German Patient Blood Management Network: effectiveness and safety analysis in 1.2 million patients.

BACKGROUND: Patient Blood Management (PBM) is a patient-centred, systematic, evidence-based approach to improve patient outcomes by managing and preserving a patient's own blood whilst promoting patient safety and empowerment. The effectiveness and safety of PBM over a longer period have not yet been investigated. METHODS: We performed a prospectively designed, multicentre follow-up study with non-inferiority design. Data were retrospectively extracted case-based from electronic hospital information systems. All in-hospital patients (≥18 yr) undergoing surgery and discharged between January 1, 2010 and December 31, 2019 were included in the analysis. The PBM programme focused on three domains: preoperative optimisation of haemoglobin concentrations, blood-sparing techniques, and guideline adherence/standardisation of allogeneic blood product transfusions. The outcomes were utilisation of blood products, composite endpoint of in-hospital mortality and postoperative complications (myocardial infarction/ischaemic stroke/acute renal failure with renal replacement therapy/sepsis/pneumonia), anaemia rate at admission and discharge, and hospital length of stay. RESULTS: A total of 1 201 817 (pre-PBM: n=441 082 vs PBM: n=760 735) patients from 14 (five university/nine non-university) hospitals were analysed. Implementation of PBM resulted in a substantial reduction of red blood cell utilisation. The mean number of red blood cell units transfused per 1000 patients was 547 in the PBM cohort vs 635 in the pre-PBM cohort (relative reduction of 13.9%). The red blood cell transfusion rate was significantly lower (P<0.001) with odds ratio 0.86 (0.85-0.87). The composite endpoint was 5.8% in the PBM vs 5.6% in the pre-PBM cohort. The non-inferiority aim (safety of PBM) was achieved (P<0.001). CONCLUSIONS: Analysis of >1 million surgical patients showed that the non-inferiority condition (safety of Patient Blood Management) was fulfilled, and PBM was superior with respect to red blood cell transfusion. CLINICAL TRIAL REGISTRATION: NCT02147795.

Preoperative anaemia and red blood cell transfusion in patients with aneurysmal subarachnoid and intracerebral haemorrhage - a multicentre subanalysis of the German PBM Network Registry.

PURPOSE: Anaemia is common in patients presenting with aneurysmal subarachnoid (aSAH) and intracerebral haemorrhage (ICH). In surgical patients, anaemia was identified as an idenpendent risk factor for postoperative mortality, prolonged hospital length of stay (LOS) and increased risk of red blood cell (RBC) transfusion. This multicentre cohort observation study describes the incidence and effects of preoperative anaemia in this critical patient collective for a 10-year period. METHODS: This multicentre observational study included adult in-hospital surgical patients diagnosed with aSAH or ICH of 21 German hospitals (discharged from 1 January 2010 to 30 September 2020). Descriptive, univariate and multivariate analyses were performed to investigate the incidence and association of preoperative anaemia with RBC transfusion, in-hospital mortality and postoperative complications in patients with aSAH and ICH. RESULTS: A total of n = 9081 patients were analysed (aSAH n = 5008; ICH n = 4073). Preoperative anaemia was present at 28.3% in aSAH and 40.9% in ICH. RBC transfusion rates were 29.9% in aSAH and 29.3% in ICH. Multivariate analysis revealed that preoperative anaemia is associated with a higher risk for RBC transfusion (OR = 3.25 in aSAH, OR = 4.16 in ICH, p < 0.001), for in-hospital mortality (OR = 1.48 in aSAH, OR = 1.53 in ICH, p < 0.001) and for several postoperative complications. CONCLUSIONS: Preoperative anaemia is associated with increased RBC transfusion rates, in-hospital mortality and postoperative complications in patients with aSAH and ICH. TRIAL REGISTRATION: ClinicalTrials.gov , NCT02147795, https://clinicaltrials.gov/ct2/show/NCT02147795.

Il-23/Th17 cell pathway: A promising target to alleviate thymic inflammation maintenance in myasthenia gravis.

IL-23/Th17 pathway has been identified to sustain inflammatory condition in several autoimmune diseases and therefore being targeted in various therapeutic and effective approaches. Patients affected with autoimmune myasthenia gravis exhibit a disease effector tissue, the thymus, that harbors ectopic germinal centers that sustain production of auto-antibodies, targeting proteins located in the neuromuscular junction, cause of the organ-specific chronic autoimmune disease. The present study aims to investigate the IL-23/Th17 cell pathway in the thymic inflammatory and pathogenic events. We found that thymuses of MG patients displayed overexpression of Interleukin-17, signature cytokine of activated Th17 cells. This activation was sustained by a higher secretion of Interleukin-23 by TEC, in addition to the increased expression of cytokines involved in Th17 cell development. The overexpression of Interleukin-23 was due to a dysregulation of interferon type I pathway. Besides, Interleukin-17 secreted, and Th17 cells were localized around thymic ectopic germinal centers. These cells expressed podoplanin, a protein involved in B-cell maturation and antibody secretion. Finally, production of Interleukin-23 was also promoted by Interleukin-17 secreted itself by Th17 cells, highlighting a chronic loop of inflammation sustained by thymic cell interaction. Activation of the IL-23/Th17 pathway in the thymus of autoimmune myasthenia gravis patients creates an unstoppable loop of inflammation that may participate in ectopic germinal center maintenance. To alleviate the physio-pathological events in myasthenia gravis patients, this pathway may be considered as a new therapeutic target.

From drab to Fab; PLP1's fit is redressed for MS.

Curated expression of proteolipid protein 1 (PLP1) is essential for multiple sclerosis-derived autoantibody recognition.

Association of anaemia, co-morbidities and red blood cell transfusion according to age groups: multicentre sub-analysis of the German Patient Blood Management Network Registry.

BACKGROUND: Blood transfusions are common medical procedures and every age group requires detailed insights and treatment bundles. The aim of this study was to examine the association of anaemia, co-morbidities, complications, in-hospital mortality, and transfusion according to age groups to identify patient groups who are particularly at risk when undergoing surgery. METHODS: Data from 21 Hospitals of the Patient Blood Management Network Registry were analysed. Patients were divided into age subgroups. The incidence of preoperative anaemia, co-morbidities, surgical disciplines, hospital length of stay, complications, in-hospital mortality rate, and transfusions were analysed by descriptive and multivariate regression analysis. RESULTS: A total of 1 117 919 patients aged 18-108 years were included. With increasing age, the number of co-morbidities and incidence of preoperative anaemia increased. Complications, hospital length of stay, and in-hospital mortality increased with age and were higher in patients with preoperative anaemia. The mean number of transfused red blood cells (RBCs) peaked, whereas the transfusion rate increased continuously. Multivariate regression analysis showed that increasing age, co-morbidities, and preoperative anaemia were independent risk factors for complications, longer hospital length of stay, in-hospital mortality, and the need for RBC transfusion. CONCLUSION: Increasing age, co-morbidities, and preoperative anaemia are independent risk factors for complications, longer hospital length of stay, in-hospital mortality, and the need for RBC transfusion. Anaemia diagnosis and treatment should be established in all patients.

Aldehyde dehydrogenases contribute to skeletal muscle homeostasis in healthy, aging, and Duchenne muscular dystrophy patients.

BACKGROUND: Aldehyde dehydrogenases (ALDHs) are key players in cell survival, protection, and differentiation via the metabolism and detoxification of aldehydes. ALDH activity is also a marker of stem cells. The skeletal muscle contains populations of ALDH-positive cells amenable to use in cell therapy, whose distribution, persistence in aging, and modifications in myopathic context have not been investigated yet. METHODS: The Aldefluor® (ALDEF) reagent was used to assess the ALDH activity of muscle cell populations, whose phenotypic characterizations were deepened by flow cytometry. The nature of ALDH isoenzymes expressed by the muscle cell populations was identified in complementary ways by flow cytometry, immunohistology, and real-time PCR ex vivo and in vitro. These populations were compared in healthy, aging, or Duchenne muscular dystrophy (DMD) patients, healthy non-human primates, and Golden Retriever dogs (healthy vs. muscular dystrophic model, Golden retriever muscular dystrophy [GRMD]). RESULTS: ALDEF+ cells persisted through muscle aging in humans and were equally represented in several anatomical localizations in healthy non-human primates. ALDEF+ cells were increased in dystrophic individuals in humans (nine patients with DMD vs. five controls: 14.9 ± 1.63% vs. 3.6 ± 0.39%, P = 0.0002) and dogs (three GRMD dogs vs. three controls: 10.9 ± 2.54% vs. 3.7 ± 0.45%, P = 0.049). In DMD patients, such increase was due to the adipogenic ALDEF+ /CD34+ populations (11.74 ± 1.5 vs. 2.8 ± 0.4, P = 0.0003), while in GRMD dogs, it was due to the myogenic ALDEF+ /CD34- cells (3.6 ± 0.6% vs. 1.03 ± 0.23%, P = 0.0165). Phenotypic characterization associated the ALDEF+ /CD34- cells with CD9, CD36, CD49a, CD49c, CD49f, CD106, CD146, and CD184, some being associated with myogenic capacities. Cytological and histological analyses distinguished several ALDH isoenzymes (ALDH1A1, 1A2, 1A3, 1B1, 1L1, 2, 3A1, 3A2, 3B1, 3B2, 4A1, 7A1, 8A1, and 9A1) expressed by different cell populations in the skeletal muscle tissue belonging to multinucleated fibres, or myogenic, endothelial, interstitial, and neural lineages, designing them as potential new markers of cell type or of metabolic activity. Important modifications were noted in isoenzyme expression between healthy and DMD muscle tissues. The level of gene expression of some isoenzymes (ALDH1A1, 1A3, 1B1, 2, 3A2, 7A1, 8A1, and 9A1) suggested their specific involvement in muscle stability or regeneration in situ or in vitro. CONCLUSIONS: This study unveils the importance of the ALDH family of isoenzymes in the skeletal muscle physiology and homeostasis, suggesting their roles in tissue remodelling in the context of muscular dystrophies.

The Muscle Is Not a Passive Target in Myasthenia Gravis.

Myasthenia gravis (MG) is a rare autoimmune disease mediated by pathogenic antibodies (Ab) directed against components of the neuromuscular junction (NMJ), mainly the acetylcholine receptor (AChR). The etiological mechanisms are not totally elucidated, but they include a combination of genetic predisposition, triggering event(s), and hormonal components. MG disease is associated with defective immune regulation, chronic cell activation, inflammation, and the thymus is frequently abnormal. MG is characterized by muscle fatigability that is very invalidating and can be life-threatening when respiratory muscles are affected. MG is not cured, and symptomatic treatments with acetylcholinesterase inhibitors and immunosuppressors are life-long medications associated with severe side effects (especially glucocorticoids). While the muscle is the ultimate target of the autoimmune attack, its place and role are not thoroughly described, and this mini-review will focus on the cascade of pathophysiologic mechanisms taking place at the NMJ and its consequences on the muscle biology, function, and regeneration in myasthenic patients, at the histological, cellular, and molecular levels. The fine structure of the synaptic cleft is damaged by the Ab binding that is coupled to focal complement-dependent lysis in the case of MG with anti-AChR antibodies. Cellular and molecular reactions taking place in the muscle involve several cell types as well as soluble factors. Finally, the regenerative capacities of the MG muscle tissue may be altered. Altogether, the studies reported in this review demonstrate that the muscle is not a passive target in MG, but interacts dynamically with its environment in several ways, activating mechanisms of compensation that limit the pathogenic mechanisms of the autoantibodies.

Respuesta inmunitaria al SARS-CoV-2 previa a la vacunación en personal de salud de Alto Paraná, Paraguay, un estudio seroepidemiológico / Immune response to SARS-CoV-2 prior to vaccination among healthcare workers from Alto Paraná, Paraguay, a seroepidemiological study

INTRODUCCIÓN: La comprensión del comportamiento de la respuesta humoral en COVID-19 continúa siendo un desafío para la producción de vacunas que proporcionen inmunidad más duradera. OBJETIVO: Describir la respuesta humoral natural inducida por SARS- CoV-2 en personal de salud con base en el perfil epidemiológico y clínico. MATERIALES Y MÉTODOS: Estudio transversal en personal de salud de hospitales públicos de referencia del Departamento de Alto Paraná, Paraguay. Se incluyeron 962 participantes, mediante muestreo no probabilístico de tipo consecutivo, aplicación de cuestionario y toma de muestras sanguíneas. Se buscaron anticuerpos por ensayo inmunocromatográfico para detección de IgM e IgG contra SARS- CoV-2 y por el método ELISA de captura de IgG específicos contra la proteína spike (SARS-CoV-2) y se evaluaron factores asociados a la seropositividad. RESULTADOS: La seroprevalencia global fue 36,5% (IC 95%: 33,4 - 39,5); 59,3% (n: 571) de los encuestados refirió haber tenido síntomas compatibles al COVID-19 entre el inicio de la pandemia y la fecha de toma de muestra, de estos 44% (n: 251) resultó seropositivo; 10,4% (n: 100) manifestó no haber tenido síntomas en el periodo estudiado, pero tuvo un resultado positivo. Los factores asociados a la seropositividad fueron: presencia de síntomas (p 90 días). CONCLUSIONES: Las características clínicas fueron mayormente asociadas con la seropositividad y la seropreva- lencia en los sintomáticos varió de acuerdo con el tiempo transcurrido desde el inicio de los síntomas y la serología.

BACKGROUND: Understanding the behavior of humoral response in COVID-19 continues to be a challenge to produce vaccines that provide long-lasting immunity. AIM: To describe the natural humoral response induced by SARS-CoV-2 among healthcare workers based on epidemiological and clinical profiles. METHODS: Cross-sectional study in healthcare workers from public hospitals in the Department of Alto Paraná, Paraguay, 962 participants were recruited through consecutive sampling, using a questionnaire and blood sampling. Antibodies were determined by immunochromatography assay for detection of IgM and IgG and by SARS-CoV-2 IgG anti-spike capture ELISA method and factors associated with seropositivity were evaluated. RESULTS: The overall seropositivity was 36.5% (95% CI: 33.4 - 39.5); 59.3% (n: 571) of respondents reported symptoms compatible with COVID-19 since the start of the pandemic and the date of blood draw, 44% (n: 251) of them tested positive; 10.4% (n: 100) who reported no history of symptoms tested positive. The factors associated with seropositivity were the presence of symptoms (p 90 days). CONCLUSIONS: Clinical characteristics were mostly associated with seropositivity and sero prevalence in symptomatic participants varied according to the time elapsed from the onset of symptoms to serology.

Coronas cementadas comparado con coronas atornilladas para pacientes con restauraciones fijas implantosoportadas / Cement-retained versus screw-retained crowns in patients with implant rehabilitation

RESUMEN: Introducción: Los implantes dentales se han transformado en una opción de tratamiento de suma relevancia para pacientes parcial o totalmente desdentados. El éxito del tratamiento puede verse afectado por la elección del tipo de retención de estos (cementada o atornillada). A pesar que ambas presentan ventajas, aún no existe consenso sobre el mejor tipo de retención para restauraciones fijas implantosoportadas. Métodos: Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. Resultados y conclusiones: Identificamos 14 revisiones sistemáticas que en conjunto incluyeron 43 estudios primarios, de los cuales cinco corresponden a ensayos aleatorizados. De estos, solamente dos ensayos responden a la pregunta de interés de manera directa. Concluimos que las coronas atornilladas podrían aumentar levemente el riesgo de pérdida de implante a largo plazo, podrían resultar en nula o poca diferencia en el riesgo de pérdida de implante a mediano plazo, reabsorción ósea y periimplantitis, pero la certeza de evidencia ha sido evaluada como baja. Por otro lado, no es posible establecer con claridad si las coronas cementadas disminuyen el riesgo de complicaciones estéticas y protésicas, ya que la certeza de la evidencia existente ha sido evaluada como muy baja.

ABSTRACT: Introduction: Dental implants have become a highly relevant treatment option for partially or totally edentulous patients. Implant retention systems (cemented or screwed) can influence the treatment success. Although both have advantages, there is still no consensus on the best type of retention for implant-supported fixed restorations. Methods: We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. Results and conclusions: We identified 14 systematic reviews including 43 primary studies overall, of which five were randomized trials. Of these, only two trials answer the question of interest. We concluded that screw-retained crowns may increase long-term implant loss, may make little or no difference in the risk of medium-term implant loss, bone resorption, and peri-implantitis, but the certainty of the evidence has been assessed as low. On the other hand, it is not possible to clearly establish whether cemented crowns reduce the risk of cosmetic and prosthetic complications, since the certainty of the evidence has been assessed as very low.