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Background: The recently developed Spine Oncology Study Group Outcomes Questionnaire (SOSGOQ2.0) was proven a valid and reliable instrument measuring health-related quality of life (HRQOL) for patients with spinal malignancies. A German version was not available.Objective: A cross-cultural adaptation of the SOSGOQ2.0 to the German language and its multicenter evaluation.Methods: In a multistep process, a cross-cultural adaptation of the SOSGOQ2.0 was conducted. Subsequently, a multicenter, prospective observational cohort study was initiated to assess the reliability and validity of the German adaptation. To assess external construct validity of the cross-cultural adapted questionnaire, a comparison to the established questionnaire QLQ-C30 from the European Organisation for Research and Treatment of Cancer was conducted. Mean-difference plots were used to measure the agreement between the questionnaires in total score and by domain (deviation from mean up to 10% allowed). Further reliability and validity tests were carried out. Change to baseline was analysed 3-16 weeks later after different interventions occurred. Clinically relevant thresholds in comparison to the EORTC QLQ-C30 questionnaire were evaluated by ROC curve analysis.Results: We could enroll 113 patients from four different university hospitals (58 females, 55 males). Mean age was 64.11 years (sd 11.9). 80 patients had an ECOG performance status of 2 or higher at baseline. External construct validity in comparison to the EORTC QLQ-C30 questionnaire in total score and by domain was confirmed (range of deviation 4.4 to 9.0%). Good responsiveness for the domains Physical Functioning (P < .001) and Pain (P < .001) could be shown. The group mean values also displayed a difference in the domains of Social Functioning (P = .331) and Mental Health (P = .130), but not significant. The minimum clinically relevant threshold values for the questionnaire ranged from 4.0 to 7.5 points.Conclusions: According to our results, the cross-cultural adapted questionnaire is a reliable and valid tool to measure HRQOL in German speaking patients with spinal malignancies. Especially the domains Physical Functioning and Pain showed overall good psychometric characteristics. In this way, a generic questionnaire, such as the EORTC QLQ-C30, can be usefully supplemented by spine-specific questions to increase the overall accuracy measuring HRQOL in patients with spinal malignancies. [ABSTRACT FROM AUTHOR]

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Background: Standardized outcome reporting is crucial for trial evidence synthesis and translation of findings into clinical decision‐making. The OMERACT 2.0 Filter and COMET outcome domain taxonomy propose frameworks for consistent reporting of outcomes. There is an absence of a uniform dermatology‐specific reporting strategy that uses precise and consistent outcome definitions. Objectives: Our aim was to map efficacy/effectiveness outcomes assessed in dermatological trials to the OMERACT 2.0 Filter as a starting point for developing an outcome taxonomy in dermatology. Methods: We critically appraised 10 Cochrane Skin Reviews randomly selected from all 69 Cochrane Skin Reviews published until 01/2015 and the 220 trials included covering a broad spectrum of dermatological conditions and interventions. Efficacy/effectiveness outcomes were mapped to core areas and domains according to the OMERACT 2.0 Filter. The extracted trial outcomes were used for critical appraisal of outcome reporting in dermatology trials and for the preliminary development of a dermatology‐specific outcome taxonomy. Results: The allocation of 1086 extracted efficacy/effectiveness outcomes to the OMERACT 2.0 Filter resulted in a hierarchically structured dermatology‐specific outcome classification. In 506 outcomes (47%), the outcome concept to be measured was insufficiently described, hindering meaningful evidence synthesis. Although the core areas assessed in different dermatology trials of the same condition overlap considerably, quantitative evidence synthesis usually failed due to imprecise outcome definitions, non‐comparable outcome measurement instruments, metrics and reporting. Conclusions: We present an efficacy/effectiveness outcome classification as a starting point for a dermatology‐specific taxonomy to provide trialists and reviewers with the opportunity to better synthesize and compare evidence. Linked Commentary: A. Ragamin et al. J Eur Acad Dermatol Venereol 2021; 35: 276‐277. https://doi.org/10.1111/jdv.17103. [ABSTRACT FROM AUTHOR]

Abstract Background Bats of the family Phyllostomidae show a unique diversity in feeding specializations. This taxon includes species that are highly specialized on insects, blood, small vertebrates, fruits or nectar, and pollen. Feeding specialization is accompanied by morphological, physiological and behavioural adaptations. Several attempts were made to resolve the phylogenetic relationships within this family in order to reconstruct the evolutionary transitions accompanied by nutritional specialization. Nevertheless, the evolution of nectarivory remained equivocal. Results Phylogenetic reconstructions, based on a concatenated nuclear-and mitochondrial data set, revealed a paraphyletic relationship of nectarivorous phyllostomid bats. Our phylogenetic reconstructions indicate that the nectarivorous genera Lonchophylla and Lionycteris are closer related to mainly frugivorous phyllostomids of the subfamilies Rhinophyllinae, Stenodermatinae, Carolliinae, and the insectivorous Glyphonycterinae rather than to nectarivorous bats of the Glossophaginae. This suggests an independent origin of morphological adaptations to a nectarivorous lifestyle within Lonchophyllinae and Glossophaginae. Molecular clock analysis revealed a relatively short time frame of about ten million years for the divergence of subfamilies. Conclusions Our study provides strong support for diphyly of nectarivorous phyllostomids. This is remarkable, since their morphological adaptations to nutrition, like elongated rostrums and tongues, reduced teeth and the ability to use hovering flight while ingestion, closely resemble each other. However, more precise examinations of their tongues (e.g. type and structure of papillae and muscular innervation) revealed levels of difference in line with an independent evolution of nectarivory in these bats.

Background : A standard method of assessing postural control is to measure while standing. However, its implementation is usually limited. Recording postural control directly on the trunk in a seated position could provide an alternative diagnostic method for quantifying neuromuscular control. Methods : A comparison of center of pressure (CoP) measurements in the standing and sitting positions was performed on 66 healthy adult subjects. The reliability of the measurements in the sitting position was tested in 23 subjects. In addition, the extension force of all test subjects was recorded. Results : The assessments of CoP fluctuations in standing and seated positions showed adequate agreement (deviation 9.1%). Furthermore, good internal consistencies with a sufficient test-retest reliability could be demonstrated for the measurements in seated position. Both CoP measurement methods showed a comparable Spearman correlation to obtained extension force measurements (standing: 0.24, seated: 0.23). Conclusions : Our results show that recording CoP fluctuations in the sitting position is a reliable and valid adjunct to single-leg stance measurements. It could serve as an additional alternative to quantify neuromuscular control in impaired patients who cannot adequately perform the single-leg stance. In addition, measurement in the seated position allows direct recording of neuromuscular control at the trunk.

Background: Approximately 70 % of proximal humerus fractures (PHF) occur after the age of 60. High complication rates have been described in correlation with the treatment of PHF. Major risk factors for the outcome might be frailty, mobility and comorbidities of patients at the time of hospital admission. The aim of this study was to create risk adjusted quality indicators for surgical treatment of proximal humerus fractures based on German claims data and to evaluate the impact of the Hospital Frailty Risk Score (HFRS) on risk adjustment., Methods: Retrospective claims data (2015-2021) were used to create risk adjusted quality indicators for eight outcomes by clustered multivariable logistic regression. The comparison of different risk adjustment model performances was done by ROC-AUC and Standardized Mortality/Morbidity Ratios., Results: In total, N = 34,912 patients (median age 75 years, 80.3 % female) were included. The most common surgical procedure was open reduction and internal fixation with plate osteosynthesis with 39.7 %, followed by reverse shoulder arthroplasty with 25.3 %. The most influential risk factor for all outcomes was a high HFRS with an Odds Ratio of 2.0 (95 %-Confidence Interval 1.8-2.3) for any secondary surgery (365 days) up to an Odds Ratio of 17.6 (95 %-Confidence Interval 14.9-20.8) for general complications during the index stay., Conclusion: Comparative quality reporting for the surgical treatment of PHF appears feasible with the developed models for risk adjustment using claims data. Preoperative evaluation of HFRS in PHF can contribute to risk assessment, and individual patient management. It therefore enables personalized treatment decisions., Competing Interests: Declaration of competing interest Jochen Schmitt reports institutional grants for investigator-initiated research from the German GBA, BMG, BMBF, EU, Federal State of Saxony, Novartis, Sanofi, ALK, and Pfizer. He also participated in advisory board meetings as a paid consultant for Sanofi, Lilly, and ALK. JS is a member of the Expert Council on Health and Care at the Federal Ministry of Health and a member of the government commission for modern and needs-based hospital care of the current German Coalition. All other authors report no conflicts of interest regarding the submitted work., (Copyright © 2024. Published by Elsevier B.V.)

Clinics and practices in the field of ear, nose and throat medicine (ENT) are experiencing a significant increase in the number of emergency patients, which has multiple reasons. There is broad consent that a reform of emergency structures is necessary.The government commission for modern and needs-based hospital care has made recommendations with statements on the reform of emergency and acute care in the areas of "emergency services and financing" and "integrated emergency centers and integrated control centers". For this purpose a reliable foundation will be created with participation of specialist societies and professional associations, also linked to the hope of initiating the urgently needed relief of medical staff in clinics and practices.The present manuscript describes the health policy history and current problems in emergency care, focusing on proposed solutions with reference to the special features of ENT medicine. This position paper is linked to an appeal to self-administration and politicians to quickly implement a sustainable concept for emergency care, as financing and staff availability are becoming increasingly critical and the unregulated wave of emergency patients must be given a helping hand., Competing Interests: Mitgliedschaften bei Fachgesellschaften DGHNO und Berufsverband bei allen Autoren außer Thomas Dazmann (hier DGAI), Beraterhonorare/Advisory Board ohne Zusammenhang mit der Arbeit., (Thieme. All rights reserved.)

Epidemiological data suggest that moderate hyperoxemia may be associated with an improved outcome after traumatic brain injury. In a prospective, randomized investigation of long-term, resuscitated acute subdural hematoma plus hemorrhagic shock (ASDH + HS) in 14 adult, human-sized pigs, targeted hyperoxemia (200 < P a O 2 < 250 mmHg vs. normoxemia 80 < P a O 2 < 120 mmHg) coincided with improved neurological function. Since brain perfusion, oxygenation and metabolism did not differ, this post hoc study analyzed the available material for the effects of targeted hyperoxemia on cerebral tissue markers of oxidative/nitrosative stress (nitrotyrosine expression), blood-brain barrier integrity (extravascular albumin accumulation) and fluid homeostasis (oxytocin, its receptor and the H 2 S-producing enzymes cystathionine-β-synthase and cystathionine-γ-lyase). After 2 h of ASDH + HS (0.1 mL/kgBW autologous blood injected into the subdural space and passive removal of 30% of the blood volume), animals were resuscitated for up to 53 h by re-transfusion of shed blood, noradrenaline infusion to maintain cerebral perfusion pressure at baseline levels and hyper-/normoxemia during the first 24 h. Immediate postmortem, bi-hemispheric (i.e., blood-injected and contra-lateral) prefrontal cortex specimens from the base of the sulci underwent immunohistochemistry (% positive tissue staining) analysis of oxidative/nitrosative stress, blood-brain barrier integrity and fluid homeostasis. None of these tissue markers explained any differences in hyperoxemia-related neurological function. Likewise, hyperoxemia exerted no deleterious effects.

Introduction: The operating room (OR) is a high-cost and high-revenue area in a hospital comprising extremely complex process steps to treat patients. The perioperative process quality can be optimized through an efficiency-oriented central OR management based on performance indices. However, during the COVID-19 pandemic with the corresponding OR restrictions, there was a significant nation- and worldwide decline in the performance, which may have a lasting impact. Therefore, we proposed the hypothesis that COVID-19 pandemic-related OR restrictions could reduce operative performance in the long term., Methods: A retrospective, descriptive analysis of perioperative processing times was conducted exemplarily at the University Hospital Ulm using a pre-post design, examining the corresponding second quarters of 2019 to 2022. In total, n = 18,489 operations with n = 314,313 individual time intervals were analyzed. The statistical analyses included the Kruskal-Wallis test adjusted for multiple testing, and the significance level was set at p < 0.01., Results: The results revealed not only a significant decrease in the case volume by 31% (2020) and 23% (2021) during the COVID-19 crisis years, but also significant time delays in various process steps; e.g. the median patient's OR occupancy time (column time) rose from 65 min (2019) to 87 min (2020) and remained elevated (72 min in 2021 and 74 min in 2022, respectively). Even in 2022, beyond the pandemic, the net anaesthesia time was permanently enhanced by 9 min per case. Furthermore, both, the incision-to-closure time and surgeon attachment time were each significantly prolonged by 7 additional minutes, and the time from the end of anaesthesia to the release of the next patient was extended by 4 min. Selected standardized index operations showed only a trend towards these changes, even with a decrease in the incision-to-closure time over time., Conclusion: Overall, long-term changes were found in essential perioperative process times even after retraction of the COVID-19 restrictions, indicating some processual "slow down" after the Covid-19-induced "shut down". Further analyses are needed to determine the appropriate targeted control measures to improve processing times and increase the process quality., (© 2024. The Author(s).)

Introduction: Supplementation with increased inspired oxygen fractions has been suggested to alleviate the harmful effects of tissue hypoxia during hemorrhagic shock (HS) and traumatic brain injury. However, the utility of therapeutic hyperoxia in critical care is disputed to this day as controversial evidence is available regarding its efficacy. Furthermore, in contrast to its hypoxic counterpart, the effect of hyperoxia on the metabolism of circulating immune cells remains ambiguous. Both stimulating and detrimental effects are possible; the former by providing necessary oxygen supply, the latter by generation of excessive amounts of reactive oxygen species (ROS). To uncover the potential impact of increased oxygen fractions on circulating immune cells during intensive care, we have performed a 13 C-metabolic flux analysis (MFA) on PBMCs and granulocytes isolated from two long-term, resuscitated models of combined acute subdural hematoma (ASDH) and HS in pigs with and without cardiovascular comorbidity., Methods: Swine underwent resuscitation after 2 h of ASDH and HS up to a maximum of 48 h after HS. Animals received normoxemia (P a O 2 = 80 - 120 mmHg) or targeted hyperoxemia (P a O 2 = 200 - 250 mmHg for 24 h after treatment initiation, thereafter P a O 2 as in the control group). Blood was drawn at time points T1 = after instrumentation, T2 = 24 h post ASDH and HS, and T3 = 48 h post ASDH and HS. PBMCs and granulocytes were isolated from whole blood to perform electron spin resonance spectroscopy, high resolution respirometry and 13 C-MFA. For the latter, we utilized a parallel tracer approach with 1,2- 13 C 2 glucose, U- 13 C glucose, and U- 13 C glutamine, which covered essential pathways of glucose and glutamine metabolism and supplied redundant data for robust Bayesian estimation. Gas chromatography-mass spectrometry further provided multiple fragments of metabolites which yielded additional labeling information. We obtained precise estimations of the fluxes, their joint credibility intervals, and their relations, and characterized common metabolic patterns with principal component analysis (PCA)., Results: 13 C-MFA indicated a hyperoxia-mediated reduction in tricarboxylic acid (TCA) cycle activity in circulating granulocytes which encompassed fluxes of glutamine uptake, TCA cycle, and oxaloacetate/aspartate supply for biosynthetic processes. We further detected elevated superoxide levels in the swine strain characterized by a hypercholesterolemic phenotype. PCA revealed cell type-specific behavioral patterns of metabolic adaptation in response to ASDH and HS that acted irrespective of swine strains or treatment group., Conclusion: In a model of resuscitated porcine ASDH and HS, we saw that ventilation with increased inspiratory O 2 concentrations (P a O 2 = 200 - 250 mmHg for 24 h after treatment initiation) did not impact mitochondrial respiration of PBMCs or granulocytes. However, Bayesian 13 C-MFA results indicated a reduction in TCA cycle activity in granulocytes compared to cells exposed to normoxemia in the same time period. This change in metabolism did not seem to affect granulocytes' ability to perform phagocytosis or produce superoxide radicals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wolfschmitt, Vogt, Hogg, Wachter, Stadler, Kapapa, Datzmann, Messerer, Hoffmann, Gröger, Münz, Mathieu, Mayer, Merz, Asfar, Calzia, Radermacher and Zink.)

Introduction: Translational research is important, especially in medicine where decisions affect people's lives. Clinical registries and the studies embedded in them allow the depiction of actual care practice under routine conditions. Translating the findings of health services research back into clinical research through prospective cohort studies has the potential to drive medical innovations faster, more effectively and, above all, in a more targeted manner. These must therefore be a central component of cutting-edge oncological research., Objective: The aim of the registry is the establishment of clinical cohorts and the provision of a comprehensive, high-quality data set for oncological diseases., Methods/design: The registry will prospectively record all patients treated for cancer at Dresden University Hospital (UKD). In addition to the data from the hospital information systems (ORBIS, TDS, GEPADO, etc.), monitoring of health-related quality of life (HRQOL) is to be carried out at regular intervals at the beginning and during the course of treatment. In addition, individual linkage with data from clinical cancer registries and health insurance companies (including AOK PLUS) is planned for a period of five years before and after inclusion. All these data will be merged in a registry database. The selection of variables and measurement time points is closely based on the guidelines for colorectal carcinoma of the international initiative ICHOM (International Consortium for Health Outcomes Measurement). The study management software (STeVe) separates personal identification characteristics (IDAT) and medical data (MDAT) at an early stage. The independent trust centre of the TU Dresden (Treuhandstelle) ensures that no personal data enter the registry database. It is thereby also ensured that the data owners involved (UKD, biobank, health insurance company, cancer registry, patient) only receive the personal data they need for allocation. The MOSAIC software tools recommended by the TMF (Technologie- und Methodenplattform für die vernetzte medizinische Forschung e.V.) are used to manage the pseudonyms., Discussion/conclusion: With the registry, previously missing evidence on the effectiveness, safety and costs of diagnostic and therapeutic measures can be made, taking into account long-term and patient-reported outcomes of routine care. The data potentially allow for the identification of barriers to and facilitators of innovative promising cancer diagnostics and therapies. They also enable generation of scientifically relevant hypotheses in the field of translational and outcomes research., Competing Interests: Unabhängig von dieser Studie erhielt JS institutionelle Förderung für von Forschern initiierte Forschung („investigator-initiated-research“) von Sanofi, Pfizer, Novartis und ALK und war als bezahlter Berater für Sanofi, Novartis, ALK und Lilly tätig. OS ist Mitglied in der Zertifizierungskommission „Hautkrebszentren“ der Deutschen Krebsgesellschaft. MB gab die Anstellung am UKD, Mitglied des NCT-Boards (Projektfinanzierung), Honorare und Reisekosten von den Firmen Jazz, Alexion, Novartis und Projektfinanzierung von AbbVie, Roche, sowie Ad-Board bei Jazz an. Die anderen Autoren erklären, dass sie sich in keinem Interessenkonflikt befinden., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Severe physical injuries and associated traumatic brain injury and/or hemorrhagic shock (HS) remain leading causes of death worldwide, aggravated by accompanying extensive inflammation. Retrospective clinical data indicated an association between mild hyperoxemia and improved survival and outcome. However, corresponding prospective clinical data, including long-term resuscutation, are scarce. Therefore, the present study explored the effect of mild hyperoxemia for 24 hours in a prospective randomized controlled trial in a long-term resuscitated model of combined acute subdural hematoma (ASDH) and HS. ASDH was induced by injecting 0.1 ml × kg -1 autologous blood into the subdural space and HS was triggered by passive removal of blood. After 2 hours, the animals received full resuscitation, including retransfusion of the shed blood and vasopressor support. During the first 24 hours, the animals underwent targeted hyperoxemia (P a O 2 = 200 - 250 mmHg) or normoxemia (P a O 2 = 80 - 120 mmHg) with a total observation period of 55 hours after the initiation of ASDH and HS. Survival, cardiocirculatory stability, and demand for vasopressor support were comparable between both groups. Likewise, humoral markers of brain injury and systemic inflammation were similar. Multimodal brain monitoring, including microdialysis and partial pressure of O 2 in brain tissue, did not show significant differences either, despite a significantly better outcome regarding the modified Glasgow Coma Scale 24 hours after shock that favors hyperoxemia. In summary, the present study reports no deleterious and few beneficial effects of mild targeted hyperoxemia in a clinically relevant model of ASDH and HS with long-term resuscitation in otherwise healthy pigs. Further beneficial effects on neurological function were probably missed due to the high mortality in both experimental groups. The present study remains exploratory due to the unavailability of an a priori power calculation resulting from the lack of necessary data., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest., (Copyright © 2023 Datzmann, Münz, Hoffmann, Moehrke, Binzenhöfer, Gröger, Kapapa, Mathieu, Mayer, Zink, Gässler, Wolfschmitt, Hogg, Merz, Calzia, Radermacher and Messerer.)

Introduction: Sodium thiosulfate (Na 2 S 2 O 3 ), an H 2 S releasing agent, was shown to be organ-protective in experimental hemorrhage. Systemic inflammation activates immune cells, which in turn show cell type-specific metabolic plasticity with modifications of mitochondrial respiratory activity. Since H 2 S can dose-dependently stimulate or inhibit mitochondrial respiration, we investigated the effect of Na 2 S 2 O 3 on immune cell metabolism in a blinded, randomized, controlled, long-term, porcine model of hemorrhage and resuscitation. For this purpose, we developed a Bayesian sampling-based model for 13 C isotope metabolic flux analysis (MFA) utilizing 1,2- 13 C 2 -labeled glucose, 13 C 6 -labeled glucose, and 13 C 5 -labeled glutamine tracers., Methods: After 3 h of hemorrhage, anesthetized and surgically instrumented swine underwent resuscitation up to a maximum of 68 h. At 2 h of shock, animals randomly received vehicle or Na 2 S 2 O 3 (25 mg/kg/h for 2 h, thereafter 100 mg/kg/h until 24 h after shock). At three time points (prior to shock, 24 h post shock and 64 h post shock) peripheral blood mononuclear cells (PBMCs) and granulocytes were isolated from whole blood, and cells were investigated regarding mitochondrial oxygen consumption (high resolution respirometry), reactive oxygen species production (electron spin resonance) and fluxes within the metabolic network (stable isotope-based MFA)., Results: PBMCs showed significantly higher mitochondrial O 2 uptake and lower O 2 • - production in comparison to granulocytes. We found that in response to Na 2 S 2 O 3 administration, PBMCs but not granulocytes had an increased mitochondrial oxygen consumption combined with a transient reduction of the citrate synthase flux and an increase of acetyl-CoA channeled into other compartments, e.g., for lipid biogenesis., Conclusion: In a porcine model of hemorrhage and resuscitation, Na 2 S 2 O 3 administration led to increased mitochondrial oxygen consumption combined with stimulation of lipid biogenesis in PBMCs. In contrast, granulocytes remained unaffected. Granulocytes, on the other hand, remained unaffected. O 2 • - concentration in whole blood remained constant during shock and resuscitation, indicating a sufficient anti-oxidative capacity. Overall, our MFA model seems to be is a promising approach for investigating immunometabolism; especially when combined with complementary methods., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer JB declared a past collaboration with the authors E-MW, MG and MH to the handling editor., (Copyright © 2023 Wolfschmitt, Hogg, Vogt, Zink, Wachter, Hezel, Zhang, Hoffmann, Gröger, Hartmann, Gässler, Datzmann, Merz, Hellmann, Kranz, Calzia, Radermacher and Messerer.)

Background: The restriction of hydroxyethylstarch (HES) necessitated changes in volume management in cardiac surgery, increasing the use of gelatin (GELA) and crystalloid (CRYS) mono strategies., Methods: This retrospective study evaluated the effects of changed volume replacement management to a GELA or CRYS mono therapy on mortality, acute kidney injury (AKI), blood loss, and transfusion in cardiac surgery patients with at least one coronary artery bypass grafting (CABG) at a university hospital. Three groups (HES n=938, GELA n=397, CRYS n=205) were derived from 1,540 patients with complete data sets. Data were analyzed by multiple regression models., Results: Patients had similar risk profiles, comorbidities, and preoperative routine diagnostics prior to surgery. No difference was observed in mortality and AKI. HES treated patients showed highest blood loss, followed by GELA while CRYS patients had the lowest (P<0.0001). Patients in the HES group had highest transfusion of packed red blood cells (PRBCs) and platelet concentrates (PCs), followed by GELA, whereas CRYS had the lowest (P<0.0001). Fresh frozen plasma (FFP) transfusion, administration of fibrinogen, and prothrombin complex concentrates (PCCs) were highest in HES group. CRYS showed the shortest time of mechanical ventilation (P<0.0001) and left the intensive care unit (ICU) significantly earlier (P<0.0001). Multivariable regression analysis found that colloid volume significantly predicted hospital mortality and renal replacement therapy (RRT), but not AKI., Conclusions: Administration of crystalloids without any colloid showed no differences in mortality or AKI, but less blood loss and transfusion. Colloids should be considered critically and further studies should investigate effects of GELA in cardiac surgery., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-22-450/coif). The authors have no conflicts of interest to declare., (2022 Journal of Thoracic Disease. All rights reserved.)

Controversial evidence is available regarding suitable targets for the arterial O 2 tension (P a O 2 ) after traumatic brain injury and/or hemorrhagic shock (HS). We previously demonstrated that hyperoxia during resuscitation from hemorrhagic shock attenuated cardiac injury and renal dysfunction in swine with coronary artery disease. Therefore, this study investigated the impact of targeted hyperoxemia in a long-term, resuscitated model of combined acute subdural hematoma (ASDH)-induced brain injury and HS. The prospective randomized, controlled, resuscitated animal investigation consisted of 15 adult pigs. Combined ASDH plus HS was induced by injection of 0.1 ml/kg autologous blood into the subdural space followed by controlled passive removal of blood. Two hours later, resuscitation was initiated comprising re-transfusion of shed blood, fluids, continuous i.v. noradrenaline, and either hyperoxemia (target P a O 2 200 - 250 mmHg) or normoxemia (target P a O 2 80 - 120 mmHg) during the first 24 h of the total of 54 h of intensive care. Systemic hemodynamics, intracranial and cerebral perfusion pressures, parameters of brain microdialysis and blood biomarkers of brain injury did not significantly differ between the two groups. According to the experimental protocol, P a O 2 was significantly higher in the hyperoxemia group at the end of the intervention period, i.e., at 24 h of resuscitation, which coincided with a higher brain tissue PO 2 . The latter persisted until the end of observation period. While neurological function as assessed using the veterinary Modified Glasgow Coma Score progressively deteriorated in the control group, it remained unaffected in the hyperoxemia animals, however, without significant intergroup difference. Survival times did not significantly differ in the hyperoxemia and control groups either. Despite being associated with higher brain tissue PO 2 levels, which were sustained beyond the intervention period, targeted hyperoxemia exerted neither significantly beneficial nor deleterious effects after combined ASDH and HS in swine with pre-existing coronary artery disease. The unavailability of a power calculation and, thus, the limited number of animals included, are the limitations of the study., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Datzmann, Messerer, Münz, Hoffmann, Gröger, Mathieu, Mayer, Gässler, Zink, McCook, Merz, Scheuerle, Wolfschmitt, Thebrath, Zuech, Calzia, Asfar, Radermacher and Kapapa.)

We previously demonstrated marked lung-protective properties of the H 2 S donor sodium thiosulfate (Na 2 S 2 O 3 , STS) in a blinded, randomized, controlled, long-term, resuscitated porcine model of swine with coronary artery disease, i.e., with decreased expression of the H 2 S-producing enzyme cystathionine-γ-lyase (CSE). We confirmed these beneficial effects of STS by attenuation of lung, liver and kidney injury in mice with genetic CSE deletion (CSE-ko) undergoing trauma-and-hemorrhage and subsequent intensive care-based resuscitation. However, we had previously also shown that any possible efficacy of a therapeutic intervention in shock states depends both on the severity of shock as well as on the presence or absence of chronic underlying co-morbidity. Therefore, this prospective, randomized, controlled, blinded experimental study investigated the effects of the STS in cardiovascular healthy swine. After anesthesia and surgical instrumentation, 17 adult Bretoncelles-Meishan-Willebrand pigs were subjected to 3 hours of hemorrhage by removal of 30% of the blood volume and titration of the mean arterial pressure (MAP) ≈ 40 ± 5 mmHg. Afterwards, the animals received standardized resuscitation including re-transfusion of shed blood, fluids, and, if needed, continuous i.v. noradrenaline to maintain MAP at pre-shock values. Animals were randomly allocated to either receive Na 2 S 2 O 3 or vehicle control starting 2 hours after initiation of shock until 24 hours of resuscitation. The administration of Na 2 S 2 O 3 did not alter survival during the observation period of 68 hours after the initiation of shock. No differences in cardio-circulatory functions were noted despite a significantly higher cardiac output, which coincided with significantly more pronounced lactic acidosis at 24 hours of resuscitation in the Na 2 S 2 O 3 group. Parameters of liver, lung, and kidney function and injury were similar in both groups. However, urine output was significantly higher in the Na 2 S 2 O 3 group at 24 hours of treatment. Taken together, this study reports no beneficial effect of Na 2 S 2 O 3 in a clinically relevant model of hemorrhagic shock-and-resuscitation in animals without underlying chronic cardiovascular co-morbidity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Messerer, Gaessler, Hoffmann, Gröger, Benz, Huhn, Hezel, Calzia, Radermacher and Datzmann.)

Background: Calcitonin gene-related peptide (CGRP) and procalcitonin, which are overexpressed in sepsis, exert distinct immunomodulatory effects mediated through the CGRP receptor. The CGRP receptor antagonist olcegepant improves survival in murine sepsis. This study evaluated whether CGRP receptor antagonism is similarly beneficial in a porcine model of polymicrobial sepsis., Methods: We conducted a prospective randomised, controlled, investigator-blinded trial in adult pigs of either sex, that were anaesthetised and ventilated before sepsis was induced by polymicrobial (autologous) faecal peritonitis. After the onset of early septic shock (systolic blood pressure <90 mm Hg or >10% decline from baseline MAP), pigs were resuscitated (i.v. fluid/antibiotics/vasopressors) and randomised to receive either i.v. olcegepant (n=8) or vehicle control (n=8). The primary outcome was time to death, euthanasia required up to 72 h after surgery (according to predefined severe cardiorespiratory failure), or both. Secondary outcomes included haemodynamic changes, and systemic as well as organ inflammation (mRNA expression)., Results: Septic shock developed 8.7 h (inter-quartile range, 5.8-11.1 h) after the onset of faecal peritonitis. Olcegepant worsened survival, with 6/8 pigs randomised to the control group surviving 72.0 h (50.9-72.0 h), compared with 3/8 pigs receiving olcegepant surviving 51.3 h (12.5-72.0 h; P=0.01). At 48 h, lower MAP and higher cardiac output occurred in pigs receiving olcegepant. Cardiac, hepatic, and renal injury was not different between pigs randomised to receive olcegepant or vehicle. Olcegepant reduced mRNA expression of several inflammation-related cytokines and CD68 + macrophages in liver but not in lung tissue., Conclusions: CGRP receptor antagonism with olcegepant was not beneficial in this porcine model of polymicrobial sepsis, which closely mimics human sepsis., (Copyright © 2022 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Ever since the discovery of endogenous H 2 S and the identification of its cytoprotective properties, efforts have been made to develop strategies to use H 2 S as a therapeutic agent. The ability of H 2 S to regulate vascular tone, inflammation, oxidative stress, and apoptosis might be particularly useful in the therapeutic management of critical illness. However, neither the inhalation of gaseous H 2 S, nor the administration of inorganic H 2 S-releasing salts or slow-releasing H 2 S-donors are feasible for clinical use. Na 2 S 2 O 3 is a clinically approved compound with a good safety profile and is able to release H 2 S, in particular under hypoxic conditions. Pre-clinical studies show promise for Na 2 S 2 O 3 in the acute management of critical illness. A current clinical trial is investigating the therapeutic potential for Na 2 S 2 O 3 in myocardial infarct. Pre-eclampsia and COVID-19 pneumonia might be relevant targets for future clinical trials.

(1) Background: Targeted (TT) and immune checkpoint inhibitor (ICI) therapies have become available in the routine care of metastatic melanoma in recent years. (2) Objective: We compared mortality in patients with metastatic melanoma and different systemic therapies. (3) Methods: A retrospective cohort study, based on pseudonymized health insurance data of about two million individuals from Saxony, Germany, was conducted for the years 2010 to 2020. Only patients with an advanced stage, i.e., distant metastases were considered for the main analysis. Relative survival since metastasis and predicted survivor curves derived from a Cox model were used to assess potential differences in mortality. (4) Results: Relative survival was highest in the subgroup with sequential use of ICI and TT. All treatments except interferon had significant hazard ratios (HR) in the Cox model with time-dependent effects indicating a protective effect after treatment initiation (HR 0.01-0.146) but decreasing over time (HR 1.351-2.310). The predicted survivor curves revealed best survival under ICI-TT treatment and worst survival under TT treatment alone. (5) Conclusions: We found real-world evidence for survival benefits of patients with metastatic melanoma who received sequential ICI and TT treatment. It is conceivable that the observed high survival differences were overestimated due to bias, such as confounding by indication.

Hospital certification has become an important measure to improve cancer care quality, with the potential effect of prolonging patient survival and reducing medical spending. However, yet to be explored is the cost-effectiveness of cancer care provided in certified hospitals, considering significant additional costs incurred from certification requirements. We performed a cost-effectiveness analysis (CEA) using two colon cancer populations (N = 1909) treated in different levels of certified hospitals (CHs) vs noncertified hospitals (NCHs) from a healthcare system's perspective. We matched patient-level data of incident colon cancer cases, diagnosed between 2008 and 2013 from a large statutory health insurance in Saxony, Germany, to calculate net treatment costs by phase (initial, continuing and terminal phase). The costs were supplemented with extra costs from 31 additional services required for certification. Effectiveness measure was total survival time in life-years. Outcome of interest was incremental costs per additional life-year. The annualized net colon cancer treatment costs by phase showed a U shape with high costs in the initial (mean €26 855; 95% CI €25 058-€28 652) and the terminal phases (mean €30 096; 95% CI €26 199-€33 993). The base-case CEA results and all sensitivity analyses consistently demonstrated longer survival and lower costs for the colon cancer cohort treated in CHs vs NCHs. To conclude, we used administrative data to derive the first cost-effectiveness evidence supporting that colon cancer care delivered in the certified cancer centers in Germany improves survival outcomes and saves costs from a healthcare system's perspective. Generalization of the study results should be exercised with caution., (© 2021 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Competing Interests: The authors report no conflicts of interest.

Updating systematic reviews is often a time-consuming process that involves a lot of human effort and is therefore not conducted as often as it should be. The aim of our research project was to explore the potential of machine learning methods to reduce human workload. Furthermore, we evaluated the performance of deep learning methods in comparison to more established machine learning methods. We used three available reviews of diagnostic test studies as the data set. In order to identify relevant publications, we used typical text pre-processing methods. The reference standard for the evaluation was the human-consensus based on binary classification (inclusion, exclusion). For the evaluation of the models, various scenarios were generated using a grid of combinations of data preprocessing steps. Moreover, we evaluated each machine learning approach with an approach-specific predefined grid of tuning parameters using the Brier score metric. The best performance was obtained with an ensemble method for two of the reviews, and by a deep learning approach for the other review. Yet, the final performance of approaches strongly depends on data preparation. Overall, machine learning methods provided reasonable classification. It seems possible to reduce human workload in updating systematic reviews by using machine learning methods. Yet, as the influence of data preprocessing on the final performance seems to be at least as important as choosing the specific machine learning approach, users should not blindly expect a good performance by solely using approaches from a popular class, such as deep learning., (© 2021 The Authors. Research Synthesis Methods published by John Wiley & Sons Ltd.)

There is an ongoing discussion whether hyperoxia, i.e. ventilation with high inspiratory O 2 concentrations (F I O 2 ), and the consecutive hyperoxaemia, i.e. supraphysiological arterial O 2 tensions (PaO 2 ), have a place during the acute management of circulatory shock. This concept is based on experimental evidence that hyperoxaemia may contribute to the compensation of the imbalance between O 2 supply and requirements. However, despite still being common practice, its use is limited due to possible oxygen toxicity resulting from the increased formation of reactive oxygen species (ROS) limits, especially under conditions of ischaemia/reperfusion. Several studies have reported that there is a U-shaped relation between PaO 2 and mortality/morbidity in ICU patients. Interestingly, these mostly retrospective studies found that the lowest mortality coincided with PaO 2  ~ 150 mmHg during the first 24 h of ICU stay, i.e. supraphysiological PaO 2 levels. Most of the recent large-scale retrospective analyses studied general ICU populations, but there are major differences according to the underlying pathology studied as well as whether medical or surgical patients are concerned. Therefore, as far as possible from the data reported, we focus on the need of mechanical ventilation as well as the distinction between the absence or presence of circulatory shock. There seems to be no ideal target PaO 2 except for avoiding prolonged exposure (> 24 h) to either hypoxaemia (PaO 2  < 55-60 mmHg) or supraphysiological (PaO 2  > 100 mmHg). Moreover, the need for mechanical ventilation, absence or presence of circulatory shock and/or the aetiology of tissue dysoxia, i.e. whether it is mainly due to impaired macro- and/or microcirculatory O 2 transport and/or disturbed cellular O 2 utilization, may determine whether any degree of hyperoxaemia causes deleterious side effects.

Abstract: In activated immune cells, differentiation and function are determined by cell type-specific modifications of metabolic patterns. After traumatic brain injury both immune cell activation and suppression were reported. Therefore, we sought to explore immune cell energy metabolism in a long-term, resuscitated porcine model of acute subdural hematoma (ASDH)-induced acute brain injury devoid of impaired systemic hemodynamics and oxygen transport.Before and up to 50 h after induction of ASDH, peripheral blood mononuclear cells (PBMCs) were separated by density gradient centrifugation, and cell metabolism was analyzed using high-resolution respirometry for mitochondrial respiration and electron spin resonance for reactive oxygen species production. After incubation with stable isotope-labeled 1,2-13C2-glucose or 13C5-glutamine, distinct labeling patterns of intermediates of glycolysis or tricarboxylic acid (TCA) cycle and 13CO2 production were measured by gas chromatography-mass spectroscopy. Principal component analysis was followed by a varimax rotation on the covariance across all measured variables and all measured time points.After ASDH induction, average PBMC metabolic activity remained unaffected, possibly because strict adherence to intensive care unit guidelines limited trauma to ASDH induction without any change in parameters of systemic hemodynamics, oxygen transport, and whole-body metabolism. Despite decreased glycolytic activity fueling the TCA cycle, the principal component analysis indicated a cell type-specific activation pattern with biosynthetic and proliferative characteristics., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 by the Shock Society.)

Introduction: Medical care of soft-tissue sarcoma (STS) and bone sarcoma (BS) patients in Germany has rarely been investigated. The objectives of this article were (1) to investigate medical care and survival in STS and BS patients, and (2) to examine methodological aspects of corresponding analyses based on administrative healthcare data., Methods: We analyzed data from a statutory health insurance located in Saxony, Germany, covering approximately 2 million individuals. We identified incident STS and BS patients in the period 2012-2016 using 4 different case definitions. We examined treatment rates and visits to medical oncologists and medical practices descriptively, and then compared results between case definitions. We investigated survival prospects using a relative survival analysis and estimated hazard ratios (HRs) for risk factors for mortality using Cox regression., Results: Across case definitions, the number of included sarcoma patients (STS: n = 871-1,757; BS: n = 216-689) and applied treatments (STS: 42.2-83.1%; BS: 28.3-77.8%) varied substantially. Irrespective of the case definition, the minority of patients visited medical oncologists (STS: 9.8-10.8% BS: 4.4-7.9%) and "experienced" medical practices (STS: 27.7-38.4%; BS: 18.3-23.6%). Survival prospects were better for patients who visited "experienced" medical practices (STS: HR = 0.55; BS: HR = 0.42)., Conclusion: Treatment rates clearly <100% and evidence from survival analyses indicate the potential for improvements in the care of sarcoma patients in Germany, e.g., by physicians in "experienced" medical practices., (© 2020 S. Karger AG, Basel.)

This review addresses the plausibility of hydrogen sulfide (H 2 S) therapy for acute lung injury (ALI) and circulatory shock, by contrasting the promising preclinical results to the present clinical reality. The review discusses how the narrow therapeutic window and width, and potentially toxic effects, the route, dosing, and timing of administration all have to be balanced out very carefully. The development of standardized methods to determine in vitro and in vivo H 2 S concentrations, and the pharmacokinetics and pharmacodynamics of H 2 S-releasing compounds is a necessity to facilitate the safety of H 2 S-based therapies. We suggest the potential of exploiting already clinically approved compounds, which are known or unknown H 2 S donors, as a surrogate strategy.

Introduction: Extracorporeal life support is an increasingly used technique for respiratory and cardiocirculatory support. Besides primary organ dysfunction, an excessive systemic hyperinflammatory response can be the underlying cause for acute organ failure necessitating extracorporeal life support therapy, or it may be associated with the extracorporeal life support itself. Controlling this overwhelming inflammatory response using CytoSorb ® hemoadsorption has been shown to be associated with improved hemodynamics and restored metabolic balance resulting in preserved organ functions., Methods: In this retrospective case series, we describe 23 patients undergoing extracorporeal life support therapy and CytoSorb hemoadsorption. Cytokine levels were monitored, hemodynamic and metabolic variables were recorded, and outcome measures such as duration of organ support, intensive care unit mortality, and hospital mortality were noted., Results: CytoSorb treatment was associated with a trend toward a reduction in plasma cytokine levels (first treatment median interleukin-6 pre 595 vs post 350 pg/mL (n.s.); second treatment median interleukin-6 317 vs 108 pg/mL, p < 0.05), a reduced vasoplegic response resulting in a reduction in vasopressor requirements (first treatment median norepinephrine pre 0.15 vs post 0.02 µg/kg/min (n.s.); second treatment median norepinephrine 0.1 vs 0.02 µg/kg/min, p < 0.05) as well as rebalancing of deranged metabolic parameters (first treatment median lactate pre-treatment 6 vs post-treatment median lactate 2 mmol/L, p < 0.05). The hemoperfusion treatment was well tolerated and safe, without the occurrence of any CytoSorb device-related adverse events., Conclusion: Hemoadsorption may offer a potentially promising therapeutic option for critically ill patients undergoing extracorporeal life support therapy, with cytokine reduction and a consecutively mitigated inflammatory response, decreased vasoplegia, and improved organ function as seen in our patients.

Purpose: The need for drug-related safety warnings is undisputed, and their impact should also be evaluated. This systematic review investigates and assesses the impact of safety warnings on drug therapy., Methods: Studies published in English between January 1998 and December 2018 were searched in EMBASE and MEDLINE, complemented by manual search. Randomised controlled trials, cohort studies with a before/after component, and case-control studies were included, selected to predefined criteria, and assessed for their reporting and methodological quality., Results: Out of 7454 references identified, 72 studies were included. A total of 28/72 (39%) studies described the impact of safety warnings on drug therapy as being effective, whereas 12/72 (17%) studies did not. Further, 26/72 (36%) studies described a partial implementation of the warnings (one part of the warning had an impact on drug therapy and another did not). Unintended effects were investigated in 6/72 (8%) studies. While 34 (47%) studies examined safety warnings on psychotropic drugs using an interrupted time series (ITS) design (53%), a before/after (26%), and a time series design (21%), 38 (53%) studied other substances using an ITS design (34%), a before/after (40%), and a time series design (26%). The proportion of an effective impact on drug therapy was lower in the "psychotropic drugs" group (23%) than in the "others" group (53%)., Conclusion: Drug-related safety warnings induce intended and unintended effects. The included studies are of broadly varying methodological quality. To better compare their effectiveness, studies should be conducted using standardised procedures., (© 2020 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Controversial data are available on hydrogen sulfide (H 2 S) during hemorrhage and resuscitation, depending on timing, dosing, mode of application, and the H 2 S donor used. Sodium thiosulfate (Na 2 S 2 O 3 ) is a recognized drug devoid of major side effects, which attenuated murine acute lung injury and cerebral ischemia/reperfusion injury. Therefore, we tested the hypothesis whether Na 2 S 2 O 3 would mitigate organ dysfunction in porcine hemorrhage-and-resuscitation. We studied animals with pre-existing coronary artery disease because of the reduced coronary arterial expression of the H 2 S producing enzyme cystathionine-γ-lyase (CSE) in this prospective, randomized, controlled, blinded experimental study. 20 anesthetized and instrumented pigs underwent 3 h of hemorrhage (removal of 30 % of the blood volume and subsequent titration of mean arterial pressure to 40 mmHg). Resuscitation (72 h) comprised re-transfusion of shed blood, crystalloids, and continuous i.v. norepinephrine. Animals randomly received vehicle or Na 2 S 2 O 3 (0.1 g·kg -1  h -1 ) for 24 h. Before, at the end of and every 24 h after shock, hemodynamics, metabolism, blood gases, lung, heart, kidney, and liver function and injury were evaluated together with cytokines and parameters of oxidative and nitrosative stress. Immediate post mortem lung, kidney, heart, and liver specimen were analyzed for marker proteins of inflammation and oxidative and nitrosative stress and mitochondrial respiratory activity in the heart, kidney, and liver. Immuno-histochemical analysis comprised lung extra-vascular albumin accumulation, nitrotyrosine formation, and CSE and glucocorticoid receptor (GCR) expression. Na 2 S 2 O 3 significantly attenuated shock-induced impairment of lung mechanics and gas exchange (plateau and positive end-expiratory pressure at 72 h p = 0.0006/p = 0.0264; Horovitz index at 48 h p = 0.0261), which coincided with a higher tissue GCR expression (p = 0.0415). During resuscitation from hemorrhagic shock Na 2 S 2 O 3 attenuated shock-induced acute lung injury in co-morbid swine, most likely due to a GCR expression related mechanism., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: Acute subdural hematoma (ASDH) is a leading entity in brain injury. Rodent models mostly lack standard intensive care, while large animal models frequently are only short term. Therefore, the authors developed a long-term, resuscitated porcine model of ASDH-induced brain injury and report their findings., Methods: Anesthetized, mechanically ventilated, and instrumented pigs with human-like coagulation underwent subdural injection of 20 mL of autologous blood and subsequent observation for 54 hours. Continuous bilateral multimodal brain monitoring (intracranial pressure [ICP], cerebral perfusion pressure [CPP], partial pressure of oxygen in brain tissue [PbtO2], and brain temperature) was combined with intermittent neurological assessment (veterinary modified Glasgow Coma Scale [MGCS]), microdialysis, and measurement of plasma protein S100β, GFAP, neuron-specific enolase [NSE], nitrite+nitrate, and isoprostanes. Fluid resuscitation and continuous intravenous norepinephrine were targeted to maintain CPP at pre-ASDH levels. Immediately postmortem, the brains were taken for macroscopic and histological evaluation, immunohistochemical analysis for nitrotyrosine formation, albumin extravasation, NADPH oxidase 2 (NOX2) and GFAP expression, and quantification of tissue mitochondrial respiration., Results: Nine of 11 pigs survived the complete observation period. While ICP significantly increased after ASDH induction, CPP, PbtO2, and the MGCS score remained unaffected. Blood S100β levels significantly fell over time, whereas GFAP, NSE, nitrite+nitrate, and isoprostane concentrations were unaltered. Immunohistochemistry showed nitrotyrosine formation, albumin extravasation, NOX2 expression, fibrillary astrogliosis, and microglial activation., Conclusions: The authors describe a clinically relevant, long-term, resuscitated porcine model of ASDH-induced brain injury. Despite the morphological injury, maintaining CPP and PbtO2 prevented serious neurological dysfunction. This model is suitable for studying therapeutic interventions during hemorrhage-induced acute brain injury with standard brain-targeted intensive care.

Hyperoxia (ventilation with FIO2 = 1.0) has vasoconstrictor properties, in particular in the coronary vascular bed, and, hence, may promote cardiac dysfunction. However, we previously showed that hyperoxia attenuated myocardial injury during resuscitation from hemorrhage in swine with coronary artery disease. Therefore, we tested the hypothesis whether hyperoxia would also mitigate myocardial injury and improve heart function in the absence of chronic cardiovascular comorbidity.After 3 h of hemorrhage (removal of 30% of the calculated blood volume and subsequent titration of mean arterial pressure to 40 mm Hg) 19 anesthetized, mechanically ventilated, and instrumented pigs received FIO2 = 0.3(control) or hyperoxia(FIO2 = 1.0) during the first 24 h. Before, at the end of and every 12 h after shock, hemodynamics, blood gases, metabolism, cytokines, and cardiac function (pulmonary artery thermodilution, left ventricular pressure-conductance catheterization) were recorded. At 48 h, cardiac tissue was harvested for western blotting, immunohistochemistry, and mitochondrial respiration.Except for higher left ventricular end-diastolic pressures at 24 h (hyperoxia 21 (17;24), control 17 (15;18) mm Hg; P = 0.046), hyperoxia affected neither left ventricular function cardiac injury (max. Troponin I at 12 h: hyperoxia:9 (6;23), control:17 (11;24) ng mL; P = 0.395), nor plasma cytokines (except for interleukin-1β: hyperoxia 10 (10;10) and 10 (10;10)/control 14 (10;22), 12 (10;15) pg mL, P = 0.023 and 0.021 at 12 and 24 h, respectively), oxidation and nitrosative stress, and mitochondrial respiration. However, hyperoxia decreased cardiac tissue three-nitrotyrosine formation (P < 0.001) and inducible nitric oxide synthase expression (P = 0.016). Ultimately, survival did not differ significantly either.In conclusion, in contrast to our previous study in swine with coronary artery disease, hyperoxia did not beneficially affect cardiac function or tissue injury in healthy swine, but was devoid of deleterious side effects.

Aims: The potential influence of angiotensin-receptor blockers (ARBs) on carcinogenesis is a much-debated topic. Both observational, as well as preclinical studies in rodent carcinogenic assays, suggest a major role of the Renin-Angiotensin-Aldosterone-System (RAAS) in cancer development. Therefore, a systematic review and meta-analysis with available study data on ARBs and carcinogenicity in general as primary outcome were conducted. Secondary outcomes were defined as tumour-specific mortality rates and the frequency of new cases of specific tumour types with particular emphasis on lung, breast, and prostate cancer., Methods: A systematic literature research was performed in MEDLINE, EMBASE, Cochrane Library, and TOXLINE. We used a combination of MeSH terms, keywords and substance names of ARBs and searched between 1950 and 2016. At least 100 participants in each study arm and a minimum follow-up for one year were necessary for study inclusion. Odds ratios (OR) were calculated by a random-effects model., Results: A total of 8818 potentially eligible publications were identified of whom seven randomised controlled trials, four case-control studies and one cohort study met our inclusion criteria. As a key result, we found no effect on carcinogenesis in randomised controlled trials for ARB usage. (OR 1.02, 95% CI 0.87-1.19; p = .803). Conflicting results with observational studies could be explained by poor reporting- and study qualities., Conclusions: The results of our meta-analysis focusing only on high evidence levels and study designs (RCTs) did not reveal any relationship between pharmacotherapy with an ARB and an increased risk for cancer in general., (Copyright © 2019 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

The long-tailed parakeets of the genus Psittacula Cuvier, 1800 have thus far been regarded as a homogeneous and monophyletic group of parrots. We used nucleotide sequences of two genetic markers (mitochondrial CYTB, nuclear RAG-1) to reconstruct the phylogenetic relationships of Psittacula and closely related species. We found that the Asian genus Psittacula is apparently paraphyletic because two genera of short-tailed parrots, Psittinus Blyth, 1842 and Tanygnathus Wagler, 1832, cluster within Psittacula, as does †Mascarinus Lesson, 1830. To create monophyletic genera, we propose recognition of the following genera: Himalayapsitta Braun, 2016 for P. himalayana, P. finschii, P. roseata, and P. cyanocephala; Nicopsitta Braun, 2016 for P. columboides and P. calthrapae; Belocercus S. Müller, 1847 for P. longicauda; Psittacula Cuvier, 1800 for P. alexandri and P. derbiana; Palaeornis Vigors, 1825 for †P. wardi and P. eupatria; and Alexandrinus Braun, 2016 for P. krameri, †P. exsul, and P. (eques) echo. Additionally, Psittacula krameri and P. alexandri are paraphyletic species, which should be split to form monophyletic species.

Background: Attention deficit hyperactivity disorder (ADHD) is a frequently occurring neurodevelopmental disorder, symptoms of which first appear in early childhood. Etiology of ADHD is not well understood. We investigated whether outdoor air pollution and greenspace affect ADHD incidence in children residing in Saxony., Methods: 66,823 children, all beneficiaries of the statutory health insurance company AOK PLUS and born between 2000 and 2004, were followed until 2014. We considered any child with at least one ICD-10-GM F90 diagnosis by a child/adolescent psychiatrist, neuropaediatrician, or psychotherapist an ADHD case. Children's home addresses were known up to their four-digit postal code area. Population-weighted mean values of particulate matter with diameter of < 10 μm (PM 10 ), nitrogen dioxide (NO 2 ), and MODIS Normalized Difference Vegetation Index (NDVI) were calculated for 186 postal code areas. Associations with each exposure were assessed by two-level adjusted Poisson regression models., Results: 2044 children (3.06%) were diagnosed with ADHD within the observation period. An increase of PM 10 and NO 2 by 10 μg/m 3 raised the relative risk of ADHD by a factor of 1.97 [95% CI: 1.35-2.86] and 1.32 [1.10-1.58], respectively. A 0.1-unit increase in NDVI decreased the relative risk of ADHD by a factor of 0.82 [0.68-0.98]. Better access to child/adolescent psychiatrists was the most important confounder that increased ADHD risk across all models., Conclusion: Our results provide some evidence that air pollution might affect ADHD. Future studies with more detailed address information and better control for confounders, in particular socioeconomic status and parental psychopathology, should replicate the observed associations., (Copyright © 2018 Elsevier B.V. All rights reserved.)