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INTRODUCTION: Although non-fracture-related syndesmotic injuries of the ankle are relatively rare, they may lead to poor clinical outcome if initially undiagnosed or managed improperly. Despite a variety of literature regarding possibilities for treatment of isolated syndesmotic injuries, little is known about effective applications of different therapeutic methods in day-to-day work. The aim of this study was to assess the current status of the treatment of isolated syndesmotic injuries in Germany. MATERIALS AND METHODS: An online-questionnaire, capturing the routine diagnostic workup including clinical examination, radiologic assessment and treatment strategies, was sent to all members of the German Society of Orthopedic Surgery and Traumatology (DGOU) and Association of Arthroscopic and Joint Surgery (AGA). Statistical analysis was performed using Microsoft excel and SPSS. RESULTS: Each question of the questionnaire was on average answered by 431 ± 113 respondents. External rotation stress test (66%), squeeze test (61%) and forced dorsiflexion test (40%) were most commonly used for the clinical examination. In the diagnostic workup, most clinicians relied on MRI (83%) and conventional X-ray analysis (anterior-posterior 58%, lateral 41%, mortise view 38%). Only 15% of the respondents stated that there is a role for arthroscopic evaluation for the assessment of isolated syndesmotic injuries. Most frequently used fixation techniques included syndesmotic screw fixation (80%, 42% one syndesmotic screw, 38% two syndesmotic screws), followed by suture-button devices in 13%. Syndesmotic screw fixation was mainly performed tricortically (78%). While 50% of the respondents stated that syndesmotic screw fixation and suture-button devices are equivalent in the treatment of isolated syndesmotic injuries with respect to clinical outcome, 36% answered that syndesmotic screw fixation is superior compared to suture-button devices. CONCLUSIONS: While arthroscopy and suture-button devices do not appear to be widely used, syndesmotic screw fixation after diagnostic work-up by MRI seems to be the common treatment algorithm for non-fracture-related syndesmotic injuries in Germany.
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Traumatismos del Tobillo , Humanos , Traumatismos del Tobillo/epidemiología , Traumatismos del Tobillo/terapia , Articulación del Tobillo , Tornillos Óseos , Fijación Interna de Fracturas , Alemania/epidemiologíaRESUMEN
Flexible adult acquired flatfoot deformity includes a wide spectrum of fore- and hindfoot pathologies and remains a complex clinical challenge. Clinical history, inspection and accurate physical examination are paramount for diagnosis. Early stages of flexible adult acquired flatfoot deformity present with increased hindfoot valgus and medial arch collapse. Operative management typically consists of an open medializing calcaneal osteotomy and an augmentation of the insufficient posterior tibial muscle using a flexor digitorum longus tendon transfer. New surgical techniques and a deeper understanding of pathophysiology may change traditional treatment pathways.
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Calcáneo , Pie Plano/cirugía , Deformidades Adquiridas del Pie/cirugía , Osteotomía/métodos , Transferencia Tendinosa/métodos , Adulto , Calcáneo/cirugía , Pie Plano/diagnóstico por imagen , Pie/diagnóstico por imagen , Deformidades Adquiridas del Pie/diagnóstico , Humanos , Resultado del TratamientoRESUMEN
There is an ongoing discussion about demographic change, a possible lack of young doctors and its impact on the healthcare system in Germany. Up to now, no valid data has been available on the exact numbers of residents in orthopedics and trauma surgery. Therefore, the aim of this study was to determine the actual number of residents in Germany in 2013/2014. We generated a database with all eligible providers of postgraduate training in orthopedics and trauma surgery in Germany. All of these were asked to fill out a questionnaire about the number of trainees, their gender and year of training. We achieved an 80% response rate (1509 questionnaires). Within these institutions, 4310 residents are trained. For Germany, this means an estimated number of about 5300 residents in the year 2013/2014. Ninety percent of postgraduate training is performed within a hospital and one-third of the residents are female. Looking at the expected number of doctors who will retire within the next five years, there seems to be enough young doctors to fill the gap. However, by 2040, an increased demand for othopedic and trauma surgeons is experted. Thus, we recommend centrally analyzing and coordinating the demand of residents in orthopedics and trauma surgery in Germany.
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Selección de Profesión , Fuerza Laboral en Salud/estadística & datos numéricos , Internado y Residencia/estadística & datos numéricos , Evaluación de Necesidades/estadística & datos numéricos , Ortopedia , Admisión y Programación de Personal/estadística & datos numéricos , Traumatología , Adulto , Femenino , Alemania , Humanos , Masculino , Distribución por Sexo , Adulto JovenRESUMEN
PURPOSE: Advanced Trauma Life Support (ATLS®) is one of the world's best-known training programs for medical providers. Revisions of the ATLS manual have been evidence based for a number of years. In 2011, a level 3 (S3) evidence- and consensus-based guideline on the treatment of patients with severe and multiple injuries was published in Germany. The scope of this study was the systematic comparison of the educational content of the ATLS concept and the interdisciplinary "S3 polytrauma guideline." METHODS: A total of 123 key recommendations of the guideline were compared with the content of the ATLS manual (9th edition). Depending on the level of agreement, the recommendations were classed in the following categories: (1) Agreement. (2) Minor variation. (3) Major variation. RESULTS: An overall 86% conformity was found between the key recommendations of the guideline and the ATLS® manual. The ATLS® primary survey (ABCDE) showed an 85% conformity. The degree of conformity for the individual priorities was as follows: A (Airway) 79%, B (Breathing) 79%, C (Circulation) 86%, D (Disability) 93%, E (Exposure) 100%. The ATLS® secondary survey showed a 94% conformity. The main differences were in the areas of anesthetic induction, fluid administration, and coagulation therapy. CONCLUSIONS: According to our comparison, the educational content and manual of the ATLS are largely compatible with a high level of evidence S3 guideline. However, subsequent editions of both the ATLS® and the S3 guideline should re-examine and reassess a number of aspects.
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Atención de Apoyo Vital Avanzado en Trauma/métodos , Medicina Basada en la Evidencia , Traumatismo Múltiple/terapia , Guías de Práctica Clínica como Asunto , Alemania , Humanos , Índices de Gravedad del TraumaRESUMEN
OBJECTIVE: For the early recognition and management of hypovolaemic shock, ATLS suggests four shock classes based upon an estimated blood loss in percent. The aim of this study was to assess the confidence and acceptance of the ATLS classification of hypovolaemic shock among ATLS course directors and instructors in daily trauma care. METHODS: During a 2-month period, ATLS course directors and instructors from the ATLS region XV (Europe) were invited to participate in an online survey comprising 15 questions. RESULTS: A total of 383 responses were received. Ninety-eight percent declared that they would follow the 'A, B, C, D, E' approach by ATLS in daily trauma care. However, only 48% assessed 'C-Circulation' according to the ATLS classification of hypovolaemic shock. One out of four respondents estimated that in daily clinical routine, less than 50% of all trauma patients can be classified according to the current ATLS classification of hypovolaemic shock. Additionally, only 10.9% considered the ATLS classification of hypovolaemic shock as a 'good guide' for fluid resuscitation and blood product transfusion, whereas 45.1% stated that this classification only 'may help' or has 'no impact' to guide resuscitation strategies. CONCLUSIONS: Although the 'A, B, C, D, E' approach according to ATLS is widely implemented in daily trauma care, the use of the ATLS classification of hypovolaemic shock in daily practice is limited. Together with previous analyses, this study supports the need for a critical reassessment of the current ATLS classification of hypovolaemic shock.
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Atención de Apoyo Vital Avanzado en Trauma/clasificación , Choque/clasificación , Heridas y Lesiones/complicaciones , Adulto , Actitud del Personal de Salud , Femenino , Hemodinámica/fisiología , Humanos , Masculino , Persona de Mediana Edad , Resucitación/métodos , Choque/diagnóstico , Choque/etiología , Choque/terapia , Encuestas y Cuestionarios , Heridas y Lesiones/diagnósticoRESUMEN
OBJECTIVE: Validation of the classification of hypovolaemic shock suggested by the prehospital trauma life support (PHTLS) in its sixth student course manual. METHODS: Adults, entered into the TraumaRegister DGU(®) database between 2002 and 2011, were classified into reference ranges for heart rate (HR), systolic blood pressure (SBP) and Glasgow coma scale (GCS) according to the PHTLS classification of hypovolaemic shock. First, patients were grouped by a combination of all three parameters (HR, SBP and GCS) as suggested by PHTLS. Second, patients were classified by only one parameter (HR, SBP or GCS) according to PHTLS and alterations in the remaining two parameters were assessed. Furthermore, subgroup analysis for trauma mechanism and traumatic brain injury (TBI) were performed. RESULTS: Out of 46 689 patients, only 12 432 (26.5%) could be adequately classified according to PHTLS if a combination of all three criteria was assessed. In TBI patients, only 12.2% could be classified adequately, whereas trauma mechanism had no significant influence. When patients were grouped by HR, there was only a slight reduction in SBP. When grouped by SBP, GCS dropped from 14 to 8, while no significant tachycardia was observed in any group. In patients with a GCS less than 12, HR was unaltered whereas SBP was slightly reduced to 114 (±42) mm Hg. On average, GCS in TBI patients was lower within all shock groups. In penetrating trauma patients, changes in HR and SBP were more distinct, but still less than predicted by PHTLS. CONCLUSIONS: The PHTLS classification of hypovolaemic shock displays substantial deficits in adequately risk-stratifying trauma patients.
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Choque/clasificación , Adulto , Presión Sanguínea , Femenino , Escala de Coma de Glasgow , Frecuencia Cardíaca , Humanos , Masculino , Persona de Mediana Edad , Choque/diagnóstico , Choque/etiologíaRESUMEN
INTRODUCTION: The recognition and management of hypovolemic shock still remain an important task during initial trauma assessment. Recently, we have questioned the validity of the Advanced Trauma Life Support (ATLS) classification of hypovolemic shock by demonstrating that the suggested combination of heart rate, systolic blood pressure and Glasgow Coma Scale displays substantial deficits in reflecting clinical reality. The aim of this study was to introduce and validate a new classification of hypovolemic shock based upon base deficit (BD) at emergency department (ED) arrival. METHODS: Between 2002 and 2010, 16,305 patients were retrieved from the TraumaRegister DGU® database, classified into four strata of worsening BD [class I (BD≤2 mmol/l), class II (BD>2.0 to 6.0 mmol/l), class III (BD>6.0 to 10 mmol/l) and class IV (BD>10 mmol/l)] and assessed for demographics, injury characteristics, transfusion requirements and fluid resuscitation. This new BD-based classification was validated to the current ATLS classification of hypovolemic shock. RESULTS: With worsening of BD, injury severity score (ISS) increased in a step-wise pattern from 19.1 (±11.9) in class I to 36.7 (±17.6) in class IV, while mortality increased in parallel from 7.4% to 51.5%. Decreasing hemoglobin and prothrombin ratios as well as the amount of transfusions and fluid resuscitation paralleled the increasing frequency of hypovolemic shock within the four classes. The number of blood units transfused increased from 1.5 (±5.9) in class I patients to 20.3 (±27.3) in class IV patients. Massive transfusion rates increased from 5% in class I to 52% in class IV. The new introduced BD-based classification of hypovolemic shock discriminated transfusion requirements, massive transfusion and mortality rates significantly better compared to the conventional ATLS classification of hypovolemic shock (p<0.001). CONCLUSIONS: BD may be superior to the current ATLS classification of hypovolemic shock in identifying the presence of hypovolemic shock and in risk stratifying patients in need of early blood product transfusion.
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Bases de Datos Factuales/clasificación , Sistema de Registros/clasificación , Choque/clasificación , Índices de Gravedad del Trauma , Heridas y Lesiones/clasificación , Adulto , Anciano , Bases de Datos Factuales/normas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sistema de Registros/normas , Choque/diagnóstico , Heridas y Lesiones/diagnóstico , Adulto JovenRESUMEN
INTRODUCTION: Isolated vital signs (for example, heart rate or systolic blood pressure) have been shown unreliable in the assessment of hypovolemic shock. In contrast, the Shock Index (SI), defined by the ratio of heart rate to systolic blood pressure, has been advocated to better risk-stratify patients for increased transfusion requirements and early mortality. Recently, our group has developed a novel and clinical reliable classification of hypovolemic shock based upon four classes of worsening base deficit (BD). The objective of this study was to correlate this classification to corresponding strata of SI for the rapid assessment of trauma patients in the absence of laboratory parameters. METHODS: Between 2002 and 2011, data for 21,853 adult trauma patients were retrieved from the TraumaRegister DGU database and divided into four strata of worsening SI at emergency department arrival (group I, SI <0.6; group II, SI ≥0.6 to <1.0; group III, SI ≥1.0 to <1.4; and group IV, SI ≥1.4) and were assessed for demographics, injury characteristics, transfusion requirements, fluid resuscitation and outcomes. The four strata of worsening SI were compared with our recently suggested BD-based classification of hypovolemic shock. RESULTS: Worsening of SI was associated with increasing injury severity scores from 19.3 (± 12) in group I to 37.3 (± 16.8) in group IV, while mortality increased from 10.9% to 39.8%. Increments in SI paralleled increasing fluid resuscitation, vasopressor use and decreasing hemoglobin, platelet counts and Quick's values. The number of blood units transfused increased from 1.0 (± 4.8) in group I to 21.4 (± 26.2) in group IV patients. Of patients, 31% in group III and 57% in group IV required ≥10 blood units until ICU admission. The four strata of SI discriminated transfusion requirements and massive transfusion rates equally with our recently introduced BD-based classification of hypovolemic shock. CONCLUSION: SI upon emergency department arrival may be considered a clinical indicator of hypovolemic shock in respect to transfusion requirements, hemostatic resuscitation and mortality. The four SI groups have been shown to equal our recently suggested BD-based classification. In daily clinical practice, SI may be used to assess the presence of hypovolemic shock if point-of-care testing technology is not available.
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Transfusión Sanguínea , Sistema de Registros , Choque/diagnóstico , Choque/terapia , Índices de Gravedad del Trauma , Adulto , Anciano , Transfusión Sanguínea/normas , Femenino , Alemania/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Sistema de Registros/normas , Estudios Retrospectivos , Choque/epidemiología , Factores de TiempoRESUMEN
BACKGROUND: Currently, there are no data available on dropouts from residency programs and changes of clinic in orthopedics and trauma surgery (O&T). The aim of the study is to identify personal and structural risk factors leading to dropout or switching of postgraduate training in O&T in order to present solution strategies. METHODS: A nationwide anonymous online survey was conducted among residents in O&T in summer 2020. Official mail addresses were identified via the Traumanetzwerk© of the DGU and the German Hospital Federation (nâ¯= 2090). A questionnaire (51 questions) was administered using SurveyMonkey (San Mateo, CA, USA). All residents who worked in O&T for at least 1 month in the 6 years prior to the start of the survey (from 07/2014) were eligible to participate. A binary logistic regression was calculated to identify the risk factors. The significance level was pâ¯= 0.05. RESULTS: Of the 221 respondents, 37% switched hospital and 5% dropped out altogether. The regression revealed 3 significant risk factors for switching hospitals. Living in a partnership (pâ¯= 0.029, RR: 2.823) and less than 2 days of shadowing before the start of residency (pâ¯= 0.002, RR: 2.4) increased the risk of switching. Operating room (OR) allocation of residents according to the training plan/status (pâ¯= 0.028, RR: 0.48) reduces the risk of switching. Significant risk factors for leaving postgraduate training could not be determined (insufficient number of cases, nâ¯= 11). DISCUSSION: Switching the hospital and residency dropouts in O&T are a relevant problem (42%). Gender has no significant influence. Tools such as longer job shadowing, as well as OR allocation according to the training plan/status can minimize the risk of switching.
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Internado y Residencia , Procedimientos Ortopédicos , Ortopedia , Ortopedia/educación , Encuestas y Cuestionarios , Factores de RiesgoRESUMEN
INTRODUCTION: The early aggressive management of the acute coagulopathy of trauma may improve survival in the trauma population. However, the timely identification of lethal exsanguination remains challenging. This study validated six scoring systems and algorithms to stratify patients for the risk of massive transfusion (MT) at a very early stage after trauma on one single dataset of severely injured patients derived from the TR-DGU (TraumaRegister DGU of the German Trauma Society (DGU)) database. METHODS: Retrospective internal and external validation of six scoring systems and algorithms (four civilian and two military systems) to predict the risk of massive transfusion at a very early stage after trauma on one single dataset of severely injured patients derived from the TraumaRegister DGU database (2002-2010). Scoring systems and algorithms assessed were: TASH (Trauma-Associated Severe Hemorrhage) score, PWH (Prince of Wales Hospital/Rainer) score, Vandromme score, ABC (Assessment of Blood Consumption/Nunez) score, Schreiber score and Larsen score. Data from 56,573 patients were screened to extract one complete dataset matching all variables needed to calculate all systems assessed in this study. Scores were applied and area-under-the-receiver-operating-characteristic curves (AUCs) were calculated. From the AUC curves the cut-off with the best relation of sensitivity-to-specificity was used to recalculate sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV). RESULTS: A total of 5,147 patients with blunt trauma (95%) was extracted from the TR-DGU. The mean age of patients was 45.7 ± 19.3 years with a mean ISS of 24.3 ± 13.2. The overall MT rate was 5.6% (n = 289). 95% (n = 4,889) patients had sustained a blunt trauma. The TASH score had the highest overall accuracy as reflected by an AUC of 0.889 followed by the PWH-Score (0.860). At the defined cut-off values for each score the highest sensitivity was observed for the Schreiber score (85.8%) but also the lowest specificity (61.7%). The TASH score at a cut-off ≥ 8.5 showed a sensitivity of 84.4% and also a high specificity (78.4%). The PWH score had a lower sensitivity (80.6%) with comparable specificity. The Larson score showed the lowest sensitivity (70.9%) at a specificity of 80.4%. CONCLUSIONS: Weighted and more sophisticated systems such as TASH and PWH scores including higher numbers of variables perform superior over simple non-weighted models. Prospective validations are needed to improve the development process and use of scoring systems in the future.
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Algoritmos , Transfusión Sanguínea/estadística & datos numéricos , Hemorragia/etiología , Índices de Gravedad del Trauma , Heridas y Lesiones/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Sistema de Registros , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
PURPOSE: Acute traumatic coagulopathy can result in uncontrolled haemorrhage responsible for the majority of early deaths after adult trauma. Data on the frequency, transfusion practice and outcome of severe trauma haemorrhage in paediatric patients are inconsistent. METHODS: Datasets from paediatric trauma patients were retrieved from the registry of the German trauma society (TR-DGU®) between 2009 and 2016. Coagulopathy was defined by a Quick's value < 70% (INR (international normalized ratio) > 1.4) and/or thrombocytes ≤ 100 k upon emergency room admission. Children were grouped according to age in 4 different groups (A: 1-5, B: 6-10, C: 11-15 and D: 16-17 years). Prevalence of coagulopathy was assessed. Demographics, injury severity, haemostatic management including transfusions and mortality were described. RESULTS: 5351 primary admitted children ≤ 17 years with an abbreviated injury scale (AIS) ≥ 3 and complete datasets were included. The prevalence of coagulopathy was 13.7% (733/5351). The majority of the children sustained blunt trauma (more than 90% independent of age group) and a combination of traumatic brain injury (TBI) and any other trauma in more than 60% (A, C, D) and in 53.8% in group B. Coagulopathy occurred the most among the youngest (A: 18.2%), followed by all other age groups with approximately 13%. Overall mortality was the highest in the youngest (A: 40.9%) and among the youngest patients with traumatic brain injury (A: 71.4% and B: 47.1%). Transfusion of packed red blood cells (pRBCs) and fresh frozen plasma (FFPs) occurred almost in a 2:1 ratio (or less) across all age subgroups. CONCLUSION: Traumatic haemorrhage in association with coagulopathy and severe shock is a major challenge in paediatric trauma across all age groups.
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Trastornos de la Coagulación Sanguínea , Transfusión Sanguínea , Escala Resumida de Traumatismos , Adolescente , Trastornos de la Coagulación Sanguínea/etiología , Trastornos de la Coagulación Sanguínea/terapia , Niño , Humanos , Puntaje de Gravedad del Traumatismo , Plasma , Estudios RetrospectivosRESUMEN
INTRODUCTION: Surgical departments are discredited as guardians of traditional structures of hierarchy. Hierarchy and working climate have a large share in human factor, being made responsible for 70% of avoidable errors in medicine. Aim of this study was the assessment of these topics amongst physicians in the field of orthopedics and traumatology. MATERIAL AND METHODS: A questionnaire of 10 questions was digitally handed to DGOU members. 799 questionnaires were answered. RESULTS: We found significant differences in the assessment of hierarchy and working atmosphere amongst the physician groups. Working atmosphere was perceived as not appreciative by registrars only. All groups were in favor of a hierarchy rather close to, but nut absolutely on equal terms. All groups attach high influence of working atmosphere on quality of daily work. DISCUSSION: Literature shows that hierarchic differentiation can increase performance of a team, while rigid hierarchy structures can lead to mistakes. Although hierarchy in orthopedics and traumatology seems to be less pronounced than assumed, hierarchy has great influence on daily work. CONCLUSION: In order to achieve a safety oriented medical environment, it will be of great importance to define hierarchy structures in clinics and to utilize them efficiently as a part of safety culture.
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Ortopedia , Cirujanos , Traumatología , Atmósfera , Alemania , Humanos , Encuestas y CuestionariosRESUMEN
BACKGROUND: Blood alcohol level (BAL) has previously been considered as a factor influencing the outcome of injured patients. Despite the well-known positive correlation between alcohol-influenced traffic participation and the risk of accidents, there is still no clear evidence of a positive correlation between blood alcohol levels and severity of injury. The aim of the study was to analyze data of the TraumaRegister DGU® (TR-DGU), to find out whether the blood alcohol level has an influence on the type and severity of injuries as well as on the outcome of multiple-trauma patients. METHODS: Datasets from 11,842 trauma patients of the TR-DGU from the years 2015 and 2016 were analyzed retrospectively and 6268 patients with a full dataset and an AIS ≥ 3 could be used for evaluation. Two groups were formed for data analysis. A control group with a BAL = 0 (BAL negative) was compared to an alcohol group with a BAL of ≥0.3 to < 4.0 (BAL positive). Patients with a BAL > 0 and < 0.3 were excluded. They were compared with regard to various preclinical, clinical and physiological parameters. Additionally, a subgroup analysis with a focus on patients with a traumatic brain injury (TBI) was performed. A total of 5271 cases were assigned to the control group and 832 cases to the BAL positive group. 70.3% (3704) of the patients in the control group were male. The collective of the control group was on average 5.7 years older than the patients in the BAL positive group (p < .001). The control group showed a mean ISS of 20.3 and the alcohol group of 18.9 (p = .007). In terms of the injury severity of head, the BAL positive group was significantly higher on average than the control group (p < 0.001), whereas the control group showed a higher AIS to thorax and extremities (p < 0.001). The mean Glasgow Coma Scale (GCS) was 10.8 in the BAL positive group and 12.0 in the control group (p < 0.001). Physiological parameters such as base excess (BE) and International Normalized Ratio (INR) showed reduced values ââfor the BAL positive group. However, neither the 24-h mortality nor the overall mortality showed a significant difference in either group (p = 0.19, p = 0.14). In a subgroup analysis, we found that patients with a relevant head injury (AIS: Abbreviated Injury Scale head ≥3) and positive BAL displayed a higher survival rate compared to patients in the control group with isolated TBI (p < 0.001). CONCLUSIONS: This retrospective study analyzed the influence of the blood alcohol level in severely injured patients in a large national dataset. BAL positive patients showed worse results with regard to head injuries, the GCS and to some other physiological parameters. Finally, neither the 24-h mortality nor the overall mortality showed a significant difference in either group. Only in a subgroup analysis the mortality rate in BAL negative patients with TBI was significantly higher than the mortality rate of BAL positive patients with TBI. This mechanism is not yet fully understood and is discussed controversially in the literature.
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Nivel de Alcohol en Sangre , Traumatismo Múltiple , Escala Resumida de Traumatismos , Alemania , Escala de Coma de Glasgow , Humanos , Puntaje de Gravedad del Traumatismo , Masculino , Sistema de Registros , Estudios RetrospectivosRESUMEN
Proliferation of pancreatic stellate cells (PSCs) plays a cardinal role during fibrosis development. Therefore, the suppression of PSC growth represents a therapeutic option for the treatment of pancreatic fibrosis. It has been shown that up-regulation of the enzyme heme oxygenase-1 (HO-1) could exert antiproliferative effects on PSCs, but no information is available on the possible role of carbon monoxide (CO), a catalytic byproduct of the HO metabolism, in this process. In the present study, we have examined the effect of CO releasing molecule-2 (CORM-2) liberated CO on PSC proliferation and have elucidated the mechanisms involved. Using primary rat PSCs, we found that CORM-2 inhibited PSC proliferation at nontoxic concentrations by arresting cells at the G(0)/G(1) phase of the cell cycle. This effect was associated with activation of p38 mitogen-activated protein kinase (MAPK) signaling, induction of HO-1 protein, and up-regulation of the cell cycle inhibitor p21(Waf1/Cip1). The p38 MAPK inhibitor 4-(4-flurophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)imidazole (SB203580) abolished the inhibitory effect of CORM-2 on PSC proliferation and prevented both CORM-2-induced HO-1 and p21(Waf1/Cip1) up-regulation. Treatment with tin protoporphyrin IX, an HO inhibitor, or transfection of HO-1 small interfering RNA abolished the inductive effect of CORM-2 on p21(Waf1/Cip1) and reversed the suppressive effect of CORM-2 on PSC growth. The ability of CORM-2 to induce cell cycle arrest was abrogated in p21(Waf1/Cip1)-silenced cells. Taken together, our results suggest that CORM-2 inhibits PSC proliferation by activation of the p38/HO-1 pathway. These findings may indicate a therapeutic potential of CO carriers in the treatment of pancreatic fibrosis.
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Hemo-Oxigenasa 1/fisiología , Compuestos Organometálicos/farmacología , Páncreas/efectos de los fármacos , Transducción de Señal/fisiología , Proteínas Quinasas p38 Activadas por Mitógenos/fisiología , Animales , Monóxido de Carbono/farmacología , Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/análisis , Sistema de Señalización de MAP Quinasas , Masculino , Compuestos Organometálicos/uso terapéutico , Páncreas/citología , Ratas , Ratas WistarRESUMEN
PURPOSE: Trauma-induced coagulopathy (TIC) is recognised as an own clinical entity which includes all components of haemostasis following rapidly tissue injury, hypoperfusion and shock. Microparticles (MP) are known to be released in large quantities from different cell types after trauma. The present study aimed to perform a phenotypic MP profiling after major trauma and to elucidate potential procoagulative function of MP under simulated conditions of lethal triad. METHODS: For MP isolation, 20 trauma patients (median ISS 24) were included. To produce a Standard MP Phenotype Profile after trauma, samples were pooled, extracted and concentrated by using an ultracentrifuge protocol. Specific cell surface markers were measured by flow cytometry. Our Standard MP Phenotype Profile was subsequently added in high and low concentration to an in vitro lethal triad assay, simulating coagulopathy via induced hypothermia, dilution and acidosis. A comprehensive analysis of coagulation function was performed. RESULTS: Within our Standard MP Phenotype Profile, PDMP (56%) were found as predominant phenotype followed by EDMP (33%) and MDMP (11%). EDMP characterized by CD144, CD62E and Annexin were determined most frequently but also EDMP expressing CD62P. In addition, tissue factor (TF) was expressed on all MP entities (EDMP 63%, PDMP 30%, MDMP 7%). Within our lethal triad simulation assay, the addition of low and high concentrated MP did not cause any significant alteration in standard coagulation assays, coagulation initiation, clot kinetics or stability. Addition of high concentrated MP increased platelet function and P-selectin expression significantly. CONCLUSION: Our data confirm the assumption that there is a characteristic MP phenotype pattern in trauma, which may alter haemostatic capacity at least in part mediated via augmenting in primary haemostasis resulting in an improved contribution of platelets to clot formation. There are indications that expression of selectins on MP surface is involved in this activation process, but this pathway needs to be investigated in more detail.
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Trastornos de la Coagulación Sanguínea/sangre , Micropartículas Derivadas de Células/metabolismo , Activación Plaquetaria , Heridas y Lesiones/sangre , Acidosis/sangre , Trastornos de la Coagulación Sanguínea/etiología , Plaquetas , Células Endoteliales , Citometría de Flujo , Hemodilución , Humanos , Hipotermia Inducida , Técnicas In Vitro , Puntaje de Gravedad del Traumatismo , Monocitos , Fenotipo , Pruebas de Función Plaquetaria , Tromboelastografía , Heridas y Lesiones/complicacionesRESUMEN
To describe the incidence, therapy and outcome of traumatic tracheobronchial injuries (TTBI) in trauma patients with multiple injuries derived from the DGU TraumaRegister. We analyzed the data on all patients listed on the TraumaRegister DGU (TR-DGU) in Germany between 2002 and 2015 aged 16 years or older and with an Injury Severity Score (ISS) of ≥ 9. We analyzed the data on 136,389 trauma patients, 561 of whom had suffered tracheobronchial injuries (0.4%). The majority were male (73.4%) and had a mean age of 43.7 years. In total, 84.0% of all TTBI injuries occurred secondary to blunt trauma, caused mainly by accidents (71.2%). TTBI was accompanied by several concomitant thoracic injuries such as pneumo- (41.2%) and hemothorax (23.2%), lacerations (7.8%) and contusions (32.3%) of the lung, as well as multiple rib fractures (29.6%). The severity of injury was classified via the abbreviated injury scale (AIS): 39.3% with AIS = 3, 51.3% with AIS = 4 and 60% with AIS = 5 patients underwent surgical interventions. The mortality of patients with tracheobronchial injuries was higher: 24.6%, versus 13.7% in all patients (control group). This high percentage reflects their generally severe injury burden through concomitant injuries. The incidence of TTBI in this large cohort of trauma patients is very low. However, its high mortality rate emphasizes its importance. Mortality was associated with higher ISS and AIS scores. Higher rates of concomitant injuries were therefore associated with a higher mortality rate. TTBI injuries revealed a higher rate of progression to surgical management, with 35% undergoing surgery within the first 24 h. This excessive mortality rate demonstrates a high overall injury burden in patients with TTBI and high mortality of associated injuries. A surgical intervention's impact on mortality cannot be assessed in this study, as it would need to be investigated in a case-matched study.
Asunto(s)
Traumatismo Múltiple/mortalidad , Traumatismos Torácicos/mortalidad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Bronquios/lesiones , Femenino , Alemania/epidemiología , Humanos , Puntaje de Gravedad del Traumatismo , Masculino , Persona de Mediana Edad , Sistema de Registros , Factores de Riesgo , Tráquea/lesiones , Centros Traumatológicos , Heridas no PenetrantesRESUMEN
The transcription factor Nuclear Factor-Erythroid 2 (NF-E2) is overexpressed in the vast majority of patients with polycythaemia vera (PV). In murine models, NF-E2 overexpression increases proliferation and promotes cellular viability in the absence of erythropoietin (EPO). EPO-independent growth is a hallmark of PV. We therefore hypothesized that NF-E2 overexpression contributes to erythrocytosis, the pathognomonic feature of PV. Consequently, we investigated the effect of NF-E2 overexpression in healthy CD34+ cells. NF-E2 overexpression led to a delay in erythroid maturation, manifested by a belated appearance of glycophorin A-positive erythroid precursors. Maturation delay was similarly observed in primary PV patient erythroid cultures compared to healthy controls. Protracted maturation led to a significant increase in the accumulated number of erythroid cells both in PV cultures and in CD34+ cells overexpressing NF-E2. Similarly, NF-E2 overexpression altered erythroid colony formation, leading to an increase in erythroid burst-forming unit formation. These data indicate that NF-E2 overexpression delays the early phase of erythroid maturation, resulting in an expansion of erythroid progenitors, thereby increasing the number of erythrocytes derived from one CD34+ cell. These data propose a role for NF-E2 in mediating the erythrocytosis of PV.
Asunto(s)
Eritrocitos/metabolismo , Eritropoyesis/fisiología , Factor de Transcripción NF-E2/metabolismo , Policitemia Vera/etiología , Antígenos CD34 , Células Precursoras Eritroides/metabolismo , Humanos , Policitemia/etiología , Policitemia Vera/sangre , Policitemia Vera/metabolismoAsunto(s)
Hemorragia , Traumatismo Múltiple , Índices de Gravedad del Trauma , Anciano , Femenino , Hemorragia/diagnóstico , Hemorragia/fisiopatología , Hemorragia/terapia , Humanos , Masculino , Persona de Mediana Edad , Traumatismo Múltiple/diagnóstico , Traumatismo Múltiple/fisiopatología , Traumatismo Múltiple/terapia , Factores de TiempoRESUMEN
Work-time constraints during surgical residency along with managing a private life usually take up the majority of the time of young surgeons. For many, work with a surgical society seems like something neither generally promising nor personally worthwhile, thus raising the question, why bother? This article sets out to show examples of the effects that surgical societies and young surgeon committees can have on surgery and residency training. Additionally, we highlight the personal side of being active on a committee. Our aim is to raise interest in participating in societal work by showing the rewarding general effects as well as personal benefits. While this article is based primarily on experiences made in Germany, we believe that aspects can be transferred to other medical systems.
RESUMEN
PURPOSE: Over the last decade, the pivotal role of trauma-induced coagulopathy has been described and principal drivers have been identified. We hypothesized that the increased knowledge on coagulopathy of trauma would translate into a more cautious treatment, and therefore, into a reduced overall incidence rate of coagulopathy upon ER admission. PATIENTS AND METHODS: Between 2002 and 2013, 61,212 trauma patients derived from the TraumaRegister DGU® had a full record of coagulation parameters and were assessed for the presence of coagulopathy. Coagulopathy was defined by a Quick's value < 70% and/or platelet counts < 100,000/µl upon ER admission. For each year, the incidence of coagulopathy, the amount of pre-hospital administered i.v.-fluids and transfusion requirements were assessed. RESULTS: Coagulopathy upon ER admission was present in 24.5% of all trauma patients. Within the years 2002-2013, the annual incidence of coagulopathy decreased from 35 to 20%. Even in most severely injured patients (ISS > 50), the incidence of coagulopathy was reduced by 7%. Regardless of the injury severity, the amount of pre-hospital i.v.-fluids declined during the observed period by 51%. Simultaneously, morbidity and mortality of severely injured patients were on the decrease. CONCLUSION: During the 12 years observed, a substantial decline of coagulopathy has been observed. This was paralleled by a significant decrease of i.v.-fluids administered in the pre-hospital treatment. The reduced presence of coagulopathy translated into decreased transfusion requirements and mortality. Nevertheless, especially in the most severely injured patients, posttraumatic coagulopathy remains a frequent and life-threatening syndrome.