Introduction:Colorectal and pancreatic cancers impose profound physical, psychological, and social challenges on patients, underscoring the need for comprehensive assessments of their impact on health-related quality of life (HRQoL). This study aimed to evaluate HRQoL levels in colorectal and pancreatic cancer patients, including the comparison to the general population and the assessment of sociodemographic as well as disease- and treatment-related predictors. Methods:The analyses are based on data from a clinical registry of the NCT/UCC Dresden. Patients were recruited during consultation hours between August 2020 and December 2024. Baseline quality of life data and routine data from the tumor documentation system were used. The final analytical sample comprised n=417 patients in the colorectal study group and n=193 patients in the pancreatic study group. Multivariable linear regression analyses were calculated, with results presented as regression coefficients (b) and 95% confidence intervals (CI). Results:Colorectal and pancreatic cancer patients exhibited significantly lower HRQoL compared to the general population, with large differences in social function and medium differences in role function and global health. Pancreatic cancer patients reported lower HRQoL across most domains compared to colorectal cancer patients. In the colorectal study group, statutory health insurance (b=-14.10, CI=-22.54; -5.66), living in rural counties with some urbanization (b=-5.34, CI=-10.51; -0.17) and recent chemotherapy (b=-9.10, CI=-16.36; -1.85) predicted worse global health. With regard to pancreatic cancers, residence in rural counties with some urbanization (b=-10.26, CI=-18.93; -1.59) was associated with worse global health, whereas longer time since diagnosis (b=0.06, CI=0.01; 0.12) was associated with better global health. Conclusions:Sociodemographic factors were the most consistent predictors of HRQoL in patients with pancreatic and colorectal cancer. These findings suggest social disparities, particularly for patients in rural areas and those with lower socioeconomic status. Efforts to improve access to healthcare, provide psychosocial support, and manage symptom burden are critical to enhancing the quality of life for these patients.

Background:Statutory health insurance claims data are used for risk adjusted quality assessment of inpatient treatments. This study evaluated the impact of clinical data on quality assessment of the treatment of acute myocardial infarction (AMI), and whether the content of clinical factors can be approximated by claims data. Material and methods:In this observational study, claims data of statutory health insurance in Germany were linked retrospectively with clinical data from 14 hospitals. The hybrid study population encompassed 3148 cases with inpatient treatment of AMI who underwent coronary angiography. Quality indicators for five outcomes were developed by means of stepwise logistic regression. Using claims data from a nationwide study population of 165 130 AMI cases and a subsample of the same size as the hybrid group, the performances of the risk adjustment models were compared by receiver operating characteristic-area under the curve (ROC-AUC) and standardised mortality/morbidity ratios (SMR). Results:As clinical risk factors, a haemoglobin value of ≤10 g/dL and an estimated glomerular filtration rate of ≤60 mL/min/1.73qm were included, but did not result in a gain of ROC-AUC (w/o clinical variables: 0.74-0.86; with: 0.74-0.87). By approximating the content of these clinical factors by means of claims data, an increase in model performance of up to 4.7% was achieved (with surrogates: 0.77-0.89), but did not influence the final quality assessment by SMR. Conclusions:While replication of our findings is necessary, our models for risk adjustment and surrogates for two clinical factors show that comparative quality reporting using claims data is feasible, although with acknowledged limitations. This would minimise the data set for quality assessment of AMI treatment in accordance with the principle of data minimisation and avoid the need for additional manual documentation.

BACKGROUND:Emergencies in otorhinolaryngology are common: According to a Spanish study, approximately 12% of patients in a general emergency room have symptoms relating to the ear, nose, or throat (ENT). Such situations range in severity from minimal to lifethreatening and affect persons of all ages. These patients may pre - sent first to a general practitioner or to an emergency room without specialized ENT coverage. In this article, we discuss the assessment of clinical urgency based on symptoms, and the ensuing treatments. METHODS:This narrative review is based on pertinent publications retrieved by a literature search. Common and typical ENT emergencies are discussed, including the necessary diagnostic evaluation, time management, and treatment. For each clinical entity, "red flags" are defined, i.e., warning signs indicating the need for urgent, specialized care. RESULTS:Treatment by a specialist in otorhinolaryngology (usually surgical and in-hospital, and often as part of an interdisciplinary collaboration) is needed, in particular, for clinical entities that may be life-threatening, such as otogenic or sinugenic complications, neck abscesses, angioedema, posterior epistaxis, tumor hemorrhages, and foreign bodies in the respiratory tract, as well as inner ear diseases that cause severe vertigo and vomiting. CONCLUSION:The rising number of patients presenting to emergency rooms presents a challenge to all affected areas of the health care system. The physician in the emergency room has the task of recognizing the risk of serious complications in certain clinical situations with nonspecific symptoms that may seem harmless, and of obtaining specialized care for these patients in a timely manner. The "red flags" presented in this article can serve as an initial guide to ENT emergencies.

To evaluate whether machine learning (ML) methods (Elastic Net (EN), eXtreme Gradient Boosting (XGBoost), Feed Forward Neural Net (FNN)) can improve claims-based inpatient quality measurement by Logistic Regression. This retrospective cohort study used German claims data from the years 2015-2021. The study population encompassed inpatient cases of acute myocardial infarction ( n = 165,130) and proximal humerus fracture ( n = 34,912), for which quality related outcomes were assessed. The performances of risk adjustment models based on machine learning methods (EN, XGBoost, FNN) were compared to stepwise backwards Logistic Regression by Receiver Operating Characteristics-Area under the Curve (ROC-AUC), Precision Recall-Area under the Curve (PR-AUC), Brier Score (BS). The institution-specific quality was measured by Standardised Mortality Ratios (SMR) which were used to visualise the impact of the tested methods on quality assessment. For most of the outcomes none or only marginal gains were found for the machine learning methods. Highest gain in model performance showed the FNN in comparison to Logistic Regression with a gain in ROC-AUC of 2.4%, in PR-AUC of 4.5%, and slightly in the BS with a loss of 0.007. The FNN was followed by XGBoost with a gain in ROC-AUC of 2.3%, anyhow this improvement was not reflected in a lower BS. None of the machine learning methods tested is generally superior for creating quality indicators. Marginal gain in model performance should not be the main basis for choosing an adequate method; instead, interpretability should be emphasised, especially when dealing with new datasets with little knowledge of important risk factors.

Accurately measuring the quality of stroke care based on claims data alone is challenging. Traditional outcome metrics, e.g. mortality rates, do not capture the effectiveness of critical stroke care processes. We aimed to develop hybrid quality indicators (QIs) by integrating clinical stroke severity data with claims data. Claims data were linked to patient-level clinical data from 15 hospitals (2017-2020) and harmonized in the Observational Medical Outcome Partnership (OMOP) data model. Inclusion criteria, outcomes and risk factors were developed by medical expert panels. We applied machine learning for modeling the outcomes 30-day-mortality, reinfarction within 90 days, and care degree increase within 180 days. We compared extreme gradient boosting (XGBoost) models with and without the National Institutes of Health Stroke Scale (NIHSS) using Receiver-Operating-Characteristic-Area-Under-the-Curve (ROC-AUC) and Brier Score (BS). Hospitals were ranked according to the impact of each QI using Standardized Mortality Ratios (SMRs). The study included 9,348 ischemic (I63) and 1,554 hemorrhagic (I61) strokes, with NIHSS available for 5,012 patients. For all three outcomes, disease severity as measured by NIHSS was the most important determinant. The predictive power of the hybrid models was higher than that of models based on claims data alone. For SMR, the influence of NIHSS was greater than that of age, the most important variable in the claims data model. The results were consistent between the two entities, different outcomes, and sensitivity analyses. Including NIHSS information alongside claims data improves the risk adjustment of quality indicators.

Traumatic brain injury (TBI) remains one of the leading causes of death. Because of the individual nature of the trauma (brain, circumstances and forces), humans experience individual TBIs. This makes it difficult to generalise therapies. Clinical management issues such as whether intracranial pressure (ICP), cerebral perfusion pressure (CPP) or decompressive craniectomy improve patient outcome remain partly unanswered. Experimental drug approaches for the treatment of secondary brain injury (SBI) have not found clinical application. The complex, cellular and molecular pathways of SBI remain incompletely understood, and there are insufficient experimental (animal) models that reflect the pathophysiology of human TBI to develop translational therapeutic approaches. Therefore, we investigated different injury patterns after acute subdural hematoma (ASDH) as TBI in a post-hoc approach to assess the impact on SBI in a long-term, human-sized porcine TBI animal model. Post-mortem brain tissue analysis, after ASDH, bilateral ICP, CPP, cerebral oxygenation and temperature monitoring, and biomarker analysis were performed. Extracerebral, intraparenchymal–extraventricular and intraventricular blood, combined with brainstem and basal ganglia injury, influenced the experiment and its outcome. Basal ganglia injury affects the duration of the experiment. Recognition of these different injury patterns is important for translational interpretation of results in this animal model of SBI after TBI.

Background: Emergencies in otorhinolaryngology are common: According to a Spanish study, approximately 12% of patients in a general emergency room have symptoms relating to the ear, nose, or throat (ENT). Such situations range in severity from minimal to life-threatening and affect persons of all ages. These patients may pre-sent first to a general practitioner or to an emergency room without specialized ENT coverage. In this article, we discuss the assessment of clinical urgency based on symptoms, and the ensuing treatments. Methods: This narrative review is based on pertinent publications retrieved by a literature search. Common and typical ENT emergencies are discussed, including the necessary diagnostic evaluation, time management, and treatment. For each clinical entity, "red flags" are defined, i.e., warning signs indicating the need for urgent, specialized care. Results: Treatment by a specialist in otorhinolaryngology (usually surgical and in-hospital, and often as part of an interdisciplinary collaboration) is needed, in particular, for clinical entities that may be life-threatening, such as otogenic or sinugenic complications, neck abscesses, angioedema, posterior epistaxis, tumor hemorrhages, and foreign bodies in the respiratory tract, as well as inner ear diseases that cause severe vertigo and vomiting. Conclusion: The rising number of patients presenting to emergency rooms presents a challenge to all affected areas of the health care system. The physician in the emergency room has the task of recognizing the risk of serious complications in certain clinical situations with nonspecific symptoms that may seem harmless, and of obtaining specialized care for these patients in a timely manner. The "red flags" presented in this article can serve as an initial guide to ENT emergencies.

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.

IntroductionSupplementation 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 13C-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.MethodsSwine underwent resuscitation after 2 h of ASDH and HS up to a maximum of 48 h after HS. Animals received normoxemia (PaO2 = 80 – 120 mmHg) or targeted hyperoxemia (PaO2 = 200 – 250 mmHg for 24 h after treatment initiation, thereafter PaO2 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 13C-MFA. For the latter, we utilized a parallel tracer approach with 1,2-13C2 glucose, U-13C glucose, and U-13C 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).Results13C-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.ConclusionIn a model of resuscitated porcine ASDH and HS, we saw that ventilation with increased inspiratory O2 concentrations (PaO2 = 200 – 250 mmHg for 24 h after treatment initiation) did not impact mitochondrial respiration of PBMCs or granulocytes. However, Bayesian 13C-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.

ZusammenfassungDie Ereignisse bezüglich einer Reform der Notfallversorgung überschlagen sich, und ein klares Konzept ist noch nicht erkennbar, wenngleich überfällig. Kliniken und Praxen erleben im Fachgebiet der Hals-Nasen-Ohrenheilkunde (HNO) einen deutlichen Zuwachs entsprechender Patienten, die Gründe sind mannigfaltig: von dem Bedürfnis Betroffener einer sofortigen Abklärung bestimmter Symptome bis hin zu veränderten Notdienststrukturen. Verschärft hat sich die Situation durch das jüngste Urteil zur Sozialversicherungspflicht der Poolärzte mit einer „Notbremse“ im ärztlichen Bereitschaftsdienst bspw. der Kassenärztlichen Vereinigung (KV) Baden-Württemberg. Zu allem Überfluss wurde die vom Gemeinsamen Bundesausschuss erstellte Erstfassung der Richtlinie zur Ersteinschätzung des Versorgungsbedarfs in der Notfallversorgung (Ersteinschätzungsrichtlinie) durch das Bundesministerium für Gesundheit beanstandet und liegt aktuell auf Eis. Es ist allen Akteuren klar, dass in jedem Fall eine grundlegende Reform zur Filterung und Steuerung der Patientenströme notwendig wird. Die Vorschläge reichen von einer Aufklärung der Bürger zur Erlangung einer basalen Gesundheitskompetenz über die Wiedereinführung der Notfallgebühr bis hin zu den wahrscheinlichen Szenarien einer zentralen Notfallnummer, eines gemeinsamen Tresens (i.e. vertragsärztliche Notfallpraxis und entsprechende Klinik-Notfallambulanzen in unmittelbarer räumlicher Nähe) und einer Triage durch geschultes Personal mit Vergabeoptionen in die geeigneten Versorgungsbereiche. Die Regierungskommission für eine moderne und bedarfsgerechte Krankenhausversorgung hat mit Stellungnahmen zur Reform der Notfall- und Akutversorgung zu den Bereichen „Rettungsdienst und Finanzierung“ und „Integrierte Notfallzentren und Integrierte Leitstellen“ Empfehlungen abgegeben. Hierzu sollen a.e. im Verlauf des Jahres, nach Möglichkeit unter Beteiligung der Fachgesellschaften und Berufsverbände, belastbare Grundlagen geschaffen sein, auch verknüpft mit der Hoffnung, die dringend notwendige Entlastung von medizinischem Personal in Klinik und Praxis einzuleiten.Das vorliegende Manuskript beschreibt die gesundheitspolitische Historie sowie aktuelle Probleme der Notfallversorgung, wobei Lösungsvorschläge mit Bezug auf die HNO-ärztlichen Besonderheiten in den Fokus genommen werden. Das vorliegende Positionspapier ist verbunden mit einem Appell an Selbstverwaltung und Politik, nunmehr zeitnah ein tragfähiges Konzept für die Notfallversorgung in Kraft zu setzen, da Finanzierung und Personalverfügbarkeit immer kritischer werden und der ungeregelten Welle an Notfallpatienten eine ordnende Hand gereicht werden muss.

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. 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. The results revealed not only a significant decrease in the case volume by 31

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.

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.

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 < PaO2 < 250 mmHg vs. normoxemia 80 < PaO2 < 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 H2S-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.

Zusammenfassung Einleitung Translationale Forschung ist wichtig, insbesondere in der Medizin, wo Entscheidungen das Leben von Menschen beeinflussen. Klinische Register und die darin eingebetteten Studien ermöglichen die Abbildung der tatsächlichen Versorgungspraxis unter Routinebedingungen. Die Rückführung der Erkenntnisse aus der Versorgungsforschung in die klinische Forschung durch prospektive Kohortenstudien hat das Potenzial, medizinische Innovationen schneller, effektiver und vor allem zielgerichteter voranzutreiben. Dies muss daher ein zentraler Bestandteil der onkologischen Spitzenforschung sein. Zielsetzung Ziel des Registers ist der Aufbau von klinischen Kohorten und die Bereitstellung eines umfassenden, qualitativ hochwertigen Datensatzes für onkologische Erkrankungen. Methoden/Design Das Register wird prospektiv alle Patienten erfassen, die am Universitätsklinikum Dresden (UKD) wegen Krebs behandelt werden. Zusätzlich zu den Daten aus den Krankenhausinformationssystemen (ORBIS, TDS, GEPADO, etc.) soll in regelmäßigen Abständen zu Beginn und im Verlauf der Behandlung ein Monitoring der gesundheitsbezogenen Lebensqualität (HRQOL) durchgeführt werden. Darüber hinaus ist eine individuelle Verknüpfung mit Daten aus klinischen Krebsregistern und Krankenkassen (u. a. AOK PLUS) für einen Zeitraum von fünf Jahren vor und nach dem Einschluss geplant. Alle diese Daten werden in einer Registerdatenbank zusammengeführt. Die Auswahl der Variablen und Messzeitpunkte orientiert sich eng an den Leitlinien für das kolorektale Karzinom der internationalen Initiative ICHOM (International Consortium for Health Outcomes Measurement). Die Studienmanagementsoftware (STeVe) trennt frühzeitig persönliche Identifikationsmerkmale (IDAT) und medizinische Daten (MDAT). Die unabhängige Treuhandstelle der TU Dresden stellt sicher, dass keine personenbezogenen Daten in die Registerdatenbank gelangen. Damit ist auch sichergestellt, dass die beteiligten Dateneigentümer (UKD, Biobank, Krankenkasse, Krebsregister, Patient) nur die personenbezogenen Daten erhalten, die sie für die Zuordnung benötigen. Zur Verwaltung der Pseudonyme werden die von der TMF (Technologie- und Methodenplattform für die vernetzte medizinische Forschung e.V.) empfohlenen MOSAIC-Softwaretools eingesetzt. Diskussion/Schlussfolgerung Mit dem Register können bisher fehlende Erkenntnisse über die Wirksamkeit, Sicherheit und Kosten von diagnostischen und therapeutischen Maßnahmen unter Berücksichtigung von Langzeit- und patientenberichteten Outcomes aus der Routineversorgung gewonnen werden. Die Daten erlauben potenziell die Identifizierung von Barrieren und Förderfaktoren für innovative, vielversprechende Krebsdiagnostik und -therapien. Sie bieten auch die Möglichkeit, wissenschaftlich relevante Hypothesen im Bereich der Translations- und Outcome-Forschung zu generieren.

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 fur 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.

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 (PaO2 = 200 – 250 mmHg) or normoxemia (PaO2 = 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 O2 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.

Introduction Sodium thiosulfate (Na2S2O3), an H2S 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 H2S can dose-dependently stimulate or inhibit mitochondrial respiration, we investigated the effect of Na2S2O3 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 13C isotope metabolic flux analysis (MFA) utilizing 1,2-13C2-labeled glucose, 13C6-labeled glucose, and 13C5-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 Na2S2O3 (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 O2 uptake and lower O 2 • − production in comparison to granulocytes. We found that in response to Na2S2O3 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, Na2S2O3 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.