ABSTRACT
Based on a longtime voluntary registry, founded by the German Society for Thoracic and Cardiovascular Surgery (GSTCVS/DGTHG) in 1980, well-defined data of all cardiac, thoracic, and vascular surgery procedures performed in 78 German heart surgery departments during the year 2022 are analyzed. Under the decreasing interference of the worldwide coronavirus disease 2019 pandemic, a total of 162,167 procedures were submitted to the registry. A total of 93,913 of these operations are summarized as heart surgery procedures in a classical sense. The unadjusted in-hospital survival rate for the 27,994 isolated coronary artery bypass grafting procedures (relationship on-/off-pump 3.2:1) was 97.5%. For the 38,492 isolated heart valve procedures (20,272 transcatheter interventions included) it was 96.9%, and for the registered pacemaker/implantable cardioverter-defibrillator procedures (19,531) 99.1%, respectively. Concerning short- and long-term circulatory support, a total of 2,737 extracorporeal life support/extracorporeal membrane oxygenation implantations, respectively 672 assist device implantations (L-/ R-/ BVAD, TAH) were registered. In 2022, 356 isolated heart transplantations, 228 isolated lung transplantations, and 5 combined heart-lung transplantations were performed. This annually updated registry of the GSTCVS/DGTHG represents voluntary public reporting by accumulating actual information for nearly all heart surgical procedures in Germany, constitutes advancements in heart medicine, and represents a basis for quality management for all participating institutions. In addition, the registry demonstrates that the provision of cardiac surgery in Germany is up to date, appropriate, and nationwide patient treatment is always available.
Subject(s)
COVID-19 , Cardiac Surgical Procedures , Humans , Societies, Medical , Treatment Outcome , Quality Indicators, Health Care , Time Factors , Cardiac Surgical Procedures/adverse effects , Registries , Germany/epidemiologyABSTRACT
Based on a longtime voluntary registry, founded by the German Society for Thoracic and Cardiovascular Surgery (GSTCVS) in 1980, well-defined data of all cardiac, thoracic and vascular surgery procedures performed in 78 German heart surgery departments during the year 2021 are analyzed. Under more than extraordinary conditions of the further ongoing worldwide coronavirus disease 2019 (COVID-19) pandemic, a total of 161,261 procedures were submitted to the registry. In total, 92,838 of these operations are summarized as heart surgery procedures in a classical sense. The unadjusted in-hospital survival rate for the 27,947 isolated coronary artery bypass grafting procedures (relationship on-/off-pump 3.2:1) was 97.3%. For the 36,714 isolated heart valve procedures (19,242 transcatheter interventions included) it was 96.7 and 99.0% for the registered pacemaker and International Classification of Diseases (ICD) procedures (19,490), respectively. Concerning short- and long-term circulatory support, a total of 3,404 ECLS/ECMO implantations and 750 assist device implantations (L-/ R-/ BVAD, TAH), respectively were registered. In 2021 329 isolated heart transplantations, 254 isolated lung transplantations, and one combined heart-lung transplantations were performed.This annually updated registry of the GSTCVS represents voluntary public reporting by accumulating actual information for nearly all heart surgical procedures in Germany, constitutes advancements in heart medicine and represents a basis for quality management for all participating institutions. In addition, the registry demonstrates that the provision of cardiac surgery in Germany is up to date, appropriate, and nationwide patient treatment is guaranteed all the time.
Subject(s)
COVID-19 , Cardiac Surgical Procedures , Thoracic Surgery , Cardiac Surgical Procedures/adverse effects , Germany/epidemiology , Hospital Mortality , Humans , Quality Indicators, Health Care , Registries , Societies, Medical , Time Factors , Treatment OutcomeABSTRACT
INTRODUCTION: Targeting CD74 as the invariant chain of major histocompatibility complexes (MHC) became possible by the availability of a specific humanized monoclonal antibody, milatuzumab, which is under investigation in patients with hematological neoplasms. CD74 has been reported to regulate chemo-attractant migration of macrophages and dendritic cells, while the role of CD74 on peripheral naïve and memory B cells also expressing CD74 remains unknown. Therefore, the current study addressed the influence of milatuzumab on B-cell proliferation, chemo-attractant migration, and adhesion molecule expression. METHODS: Surface expression of CD74 on CD27- naïve and CD27+ memory B cells as well as other peripheral blood mononuclear cells (PBMCs) obtained from normals, including the co-expression of CD44, CXCR4, and the adhesion molecules CD62L, ß7-integrin, ß1-integrin and CD9 were studied after binding of milatuzumab using multicolor flow cytometry. The influence of the antibody on B-cell proliferation and migration was analyzed in vitro in detail. RESULTS: In addition to monocytes, milatuzumab also specifically bound to human peripheral B cells, with a higher intensity on CD27+ memory versus CD27- naïve B cells. The antibody reduced B-cell proliferation significantly but moderately, induced enhanced spontaneous and CXCL12-dependent migration together with changes in the expression of adhesion molecules, CD44, ß7-integrin and CD62L, mainly of CD27- naïve B cells. This was independent of macrophage migration-inhibitory factor as a ligand of CD74/CD44 complexes. CONCLUSIONS: Milatuzumab leads to modestly reduced proliferation, alterations in migration, and adhesion molecule expression preferentially of CD27- naïve B cells. It thus may be a candidate antibody for the autoimmune disease therapy by modifying B cell functions.
Subject(s)
Antibodies, Monoclonal, Humanized/physiology , Antigens, Differentiation, B-Lymphocyte/metabolism , B-Lymphocyte Subsets/immunology , B-Lymphocyte Subsets/pathology , Cell Adhesion Molecules/metabolism , Cell Proliferation , HLA-DR alpha-Chains/metabolism , Histocompatibility Antigens Class II/metabolism , Adult , Aged , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/metabolism , B-Lymphocyte Subsets/metabolism , Cell Adhesion Molecules/biosynthesis , Cell Movement/drug effects , Cell Movement/immunology , Cell Proliferation/drug effects , Drug Delivery Systems/methods , Female , Gene Expression Regulation/immunology , Humans , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/metabolism , Male , Middle Aged , Young AdultABSTRACT
INTRODUCTION: Epratuzumab, a humanized anti-CD22 monoclonal antibody, is under investigation as a therapeutic antibody in non-Hodgkin's lymphoma and systemic lupus erythematosus (SLE), but its mechanism of action on B-cells remains elusive. Treatment of SLE patients with epratuzumab leads to a reduction of circulating CD27(negative) B-cells, although epratuzumab is weakly cytotoxic to B-cells in vitro. Therefore, potential effects of epratuzumab on adhesion molecule expression and the migration of B-cells have been evaluated. METHODS: Epratuzumab binding specificity and the surface expression of adhesion molecules (CD62L, ß7 integrin and ß1 integrin) after culture with epratuzumab was studied on B-cell subsets of SLE patients by flow cytometry. In addition, in vitro transwell migration assays were performed to analyze the effects of epratuzumab on migration towards different chemokines such as CXCL12, CXCL13 or to CXCR3 ligands, and to assess the functional consequences of altered adhesion molecule expression. RESULTS: Epratuzumab binding was considerably higher on B-cells relative to other cell types assessed. No binding of epratuzumab was observed on T-cells, while weak non-specific binding of epratuzumab on monocytes was noted. On B-cells, binding of epratuzumab was particularly enhanced on CD27(negative) B-cells compared to CD27(positive) B-cells, primarily related to a higher expression of CD22 on CD27(negative) B-cells. Moreover, epratuzumab binding led to a decrease in the cell surface expression of CD62L and ß7 integrin, while the expression of ß1 integrin was enhanced. The effects on the pattern of adhesion molecule expression observed with epratuzumab were principally confined to a fraction of the CD27(negative) B-cell subpopulation and were associated with enhanced spontaneous migration of B-cells. Furthermore, epratuzumab also enhanced the migration of CD27(negative) B-cells towards the chemokine CXCL12. CONCLUSIONS: The current data suggest that epratuzumab has effects on the expression of the adhesion molecules CD62L, ß7 integrin and ß1 integrin as well as on migration towards CXCL12, primarily of CD27(negative) B-cells. Therefore, induced changes in migration appear to be part of the mechanism of action of epratuzumab and are consistent with the observation that CD27(negative) B-cells were found to be preferentially reduced in the peripheral blood under treatment.
