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1.
Patient Saf Surg ; 18(1): 22, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38902828

ABSTRACT

Digital data processing has revolutionized medical documentation and enabled the aggregation of patient data across hospitals. Initiatives such as those from the AO Foundation about fracture treatment (AO Sammelstudie, 1986), the Major Trauma Outcome Study (MTOS) about survival, and the Trauma Audit and Research Network (TARN) pioneered multi-hospital data collection. Large trauma registries, like the German Trauma Registry (TR-DGU) helped improve evidence levels but were still constrained by predefined data sets and limited physiological parameters. The improvement in the understanding of pathophysiological reactions substantiated that decision making about fracture care led to development of patient's tailored dynamic approaches like the Safe Definitive Surgery algorithm. In the future, artificial intelligence (AI) may provide further steps by potentially transforming fracture recognition and/or outcome prediction. The evolution towards flexible decision making and AI-driven innovations may be of further help. The current manuscript summarizes the development of big data from local databases and subsequent trauma registries to AI-based algorithms, such as Parkland Trauma Mortality Index and the IBM Watson Pathway Explorer.

2.
Front Med (Lausanne) ; 11: 1362986, 2024.
Article in English | MEDLINE | ID: mdl-38707191

ABSTRACT

The strategies for the timing of fracture fixation in polytrauma patients have changed with improvements in resuscitation and patient assessment. Specifically, the criteria for damage control have been formulated, and more precise parameters have been found to determine those patients who can safely undergo primary definitive fixation of major fractures. Our current recommendations are supported by objective and data-based criteria and development groups. Those were validated and compared to existing scores. This review article introduces the concept of "safe definitive surgery" and provides an update on the parameters used to clear patients for timely fixation of major fractures.

3.
J Bone Miner Res ; 2024 Apr 13.
Article in English | MEDLINE | ID: mdl-38613445

ABSTRACT

INTRODUCTION: Evidence on the effects of Vitamin D, omega-3 s and exercise on aBMD in healthy older adults is limited. We examined whether vitamin D3, omega-3 s, or a simple home-based exercise program (SHEP), alone or in combination, over three years, improve lumbar spine (LS), femoral neck (FN) or total hip (TH) aBMD assessed by DXA. METHODS: aBMD was a secondary outcome in DO-HEALTH, a 3-year, multicenter, double-blind, randomized 2 × 2 × 2 factorial design trial in generally healthy older adults age ≥ 70 years. The study interventions were vitamin D3 (2000IU/d), omega-3 s (1 g/d), and SHEP (3 × 30 min/wk), applied alone or in combination in 8 treatment arms. Mixed effect models were used adjusting for age, sex, BMI, prior fall, study site and baseline level of the outcome. Main effects were assessed in the absence of an interaction between the interventions. Subgroup analyses by sex, physical activity level, dietary calcium intake, serum 25(OH)D levels, and fracture history were conducted. RESULTS: DXA scans were available for 1493 participants (mean age 75 years; 80.4% were physically active, 44% had 25(OH)D levels <20 ng/ml). At the LS and FN sites, none of the treatments showed a benefit. At the TH, vitamin D vs. no vitamin D treatment showed a significant benefit across 3 years (difference in adjusted means [AM]: 0.0035 [95% CI 0.0011, 0.0059] g/cm2). Furthermore, there was a benefit for vitamin D vs. no vitamin D treatment on LS aBMD in the male subgroup of (interaction P = 0.003; ∆AM: 0.0070 [95% CI 0.0007, 0.0132] g/cm2). CONCLUSIONS: Omega-3 and SHEP had no benefit on aBMD in healthy, active and largely vitamin D replete older adults. Our study suggests a small benefit of 2000 IU vitamin D daily on TH aBMD overall and LS aBMD among men, however, effect sizes were very modest and the clinical impact of these findings is unclear.


Vitamin D, omega-3 fatty acids (omega-3 s) and strength training are simple but promising strategies to improve bone health, however, their effect in healthy older adults over a period of three years was unclear. In this study, we examined whether daily vitamin D supplementation (2000 IU/d), daily omega-3 s supplementation (1 g/d) or a simple strength training program performed three times per week, either applied alone (e.g., only vitamin D supplements) or in combination (e.g., vitamin D and omega-3 s supplements) could improve bone density at the spine, hip or femoral neck. We included 1493 healthy older adults from Switzerland, Germany, France and Portugal who were at least 70 years of age and who had not experienced any major health events in the five years before study start. Taking omega-3 s supplements showed no benefit for bone density. Similarly, the simple strength exercise program showed no benefit. In contrast, participants receiving daily vitamin D supplements experienced a benefit at the hip. However, it should be noted that the effect across three years was very small.

4.
Patient Saf Surg ; 18(1): 3, 2024 Jan 16.
Article in English | MEDLINE | ID: mdl-38229102

ABSTRACT

BACKGROUND: Minimally invasive surgical treatment of pelvic trauma requires a significant level of surgical training and technical expertise. Novel imaging and navigation technologies have always driven surgical technique, and with head-mounted displays being commercially available nowadays, the assessment of such Augmented Reality (AR) devices in a specific surgical setting is appropriate. METHODS: In this ex-vivo feasibility study, an AR-based surgical navigation system was assessed in a specific clinical scenario with standard pelvic and acetabular screw pathways. The system has the following components: an optical-see-through Head Mounted Display, a specifically designed modular AR software, and surgical tool tracking using pose estimation with synthetic square markers. RESULTS: The success rate for entry point navigation was 93.8%, the overall translational deviation of drill pathways was 3.99 ± 1.77 mm, and the overall rotational deviation of drill pathways was 4.3 ± 1.8°. There was no relevant theoretic screw perforation, as shown by 88.7% Grade 0-1 and 100% Grade 0-2 rating in our pelvic screw perforation score. Regarding screw length, 103 ± 8% of the planned pathway length could be realized successfully. CONCLUSION: The novel innovative system assessed in this experimental study provided proof-of-concept for the feasibility of percutaneous screw placement in the pelvis and, thus, could easily be adapted to a specific clinical scenario. The system showed comparable performance with other computer-aided solutions while providing specific advantages such as true 3D vision without intraoperative radiation; however, it needs further improvement and must still undergo regulatory body approval. Future endeavors include intraoperative registration and optimized tool tracking.

5.
Injury ; 55(2): 111214, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38029680

ABSTRACT

BACKGROUND: 3D-navigation for percutaneous sacroiliac (SI) screw fixation is becoming increasingly common and several studies report great advantages of this technology. However, there is still limited clinical evidence on the efficacy regarding radiation exposure for patient and personnel. METHODS: This is a retrospective, single-center cohort study. All patients who underwent percutaneous sacroiliac screw fixation for an injury of the posterior pelvic ring from 2014 to 2021 were screened. Inclusion criteria were: conclusive radiation dosage reports, signed informed consent, a twelve month follow up and a complete data set. Patients were stratified in two groups (3D-navigation (Group 3D-N) vs. control (Group F)) based on the imaging modality used. Primary outcomes were radiation exposure for patient and personnel. Secondary outcomes were reoperations, complications, and intraoperative precision. RESULTS: Of 392 patients screened, 174 patients (3D-N: n = 50, F: n = 124) could be included for final analysis. We noted a significant reduction of the dose corresponding to potential radiation exposure for medical personnel (-15.3 mGy, 95 %CI: -2.1 to -28.5, p = 0.0232), but also a significant increase of the dose quantifying radiation exposure for patients (+77.0 mGy, 95 %CI: +53.3 to +100.6, p < 0.0001), when using navigation. In addition, the rate of radiographic malplacement was significantly reduced (F: 11.3% vs. 3D-N: 0 %, p = 0.0113) despite a substantial increase in transsacral screw placement (F: 19.4% vs. 3D-N: 76 %). CONCLUSION: Our data clearly suggests that the use of 3D-navigation for percutaneous SI screw fixation decreases radiation exposure for medical personnel, while increasing radiation exposure for patients. Furthermore, intraoperative precision is improved, even in more challenging operations.


Subject(s)
Fractures, Bone , Pelvic Bones , Radiation Exposure , Surgery, Computer-Assisted , Humans , Fractures, Bone/surgery , Fracture Fixation, Internal/methods , Cohort Studies , Retrospective Studies , Surgery, Computer-Assisted/methods , Bone Screws , Radiation Exposure/prevention & control , Fluoroscopy/methods , Pelvic Bones/injuries
7.
Brain ; 146(8): 3500-3512, 2023 08 01.
Article in English | MEDLINE | ID: mdl-37370200

ABSTRACT

Infections are prevalent after spinal cord injury (SCI), constitute the main cause of death and are a rehabilitation confounder associated with impaired recovery. We hypothesize that SCI causes an acquired lesion-dependent (neurogenic) immune suppression as an underlying mechanism to facilitate infections. The international prospective multicentre cohort study (SCIentinel; protocol registration DRKS00000122; n = 111 patients) was designed to distinguish neurogenic from general trauma-related effects on the immune system. Therefore, SCI patient groups differing by neurological level, i.e. high SCI [thoracic (Th)4 or higher]; low SCI (Th5 or lower) and severity (complete SCI; incomplete SCI), were compared with a reference group of vertebral fracture (VF) patients without SCI. The primary outcome was quantitative monocytic Human Leukocyte Antigen-DR expression (mHLA-DR, synonym MHC II), a validated marker for immune suppression in critically ill patients associated with infection susceptibility. mHLA-DR was assessed from Day 1 to 10 weeks after injury by applying standardized flow cytometry procedures. Secondary outcomes were leucocyte subpopulation counts, serum immunoglobulin levels and clinically defined infections. Linear mixed models with multiple imputation were applied to evaluate group differences of logarithmic-transformed parameters. Mean quantitative mHLA-DR [ln (antibodies/cell)] levels at the primary end point 84 h after injury indicated an immune suppressive state below the normative values of 9.62 in all groups, which further differed in its dimension by neurological level: high SCI [8.95 (98.3% confidence interval, CI: 8.63; 9.26), n = 41], low SCI [9.05 (98.3% CI: 8.73; 9.36), n = 29], and VF without SCI [9.25 (98.3% CI: 8.97; 9.53), n = 41, P = 0.003]. Post hoc analysis accounting for SCI severity revealed the strongest mHLA-DR decrease [8.79 (95% CI: 8.50; 9.08)] in the complete, high SCI group, further demonstrating delayed mHLA-DR recovery [9.08 (95% CI: 8.82; 9.38)] and showing a difference from the VF controls of -0.43 (95% CI: -0.66; -0.20) at 14 days. Complete, high SCI patients also revealed constantly lower serum immunoglobulin G [-0.27 (95% CI: -0.45; -0.10)] and immunoglobulin A [-0.25 (95% CI: -0.49; -0.01)] levels [ln (g/l × 1000)] up to 10 weeks after injury. Low mHLA-DR levels in the range of borderline immunoparalysis (below 9.21) were positively associated with the occurrence and earlier onset of infections, which is consistent with results from studies on stroke or major surgery. Spinal cord injured patients can acquire a secondary, neurogenic immune deficiency syndrome characterized by reduced mHLA-DR expression and relative hypogammaglobulinaemia (combined cellular and humoral immune deficiency). mHLA-DR expression provides a basis to stratify infection-risk in patients with SCI.


Subject(s)
HLA-DR Antigens , Spinal Cord Injuries , Humans , Cohort Studies , Prospective Studies , Spinal Cord Injuries/complications , Syndrome , Monocytes
8.
Swiss Med Wkly ; 150: w20325, 2020 Sep 07.
Article in English | MEDLINE | ID: mdl-33035352

ABSTRACT

AIMS OF THE STUDY: Mobility disability due to spinal stenosis is common in the senior population and often surgery is warranted for patients with severe symptoms and neurological dysfunction. However, although current clinical guidelines recommend stabilisation surgery in addition to decompression in patients with spinal stenosis and instability due to degenerative spondylolisthesis, the relationship between outcomes and the specific type of surgery have not been well studied. We therefore assessed the postoperative recovery timeline for 12 months and compared patient-reported outcomes dependent on the extent of decompression and additional stabilisation among seniors undergoing spinal stenosis surgery. METHODS: We investigated 457 patients (mean age 76.0 ± 10.7 years, 58% women) from a consecutive cohort prior to spinal stenosis surgery. Follow-up was at 3 or 6months and at 12 months postoperatively. At each visit, pain, neurological dysfunction and disability were assessed using the North American Spine Society questionnaire. Repeated-measures analysis compared outcomes by type of surgery adjusting for baseline symptoms, gender, age, number of comorbidities, centre and year of surgery. RESULTS: Most improvement occurred within the first 3 to 6 months with little or no further improvement at 12 months. Over 12 months and in adjusted models, patients receiving one-segment versus multi-segment decompression experienced significantly greater reduction of pain (−49.2% vs −41.9%, p = 0.013) and neurological dysfunction (−37.1% vs −25.9%, p <0.0001), but only borderline greater reduction of disability (−32.7% vs −28.2%, p = 0.051). Moreover, reduction in pain and neurological function did not differ with or without additional stabilisation and extend of decompression. However, patients who received one-segment (−28.9%) or multi-segment (−28.3%) stabilisation experienced significantly less reduction in disability after surgery compared with those who were not stabilised (−34.1%, p <0.043). CONCLUSIONS: Among senior patients undergoing spinal stenosis surgery, recovery was largely complete by 3 to 6 months after surgery and differed little by type of surgery independently of symptoms prior to surgery and other covariates. However we could document a trend toward more improvement in particularly neurological dysfunction and disability with less invasive surgery.


Subject(s)
Spinal Stenosis , Adult , Aged , Aged, 80 and over , Decompression, Surgical , Female , Humans , Lumbar Vertebrae/surgery , Male , Middle Aged , Neurosurgical Procedures , Spinal Stenosis/complications , Spinal Stenosis/surgery , Surveys and Questionnaires , Treatment Outcome
9.
Radiologe ; 60(7): 642-651, 2020 Jul.
Article in German | MEDLINE | ID: mdl-32507969

ABSTRACT

CLINICAL PROBLEM: The indication for resuscitation room care is an acute (potentially) life-threatening patient condition. Typical causes for this are polytrauma, acute neurological symptoms, acute chest and abdominal pain or the cause remains unclear at first. The care is always provided in a suitably composed interdisciplinary team. This requires cause-specific standards tailored to the care facility and requires a mutual understanding of the partners involved with regard to specialist interests and care processes. STANDARD RADIOLOGICAL METHODS: Whole-body CT is established for polytrauma imaging and usually each institution has already defined an institutional standard. For the other causes, first imaging with CT is just as common, but the protocols and procedures to be used are often not as clear as in the case of polytrauma. METHODICAL INNOVATION AND EVALUATION: For polytrauma service, ATLS and procedures according to ABCDE already serve as a largely standardized framework in the resuscitation room. For every other group of causes, comparable concepts should be developed and institutionally strive for objectification of continuous improvement. This refers not only to the resuscitation room stay but also to the interfaces before and after resuscitation room service. PRACTICAL RECOMMENDATIONS: After the patient has arrived, it has to be determined whether the assessment of a vital risk is retained. If so, institutionally defined care standards must be followed for the various causes. This concerns the interface logistics, the definition of a team leader including associated tasks, the supply processes including the CT examination protocols as well as the close communication.


Subject(s)
Emergency Service, Hospital , Multiple Trauma , Resuscitation , Humans
10.
J Crit Care ; 44: 229-237, 2018 04.
Article in English | MEDLINE | ID: mdl-29175047

ABSTRACT

Polytrauma (PT) is frequently associated with hemorrhagic shock (HS), which increases morbidity and mortality. Although various aspects of HS have been addressed in PT patients, the impact of an additional HS is largely unknown regarding the development of multiple organ dysfunction associated with disturbed glycocalyx and barrier function early after trauma. A prospective, longitudinal, mono-centered, observational study enrolling severely injured patients (Injury Severity Score, ISS=38.1±2.6) served for an in-depth analysis of blood (drawn on days 0, 1, 2, 3 and 5) and clinical data (up to 21days) of 30 patients who were then stratified into PT with and without HS. HS significantly enhanced signs of acute organ injury, assessed by increased serum concentrations of novel damage markers. Moreover, indicators of glycocalyx and tight-junction dysfunction were found in PT patients all of which were significantly enhanced in co-presence of HS. These markers revealed multiple significant correlations with specific barrier, fluid-balance, coagulation, inflammation, and clinical-outcome parameters. Strikingly, mucosa fragments, which affected clotting, could be detected in serum after PT/HS. The results point to HS as a main driver for glycocalyx and barrier breakdown and suggest novel tools for the monitoring of organ dysfunction in the early course after PT.


Subject(s)
Biomarkers/blood , Glycocalyx/metabolism , Multiple Trauma , Shock, Hemorrhagic/mortality , Adolescent , Adult , Aged , Aged, 80 and over , Emergency Service, Hospital , Female , Germany/epidemiology , Humans , Injury Severity Score , Longitudinal Studies , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , Shock, Hemorrhagic/blood , Young Adult
12.
Nat Cell Biol ; 19(7): 763-773, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28604677

ABSTRACT

Naive pluripotency is established in preimplantation epiblast. Embryonic stem cells (ESCs) represent the immortalization of naive pluripotency. 2i culture has optimized this state, leading to a gene signature and DNA hypomethylation closely comparable to preimplantation epiblast, the developmental ground state. Here we show that Pramel7 (PRAME-like 7), a protein highly expressed in the inner cell mass (ICM) but expressed at low levels in ESCs, targets for proteasomal degradation UHRF1, a key factor for DNA methylation maintenance. Increasing Pramel7 expression in serum-cultured ESCs promotes a preimplantation epiblast-like gene signature, reduces UHRF1 levels and causes global DNA hypomethylation. Pramel7 is required for blastocyst formation and its forced expression locks ESCs in pluripotency. Pramel7/UHRF1 expression is mutually exclusive in ICMs whereas Pramel7-knockout embryos express high levels of UHRF1. Our data reveal an as-yet-unappreciated dynamic nature of DNA methylation through proteasome pathways and offer insights that might help to improve ESC culture to reproduce in vitro the in vivo ground-state pluripotency.


Subject(s)
Antigens, Neoplasm/metabolism , Blastocyst/enzymology , Embryonic Stem Cells/enzymology , Epigenesis, Genetic , Neoplasm Proteins/metabolism , Nuclear Proteins/metabolism , Pluripotent Stem Cells/enzymology , Proteasome Endopeptidase Complex/metabolism , Animals , Antigens, Neoplasm/genetics , Blastocyst/cytology , CCAAT-Enhancer-Binding Proteins , Cullin Proteins/metabolism , DNA Methylation , Gene Expression Regulation, Developmental , HEK293 Cells , Humans , Mice, Inbred C57BL , Neoplasm Proteins/genetics , Nuclear Proteins/genetics , Phenotype , Protein Interaction Domains and Motifs , Protein Stability , Proteolysis , RNA Interference , Time Factors , Transcriptome , Transfection , Ubiquitin-Protein Ligases
13.
Clin Spine Surg ; 30(3): E265-E269, 2017 04.
Article in English | MEDLINE | ID: mdl-28323710

ABSTRACT

STUDY DESIGN: Retrospective data analysis. OBJECTIVE: The aim of this study was to analyze correlations between spinopelvic configuration and fracture pattern or location in traumatic vertebral fractures. SUMMARY OF BACKGROUND DATA: The spinopelvic configuration represented by the pelvic incidence (PI) angle showed to have a strong correlation with the occurrence of degenerative diseases of the thoracolumbar spine. No data are available on whether there is an influence of the PI angle on traumatic vertebral lesions as well. MATERIALS AND METHODS: In a consecutive series of patients sustaining traumatic vertebral fractures, we retrospectively analyzed spinopelvic computed tomography data sets of 197 patients (121 male and 76 female patients; mean age, 51 years). Measurements included the PI angle, level of fracture(s), and fracture type according to the AO classification. Statistical analysis was performed to calculate correlation between PI and fracture level and between PI and fracture type. RESULTS: An average of 1.6 fractures per patient was found in the 197 individuals included in our study. PI angle showed a mean of 50.6 degrees for the left hip and a mean of 49.9 degrees for the right hip. There were no significant differences of the PI angle between male and female patients as well. Neither a significant effect of the PI angle on the vertebral fracture level (P=0.64) nor a significant relationship between the PI angle and the fracture type according to the AO classification (P=0.52) was found. CONCLUSIONS: The spinopelvic configuration represented by PI angle seems to influence neither the level nor the type of vertebral fractures in trauma patients.


Subject(s)
Pelvic Bones/diagnostic imaging , Pelvic Bones/pathology , Pelvis/diagnostic imaging , Spinal Fractures/diagnostic imaging , Spinal Fractures/surgery , Tomography Scanners, X-Ray Computed , Female , Humans , Linear Models , Male , Middle Aged , Pelvic Bones/surgery , Retrospective Studies , Spinal Fractures/classification
14.
Eur J Radiol ; 88: 135-140, 2017 Mar.
Article in English | MEDLINE | ID: mdl-28189198

ABSTRACT

OBJECTIVES: To identify the number of CT scans repeated in acute trauma patients receiving imaging before being referred to a trauma center, to define indications, and to assess radiation doses and costs of repeated CT. METHODS: This retrospective study included all adult trauma patients transferred from other hospitals to a Level-I trauma center during 2014. Indications for repeated CT scans were categorized into: inadequate CT image data transfer, poor image quality, repetition of head CT after head injury together with completion to whole-body CT (WBCT), and follow-up of injury known from previous CT. Radiation doses from repeated CT were determined; costs were calculated using a nation-wide fee schedule. RESULTS: Within one year, 85/298 (28.5%) trauma patients were transferred from another hospital because of severe head injury (n=45,53%) and major body trauma (n=23;27%) not manageable in the referring hospital, repatriation from a foreign country (n=14;16.5%), and no ICU-capacity (n=3;3.5%). Of these 85 patients, 74 (87%) had repeated CT in our center because of inadequate CT data transfer (n=29;39%), repetition of head CT with completion to WBCT (n=24;32.5%), and follow-up of known injury (n=21;28.5%). None occurred because of poor image quality. Cumulative dose length product (DLP) and annual costs of potential preventable, repeated CT (inadequate data transfer) was 631mSv (81'304mGy*cm) and 35'233€, respectively. CONCLUSION: A considerable number of transferred trauma patients undergo potentially preventable, repeated CT, adding radiation dose to patients and costs to the health care system.


Subject(s)
Radiation Dosage , Radiation Exposure/statistics & numerical data , Tomography, X-Ray Computed/economics , Tomography, X-Ray Computed/statistics & numerical data , Trauma Centers/economics , Trauma Centers/statistics & numerical data , Craniocerebral Trauma , Female , Humans , Male , Middle Aged , Patient Transfer , Radiation Exposure/economics , Referral and Consultation , Retrospective Studies , Tomography, X-Ray Computed/methods
15.
Eur J Med Res ; 21(1): 37, 2016 Oct 06.
Article in English | MEDLINE | ID: mdl-27716419

ABSTRACT

BACKGROUND: Although under discussion, induced hypothermia (IH) is an established therapy for patients with cardiac arrest or traumatic brain injuries. The influences on coagulopathy and bleeding tendency in severely injured patients (SIP) with concomitant traumatic brain injury are most widely unclear. Therefore, the aim of this study was to quantify the effect of mild IH in SIP with concomitant severe traumatic brain injuries on transfusion rate and mortality. METHODS: In this retrospective multi-centre study, SIP from three European level-1 trauma centres with an ISS ≥16 between 2009 and 2011 were included. At hospital A, patients qualified for IH with age ≤70 years and a severe head injury with an abbreviated injury scale (AISHead) of ≥3. IH was defined as target core body temperature of 35 °C. Hypothermic patients were matched with two patients, one from hospital B and one from hospital C using age and AISHead. The effect of IH on the transfusion rate, complications and mortality was quantified with 95 % confidence intervals (CI). Patients not treated with IH in hospital A and those from hospital B and C, who were not matched, were used to adjust the CI for the effect of inter-hospital therapy protocol differences. RESULTS: Mean age of patients in the IH-group (n = 43) was 35.7 years, mean ISS 30 points and sex distribution showed 83.7 % male. Mean age of matched patients in the normotherm-group (n = 86) was 36.7 years, mean ISS 33 points and there were 75.6 % males. For the hypothermic patients, we pointed out an estimate of mean difference for the number of transfused units of packed red blood cells as well as for mortality which does not indicate a decrease in the benefit gained by hypothermia. It is suggested that hypothermic patients tend to a higher rate of lung failure and thromboembolisms. CONCLUSION: Though tending to an increased rate of complications, there is no evidence for a difference in both; rate of transfusion and mortality in SIP. Mild IH as an option for severe head injuries seems as well-being practicable in the presence of multiple severe injuries. Further, clinical studies regarding the side effects are necessary.


Subject(s)
Blood Transfusion , Brain Injuries, Traumatic/mortality , Brain Injuries, Traumatic/therapy , Hypothermia, Induced , Adult , Aged , Brain Injuries, Traumatic/complications , Female , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome
16.
Ann Surg ; 264(6): 1125-1134, 2016 Dec.
Article in English | MEDLINE | ID: mdl-26727089

ABSTRACT

OBJECTIVE: The present study was aimed to identify mechanisms linked to complicated courses and adverse events after severe trauma by a systems biology approach. SUMMARY BACKGROUND DATA: In severe trauma, overwhelming systemic inflammation can result in additional damage and the development of complications, including sepsis. METHODS: In a prospective, longitudinal single-center study, RNA samples from circulating leukocytes from patients with multiple injury (injury severity score ≥17 points; n = 81) were analyzed for dynamic changes in gene expression over a period of 21 days by whole-genome screening (discovery set; n = 10 patients; 90 samples) and quantitative RT-PCR (validation set; n = 71 patients, 517 samples). Multivariate correlational analysis of transcripts and clinical parameters was used to identify mechanisms related to sepsis. RESULTS: Transcriptome profiling of the discovery set revealed the strongest changes between patients with either systemic inflammation or sepsis in gene expression of the heme degradation pathway. Using quantitative RT-PCR analyses (validation set), the key components haptoglobin (HP), cluster of differentiation (CD) 163, heme oxygenase-1 (HMOX1), and biliverdin reductase A (BLVRA) showed robust changes following trauma. Upregulation of HP was associated with the severity of systemic inflammation and the development of sepsis. Patients who received allogeneic blood transfusions had a higher incidence of nosocomial infections and sepsis, and the amount of blood transfusion as source of free heme correlated with the expression pattern of HP. CONCLUSIONS: These findings indicate that the heme degradation pathway is associated with increased susceptibility to septic complications after trauma, which is indicated by HP expression in particular.


Subject(s)
Blood Proteins/genetics , Cross Infection/blood , Cross Infection/etiology , Sepsis/blood , Sepsis/etiology , Transcriptome/genetics , Wounds and Injuries/complications , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Female , Gene Expression , Humans , Injury Severity Score , Longitudinal Studies , Male , Middle Aged , Prospective Studies , Real-Time Polymerase Chain Reaction , Risk Assessment , Risk Factors , Transfusion Reaction
17.
Cytotherapy ; 18(1): 41-52, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26563474

ABSTRACT

BACKGROUND AIMS: Fractures with a critical size bone defect (e.g., open fracture with segmental bone loss) are associated with high rates of delayed union and non-union. The prevention and treatment of these complications remain a serious issue in trauma and orthopaedic surgery. Autologous cancellous bone grafting is a well-established and widely used technique. However, it has drawbacks related to availability, increased morbidity and insufficient efficacy. Mesenchymal stromal cells can potentially be used to improve fracture healing. In particular, human fat tissue has been identified as a good source of multilineage adipose-derived stem cells, which can be differentiated into osteoblasts. The main issue is that mesenchymal stromal cells are a heterogeneous population of progenitors and lineage-committed cells harboring a broad range of regenerative properties. This heterogeneity is also mirrored in the differentiation potential of these cells. In the present study, we sought to test the possibility to enrich defined subpopulations of stem/progenitor cells for direct therapeutic application without requiring an in vitro expansion. METHODS: We enriched a CD146+NG2+CD45- population of pericytes from freshly isolated stromal vascular fraction from mouse fat tissue and tested their osteogenic differentiation capacity in vitro and in vivo in a mouse model for critical size bone injury. RESULTS: Our results confirm the ability of enriched CD146+NG2+CD45- cells to efficiently generate osteoblasts in vitro, to colonize cancellous bone scaffolds and to successfully contribute to regeneration of large bone defects in vivo. CONCLUSIONS: This study represents proof of principle for the direct use of enriched populations of cells with stem/progenitor identity for therapeutic applications.


Subject(s)
Adipose Tissue/cytology , Bone and Bones/pathology , Pericytes/transplantation , Wound Healing , Animals , Antigens, CD/metabolism , Bone Regeneration , Cell Differentiation , Cell Separation , Disease Models, Animal , Humans , Male , Mice, Inbred C57BL , Pericytes/cytology , Regeneration , Stem Cells/cytology
18.
Crit Care ; 19: 414, 2015 Nov 26.
Article in English | MEDLINE | ID: mdl-26607226

ABSTRACT

INTRODUCTION: Severe trauma triggers a systemic inflammatory response that contributes to secondary complications, such as nosocomial infections, sepsis or multi-organ failure. The present study was aimed to identify markers predicting complications and an adverse outcome of severely injured patients by an integrated clinico-transcriptomic approach. METHODS: In a prospective study, RNA samples from circulating leukocytes from severely injured patients (injury severity score ≥ 17 points; n = 104) admitted to a Level I Trauma Center were analyzed for dynamic changes in gene expression over a period of 21 days by quantitative RT-PCR. Transcriptomic candidates were selected based on whole genome screening of a representative discovery set (n = 10 patients) or known mechanisms of the immune response, including mediators of inflammation (IL-8, IL-10, TNF-α, MIF, C5, CD59, SPHK1), danger signaling (HMGB1, TLR2, CD14, IL-33, IL-1RL1), and components of the heme degradation pathway (HP, CD163, HMOX1, BLVRA, BLVRB). Clinical markers comprised standard physiological and laboratory parameters and scoring systems routinely determined in trauma patients. RESULTS: Leukocytes, thrombocytes and the expression of sphingosine kinase-1 (SPHK1), complement C5, and haptoglobin (HP) have been identified as markers with the best performance. Leukocytes showed a biphasic course with peaks on day 0 and day 11 after trauma, and patients with sepsis exhibited significantly higher leukocyte levels. Thrombocyte numbers showed a typical profile with initial thrombopenia and robust thrombocytosis in week 3 after trauma, ranging 2- to 3-fold above the upper normal value. 'Relative thrombocytopenia' was associated with multi-organ dysfunction, the development of sepsis, and mortality, the latter of which could be predicted within 3 days prior to the time point of death. SPHK1 expression at the day of admission indicated mortality with excellent performance. C5-expression on day 1 after trauma correlated with an increased risk for the development of nosocomial infections during the later course, while HP was found to be a marker for the development of sepsis. CONCLUSIONS: The combination of clinical and transcriptomic markers improves the prognostic performance and may represent a useful tool for individual risk stratification in trauma patients.


Subject(s)
Multiple Organ Failure/diagnosis , Risk Assessment/methods , Sepsis/diagnosis , Systemic Inflammatory Response Syndrome/diagnosis , Biomarkers/analysis , Biomarkers/blood , Complement C5/analysis , Complement C5/biosynthesis , Haptoglobins/analysis , Haptoglobins/biosynthesis , Humans , Injury Severity Score , Multiple Organ Failure/blood , Phosphotransferases (Alcohol Group Acceptor)/analysis , Phosphotransferases (Alcohol Group Acceptor)/blood , Prospective Studies , Sepsis/blood , Systemic Inflammatory Response Syndrome/blood
19.
Transfusion ; 55(12): 2807-15, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26264557

ABSTRACT

BACKGROUND: Patient blood management (PBM) measures have been shown to be effective in reducing transfusions while maintaining patient outcome. The issuance of transfusion guidelines is seen as being key to the success of PBM programs. As the introduction of guidelines alone did not visibly reduce transfusions in our center, a monitoring and feedback program was established. The aim of our study was to show the effectiveness of such measures in reducing transfusions and cost. STUDY DESIGN AND METHODS: We designed a prospective, interventional cohort study with a 3-year time frame (January 1, 2012 to December 31, 2014). In total, 101,794 patients aged 18 years or older were included. The PBM monitoring and feedback program was introduced on January 1, 2014, with the subsequent issuance of quarterly reporting. RESULTS: Within the first year of introduction, transfusion of all allogeneic blood products per 1000 patients was reduced by 27% (red blood cell units, -24%; platelet units, -25%; and fresh-frozen plasma units, -37%; all p < 0.001) leading to direct allogeneic blood product related savings of more than 2 million USD. The number of blood products transfused per case was significantly reduced from 9 ± 19 to 7 ± 14 (p < 0.001). With an odds ratio of 0.86 (95% confidence interval, 0.82-0.91), the introduction of our PBM monitoring and feedback program was a significant independent factor in the reduction of transfusion probability (p < 0.001). CONCLUSION: Our PBM monitoring and feedback program was highly efficacious in reducing the transfusion of allogeneic blood products and transfusion-related costs.


Subject(s)
Blood Transfusion/economics , Blood Transfusion/statistics & numerical data , Adult , Aged , Cohort Studies , Feedback , Female , Humans , Logistic Models , Male , Middle Aged , Practice Guidelines as Topic , Prospective Studies
20.
Article in English | MEDLINE | ID: mdl-26085840

ABSTRACT

BACKGROUND: A significant proportion of patients admitted to hospital with multiple traumas exhibit facial injuries. The aim of this study is to evaluate the incidence and cause of facial injuries in severely injured patients and to examine the role of plastic and maxillofacial surgeons in treatment of this patient collective. METHODS: A total of 67 patients, who were assigned to our trauma room with maxillofacial injuries between January 2009 and December 2010, were enrolled in the present study and evaluated. RESULTS: The majority of the patients were male (82 %) with a mean age of 44 years. The predominant mechanism of injury was fall from lower levels (<5 m) and occurred in 25 (37 %) cases. The median ISS was 25, with intracranial bleeding found as the most common concomitant injury in 48 cases (72 %). Thirty-one patients (46 %) required interdisciplinary management in the trauma room; maxillofacial surgeons were involved in 27 cases. A total of 35 (52 %) patients were treated surgically, 7 in emergency surgery, thereof. CONCLUSION: Maxillofacial injuries are often associated with a risk of other serious concomitant injuries, in particular traumatic brain injuries. Even though emergency operations are only necessary in rare cases, diagnosis and treatment of such concomitant injuries have the potential to be overlooked or delayed in severely injured patients.

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