HbA1c als Prädiktor für das Auftreten von Frühkomplikationen nach chirurgischer Koronarrevaskularisation

Diabetes mellitus ist ein nachgewiesener Risikofaktor für postoperative Komplikationen nach kardiochirurgischen Eingriffen, insbesondere Bypass-Operationen. Zur Beurteilung des Therapieerfolgs bei Diabetikern hat sich der HbA1c-Wert als Langzeitparameter etabliert. In dieser Studie wird untersucht, ob der HbA1c die Inzidenz von Mortalität und Morbidität, einschließlich Intensivstations- und Krankenhausaufenthaltsdauer, nach einer aortokoronaren Bypass-Operation vorhersagen kann. In die Studie wurden 306 volljährige Patienten eingeschlossen, bei denen eine reine chirurgische Koronarrevaskularisation (CABG oder OPCAB) oder ein Kombinationseingriff aus CABG und Klappeneingriff durchgeführt wurde, sofern klinisch keine präoperativen Entzündungszeichen vorhanden waren. Im Rahmen der klinisch-retrospektiven Studie wurde der präoperative HbA1c u. a. bei 306 Herzbypasspatienten gemessen und die postoperativen Komplikationen bis zur Krankenhausentlassung oder Verlegung, sowie die Intensivstations- und Krankenhausaufenthaltsdauer erhoben. Es wurde gezeigt, dass folgende Komplikationen in absteigender Reihenfolge mit statistisch signifikant höheren HbA1c-Werten einhergingen: Das Multiorganversagen, der Tod, die Wundheilungsstörungen, das akute Nierenversagen und der vasodilatative Schock. Diese Komplikationen traten statistisch signifikant häufiger ab einem HbA1c = 6,4 % auf. Die höchsten HbA1c-Mittelwerte = 6,5 % hatten nur die Patienten, die ein Multiorganversagen postoperativ bekamen oder verstorben sind. Tendenziell, aber nicht signifikant höhere HbA1c-Werte hatten Patienten, die einen kardiogenen Schock, eine Rethorakotomie und ein Vorhofflimmern nach der Operation aufwiesen, sowie die Patienten mit einer längeren Intensivstations- und Krankenhausaufenthaltsdauer bis zur Entlassung oder Verlegung. Im Gegensatz dazu zeigte sich bei reanimierten Patienten und bei Patienten, die einen Apoplex oder eine TIA postoperativ erlitten, niedrigere HbA1c-Werte als Patienten ohne diese Komplikationen. Einige Parameter erbrachten in der multiplen logistischen Regressionsanalyse eine signifikant höhere Inzidenz für eine Komplikation und konnten so als unabhängige Risikofaktoren oder Schutzfaktoren (Prädiktoren) identifiziert werden. Der HbA1c gehörte nicht zu den unabhängigen Prädiktoren. Die Nüchternplasmaglukose wurde als unabhängiger Risikofaktor für die Wundheilungsstörungen; das Alter und die Zeit an der Herz-Lungen-Maschine (HLM) für ein akutes Nierenversagen identifiziert. Die OP-Dauer war ein unabhängiger Risikofaktor für einen vasodilatativen Schock und für einen kardiogenen Schock waren es die pulmonale Hypertonie und die HLM-Zeit. Als Schutzfaktoren konnten Voroperation am Herzen mit Perikarderöffnung für einen vasodilatativen Schock, sowie die Dyslipoproteinämie für einen kardiogenen Schock identifiziert werden

Evolutionary diversity of proton and water channels on the oxidizing side of photosystem II and their relevance to function

One of the reasons for the high efficiency and selectivity of biological catalysts arise from their ability to control the pathways of substrates and products using protein channels, and by modulating the transport in the channels using the interaction with the protein residues and the water/hydrogen-bonding network. This process is clearly demonstrated in Photosystem II (PS II), where its light-driven water oxidation reaction catalyzed by the Mn4CaO5 cluster occurs deep inside the protein complex and thus requires the transport of two water molecules to and four protons from the metal center to the bulk water. Based on the recent advances in structural studies of PS II from X-ray crystallography and cryo-electron microscopy, in this review we compare the channels that have been proposed to facilitate this mass transport in cyanobacteria, red and green algae, diatoms, and higher plants. The three major channels (O1, O4, and Cl1 channels) are present in all species investigated; however, some differences exist in the reported structures that arise from the different composition and arrangement of membrane extrinsic subunits between the species. Among the three channels, the Cl1 channel, including the proton gate, is the most conserved among all photosynthetic species. We also found at least one branch for the O1 channel in all organisms, extending all the way from Ca/O1 via the ‘water wheel’ to the lumen. However, the extending path after the water wheel varies between most species. The O4 channel is, like the Cl1 channel, highly conserved among all species while having different orientations at the end of the path near the bulk. The comparison suggests that the previously proposed functionality of the channels in T. vestitus (Ibrahim et al., Proc Natl Acad Sci USA 117:12624–12635, 2020; Hussein et al., Nat Commun 12:6531, 2021) is conserved through the species, i.e. the O1-like channel is used for substrate water intake, and the tighter Cl1 and O4 channels for proton release. The comparison does not eliminate the potential role of O4 channel as a water intake channel. However, the highly ordered hydrogen-bonded water wire connected to the Mn4CaO5 cluster via the O4 may strongly suggest that it functions in proton release, especially during the S0 → S1 transition (Saito et al., Nat Commun 6:8488, 2015; Kern et al., Nature 563:421–425, 2018; Ibrahim et al., Proc Natl Acad Sci USA 117:12624–12635, 2020; Sakashita et al., Phys Chem Chem Phys 22:15831–15841, 2020; Hussein et al., Nat Commun 12:6531, 2021).Peer Reviewe

O estágio voluntário na percepção de acadêmicos de enfermagem

The aim of this study was knowing the perceptions experienced by the Nursing students during a voluntary training. The data collected from 12 participants in a university hospital, during the period from May to July 2002 were analyzed through the content analysis technique, resulting in four categories: the nursing staff, the hospital admission unit, nurses’ attitudes that promote the students’ growth, and the value of the experience for the academic students. The statements evidenced the significance of this practice for the academic student and allowed a reflection on the aspects that must be improved to make the learning process easier.El objetivo de esta investigación fue conocer las percepciones vividas por los académicos de enfermería en entrenamiento voluntario. Las informaciones colectadas con doce participantes, en el periodo de mayo a julio de 2002, en un hospital universitario fueron analizadas a través de la técnica de análisis de contenido. Los resultados indicaron cuatro categorías: el equipo de enfermería, la unidad de internación hospitalaria, actitudes de los enfermeros que favorecen el crecimiento del estudiante y el valor de la experiencia para los alumnos. Los testimonios evidenciaron lo cuanto esta practica es significativa para el académico y permitió reflexionar sobre los aspectos que necesitan ser perfeccionados para facilitar su aprendizaje.O objetivo deste estudo foi conhecer as percepções vivenciadas por alunos de enfermagem, em estágio voluntário. As informações coletadas com doze participantes, no período de maio a julho de 2002, num hospital Universitário, foram analisadas, através da técnica de análise de conteúdo. Os achados apontaram quatro categorias: a equipe de enfermagem; a unidade de internação; atitudes dos enfermeiros que favorecem o crescimento do aluno e valor da experiência para os alunos. Os depoimentos evidenciaram o quanto esta prática é significativa para o acadêmico, e nos fez refletir sobre aspectos que necessitam ser aprimorados para facilitar seu aprendizado

Nanoinformatics: developing new computing applications for nanomedicine

Nanoinformatics has recently emerged to address the need of computing applications at the nano level. In this regard, the authors have participated in various initiatives to identify its concepts, foundations and challenges. While nanomaterials open up the possibility for developing new devices in many industrial and scientific areas, they also offer breakthrough perspectives for the prevention, diagnosis and treatment of diseases. In this paper, we analyze the different aspects of nanoinformatics and suggest five research topics to help catalyze new research and development in the area, particularly focused on nanomedicine. We also encompass the use of informatics to further the biological and clinical applications of basic research in nanoscience and nanotechnology, and the related concept of an extended ?nanotype? to coalesce information related to nanoparticles. We suggest how nanoinformatics could accelerate developments in nanomedicine, similarly to what happened with the Human Genome and other -omics projects, on issues like exchanging modeling and simulation methods and tools, linking toxicity information to clinical and personal databases or developing new approaches for scientific ontologies, among many others

Pseudomonas aeruginosa bloodstream infections in patients with cancer: differences between patients with hematological malignancies and solid tumors

Objectives: To assess the clinical features and outcomes of Pseudomonas aeruginosa bloodstream infection (PA BSI) in neutropenic patients with hematological malignancies (HM) and with solid tumors (ST), and identify the risk factors for 30-day mortality. Methods: We performed a large multicenter, retrospective cohort study including onco-hematological neutropenic patients with PA BSI conducted across 34 centers in 12 countries (January 2006-May 2018). Episodes occurring in hematologic patients were compared to those developing in patients with ST. Risk factors associated with 30-day mortality were investigated in both groups. Results: Of 1217 episodes of PA BSI, 917 occurred in patients with HM and 300 in patients with ST. Hematological patients had more commonly profound neutropenia (0.1 × 109 cells/mm) (67% vs. 44.6%; p < 0.001), and a high risk Multinational Association for Supportive Care in Cancer (MASCC) index score (32.2% vs. 26.7%; p = 0.05). Catheter-infection (10.7% vs. 4.7%; p = 0.001), mucositis (2.4% vs. 0.7%; p = 0.042), and perianal infection (3.6% vs. 0.3%; p = 0.001) predominated as BSI sources in the hematological patients, whereas pneumonia (22.9% vs. 33.7%; p < 0.001) and other abdominal sites (2.8% vs. 6.3%; p = 0.006) were more common in patients with ST. Hematological patients had more frequent BSI due to multidrug-resistant P. aeruginosa (MDRPA) (23.2% vs. 7.7%; p < 0.001), and were more likely to receive inadequate initial antibiotic therapy (IEAT) (20.1% vs. 12%; p < 0.001). Patients with ST presented more frequently with septic shock (45.8% vs. 30%; p < 0.001), and presented worse outcomes, with increased 7-day (38% vs. 24.2%; p < 0.001) and 30-day (49% vs. 37.3%; p < 0.001) case-fatality rates. Risk factors for 30-day mortality in hematologic patients were high risk MASCC index score, IEAT, pneumonia, infection due to MDRPA, and septic shock. Risk factors for 30-day mortality in patients with ST were high risk MASCC index score, IEAT, persistent BSI, and septic shock. Therapy with granulocyte colony-stimulating factor was associated with survival in both groups. Conclusions: The clinical features and outcomes of PA BSI in neutropenic cancer patients showed some differences depending on the underlying malignancy. Considering these differences and the risk factors for mortality may be useful to optimize their therapeutic management. Among the risk factors associated with overall mortality, IEAT and the administration of granulocyte colony-stimulating factor were the only modifiable variables.Funding: This study was supported by the Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC) (CB21/13/00009; CB21/13/00079; CB21/13/00054; CB21/13/00086), Madrid, Spain. Acknowledgments: We thank the ESCMID Study Group for Bloodstream Infections, Endocarditis, and Sepsis (ESGBIES) and the ESCMID Study Group for Immunocompromised Hosts (ESGICH) for supporting the study. We thank the Centres de Recerca de Catalunya (CERCA) Program and Generalitat de Catalunya for the institutional support. We thank the Spanish Network for Research in Infectious Diseases and the Río Hortega program of the Instituto de Salud Carlos III for the financial support of pre-doctoral student J. Laporte-Amargós and A. Bergas

Pseudomonas aeruginosa Bloodstream Infections in Patients with Cancer: Differences between Patients with Hematological Malignancies and Solid Tumors

Objectives: To assess the clinical features and outcomes of Pseudomonas aeruginosa bloodstream infection (PA BSI) in neutropenic patients with hematological malignancies (HM) and with solid tumors (ST), and identify the risk factors for 30-day mortality. Methods: We performed a large multicenter, retrospective cohort study including onco-hematological neutropenic patients with PA BSI conducted across 34 centers in 12 countries (January 2006-May 2018). Episodes occurring in hematologic patients were compared to those developing in patients with ST. Risk factors associated with 30-day mortality were investigated in both groups. Results: Of 1217 episodes of PA BSI, 917 occurred in patients with HM and 300 in patients with ST. Hematological patients had more commonly profound neutropenia (0.1 x 10(9) cells/mm) (67% vs. 44.6%; p < 0.001), and a high risk Multinational Association for Supportive Care in Cancer (MASCC) index score (32.2% vs. 26.7%; p = 0.05). Catheter-infection (10.7% vs. 4.7%; p = 0.001), mucositis (2.4% vs. 0.7%; p = 0.042), and perianal infection (3.6% vs. 0.3%; p = 0.001) predominated as BSI sources in the hematological patients, whereas pneumonia (22.9% vs. 33.7%; p < 0.001) and other abdominal sites (2.8% vs. 6.3%; p = 0.006) were more common in patients with ST. Hematological patients had more frequent BSI due to multidrug-resistant P. aeruginosa (MDRPA) (23.2% vs. 7.7%; p < 0.001), and were more likely to receive inadequate initial antibiotic therapy (IEAT) (20.1% vs. 12%; p < 0.001). Patients with ST presented more frequently with septic shock (45.8% vs. 30%; p < 0.001), and presented worse outcomes, with increased 7-day (38% vs. 24.2%; p < 0.001) and 30-day (49% vs. 37.3%; p < 0.001) case-fatality rates. Risk factors for 30-day mortality in hematologic patients were high risk MASCC index score, IEAT, pneumonia, infection due to MDRPA, and septic shock. Risk factors for 30-day mortality in patients with ST were high risk MASCC index score, IEAT, persistent BSI, and septic shock. Therapy with granulocyte colony-stimulating factor was associated with survival in both groups. Conclusions: The clinical features and outcomes of PA BSI in neutropenic cancer patients showed some differences depending on the underlying malignancy. Considering these differences and the risk factors for mortality may be useful to optimize their therapeutic management. Among the risk factors associated with overall mortality, IEAT and the administration of granulocyte colony-stimulating factor were the only modifiable variables

Pseudomonas aeruginosa Bloodstream Infections Presenting with Septic Shock in Neutropenic Cancer Patients: Impact of Empirical Antibiotic Therapy

This large, multicenter, retrospective cohort study including onco-hematological neutropenic patients with Pseudomonas aeruginosa bloodstream infection (PABSI) found that among 1213 episodes, 411 (33%) presented with septic shock. The presence of solid tumors (33.3% vs. 20.2%, p < 0.001), a high-risk Multinational Association for Supportive Care in Cancer (MASCC) index score (92.6% vs. 57.4%; p < 0.001), pneumonia (38% vs. 19.2% p < 0.001), and infection due to multidrug-resistant P. aeruginosa (MDRPA) (33.8% vs. 21.1%, p < 0.001) were statistically significantly higher in patients with septic shock compared to those without. Patients with septic shock were more likely to receive inadequate empirical antibiotic therapy (IEAT) (21.7% vs. 16.2%, p = 0.020) and to present poorer outcomes, including a need for ICU admission (74% vs. 10.5%; p < 0.001), mechanical ventilation (49.1% vs. 5.6%; p < 0.001), and higher 7-day and 30-day case fatality rates (58.2% vs. 12%, p < 0.001, and 74% vs. 23.1%, p < 0.001, respectively). Risk factors for 30-day case fatality rate in patients with septic shock were orotracheal intubation, IEAT, infection due to MDRPA, and persistent PABSI. Therapy with granulocyte colony-stimulating factor and BSI from the urinary tract were associated with improved survival. Carbapenems were the most frequent IEAT in patients with septic shock, and the use of empirical combination therapy showed a tendency towards improved survival. Our findings emphasize the need for tailored management strategies in this high-risk population

Adipose Tissue Gene Expression of Factors Related to Lipid Processing in Obesity

BACKGROUND: Adipose tissue lipid storage and processing capacity can be a key factor for obesity-related metabolic disorders such as insulin resistance and diabetes. Lipid uptake is the first step to adipose tissue lipid storage. The aim of this study was to analyze the gene expression of factors involved in lipid uptake and processing in subcutaneous (SAT) and visceral (VAT) adipose tissue according to body mass index (BMI) and the degree of insulin resistance (IR). METHODS AND PRINCIPAL FINDINGS: VLDL receptor (VLDLR), lipoprotein lipase (LPL), acylation stimulating protein (ASP), LDL receptor-related protein 1 (LRP1) and fatty acid binding protein 4 (FABP4) gene expression was measured in VAT and SAT from 28 morbidly obese patients with Type 2 Diabetes Mellitus (T2DM) or high IR, 10 morbidly obese patients with low IR, 10 obese patients with low IR and 12 lean healthy controls. LPL, FABP4, LRP1 and ASP expression in VAT was higher in lean controls. In SAT, LPL and FABP4 expression were also higher in lean controls. BMI, plasma insulin levels and HOMA-IR correlated negatively with LPL expression in both VAT and SAT as well as with FABP4 expression in VAT. FABP4 gene expression in SAT correlated inversely with BMI and HOMA-IR. However, multiple regression analysis showed that BMI was the main variable contributing to LPL and FABP4 gene expression in both VAT and SAT. CONCLUSIONS: Morbidly obese patients have a lower gene expression of factors related with lipid uptake and processing in comparison with healthy lean persons

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Genome-wide meta-analysis for Alzheimer's disease cerebrospinal fluid biomarkers

Amyloid-beta 42 (A beta 42) and phosphorylated tau (pTau) levels in cerebrospinal fluid (CSF) reflect core features of the pathogenesis of Alzheimer's disease (AD) more directly than clinical diagnosis. Initiated by the European Alzheimer & Dementia Biobank (EADB), the largest collaborative effort on genetics underlying CSF biomarkers was established, including 31 cohorts with a total of 13,116 individuals (discovery n = 8074; replication n = 5042 individuals). Besides the APOE locus, novel associations with two other well-established AD risk loci were observed; CR1 was shown a locus for A beta 42 and BIN1 for pTau. GMNC and C16orf95 were further identified as loci for pTau, of which the latter is novel. Clustering methods exploring the influence of all known AD risk loci on the CSF protein levels, revealed 4 biological categories suggesting multiple A beta 42 and pTau related biological pathways involved in the etiology of AD. In functional follow-up analyses, GMNC and C16orf95 both associated with lateral ventricular volume, implying an overlap in genetic etiology for tau levels and brain ventricular volume.Peer reviewe