 120 patients) and rituximab (TEARS; n = 120 patients) and from the 5-year follow-up of the ASSESS prospective cohort (n = 395 patients). Data were analysed at each visit for each patient, according to the day, the month of the year and the season. Linear mixed models were used to take into account the repeated structure of the data and to analyse a potential cyclic effect. RESULTS: A total of 744, 584, 848 and 682 pain, fatigue and dryness VASs were collected on 632 subjects in spring, summer, fall and winter, respectively. No significant difference was observed in pain, fatigue and dryness, according to the month of the year or the season (all p values > 0.05). CONCLUSION: In pSS, seasonality does not affect patient-reported outcomes (PROs) on fatigue, pain and dryness.