Human protein C concentrates in adult septic patients

Some case reports and case series suggest that protein C concentrates may improve the outcome in patients with congenital or acquired protein C deficiency (not only in those with sepsis induced purpura fulminans). We reviewed the published literature on the use of protein C concentrates in adult septic patients and found that it is limited to less than 70 patients reported in observational studies with a 70% survival, and added our personal experience (two adult patients with sepsis and contraindications to recombinant activated protein C)

Estimation of Spatiotemporal Gait Parameters in Walking on a Photoelectric System: Validation on Healthy Children by Standard Gait Analysis

The use of stereophotogrammetry systems is challenging when targeting children's gait analysis due to the time required and the need to keep physical markers in place. For this reason, marker-less photoelectric systems appear to be a solution for accurate and fast gait analysis in youth. The aim of this study is to validate a photoelectric system and its configurations (LED filter setting) on healthy children, comparing the kinematic gait parameters with those obtained from a three-dimensional stereophotogrammetry system. Twenty-seven healthy children were enrolled. Three LED filter settings for the OptoGait were compared to the BTS P6000. The analysis included the non-parametric 80% limits of agreement and the intraclass correlation coefficient (ICC). Additionally, normalised limits of agreement and bias (NLoAs and Nbias) were compared to the clinical experience of physical therapists (i.e., assuming an error lower than 5% is acceptable). ICCs showed excellent consistency for most of the parameters and filter settings; NLoAs varied between 1.39% and 12.62%. An inverse association between the number of LEDs for filter setting and the bias values was also observed. Observations confirm the validity of the OptoGait system for the evaluation of spatiotemporal gait parameters in children

Characterization and outcomes of 414 patients with primary SS who developed haematological malignancies

Objective To characterize 414 patients with primary SS who developed haematological malignancies and to analyse how the main SS- and lymphoma-related features can modify the presentation patterns and outcomes. Methods By January 2021, the Big Data Sjögren Project Consortium database included 11¿966 patients fulfilling the 2002/2016 classification criteria. Haematological malignancies diagnosed according to the World Health Organization (WHO) classification were retrospectively identified. Results There were 414 patients (355 women, mean age 57¿years) with haematological malignancies (in 43, malignancy preceded at least one year the SS diagnosis). A total of 376 (91%) patients had mature B-cell malignancy, nearly half had extranodal marginal zone lymphoma (MZL) of mucosa-associated lymphoid tissue (MALT lymphoma) (n¿=¿197), followed by diffuse large B-cell lymphoma (DLBCL) (n¿=¿67), nodal MZL lymphoma (n¿=¿29), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (n¿=¿19) and follicular lymphoma (FL) (n¿=¿17). Rates of complete response, relapses and death were 80%, 34% and 13%, respectively, with a 5-year survival rate of 86.5% after a mean follow-up of 8¿years. There were significant differences in age at diagnosis (younger in MALT, older in CLL/SLL), predominant clinical presentation (glandular enlargement in MALT lymphoma, peripheral lymphadenopathy in nodal MZL and FL, constitutional symptoms in DLBCL, incidental diagnosis in CLL/SLL), therapeutic response (higher in MALT lymphoma, lower in DLBCL) and survival (better in MALT, nodal MZL and FL, worse in DLBCL). Conclusion In the largest reported study of haematological malignancies complicating primary SS, we confirm the overwhelming predominance of B-cell lymphomas, especially MALT, with the salivary glands being the primary site of involvement. This highly-specific histopathological scenario is linked with the overall good prognosis with a 5-year survival rate of nearly 90%.Peer ReviewedPostprint (published version

Sevoflurane vs propofol in high risk cardiac surgery: design of the randomized trial “Sevo-Aifa”

Objective. Recent evidence indicates that volatile anesthetics improve post-ischemic recovery. In a meta-analysis of 22 randomized studies, the use of volatile anesthetics was associated with significant reduction in myocardial infarction and mortality. All the studies in this meta-analysis included low risk patients undergoing isolated procedures (mostly isolated coronary artery bypass grafting). We want to confirm the cardioprotective effects of volatile anesthetics, in cardiac surgery, as indicated by a reduced intensive care unit stay and/or death in a high risk population of patients, undergoing combined valvular and coronary procedures. Methods. Four centres will randomize 200 patients to receive either total intravenous anesthesia with propofol or anesthesia with sevoflurane. All patients will receive a standard average dose of opiates. Perioperative management will be otherwise identical and standardized. Transfer out of the intensive care unit will follow standard criteria. Results. Reduced cardiac damage will probably translate into better tissue perfusion and faster recovery, as documented by a reduced intensive care unit stay. The study is powered to detect a reduction in the composite end point of prolonged intensive care unit stay (>2days) and/or death from 60% to 40%. Conclusions. This will be the first multicentre randomized controlled trial comparing the effects of volatile anesthetics and total intravenous anesthesia in high risk patients undergoing cardiac procedures. Our trial should help clarify whether or not volatile agents should be recommended in high risk patients undergoing cardiac surgery

Addressing the clinical unmet needs in primary Sjögren's Syndrome through the sharing, harmonization and federated analysis of 21 European cohorts

For many decades, the clinical unmet needs of primary Sjögren's Syndrome (pSS) have been left unresolved due to the rareness of the disease and the complexity of the underlying pathogenic mechanisms, including the pSS-associated lymphomagenesis process. Here, we present the HarmonicSS cloud-computing exemplar which offers beyond the state-of-the-art data analytics services to address the pSS clinical unmet needs, including the development of lymphoma classification models and the identification of biomarkers for lymphomagenesis. The users of the platform have been able to successfully interlink, curate, and harmonize 21 regional, national, and international European cohorts of 7,551 pSS patients with respect to the ethical and legal issues for data sharing. Federated AI algorithms were trained across the harmonized databases, with reduced execution time complexity, yielding robust lymphoma classification models with 85% accuracy, 81.25% sensitivity, 85.4% specificity along with 5 biomarkers for lymphoma development. To our knowledge, this is the first GDPR compliant platform that provides federated AI services to address the pSS clinical unmet needs. © 2022 The Author(s

Epidemiological profile and north-south gradient driving baseline systemic involvement of primary Sjogren's syndrome

Objective: To characterize the systemic phenotype of primary Sjögren’s syndrome at diagnosis by analysing the EULAR-SS disease activity index (ESSDAI) scores. Methods: The Sjögren Big Data Consortium is an international, multicentre registry based on worldwide data-sharing cooperative merging of pre-existing databases from leading centres in clinical research in Sjögren’s syndrome from the five continents. Results: The cohort included 10 007 patients (9352 female, mean 53 years) with recorded ESSDAI scores available. At diagnosis, the mean total ESSDAI score was 6.1; 81.8% of patients had systemic activity (ESSDAI score ≥1). Males had a higher mean ESSDAI (8.1 vs 6.0, P < 0.001) compared with females, as did patients diagnosed at <35 years (6.7 vs 5.6 in patients diagnosed at >65 years, P < 0.001). The highest global ESSDAI score was reported in Black/African Americans, followed by White, Asian and Hispanic patients (6.7, 6.5, 5.4 and 4.8, respectively; P < 0.001). The frequency of involvement of each systemic organ also differed between ethnic groups, with Black/African American patients showing the highest frequencies in the lymphadenopathy, articular, peripheral nervous system, CNS and biological domains, White patients in the glandular, cutaneous and muscular domains, Asian patients in the pulmonary, renal and haematological domains and Hispanic patients in the constitutional domain. Systemic activity measured by the ESSDAI, clinical ESSDAI (clinESSDAI) and disease activity states was higher in patients from southern countries (P < 0.001). Conclusion: The systemic phenotype of primary Sjögren’s syndrome is strongly influenced by personal determinants such as age, gender, ethnicity and place of residence, which are key geoepidemiological players in driving the expression of systemic disease at diagnosis.

COVID-19 in rheumatic diseases in Italy: first results from the Italian registry of the Italian Society for Rheumatology (CONTROL-19)

OBJECTIVES: Italy was one of the first countries significantly affected by the coronavirus disease 2019 (COVID-19) epidemic. The Italian Society for Rheumatology promptly launched a retrospective and anonymised data collection to monitor COVID-19 in patients with rheumatic and musculoskeletal diseases (RMDs), the CONTROL-19 surveillance database, which is part of the COVID-19 Global Rheumatology Alliance. METHODS: CONTROL-19 includes patients with RMDs and proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) updated until May 3rd 2020. In this analysis, only molecular diagnoses were included. The data collection covered demographic data, medical history (general and RMD-related), treatments and COVID-19 related features, treatments, and outcome. In this paper, we report the first descriptive data from the CONTROL-19 registry. RESULTS: The population of the first 232 patients (36% males) consisted mainly of elderly patients (mean age 62.2 years), who used corticosteroids (51.7%), and suffered from multi-morbidity (median comorbidities 2). Rheumatoid arthritis was the most frequent disease (34.1%), followed by spondyloarthritis (26.3%), connective tissue disease (21.1%) and vasculitis (11.2%). Most cases had an active disease (69.4%). Clinical presentation of COVID-19 was typical, with systemic symptoms (fever and asthenia) and respiratory symptoms. The overall outcome was severe, with high frequencies of hospitalisation (69.8%), respiratory support oxygen (55.7%), non-invasive ventilation (20.9%) or mechanical ventilation (7.5%), and 19% of deaths. Male patients typically manifested a worse prognosis. Immunomodulatory treatments were not significantly associated with an increased risk of intensive care unit admission/mechanical ventilation/death. CONCLUSIONS: Although the report mainly includes the most severe cases, its temporal and spatial trend supports the validity of the national surveillance system. More complete data are being acquired in order to both test the hypothesis that RMD patients may have a different outcome from that of the general population and determine the safety of immunomodulatory treatments