To compare the efficacy to prevent flares of maintenance versus withdrawal of 5 mg/day prednisone in systemic lupus erythematosus (SLE) patients with clinically quiescent disease.
A monocentric, ...12-month, superiority, open-label, randomised (1:1) controlled trial was conducted with 61 patients continuing 5 mg/day prednisone and 63 stopping it. Eligibility criteria were SLE patients who, during the year preceding the inclusion, had a clinically inactive disease and a stable SLE treatment including 5 mg/day prednisone. The primary endpoint was the proportion of patient experiencing a flare defined with the SELENA-SLEDAI flare index (SFI) at 52 weeks. Secondary endpoints included time to flare, flare severity according to SFI and British Isles Lupus Assessment Group (BILAG) index and increase in the Systemic Lupus International Collaborating Clinics (SLICC) damage index (SDI).
Proportion of patients experiencing a flare was significantly lower in the maintenance group as compared with the withdrawal group (4 patients vs 17; RR 0.2 (95% CI 0.1 to 0.7), p=0.003). Maintenance of 5 mg prednisone was superior with respect to time to first flare (HR 0.2; 95% CI 0.1 to 0.6, p=0.002), occurrence of mild/moderate flares using the SFI (3 patients vs 12; RR 0.2 (95% CI 0.1 to 0.8), p=0.012) and occurrence of moderate/severe flares using the BILAG index (1 patient vs 8; RR 0.1 (95% CI 0.1 to 0.9), p=0.013). SDI increase and adverse events were similar in the two treatment groups. Subgroup analyses of the primary endpoint by predefined baseline characteristics did not show evidence of a different clinical response.
Maintenance of long term 5 mg prednisone in SLE patients with inactive disease prevents relapse.
NCT02558517; Results.
Temporary circulatory support (TCS) with venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used as a salvage therapy for patients with refractory cardiogenic shock. This ...article provides an overview of VA-ECMO principles, indications, management, complications, and discusses the results of recent case series and trials.
VA-ECMO is utilized as a bridge to 'decision' that includes weaning after cardiac function recovery, transplantation, long-term mechanical circulatory support, and withdrawal in case of futility. VA-ECMO is considered the first-line TCS as it allows rapid improvement in oxygenation, is less expensive, and is also suitable for patients with biventricular failure. Combining Impella (Abiomed, Danvers, MA, USA) or intra-aortic balloon pump support with VA-ECMO might decrease left ventricular pressure and improve outcomes. Massive pulmonary embolism, sepsis-associated cardiomyopathy, and refractory cardiac arrest are among emerging indications for TCS.
TCS have become the cornerstone of the management of patients with cardiogenic shock, although the evidence supporting their efficacy is limited. VA-ECMO is considered the first-line option, with a growing number of accepted and emerging indications. Randomized clinical trials are now needed to determine the place VA-ECMO in cardiogenic shock treatment strategies.
ObjectivesMaintenance of remission has become central in the management of systemic lupus erythematosus (SLE). The importance of interferon-alpha (IFN-α) in the pathogenesis of SLE notwithstanding, ...its expression in remission has been poorly studied as yet. To study its expression in remission and its prognostic value in the prediction of a disease relapse, serum IFN-α levels were determined using an ultrasensitive single-molecule array digital immunoassay which enables the measurement of cytokines at physiological concentrations.MethodsA total of 254 SLE patients in remission, according to the Definition of Remission in SLE classification, were included in the study. Serum IFN-α concentrations were determined at baseline and patients were followed up for 1 year. Lupus flares were defined according to the Safety of Estrogens in Lupus Erythematosus: National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index Flare Index, whereas the Kaplan-Meier analysis and Cox regression analysis were used to estimate the time to relapse and to identify baseline factors associated with time to relapse, respectively.ResultsOf all patients in remission, 26% displayed abnormally high IFN-α serum levels that were associated with the presence of antibodies specific for ribonucleoprotein (RNP), double stranded (ds)DNA and Ro/SSA60, as well as young age. Importantly, elevated-baseline IFN-α serum levels and remission duration were associated in an independent fashion, with shorter time to relapse, while low serum levels of complement component 3 and anti-dsDNA Abs were not.ConclusionDirect serum IFN-α assessment with highly sensitive digital immunoassay permits clinicians to identify a subgroup of SLE patients, clinically in remission, but at higher risk of relapse.
Abstract Behçet's disease (BD) is a recurrent systemic inflammatory disorder of unknown origin characterized by oral and genital mucous ulcer, uveitis, and skin lesions. Involvement of large vessels, ...central nervous system (CNS), gastrointestinal tract and thrombotic events are less frequent but can be life threatening. The aim of this review is to provide new insights into the pathogenesis of BD. Over the past year substantial advances have been done in the understanding of the genetic 1,2 and immunology 3 of BD. BD is at the crossroad between autoimmune and autoinflammatory syndromes. In common with autoimmune diseases BD shares class I MHC association. However, in contrast to autoimmune disorders, BD has clinical features that seem to be mostly autoinflammatory. The pathogenesis of BD is still unknown, but major determinants of the genetic and immune system abnormalities have been reported recently. Triggering infectious factors are supposed to participate in the outbreak of BD in genetically predisposed patients. Two recent large genome-wide association study (GWAS) conducted in Turkey and Japan reported association between single nucleotide polymorphism (SNP) of interleukin (IL)-10 and IL-23R/IL-12RB2 genes and BD. New insights into the perturbations of T cell homeostasis of BD recently emerged. We have recently demonstrated the promotion of Th17 responses and the suppression of regulatory T cells (Tregs) that were driven by interleukin (IL)-21 production and that correlates with BD activity. Inflammatory cells within BD inflammatory lesions included mostly neutrophils, Th1 and Th17 cells, and cytotoxic CD8+ and γδ T cells. Altogether, the recent progresses in the knowledge of BD pathogenesis pave the way for innovative therapy.
Purpose
To describe the characteristics, outcomes, and risk factors associated with poor outcome of venoarterial extracorporeal membrane oxygenation (VA-ECMO)-treated patients with refractory shock ...post-cardiac arrest.
Methods
We retrospectively analyzed data collected prospectively (March 2007–January 2015) in a 26-bed tertiary hospital intensive care unit. All patients implanted with VA-ECMO for refractory cardiogenic shock after successful resuscitation from cardiac arrest were included. Refractory cardiac arrest patients, given VA-ECMO under cardiopulmonary resuscitation, were excluded.
Results
Ninety-four patients received VA-ECMO for refractory shock post-cardiac arrest. Their hospital and 12-month survival rates were 28 and 27 %, respectively. All 1-year survivors were cerebral performance category 1. Multivariable analysis retained INR >2.4 (OR 4.9; 95 % CI 1.4–17.2), admission SOFA score >14 (OR 5.3; 95 % CI 1.7–16.5), and shockable rhythm (OR 0.3; 95 % CI 0.1–0.9) as independent predictors of hospital mortality, but not SAPS II, out-of-hospital cardiac arrest score, or other cardiac arrest variables. Only 10 % of patients with an admission SOFA score >14 survived, whereas 50 % of those with scores ≤14 were alive at 1 year. Restricting the analysis to the 67 patients with out-of-hospital cardiac arrest of coronary cause yielded similar results.
Conclusion
Among 94 patients implanted with VA-ECMO for refractory cardiogenic shock post-cardiac arrest resuscitation, the 24 (27 %) 1-year survivors had good neurological outcomes, but survival was significantly better for patients with admission SOFA scores <14, shockable rhythm, and INR ≤2.4. VA-ECMO might be considered a rescue therapy for patients with refractory cardiogenic shock post-cardiac arrest resuscitation.
To determine the characteristics and outcomes of patients prone-positioned during extracorporeal membrane oxygenation for severe acute respiratory distress syndrome and lung CT pattern associated ...with improved respiratory system static compliance after that intervention.
Retrospective, single-center study over 8 years.
Twenty-six bed ICU in a tertiary center.
A propensity score-matched analysis compared patients with prone-positioning during extracorporeal membrane oxygenation and those without. An increase of the static compliance greater than or equal to 3 mL/cm H2O after 16 hours of prone-positioning defined prone-positioning responders. The primary outcome was the time to successful extracorporeal membrane oxygenation weaning within 90 days of postextracorporeal membrane oxygenation start, with death as a competing risk. Among 298 venovenous extracorporeal membrane oxygenation-treated adults with severe acute respiratory distress syndrome, 64 were prone-positioning extracorporeal membrane oxygenation. Although both propensity score-matched groups had similar extracorporeal membrane oxygenation durations, prone-positioning extracorporeal membrane oxygenation patients' 90-day probability of being weaned-off extracorporeal membrane oxygenation and alive was higher (0.75 vs 0.54, p = 0.03; subdistribution hazard ratio 95% CI, 1.54 1.05-2.58) and 90-day mortality was lower (20% vs 42%, p < 0.01) than that for no prone-positioning extracorporeal membrane oxygenation patients. Extracorporeal membrane oxygenation-related complications were comparable for the two groups. Patients without improved static compliance had higher percentages of nonaerated or poorly aerated ventral and medial-ventral lung regions (p = 0.047).
Prone-positioning during venovenous extracorporeal membrane oxygenation was safe and effective and was associated with a higher probability of surviving and being weaned-off extracorporeal membrane oxygenation at 90 days. Patients with greater normally aerated lung tissue in the ventral and medial-ventral regions on quantitative lung CT-scan performed before prone-positioning are more likely to improve their static compliance after that procedure during extracorporeal membrane oxygenation.
The literature shows discrepancies in stereotactic brain biopsy complication rates, severities, and outcomes. Little is known about the timeline of postbiopsy complications. This study aimed to ...analyze 1) complications following brain biopsies, using a graded severity scale, and 2) a timeline of complication occurrence. The secondary objectives were to determine factors associated with an increased risk of complications and to assess complication-related management and extra costs.
The authors retrospectively examined 1500 consecutive stereotactic brain biopsies performed in adult patients at their tertiary medical center between April 2009 and April 2019.
Three hundred eighty-one biopsies (25.4%) were followed by a complication, including 88.2% of asymptomatic hemorrhages. Symptomatic complications involved 3.0% of the biopsies, and 0.8% of the biopsies were fatal. The severity grading scale had a 97.6% interobserver reproducibility. Twenty-three (51.1%) of the 45 symptomatic complications occurred within the 1st hour following the biopsy, while 75.6% occurred within the first 6 hours. Age ≥ 65 years, second biopsy procedures, gadolinium-enhanced lesions, glioblastomas, and lymphomas were predictors of biopsy-related complications. Brainstem biopsy-targeted lesions and cerebral toxoplasmosis were predictive of mortality. Asymptomatic hemorrhage was associated with delayed (> 6 hours) symptomatic complications. Symptomatic complications led to extended hospitalization in 86.7% of patients. The average extra cost for management of a patient with postbiopsy symptomatic complication was $35,702.
Symptomatic complications from brain biopsies are infrequent but associated with substantial adverse effects and cost implications for the healthcare system. The use of a severity grading scale, as the authors propose in this article, helps to classify complications according to the therapeutic consequences and the patient's outcome. Because this study indicates that most complications occur within the first few hours following the biopsy, postbiopsy monitoring can be tailored accordingly. The authors therefore recommend systematic monitoring for 2 hours in the recovery unit and a CT scan 2 hours after the end of the biopsy procedure. In addition, they propose a modern algorithm for optimal postoperative management of patients undergoing stereotactic biopsy.
The use of extracorporeal membrane oxygenation (ECMO) may alter blood levels of several drugs, including antibiotics, leading to under dosing of these drugs and thus to potential treatment failure. ...No data exist on pharmacokinetics of new antimicrobial, in particular ceftazidime/avibactam. We therefore perform this study to evaluate ceftazidime/avibactam blood levels in ECMO patients and find factors associated with underdosing.
Retrospective observational study of patients on ECMO having received ceftazidime/avibactam and in whom trough blood levels of ceftazidime and avibactam were available. Main outcome measurement was the number of patients with ceftazidime and avibactam blood levels above predefined cut-off values, derived from the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints for Enterobacteriaceae and Pseudomonas aeruginosa, namely 8 mg/L for ceftazidime and 4 mg/L for avibactam, and explored factors associated with underdosing.
Twenty-three ceftazidime/avibactam trough levels were available in 14 ECMO patients, all of them having received veno-venous ECMO for SARS-CoV-2-associated pneumonia. Although ceftazidime levels were above 8 mg/L in all except one patient, nine (39%) of the avibactam dosages were below 4 mg/L. Increased renal clearance (creatinine clearance > 130 mL/min) was the main factor associated with under dosing, since 7 out of the 10 dosages below the predefined cut-offs were measured in patients with this condition.
In ECMO patients receiving ceftazidime/avibactam, ceftazidime and avibactam serum levels are above EUCAST breakpoints in most cases, justifying the use of normal dosing in ECMO patients. Increased renal clearance may lead to ceftazidime and avibactam under dosing.
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