Muscular myostatin gene expression and plasma concentrations are decreased in critically ill patients.

BACKGROUND The objective was to investigate the role of gene expression and plasma levels of the muscular protein myostatin in intensive care unit-acquired weakness (ICUAW). This was performed to evaluate a potential clinical and/or pathophysiological rationale of therapeutic myostatin inhibition. METHODS A retrospective analysis from pooled data of two prospective studies to assess the dynamics of myostatin plasma concentrations (day 4, 8 and 14) and myostatin gene (MSTN) expression levels in skeletal muscle (day 15) was performed. Associations of myostatin to clinical and electrophysiological outcomes, muscular metabolism and muscular atrophy pathways were investigated. RESULTS MSTN gene expression (median [IQR] fold change: 1.00 [0.68-1.54] vs. 0.26 [0.11-0.80]; p = 0.004) and myostatin plasma concentrations were significantly reduced in all critically ill patients when compared to healthy controls. In critically ill patients, myostatin plasma concentrations increased over time (median [IQR] fold change: day 4: 0.13 [0.08/0.21] vs. day 8: 0.23 [0.10/0.43] vs. day 14: 0.40 [0.26/0.61]; p < 0.001). Patients with ICUAW versus without ICUAW showed significantly lower MSTN gene expression levels (median [IQR] fold change: 0.17 [0.10/0.33] and 0.51 [0.20/0.86]; p = 0.047). Myostatin levels were directly correlated with muscle strength (correlation coefficient 0.339; p = 0.020) and insulin sensitivity index (correlation coefficient 0.357; p = 0.015). No association was observed between myostatin plasma concentrations as well as MSTN expression levels and levels of mobilization, electrophysiological variables, or markers of atrophy pathways. CONCLUSION Muscular gene expression and systemic protein levels of myostatin are downregulated during critical illness. The previously proposed therapeutic inhibition of myostatin does therefore not seem to have a pathophysiological rationale to improve muscle quality in critically ill patients. TRIAL REGISTRATION ISRCTN77569430 -13th of February 2008 and ISRCTN19392591 17th of February 2011

Development and early diagnosis of critical illness myopathy in COVID-19 associated acute respiratory distress syndrome.

BACKGROUND The COVID-19 pandemic has greatly increased the incidence and clinical importance of critical illness myopathy (CIM), because it is one of the most common complications of modern intensive care medicine. Current diagnostic criteria only allow diagnosis of CIM at an advanced stage, so that patients are at risk of being overlooked, especially in early stages. To determine the frequency of CIM and to assess a recently proposed tool for early diagnosis, we have followed a cohort of COVID-19 patients with acute respiratory distress syndrome and compared the time course of muscle excitability measurements with the definite diagnosis of CIM. METHODS Adult COVID-19 patients admitted to the Intensive Care Unit of the University Hospital Bern, Switzerland requiring mechanical ventilation were recruited and examined on Days 1, 2, 5, and 10 post-intubation. Clinical examination, muscle excitability measurements, medication record, and laboratory analyses were performed on all study visits, and additionally nerve conduction studies, electromyography and muscle biopsy on Day 10. Muscle excitability data were compared with a cohort of 31 age-matched healthy subjects. Diagnosis of definite CIM was made according to the current guidelines and was based on patient history, results of clinical and electrophysiological examinations as well as muscle biopsy. RESULTS Complete data were available in 31 out of 44 recruited patients (mean [SD] age, 62.4 [9.8] years). Of these, 17 (55%) developed CIM. Muscle excitability measurements on Day 10 discriminated between patients who developed CIM and those who did not, with a diagnostic precision of 90% (AUC 0.908; 95% CI 0.799-1.000; sensitivity 1.000; specificity 0.714). On Days 1 and 2, muscle excitability parameters also discriminated between the two groups with 73% (AUC 0.734; 95% CI 0.550-0.919; sensitivity 0.562; specificity 0.857) and 82% (AUC 0.820; CI 0.652-0.903; sensitivity 0.750; specificity 0.923) diagnostic precision, respectively. All critically ill COVID-19 patients showed signs of muscle membrane depolarization compared with healthy subjects, but in patients who developed CIM muscle membrane depolarization on Days 1, 2 and 10 was more pronounced than in patients who did not develop CIM. CONCLUSIONS This study reports a 55% prevalence of definite CIM in critically ill COVID-19 patients. Furthermore, the results confirm that muscle excitability measurements may serve as an alternative method for CIM diagnosis and support its use as a tool for early diagnosis and monitoring the development of CIM

Sozialstaatliche Hilfen als "Verfahren". Pädagogisierung der Sozialpolitik - Politisierung Sozialer Arbeit?

Der Beitrag enthält folgende Schwerpunkte: 1. Fallorientierte Sozialpolitik? Aktuelle Konvergenzen im Verhältnis von Sozialpolitik und Sozialer Arbeit. 2. Sozialstaatliche Hilfe in biographischer Sicht. 3. Hilfe nach Verfahren: Sozialstaatliche Leistungserbringung im Schnittpunkt von Sozialpädagogik und Sozialpolitik? 4. Sozialpolitische und sozialpädagogische Folgen und Probleme (Verfahren als teilautonomer Bereich der Wohlfahrtsproduktion? - Sozialpolitische Aspekte; Herausforderungen und Impulse für die Sozialpädagogik). Abschließend wird hervorgehoben: "Diese Entwicklungen in Strukturen und Kompetenzen können in der Sozialen Arbeit nur über Lernprozesse von Personen und Organisationen vorangetrieben werden. Im Umbruch des Sozialstaats eröffnen sich vielen Akteuren Chancen, durch Projekte, durch wissenschaftlich gestützte Selbst-Evaluation, durch darauf gestützte Diskurse ihre Traditionen und Kompetenzen für die Zukunft des Sozialstaates praktisch zu nutzen." (DIPF/Sch.

Pedagogical research on adolescents after the German reunification

"Seit dem Herbst 1989 hat die deutsche Jugendforschung eine Reihe von Studien hervorgebracht. Sie zeichnen insgesamt das entproblematisierende Bild junger Generationen in den alten und neuen Bundesländern, die in ihren Einstellungen und Meinungen stark konvergieren. Jugendliche in den neuen Bundesländern befinden sich demzufolge auf dem Weg einer schon längst zu DDR-Zeiten begonnenen Anpassung an "westliche" Werthaltungen und Orientierungen. Dieser Ergebnistrend verdankt sich freilich auch theoretischen Prämissen und Forschungsmethoden, welche alltägliche Erfahrungen, Probleme, die unterschiedliche Verfügung über Ressourcen u. a. vernachlässigen; die Jugendforschung ist somit dabei, die historischen Kontextverluste wissenschaftlich zu wiederholen. Der pädagogische Diskurs wie eine problemorientierte pädagogische Praxis - z. B. in der Jugendhilfe - erfordern eine Jugendforschung, insbesondere in den neuen Bundesländern, die subjektive Welten und Milieus, alltägliche Kontexte der Lebensführung und problembezogene pädagogische Fragestellungen dezidiert berücksichtigt." In vier Punkten werden wichtige Aufgaben und Aspekte künftiger Forschungen angegeben (S. 925-927). Vor allem hinsichtlich kulturvergleichender Jugendforschung und Internationalisierung des Jugendlebens wird Bedarf benannt. Differenziertere Aussagen sind u. a. auch zu international vergleichender Forschung enthalten (S. 913). (DIPF/Ko.)Since the autumn of 1989, German research on adolescents has produced a series of studies that draw a rather unproblematic picture of the young generation both in the old and in the new Laender. According to these studies, young people in the former GDR are trying to adapt to Western values and orientations, a development already begun under the old regime. The authors show that this trend in the results gained in these studies is due not least to theoretical premises and research methods that neglect everyday experiences, problems related to the practical experience of life, and actually available resources. Yet, a research orientation that decidedly focusses on young people\u27s subjective experiences of worlds and milieus, everyday contexts of the life they lead, and problem-related pedagogical questions would be much more in line with a problem-oriented pedagogical practice and a desirable form of pedagogical discourse. (DIPF/Orig.

Critical Illness Myopathy: Glucocorticoids revisited?

Over the past decades, survival rates of critical illness have constantly increased. As a consequence, the incidences of important complications of intensive care unit (ICU) treatment become more and more prevalent. Critical illness myopathy (CIM) belongs to one of the most frequent neuromuscular complications and its presence is associated with prolonged need for mechanical ventilation and ICU stay, increased morbidity and mortality 1,2. High-dose glucocorticoid (GC) treatment was early after the initial description of CIM postulated to be a major triggering factor for the development of the disease. In the current issue of Acta Physiologica, Akkad et al. investigate the effects of two GC drugs (prednisolone and a new dissociative GC termed vamorolone) on CIM development3. This article is protected by copyright. All rights reserved

Nimodipine-Induced Blood Pressure Changes Can Predict Delayed Cerebral Ischemia.

Background: Early diagnosis of delayed cerebral ischemia (DCI) in patients after aneurysmal subarachnoid hemorrhage (aSAH) still poses a leading problem in neurointensive care. The aim of this study was to analyze the effect of oral Nimodipine administration on systemic blood pressure in patients with evolving DCI compared to patients without DCI. Methods: Systolic (SBP), mean (MAP), and diastolic (DBP) blood pressures were analyzed at the time of Nimodipine administration and additionally 30, 60, and 120 min thereafter on days 1, 3, and 5 after aSAH. Additionally, the 24 h period preceding DCI and in patients without DCI day 10 after aSAH were analyzed. Statistical analysis was performed for SBP, MAP and DBP at time of Nimodipine administration and for the maximal drop in blood pressure after Nimodipine administration. Results: Thirty patients with aSAH were retrospectively analyzed with 17 patients developing DCI ("DCI") and 13 patients who did not ("Non-DCI"). DCI patients showed a more pronounced rise in MAP and DBP over the examined time period as well as a higher decrease in SBP following Nimodipine administration. A fall of 18 mmHg in SBP after Nimodipine administration showed a sensitivity of 82.4% and specificity of 92.3% for occurrence of DCI. Conclusion: An increase of MAP and DBP after aSAH and a heightened sensitivity to Nimodipine administrations may serve as additional biomarkers for early detection of evolving DCI