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BACKGROUND: Metabolic remodeling and changes in tumor immune microenvironment (TIME) in osteosarcoma are important factors affecting prognosis and treatment. However, the relationship between metabolism and TIME needs to be further explored. METHODS: RNA-Seq data and clinical information of 84 patients with osteosarcoma from the TARGET database and an independent cohort from the GEO database were included in this study. The activity of seven metabolic super-pathways and immune infiltration levels were inferred in osteosarcoma patients. Metabolism-related genes (MRGs) were identified and different metabolic clusters and MRG-related gene clusters were identified using unsupervised clustering. Then the TIME differences between the different clusters were compared. In addition, an MRGs-based risk model was constructed and the role of a key risk gene, ST3GAL4, in osteosarcoma cells was explored using molecular biological experiments. RESULTS: This study revealed four key metabolic pathways in osteosarcoma, with vitamin and cofactor metabolism being the most relevant to prognosis and to TIME. Two metabolic pathway-related clusters (C1 and C2) were identified, with some differences in immune activating cell infiltration between the two clusters, and C2 was more likely to respond to two chemotherapeutic agents than C1. Three MRG-related gene clusters (GC1-3) were also identified, with significant differences in prognosis among the three clusters. GC2 and GC3 had higher immune cell infiltration than GC1. GC3 is most likely to respond to immune checkpoint blockade and to three commonly used clinical drugs. A metabolism-related risk model was developed and validated. The risk model has strong prognostic predictive power and the low-risk group has a higher level of immune infiltration than the high-risk group. Knockdown of ST3GAL4 significantly inhibited proliferation, migration, invasion and glycolysis of osteosarcoma cells and inhibited the M2 polarization of macrophages. CONCLUSION: The metabolism of vitamins and cofactors is an important prognostic regulator of TIME in osteosarcoma, MRG-related gene clusters can well reflect changes in osteosarcoma TIME and predict chemotherapy and immunotherapy response. The metabolism-related risk model may serve as a useful prognostic predictor. ST3GAL4 plays a critical role in the progression, glycolysis, and TIME of osteosarcoma cells.
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Neoplasias Ósseas , Osteossarcoma , Humanos , Osteossarcoma/genética , Vitaminas , Imunoterapia , Neoplasias Ósseas/genética , Redes e Vias Metabólicas , Microambiente Tumoral/genética , PrognósticoRESUMO
BACKGROUND: Despite improving the management of proximal femur fractures (PFF) with legal requirements of timing the surgery within 24 h, mortality rates in these patients remain still high. The objective of our study was to analyze potential cofactors which might influence the mortality rate within 90 days after surgery in PFF to avoid adverse events, loss of quality of life and high rates of mortality. METHODS: In this retrospective, single-center study all patients with PFF aged 65 years and older were included. We recorded gender, age, type of fracture, surgery and anesthesia, time, comorbidities and medication as well as complications and mortality rate at 90 days. Separate logistic regression models were used to assess which parameters were associated with patients' mortality. The mortality rate was neither associated with timing, time and type of surgery nor time and type of anesthesia, but with higher age (OR 1.08 per year; 95% CI 1.034-1.128), lower BMI (OR 0.915 per kg/m2; 95% CI 0.857-0.978), higher CCI (OR 1.170 per point; 95% CI 1.018-1.345), dementia (OR 2.805; 95% CI 1.616-4.869), non-surgical complications (OR 2.276; 95% CI 1.269-4.083) and if mobilization was impossible (OR 10.493; 95% CI 3.612-30.479). RESULTS: We analyzed a total of 734 patients (age ≥ 65 years) who had a PFF in 2019 and 2020 and received surgery. 129 patients (17.6%) died until 90 days at an median age of 89.7 years (range 65-101 years). CONCLUSION: The proportion of patients who died until 90 days after surgery is still high. It is less extend influenced by surgical and anaesthesiologic factors than by patient-related factors like age or lower BMI. Physicians should be aware of the importance of avoiding adverse events and the importance of patients' mobilization to reduce mortality and improve patients' outcome.
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Fraturas do Quadril , Fraturas Proximais do Fêmur , Humanos , Idoso , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Fraturas do Quadril/cirurgia , Qualidade de Vida , Centros de Atenção Terciária , Fatores de RiscoRESUMO
PURPOSE: Epicardial adipose tissue (EAT) detected by computed tomography (CT) is associated with morbidity and mortality in patients with COVID-19 and other critical care patient cohorts, whereas their prognostic relevance in trauma patients remains unclear. The present study explored associations with four potential short-term outcomes in trauma patients. METHODS: All consecutive trauma patients requiring emergency tracheal intubation and mechanical ventilation before initial whole-body CT imaging at a level-1 trauma center over a 12-year period (2008-2019) were reanalyzed for this study. EAT was measured semiquantitatively in initial CT and analyzed regarding associations with 24-hour and 30-day mortality using Cox proportional hazard models. In survivors, associations of EAT with intensive care unit length of stay (ICU LOS) and mechanical ventilation duration were analyzed using linear regression analyses. RESULTS: Four hundred fifty-five patients (74.7% male) with a median age of 49 years, and a median injury severity score (ISS) of 26 points were analyzed. In univariable analysis, EAT index was significantly associated with 24-hour and 30-day mortality (p = 0.007, and p = 0.013, respectively). After adjustment for significant predictors age, body mass index, and ISS, no significant associations were confirmed (p = 0.622, and p = 0.903, respectively). In a subanalysis of 353 survivors, EAT index was significantly associated with ICU LOS and mechanical ventilation duration in univariable analyses (p = 0.031, and p = 0.014, respectively), but not in multivariable analyses (p = 0.81 and p = 0.46, respectively). CONCLUSION: EAT index was associated with short-term outcomes in severely injured trauma patients, which not remained significant in multivariable analysis, suggesting that its prognostic capability is limited.
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Tecido Adiposo , Traumatismo Múltiplo , Respiração Artificial , Tomografia Computadorizada por Raios X , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tecido Adiposo/diagnóstico por imagem , Traumatismo Múltiplo/diagnóstico por imagem , Escala de Gravidade do Ferimento , Pericárdio/diagnóstico por imagem , Adulto , Prognóstico , Tempo de Internação/estatística & dados numéricos , COVID-19/diagnóstico por imagem , SARS-CoV-2 , Idoso , Tecido Adiposo EpicárdicoRESUMO
INTRODUCTION: Since the beginning of the pandemic in spring 2020, inpatient healthcare has been under enormous burden, which is reflected especially in overworked staff, imprecise bed planning and/or data transfer. According to the recommendation of the Science Council, university clinics should play a controlling role in regional healthcare and act in conjunction with surrounding hospitals and practices. METHODS: In September 2021, 31 representatives from 18 university hospitals were invited to a hybrid Delphi study with a total of 4 survey rounds to discuss criteria for effective inpatient care in a pandemic situation, which were extracted from previous expert interviews. Criteria that were classified as very important/relevant by≥75% of the participants in the first round of the survey (consensus definition) were then further summarized in 4 different small groups. In a third Delphi round, all participants came together again to discuss the results of the small group discussions. Subsequently, these were prioritized as Optional ("can"), Desirable ("should") or Necessary ("must") recommendations. RESULTS: Of the invited clinical experts, 21 (67.7%) participated in at least one Delphi round. In an online survey (1st Delphi round), 233 criteria were agreed upon and reduced to 84 criteria for future pandemic management in four thematic small group discussions (2nd Delphi round) and divided into the small groups as follows: "Crisis Management and Crisis Plans" (n=20), "Human Resources Management and Internal Communication" (n=16), "Regional Integration and External Communication" (n=24) and "Capacity Management and Case & Care" (n=24). In the following group discussion (3rd Delphi round), the criteria were further modified and agreed upon by the experts, so that in the end result, there were 23 essential requirements and recommendations for effective inpatient care in a pandemic situation. CONCLUSION: The results draw attention to key demands of clinical representatives, for example, comprehensive digitization, standardization of processes and better (supra) regional networking in order to be able to guarantee needs-based care even under pandemic conditions. The present consensus recommendations can serve as guidelines for future pandemic management in the inpatient care sector.
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Pacientes Internados , Pandemias , Humanos , Técnica Delphi , Alemanha/epidemiologia , Inquéritos e QuestionáriosRESUMO
Factor XIII (FXIII) is a protein involved in blood clot stabilisation which also plays an important role in processes including trauma, wound healing, tissue repair, pregnancy, and even bone metabolism. Following surgery, low FXIII levels have been observed in patients with peri-operative blood loss and FXIII administration in those patients was associated with reduced blood transfusions. Furthermore, in patients with low FXIII levels, FXIII supplementation reduced the incidence of post-operative complications including disturbed wound healing. Increasing awareness of potentially low FXIII levels in specific patient populations could help identify patients with acquired FXIII deficiency; although opinions and protocols vary, a cut-off for FXIII activity of ~ 60-70% may be appropriate to diagnose acquired FXIII deficiency and guide supplementation. This narrative review discusses altered FXIII levels in trauma, surgery and wound healing, diagnostic approaches to detect FXIII deficiency and clinical guidance for the treatment of acquired FXIII deficiency.
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Transtornos da Coagulação Sanguínea , Deficiência do Fator XIII , Transtornos da Coagulação Sanguínea/etiologia , Fator XIII/metabolismo , Fator XIII/uso terapêutico , Deficiência do Fator XIII/complicações , Deficiência do Fator XIII/diagnóstico , Deficiência do Fator XIII/tratamento farmacológico , Hemorragia/tratamento farmacológico , Humanos , CicatrizaçãoRESUMO
PURPOSE: Fibular mobility after suture button stabilization (SBS) of inferior tibiofibular joint (syndesmosis) injuries has been described. This effect is called the "flexible nature of fixation (FNF)." In this study, we aimed to quantify FNF in syndesmotic stabilization. METHODS: Postoperative bilateral computed tomography (CT) of ankle fractures with syndesmosis stabilization by SBS or syndesmotic screw (SYS) was retrospectively analyzed. The transverse offset (TO) and vertical offset (VO) were defined by evaluating the drill channels. The reduction outcome was evaluated by the side-to-side difference between the clear space and the anterior tibiofibular distance (antTFD). The calculated anterior tibiofibular distance (cal-antTFD) was calculated by subtracting the TO from the validated antTFD. Subsequently, a reevaluation of the reduction outcomes after SYS or SBS stabilization was performed using cal-antTFD. RESULTS: Sixty patients (44 with SBS and 16 with SYS stabilization) were analyzed. The intra-rater and inter-rater reliabilities for TO and VO were excellent (α > 0.92). SYS stabilization showed lower mean TO (- 0.02 mm; SD 0.14) and VO (0.11 mm; SD, 0.29 mm) than SBS stabilization (TO 1.16 mm, SD 1.4 mm; VO 0.2 mm, SD 0.8 mm; p = 0.001). The rate of malreduction according to cal-antTFD was higher than that of antFTD (p = 0.033). CONCLUSION: The presented method, which evaluates the position of the tibial to the fibular drill channel, allowed the quantification of the "FNF." The often described difference in the dynamic stabilization of SBS compared to the rigid stabilization by SYS could be objectified. Considering cal-antTFD illustrates that FNF potentially reduces the rate of malreduction in SBS stabilization.
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Traumatismos do Tornozelo , Articulação do Tornozelo , Traumatismos do Tornozelo/diagnóstico por imagem , Traumatismos do Tornozelo/cirurgia , Articulação do Tornozelo/diagnóstico por imagem , Articulação do Tornozelo/cirurgia , Parafusos Ósseos , Fíbula/diagnóstico por imagem , Fíbula/lesões , Fíbula/cirurgia , Fixação Interna de Fraturas/efeitos adversos , Fixação Interna de Fraturas/métodos , Humanos , Estudos RetrospectivosRESUMO
OBJECTIVES: Clinically, procalcitonin represents the most widely used biomarker of sepsis worldwide with unclear pathophysiologic significance to date. Pharmacologically, procalcitonin was shown to signal through both calcitonin receptor and calcitonin gene-related peptide receptor in vitro, yet the identity of its biologically relevant receptor remains unknown. DESIGN: Prospective randomized animal investigations and in vitro human blood studies. SETTING: Research laboratory of a university hospital. SUBJECTS: C57BL/6J mice and patients with post-traumatic sepsis. INTERVENTIONS: Procalcitonin-deficient mice were used to decipher a potential mediator role in experimental septic shock and identify the relevant receptor for procalcitonin. Cecal ligation and puncture and endotoxemia models were employed to investigate septic shock. Disease progression was evaluated through survival analysis, histology, proteome profiling, gene expression, and flow cytometry. Mechanistic studies were performed with cultured macrophages, dendritic cells, and gamma delta T cells. Main findings were confirmed in serum samples of patients with post-traumatic sepsis. MEASUREMENTS AND MAIN RESULTS: Procalcitonin-deficient mice are protected from septic shock and show decreased pulmonary inflammation. Mechanistically, procalcitonin potentiates proinflammatory cytokine expression in innate immune cells, required for interleukin-17A expression in gamma delta T cells. In patients with post-traumatic sepsis, procalcitonin positively correlates with systemic interleukin-17A levels. In mice with endotoxemia, immunoneutralization of interleukin-17A inhibits the deleterious effect of procalcitonin on disease outcome. Although calcitonin receptor expression is irrelevant for disease progression, the nonpeptide calcitonin gene-related peptide receptor antagonist olcegepant, a prototype of currently introduced antimigraine drugs, inhibits procalcitonin signaling and increases survival time in septic shock. CONCLUSIONS: Our experimental data suggest that procalcitonin exerts a moderate but harmful effect on disease progression in experimental septic shock. In addition, the study points towards the calcitonin gene-related peptide receptor as relevant for procalcitonin signaling and suggests a potential therapeutic application for calcitonin gene-related peptide receptor inhibitors in sepsis, which warrants further clinical investigation.
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Pró-Calcitonina/metabolismo , Receptores de Peptídeo Relacionado com o Gene de Calcitonina/metabolismo , Choque Séptico/metabolismo , Animais , Citocininas/sangue , Feminino , Citometria de Fluxo , Humanos , Camundongos Endogâmicos C57BL , Proteoma , Choque Séptico/patologia , TranscriptomaRESUMO
BACKGROUND: Trauma is the third leading cause of death worldwide after cardiovascular and oncologic diseases. Predominant causes of trauma-related death (TD) are severe traumatic brain injury (sTBI), hemorrhagic shock, and multiple organ failure. An analysis of TD is required in order to review the quality of trauma care and grasp how well the entire trauma network functions, especially for the most severely injured patients. Furthermore, autopsies not only reveal hidden injuries, but also verify clinical assumed causes of death. MATERIAL: During the study period of 3 years, a total of 517 trauma patients were admitted to our supraregional University Centre of Orthopaedics and Traumatology in Dresden. 13.7% (71/517) of the patients died after trauma, and in 25 cases (35.2%), a forensic autopsy was instructed by the federal prosecutor. The medical records, death certificates, and autopsy reports were retrospectively evaluated and the clinical findings matched to autopsy results. RESULTS: The observed mortality rates (13.7%) were 4.2% less than expected by the calculated RISC II probability of survival (mortality rate of 17.9%). The most frequent trauma victims were due to falls >3 m (n = 29), followed by traffic accidents (n = 28). The median ISS was 34, IQR 25, and the median New ISS (NISS) was 50, IQR 32. Locations of death were in emergency department (23.9%), ICU (73.2%), OR and ward (1.4%, respectively). Clinicians classified 47.9% of deaths due to sTBI (n = 34), followed by 9.9% thoracic trauma and multiple organ failure (n = 7), 8.4% multiple trauma (n = 6), and 2.8% hypoxia and exsanguination (n = 2). In 18.3%, cases were unspecific or other causes of death recorded on the death certificates. Evident differences with evident clinical consequences were ascertained in 4% (n = 1) and marginal clinical consequences in 24% (6/25). In 16% (4/25), marginal differences with minor forensic consequences were revealed. CONCLUSIONS: Even in a supraregional trauma center, specialized in multiple trauma management (4.2% survival benefit), room for improvement exists in more than a quarter of all casualties. This underlines the need for higher autopsy rates to uncover missed injuries and to understand the pathomechanism in each trauma fatality. This would also help to uncover potential insufficiencies in clinical routines with regard to diagnostics. The interdisciplinary cooperation of trauma surgeons and forensic pathologists can increase the quality of trauma patient care.
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Autopsia , Medicina Legal , Traumatologia , Ferimentos e Lesões/mortalidade , Acidentes de Trânsito/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Traumatismo Múltiplo/mortalidade , Traumatismo Múltiplo/patologia , Estudos Retrospectivos , Ferimentos e Lesões/patologia , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVE: Patient triage has a key function within the scope of the successful management of mass disasters and ensures the correct resource allocation. Analysis of unheralded hospital disaster training in Berlin hospitals revealed triage problems referring the correct classification of patients in the triage categories and relevant overtriaging and undertriaging. Therefore, a triage algorithm tailored to the clinical setting was developed in Berlin and after presentation and discussion within the circle of the representatives for clinical catastrophe protection, the algorithm was introduced as obligatory in 2015. This study was carried out to validate and investigate the effects of the triage algorithm. MATERIAL AND METHODS: This prospective observational study evaluated all unheralded hospital disaster training exercises from 2016/2017 initiated by the senate administration, with 556 roughed persons after implementation of the new triage algorithm and compared the results with disaster training exercises from the years 2010/2011 without a triage algorithm (nâ¯= 601). The correct allocation of the prescribed injury patterns to the triage category (T1-3), specificity, sensitivity and positive likelihood ratio of the algorithm are described and group differences were calculated. RESULTS: In 15 unheralded mass disaster drills with 556 actors in 2016-2017 a total of 85% of the category T1 (nâ¯= 83/98), 63% of the T2 category (nâ¯= 100/159) and 87% of the T3 category (nâ¯= 259/299) were correctly recognized. This corresponds to a significantly better triage result of 80% compared to 63% in 2010/2011. Overtriaging and undertriaging also were significantly reduced. The triage algorithm showed a specificity and sensitivity of 97% and 75%, respectively, for T1 (immediately life-threatening), 86%/67% for T2 (severely injured) and 85%/88% for T3 (slightly injured) patients. DISCUSSION: The Berlin hospital triage algorithm was successfully validated. The triage category allocation was significantly improved in all relevant aspects after implementation with a significant reduction of overtriaging and undertriaging.
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Algoritmos , Planejamento em Desastres , Incidentes com Feridos em Massa , Triagem , Berlim , Humanos , Estudos ProspectivosRESUMO
Ankle fractures and associated ligamentous injuries are the most common injuries of a load-bearing joint. There is still no general consensus with respect to the pathomechanism, the treatment indications and surgical techniques. The medium and long-term results are affected by a particularly high risk of posttraumatic arthritis in bimalleolar and trimalleolar fractures and fracture dislocations. There is consensus on the necessity of a thorough preoperative analysis and postoperative control of reduction for which 3D imaging is increasingly generously employed. This detects relevant pathologies, such as bony syndesmotic avulsion and partial impaction of the tibial plafond that may go unnoticed on plain radiographs. Anatomic reconstruction of the ankle mortise, the detection and treatment of syndesmotic instability, reconstruction of the tibial notch and exact placement of the distal fibula into the latter are important prognostic factors.
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Fraturas do Tornozelo , Traumatismos do Tornozelo , Instabilidade Articular , Fraturas do Tornozelo/terapia , Traumatismos do Tornozelo/terapia , Articulação do Tornozelo , Fíbula , HumanosRESUMO
OBJECTIVE: In sepsis, the disease course of critically ill patients is often complicated by muscle failure leading to ICU-acquired weakness. The myokine transforming growth factor-ß1 increases during inflammation and mediates muscle atrophy in vivo. We observed that the transforming growth factor-ß1 inhibitor, secreted frizzled-related protein 2, was down-regulated in skeletal muscle of ICU-acquired weakness patients. We hypothesized that secreted frizzled-related protein 2 reduction enhances transforming growth factor-ß1-mediated effects and investigated the interrelationship between transforming growth factor-ß1 and secreted frizzled-related protein 2 in inflammation-induced atrophy. DESIGN: Observational study and prospective animal trial. SETTING: Two ICUs and research laboratory. PATIENTS/SUBJECTS: Twenty-six critically ill patients with Sequential Organ Failure Assessment scores greater than or equal to 8 underwent a skeletal muscle biopsy from the vastus lateralis at median day 5 in ICU. Four patients undergoing elective orthopedic surgery served as controls. To search for signaling pathways enriched in muscle of ICU-acquired weakness patients, a gene set enrichment analysis of our recently published gene expression profiles was performed. Quantitative reverse transcriptase-polymerase chain reaction, Western blot, and immunohistochemistry were used to analyze secreted frizzled-related protein 2 expression and protein content. A mouse model of inflammation-induced skeletal muscle atrophy due to polymicrobial sepsis and cultured myocytes were used for mechanistic analyses. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Gene set enrichment analysis uncovered transforming growth factor-ß1 signaling activation in vastus lateralis from ICU-acquired weakness patients. Muscular secreted frizzled-related protein 2 expression was reduced after 5 days in ICU. Likewise, muscular secreted frizzled-related protein 2 expression was decreased early and continuously in mice with inflammation-induced atrophy. In muscle, secreted frizzled-related protein 2 was predominantly contained in fast twitch/type II myofibers. Secreted frizzled-related protein 2 physically interacted and colocalized with transforming growth factor-ß1 through its cysteine-rich domain. Finally, secreted frizzled-related protein 2 prevented transforming growth factor-ß1-induced atrophy in C2C12 myotubes. CONCLUSIONS: Muscular secreted frizzled-related protein 2 is down-regulated in ICU-acquired weakness patients and mice with inflammation-induced muscle atrophy. Decreased secreted frizzled-related protein 2 possibly establishes a positive feedback loop enhancing transforming growth factor-ß1-mediated atrophic effects in inflammation-induced atrophy.
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Inflamação/complicações , Proteínas de Membrana/fisiologia , Atrofia Muscular/etiologia , Animais , Biópsia , Western Blotting , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Humanos , Masculino , Proteínas de Membrana/efeitos adversos , Camundongos , Camundongos Endogâmicos C57BL , Fibras Musculares Esqueléticas/efeitos dos fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Atrofia Muscular/induzido quimicamente , Atrofia Muscular/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/fisiologia , Fator de Crescimento Transformador beta1/fisiologiaRESUMO
Emergency medical research is subject to special conditions. Emergency patients e.g. are generally considered to be non-capable of giving consent. This results in sparse emergency medical data when compared to clinical observation studies under controlled conditions. After emergency medical treatment, deceased patients are not rarely subject to forensic investigation. The cooperation between emergency and forensic medicine has not only emergency medical training potential in individual cases, but also scientific innovation potential especially with respect to the retrospective evaluation of pre-hospital emergency measures. Such partnerships (like in Berlin at the Charité - Universitätsmedizin Berlin between the Institute of Legal Medicine and the Center for Musculoskeletal Surgery or in Hamburg between the Institute for Legal Medicine at the University Hospital and the Municipal Fire Brigade with the Emergency Medical Service) are yet exceptional in Germany.
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Causas de Morte , Comportamento Cooperativo , Serviços Médicos de Emergência/estatística & dados numéricos , Medicina de Emergência/estatística & dados numéricos , Medicina Legal/estatística & dados numéricos , Relações Interinstitucionais , Feminino , Alemanha , Humanos , Masculino , Estudos RetrospectivosRESUMO
INTRODUCTION: ICU-acquired weakness (ICUAW) complicates the disease course of critically ill patients. Inflammation and acute-phase response occur directly within myocytes and contribute to ICUAW. We observed that tripartite motif-containing 62 (TRIM62), an E3 ubiquitin ligase and modifier of inflammation, is increased in the skeletal muscle of ICUAW patients. We investigated the regulation and function of muscular TRIM62 in critical illness. METHODS: Twenty-six critically ill patients with Sequential Organ Failure Assessment scores ≥8 underwent two skeletal muscle biopsies from the vastus lateralis at median days 5 and 15 in the ICU. Four patients undergoing elective orthopedic surgery served as controls. TRIM62 expression and protein content were analyzed in these biopsies. The kinetics of Trim62, Atrogin1 and MuRF1 expression were determined in the gastrocnemius/plantaris and tibialis anterior muscles from mouse models of inflammation-, denervation- and starvation-induced muscle atrophy to differentiate between these contributors to ICUAW. Cultured myocytes were used for mechanistic analyses. RESULTS: TRIM62 expression and protein content were increased early and remained elevated in muscles from critically ill patients. In all three animal models, muscular Trim62 expression was early and continuously increased. Trim62 was expressed in myocytes, and its overexpression activated the atrophy-inducing activator protein 1 signal transduction pathway. Knockdown of Trim62 by small interfering RNA inhibited lipopolysaccharide-induced interleukin 6 expression. CONCLUSIONS: TRIM62 is activated in the muscles of critically ill patients. It could play a role in the pathogenesis of ICUAW by activating and maintaining inflammation in myocytes. TRIAL REGISTRATION: Current Controlled Trials ID: ISRCTN77569430 (registered 13 February 2008).
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Inflamação , Músculo Esquelético/metabolismo , Atrofia Muscular/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Adulto , Idoso , Animais , Estado Terminal/terapia , Modelos Animais de Doenças , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Camundongos , Pessoa de Meia-Idade , Proteínas com Motivo Tripartido , Ubiquitina-Proteína Ligases/genéticaRESUMO
RATIONALE: Critical illness myopathy (CIM) has no known cause and no treatment. Immobilization and impaired glucose metabolism are implicated. OBJECTIVES: We assessed signal transduction in skeletal muscle of patients at risk for CIM. We also investigated the effects of evoked muscle contraction. METHODS: In a prospective observational and interventional pilot study, we screened 874 mechanically ventilated patients with a sepsis-related organ-failure assessment score greater than or equal to 8 for 3 consecutive days in the first 5 days of intensive care unit stay. Thirty patients at risk for CIM underwent euglycemic-hyperinsulinemic clamp, muscle microdialysis studies, and muscle biopsies. Control subjects were healthy. In five additional patients at risk for CIM, we performed corresponding analyses after 12-day, daily, unilateral electrical muscle stimulation with the contralateral leg as control. MEASUREMENTS AND MAIN RESULTS: We performed successive muscle biopsies and assessed systemic insulin sensitivity and signal transduction pathways of glucose utilization at the mRNA and protein level and glucose transporter-4 (GLUT4) localization in skeletal muscle tissue. Skeletal muscle GLUT4 was trapped at perinuclear spaces, most pronounced in patients with CIM, but resided at the sarcolemma in control subjects. Glucose metabolism was not stimulated during euglycemic-hyperinsulinergic clamp. Insulin signal transduction was competent up to p-Akt activation; however, p-adenosine monophosphate-activated protein kinase (p-AMPK) was not detectable in CIM muscle. Electrical muscle stimulation increased p-AMPK, repositioned GLUT4, locally improved glucose metabolism, and prevented type-2 fiber atrophy. CONCLUSIONS: Insufficient GLUT4 translocation results in decreased glucose supply in patients with CIM. Failed AMPK activation is involved. Evoked muscle contraction may prevent muscle-specific AMPK failure, restore GLUT4 disposition, and diminish protein breakdown. Clinical trial registered with http://www.controlled-trials.com (registration number ISRCTN77569430).
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Transportador de Glucose Tipo 4/metabolismo , Insulina/metabolismo , Insulina/farmacologia , Contração Muscular , Doenças Musculares/fisiopatologia , Adulto , Idoso , Análise de Variância , Biópsia/métodos , Estado Terminal , Estimulação Elétrica/métodos , Feminino , Técnica Clamp de Glucose/métodos , Transportador de Glucose Tipo 4/genética , Humanos , Hipoglicemiantes/metabolismo , Hipoglicemiantes/farmacologia , Masculino , Microdiálise/métodos , Pessoa de Meia-Idade , Doenças Musculares/complicações , Doenças Musculares/genética , Doenças Musculares/patologia , Escores de Disfunção Orgânica , Projetos Piloto , Estudos Prospectivos , Respiração Artificial , Sepse/complicações , Transdução de SinaisRESUMO
OBJECTIVES: Surgeons are exposed to high levels of physical stress while working in the operating room. In industry, so-called exoskeletons are used to support the back and shoulder area. The aim of this study was to investigate the feasibility and effects of an upper body exoskeleton on postoperative physical complaints of surgeons. METHODS: Surgeons from a university hospital in the fields of orthopedics, trauma, and visceral surgery performed 2 operations of the same type and planned length on 2 different days. The first operation was performed without an exoskeleton, the second with an exoskeleton. The participants completed questionnaires on shoulder pain (Shoulder Pain and Disability Index [SPADI]), neck pain (Visual Analogue Scale [VAS] and Neck Disability Index [NDI]), and back pain (VAS and Oswestry Disability Index [ODI]) before and after the procedure. RESULTS: A total of 25 participants were included and performed 50 surgeries with a mean surgery duration of 144 minutes without and 138 minutes with the exoskeleton. Without the exoskeleton, the activity of the operation resulted in a significant increase of the VAS neck by 1.0 point (SD 1.2; P < .001), NDI by 4.8 (SD 8.6; P = .010), VAS back by 0.7 (SD 1.0; P = .002), and ODI by 2.7 (SD 4.1; P = .003). With the exoskeleton the participants reported significantly fewer complaints after the surgery (VAS neck: P = .001; NDI: P = .003; VAS back: P = .036; ODI: P = .036; SPADI: P = .016). CONCLUSION: An upper body exoskeleton can significantly reduce the discomfort in the neck, shoulder, and back caused to surgeons by surgery.
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Exoesqueleto Energizado , Cervicalgia , Dor de Ombro , Cirurgiões , Humanos , Masculino , Adulto , Feminino , Pessoa de Meia-Idade , Dor nas Costas , Doenças Profissionais/prevenção & controle , Inquéritos e Questionários , Medição da Dor , Estudos de Viabilidade , Avaliação da DeficiênciaRESUMO
BACKGROUND: The emergency physician indication catalogue is based on outdated studies and provides limited guidance for alarm criteria following traffic accidents. Advances in vehicle safety technology and changes in available resources necessitate a re-evaluation of the indications. The aim of this retrospective registry study is to identify preclinically assessable variables for severe injuries sustained in traffic accidents. METHODS: A total of 47,145 individuals involved in accidents between 1 January 2000 and 31 December 2021 from the GIDAS database were included. Separate datasets for severe (AIS 3+) and minor injuries were evaluated. RESULTS: Ejection (PPV 80.6%), entrapment (PPV 75.6%), burning vehicles (PPV 57.1%), challenging rescue situations (PPV 56.3%), vehicle disintegration (PPV 51.6%), and amnesia (PPV 50.3%) indicated severe injuries among vehicle occupants. For vulnerable road users (motorcyclists, cyclists, pedestrians), helmet loss (PPV 61.1%), being run over/dragging (PPV 41.9%), opponent vehicle window breakage (PPV 35.8%), and subsequent collision with objects (PPV 31.1%) were also identified. The χ2-test revealed significant associations between the variables and severe injuries. Combined variables achieved PPV values above 82%. DISCUSSION: The current emergency physician indication catalogue provides limited preclinically detectable criteria and should be revised based on the objective registry data. Query models for emergency dispatchers should be tested.
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Acidentes de Trânsito , Serviços Médicos de Emergência , Sistema de Registros , Acidentes de Trânsito/estatística & dados numéricos , Humanos , Estudos Retrospectivos , Masculino , Feminino , Ferimentos e Lesões/epidemiologia , Adulto , Alemanha , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Open reduction and plate fixation is a standard procedure for treating traumatic symphyseal disruptions, but has a high incidence of implant failure. Several studies have attempted to identify predictors for implant failure and discussed its impact on functional outcome presenting conflicting results. Therefore, this study aimed to identify predictors of implant failure and to investigate the impact of implant failure on pain and functional outcome. METHODS: In a single-center, retrospective, observational non-controlled cohort study in a level-1 trauma center from January 1, 2006, to December 31, 2017, 42 patients with a plate fixation of a traumatic symphyseal disruption aged ≥ 18 years with a minimum follow-up of 12 months were included. The following parameters were examined in terms of effect on occurrence of implant failure: age, body mass index (BMI), injury severity score (ISS), polytrauma, time to definitive treatment, postoperative weight-bearing, the occurrence of a surgical site infection, fracture severity, type of posterior injury, anterior and posterior fixation. A total of 25/42 patients consented to attend the follow- up examination, where pain was assessed using the Numerical Rating Scale and functional outcome using the Majeed Pelvic Score. RESULTS: Sixteen patients had an anterior implant failure (16/42; 37%). None of the parameters studied were predictive for implant failure. The median follow-up time was six years and 8/25 patients had implant failure. There was no difference in the Numerical Rating Scale, but the work-adjusted Majeed Pelvic Score showed a better outcome for patients with implant failure. CONCLUSION: implant failure after symphyseal disruptions is not predictable, but appears to be clinically irrelevant. Therefore, an additional sacroiliac screw to prevent implant failure should be critically discussed and plate removal should be avoided in asymptomatic patients.
RESUMO
PURPOSE: The treatment of severely injured patients in the resuscitation room of an emergency department requires numerous critical decisions, often under immense time pressure, which places very high demands on the facility and the interdisciplinary team. Computer-based cognitive aids are a valuable tool, especially in education and training of medical professionals. For the management of polytrauma cases, TraumaFlow, a workflow management-based clinical decision support system, was developed. The system supports the registration and coordination of activities in the resuscitation room and actively recommends diagnosis and treatment actions. METHODS: Based on medical guidelines, a resuscitation room algorithm was developed according to the cABCDE scheme. The algorithm was then modeled using the process description language BPMN 2.0 and implemented in a workflow management system. In addition, a web-based user interface that provides assistance functions was developed. An evaluation study was conducted with 11 final-year medical students and three residents to assess the applicability of TraumaFlow in a case-based training scenario. RESULTS: TraumaFlow significantly improved guideline-based decision-making, provided more complete therapy, and reduced treatment errors. The system was shown to be beneficial not only for the education of low- and medium-experienced users but also for the training of highly experienced physicians. 92% of the participants felt more confident with computer-aided decision support and considered TraumaFlow useful for the training of polytrauma treatment. In addition, 62% acknowledged a higher training effect. CONCLUSION: TraumaFlow enables real-time decision support for the treatment of polytrauma patients. It improves guideline-based decision-making in complex and critical situations and reduces treatment errors. Supporting functions, such as the automatic treatment documentation and the calculation of medical scores, enable the trauma team to focus on the primary task. TraumaFlow was developed to support the training of medical students and experienced professionals. Each training session is documented and can be objectively and qualitatively evaluated.
RESUMO
PURPOSE: Common surgical procedures in the treatment of periprosthetic distal femur fractures (PPFF) include osteosynthesis with fixed angle locking plates (LP) and retrograde intramedullary nails (RIN). This study aimed to compare LPs to RINs with oblique fixed angle screws in terms of complications, radiographic results and functional outcome. METHODS: 63 PPFF in 59 patients who underwent treatment in between 2009 and 2020 were included and retrospectively reviewed. The anatomic lateral and posterior distal femoral angle (aLDFA and aPDFA) were measured on post-surgery radiographs. The Fracture Mobility Score (FMS) pre- and post-surgery, information about perceived instability in the operated leg and the level of pain were obtained via a questionnaire and previous follow-up (FU) examinations in 30 patients (32 fractures). RESULTS: The collective (median age: 78 years) included 22 fractures treated with a RIN and 41 fractures fixed with a LP. There was no difference in the occurrence of complications (median FU: 21.5 months) however the rate of implant failures requiring an implant replacement was higher in fractures treated with a LP (p = 0.043). The aPDFA was greater in fractures treated with a RIN (p = 0.04). The functional outcome was comparable between both groups (median FU: 24.5 months) with a lower outcome in the post-surgery FMS (p = < 0.001). CONCLUSION: Fractures treated with RIN resulted in an increased recurvation of the femur however the rate of complications and the functional outcome were comparable between the groups. The need for implant replacements following complications was higher in the LP group.