Predictors of pulmonary failure following severe trauma: a trauma registry-based analysis.

BACKGROUND: The incidence of pulmonary failure in trauma patients is considered to be influenced by several factors such as liver injury. We intended to assess the association of various potential predictors of pulmonary failure following thoracic trauma and liver injury. METHODS: Records of 12,585 trauma patients documented in the TraumaRegister DGU® of the German Trauma Society were analyzed regarding the potential impact of concomitant liver injury on the incidence of pulmonary failure using uni- and multivariate analyses. Pulmonary failure was defined as pulmonary failure of ≥ 3 SOFA-score points for at least two days. Patients were subdivided according to their injury pattern into four groups: group 1: AIS thorax < 3; AIS liver < 3; group 2: AIS thorax ≥ 3; AIS liver < 3; group 3: AIS thorax < 3; AIS liver ≥ 3 and group 4: AIS thorax ≥ 3; AIS liver ≥ 3. RESULTS: Overall, 2643 (21%) developed pulmonary failure, 12% (n= 642) in group 1, 26% (n= 697) in group 2, 16% (n= 30) in group 3, and 36% (n= 188) in group 4. Factors independently associated with pulmonary failure included relevant lung injury, pre-existing medical conditions (PMC), sex, transfusion of more than 10 units of packed red blood cells (PRBC), Glasgow Coma Scale (GCS) ≤ 8, and the ISS. However, liver injury was not associated with an increased risk of pulmonary failure following severe trauma in our setting. CONCLUSIONS: Specific factors, but not liver injury, were associated with an increased risk of pulmonary failure following trauma. Trauma surgeons should be aware of these factors for optimized intensive care treatment.

The role of TNXB single-nucleotide polymorphisms in recurrent shoulder dislocation.

Tenascin-X (TNX) is an extra-cellular matrix glycoprotein associated with collagen fibril deposition. Recent reports have linked truncated TNX mutations (TNXB) to generalized joint hypermobility and most importantly recurrent joint dislocation. In the present study, we investigated whether there is an association between joint dislocation recurrence rate and the frequency of TNXB single-nucleotide polymorphisms (SNPs). Seventy-eight patients treated for post-traumatic shoulder instability and 82 healthy controls were genotyped for selected TNXB SNP using TaqMan® Genotyping Assays. At a mean follow-up of 24 months recurrence rate and clinical outcomes were evaluated using the Constant and Murley, Rowe, and DASH scores. The association between genotypes and joint dislocation was tested using the dominant, recessive and additive models, and the model-free approach. Genotype distribution of the examined SNPs did not significantly deviate from the Hardy-Weinberg equilibrium (HWE) neither in patients nor in the controls. Moreover, there was no significant difference in genotype and allele distribution between patients and controls. Finally, no difference in genotype frequency was detected between patients who experienced a re-dislocation after the initial surgery and patients who did not sustain a re-dislocation. The SNPs investigated in this study have no clinically relevant influence on TNXB gene expression and/or TNX function. Therefore, these SNPs could not be used for predicting individual risk of recurrent shoulder dislocation.

Subsequent gene expression pattern in dendritic cells following multiple trauma.

PURPOSE: Major trauma initiates a systemic inflammatory response, which is characterized by systemic release of various chemokines. There is growing evidence for the extraordinary role of dendritic cells (DC) as professional antigen-presenting cells and activators of the immune response. Recently, the impact of severe trauma on DC transcriptomic activation was demonstrated. The purpose of the present study was to evaluate gene expression pattern in DC following multiple trauma to gain further understanding of the mechanisms of posttraumatic immune response. METHODS: Ten patients with multiple injuries aged 20 to 46 years (mean 30 ± 9.2 years) were included in this study. The mean injury severity score (ISS) was 36 ± 10.4 points. Repeated blood samples were taken on the day of admission (day 0) and on five consecutive days (day 1 to day 5). Microarray analysis and RT-qPCR were performed in primary isolated DC. RESULTS: A mean of 116,000 ± 21,466 DC with a purity of 96 ± 0,8 % were harvested. Gene expression of CCL5 and CXCL5 as well as TIMP1 and GUCY1B3 showed a significant increase within the first 4 days after trauma. The time-dependent increase of these genes correlated significantly with serum CRP concentration and the total number of DC but neither with age nor with injury severity. CONCLUSIONS: Our study provides new data regarding temporal expression patterns of CCL5, CXCL5, TIMP1, and GUCY13B in multiple trauma. DC activation following trauma may follow a uniform pattern early after admission, eventually leading to cell recruitment.

Circulating leukotriene B4 identifies respiratory complications after trauma.

BACKGROUND: Leukotriene B4 (LTB4), a proinflammatory lipid mediator correlates well with the acute phase of Acute Respiratory Distress Syndrome (ARDS). Therefore, LTB4-levels were investigated to determine whether they might be a useful clinical marker in predicting pulmonary complications (PC) in multiply traumatized patients. METHODS: Plasma levels of LTB4 were determined in 100 patients on admission (ED) and for five consecutive days (daily). Twenty healthy volunteers served as control. LTB4-levels were measured by ELISA. Thirty patients developed PC (pneumonia, respiratory failure, acute lung injury (ALI), ARDS, pulmonary embolism) and 70 had no PC (ØPC). RESULTS: LTB4-levels in the PC-group [127.8 pg/mL, IQR: 104-200pg/ml] were significantly higher compared to the ØPC-group on admission [95.6 pg/mL, IQR: 55-143 pg/mL] or control-group [58.4 pg/mL, IQR: 36-108 pg/mL]. LTB4 continuously declined to basal levels from day 1 to 5 without differences between the groups. The cutoff to predict PC was calculated at 109.6 pg/mL (72% specificity, 67% sensitivity). LTB4 was not influenced by overall or chest injury severity, age, gender or massive transfusion. Patients with PC received mechanical ventilation for a significantly longer period of time, and had prolonged intensive care unit and overall hospital stay. CONCLUSION: High LTB4-levels indicate risk for PC development in multiply traumatized patients.

Lung Organ Failure Score (LOFS): probability of severe pulmonary organ failure after multiple injuries including chest trauma.

BACKGROUND: Pulmonary complications are common in multiple trauma patients with chest injury. Factors predisposing these critically ill patients to respiratory organ failure are not fully understood. METHODS: Univariate and multivariate logistic regression analyses were used to assess the prognostic value of clinical and laboratory variables (2002-2008; n = 30,616) from the Trauma Registry of the German Trauma Society (DGU). Data from patients admitted to the ICU with lung contusion/lacerations, an Injury Severity Score ≥ 16 and age ≥ 18 were included in the study. Severe pulmonary organ failure was defined as PaO(2)/FiO(2)<200 for ≥ 3 days and based on the odds ratios (ORs) a simplified Lung Organ Failure Score (LOFS) was developed using integer values. RESULTS: 21.3% (1254) of the 5892 patients analysed developed severe pulmonary organ failure. We identified seven independent predictors with significant correlation: age, gender, head injury, fluid therapy, injury severity, degree of chest trauma and surgical interventions. The highest ORs were observed in cases of Abbreviated Injury Scale (AIS)(Thorax) = 5 (1.58), surgical intervention (1.71) and multiple surgeries (2.41). We found that patients with simplified score values ≥ 21 points were at a maximum risk (>30%) for developing severe pulmonary complications. CONCLUSION: This scoring method could help trauma surgeons determine which multiple trauma patients are at risk for pulmonary complications after trauma. Efficacy analyses of prophylactic PEEP ventilation or rotational bed therapy in subgroups with comparable risks for respiratory complication could be based on the LOFS.

Soluble triggering receptor on myeloid cells-1 is expressed in the course of non-infectious inflammation after traumatic lung contusion: a prospective cohort study.

INTRODUCTION: The triggering receptor expressed on myeloid cells-1 (TREM-1) is known to be expressed during bacterial infections. We investigated whether TREM-1 is also expressed in non-infectious inflammation following traumatic lung contusion. METHODS: In a study population of 45 adult patients with multiple trauma and lung contusion, we obtained bronchoalveolar lavage (BAL) (blind suctioning of 20 ml NaCl (0.9%) via jet catheter) and collected blood samples at two time points (16 hours and 40 hours) after trauma. Post hoc patients were assigned to one of four groups radiologically classified according to the severity of lung contusion based on the initial chest tomography. Concentration of soluble TREM-1 (sTREM-1) and bacterial growth were determined in the BAL. sTREM-1, IL-6, IL-10, lipopolysaccharide binding protein, procalcitonin, C-reactive protein and leukocyte count were assessed in blood samples. Pulmonary function was evaluated by the paO2/FiO2 ratio. RESULTS: Three patients were excluded due to positive bacterial growth in the initial BAL. In 42 patients the severity of lung contusion correlated with the levels of sTREM-1 16 hours and 40 hours after trauma. sTREM-1 levels were significantly (P < 0.01) elevated in patients with severe contusion (2,184 pg/ml (620 to 4,000 pg/ml)) in comparison with patients with mild (339 pg/ml (135 to 731 pg/ml)) or no (217 pg/ml (97 to 701 pg/ml)) contusion 40 hours following trauma. At both time points the paO2/FiO2 ratio correlated negatively with sTREM-1 levels (Spearman correlation coefficient = -0.446, P < 0.01). CONCLUSIONS: sTREM-1 levels are elevated in the BAL of patients following pulmonary contusion. Furthermore, the levels of sTREM-1 in the BAL correlate well with both the severity of radiological pulmonary tissue damage and functional impairment of gas exchange (paO2/FiO2 ratio).

Outcome after operative treatment of Vancouver type B1 and C periprosthetic femoral fractures: open reduction and internal fixation versus revision arthroplasty.

INTRODUCTION: The rate of periprosthetic femoral fractures after hip arthroplasty is rising and the estimated current lifetime incidence is 0.4-2.1%. While most authors recommend revision arthroplasty in patients with loose femoral shaft components, treatment options for patients with stable stem are not fully elucidated. METHOD: Against this background we performed a retrospective chart analysis with clinical follow-up examination of 32 cases that sustained a Vancouver type B1 or C periprosthetic fracture (stable stem). PATIENTS: Overall 16 cases were treated by open reduction and internal fixation (ORIF) by plate osteosynthesis and 16 cases by revision arthroplasty (RA). Both groups were comparable regarding age, gender, follow-up time interval, time interval from primary hip arthroplasty to fracture and rate of cemented femoral components, but more type C fractures were treated by ORIF. RESULTS: Functional outcome expressed by the median timed "Up and Go" test did not differ significantly (30 s ORIF vs. 24 s RA, P = 0.19). However, by comparable systemic complications surgery-related complications were significantly more frequent in plate osteosynthesis (ORIF n = 10 vs. RA n = 3, P = 0.03). Based on our results, further studies, preferable via a multicenter approach, should focus on identifying patients that benefit from ORIF in periprosthetic fractures. A misinterpretation of type B2 fractures with loose implant as type B1 fractures may cause implant failure in case of ORIF. CONCLUSION: The use of angular stable implants, additional cable wires or bone enhancing means is recommended.

Functional outcome and complications following PHILOS plate fixation in proximal humeral fractures.

OBJECTIVES: Proximal humeral fractures account for approximately 5% of all fractures. New plating techniques have been developed to improve stability. The purpose of this study was to evaluate functional outcome following plate fixation with the Proximal Humeral Internal Locking System (PHILOS) and to analyze potential implant-related complications. METHODS: The PHILOS plate was used for internal fixation of displaced proximal humeral fractures in 28 patients (20 females, 8 males; mean age 60.7+/-12.9 years). Fractures were caused by low-energy trauma (fall from standing height) in 21 patients, and by an accident while skiing or cycling in seven patients. Involvement was on the right in 16 cases and on the left in 12 cases. According to the Neer classification, 8, 12, and 8 patients had displaced 2-, 3-, or 4-part fractures, respectively. All patients received a similar physical therapy program following internal fixation with the PHILOS plate. The patients were assessed clinically and radiographically after a mean follow-up of 25.2+/-11.8 months. Functional outcome was assessed using the Constant-Murley score adjusted for age and gender. Range of motion and shoulder abduction strength were measured. The patients were also evaluated with the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire and a visual analog scale (VAS). Complications during the follow-up period were recorded. RESULTS: Twenty fractures (71.4%) healed in good anatomical position. At the end of the follow-up period, the mean Constant-Murley score was 57.9+/-21.7, and the mean age- and gender-adjusted Constant-Murley score was 67.5+/-23.6. The results were excellent or good in 16 patients (57.1%), moderate in one patient (3.6%), and poor in 11 patients (39.3%). The mean DASH and VAS scores were 28.3+/-24.3 and 75.4+/-21.2, respectively. Eleven complications (39.3%) were seen during the follow-up period. Reoperation was required in eight patients (72.3%). Complications included avascular necrosis of the humeral head in two patients (7.2%), subacromial impingement in six patients (21.4%), loosening of a locking head screw in one patient (3.6%), and transiently decreased radial nerve sensation in two patients (7.2%). Subacromial impingement was mainly caused by the superior plate position. CONCLUSION: Our results demonstrate that the PHILOS plate provides sufficient fracture stabilization in the treatment of proximal humeral fractures of elderly patients.

Platelet factor 4 is highly upregulated in dendritic cells after severe trauma.

Dendritic cells (DCs) represent an important linkage between the innate and adaptive immune system and express proinflammatory transcriptomic products early after trauma. The use of a genomic approach recently revealed that platelet factor 4 (PF4) is significantly upregulated in DCs in patients after multiple trauma. However, knowledge about subsequent PF4 alteration and its potential clinical relevance in the context of multiple trauma is still limited. We used quantitative reverse transcription-polymerase chain reaction to analyze PF4 expression in both myeloid DCs (MDCs) and plasmocytoid DCs (PDCs) isolated from 10 patients after multiple trauma. Intracellular PF4 as well as HLA-DR expression were detected by flow cytometry. Furthermore, DCs and peripheral blood mononuclear cells were incubated on a monolayer of human umbilical endothelial cells and their adhesion properties were analyzed. The ratio of the DC subtypes (MDC and PDC) was assessed by flow cytometry. PF4 expression significantly increased on d 1 and d 2 as measured by reverse transcription-polymerase chain reaction. Intracellular PF4 content in MDCs and PDCs was significantly elevated in trauma patients compared with healthy controls. In addition, the surface antigen HLA-DR on MDCs was significantly elevated on d 1 and d 4 after trauma in patients compared with controls. However, cell adhesion of DCs did not show any significant differences between patients and controls. PF4 concentration in MDCs and PDCs significantly correlated with the injury severity score. These results confirm an early and subsequent posttraumatic activation of PF4 in DCs. PF4 also participates in the posttraumatic activation of DCs in relation to injury severity, a role that might be preferably based on the modification of receptor expression, whereas adhesion properties are largely unaffected.

Apoptosis differs in dendritic cell subsets early after severe trauma.

Dendritic cells (DC) represent an integral part of the immune system. However it is unclear how apoptosis in myeloid DC (MDC) and plasmacytoid DC (PDC) is affected and whether pro- or antiapoptotic properties dominate during the early post-traumatic phase. Blood samples were obtained on day 1 and day 4 after hospital admission from 10 severely traumatized patients and 10 healthy volunteers. Mononucleated cells were isolated and incubated with LPS. Apoptosis of MDC and PDC was assessed by annexin-V staining using flow cytometry. Expression of genes involved in apoptosis (Caspase-8, Flice inhibitory protein [FLIP], Bcl-2, Bax, Gadd45) in DC was measured by reverse transcriptase polymerase chain reaction. For statistical evaluation, the Kruskal-Wallis test was used (p < 0.05). Severe trauma increased apoptotic MDC compared with those in healthy controls (p < 0.05), whereas apoptosis of PDC was not influenced by the trauma impact. LPS stimulation decreased MDC apoptosis until day 4 after trauma; by contrast, for PDCs this effect was present only on day 1 after trauma. The Bcl-2/Bax ratio in DCs increased significantly. We conclude that peripheral MDCs are more susceptible to undergo apoptosis after trauma compared with PDCs. However, the overall response of DCs early after trauma is characterized by an increased activation of antiapoptotic mediators that might indicate a compensatory life-prolonging reaction.

Functional variants of the human 5-lipoxygenase gene and their genetic diagnosis.

Variants in the 5-lipoxygenase (ALOX5) gene are first-line candidate causes for interindividual differences in diseases where leukotrienes play a key role, e.g., inflammatory and immune diseases, atherosclerosis, asthma or the acute respiratory distress syndrome (ARDS). We developed and validated Pyrosequencing screening assays for single nucleotide polymorphism (dbSNP-IDs rs4986832, rs4987105, rs2115819, rs3740107, rs1565096, rs2291427, rs10571382, rs2242334, rs2229136, rs3802548), and a capillary electrophoresis assay for the ALOX5 Sp1/Egr1 promoter tandem repeat polymorphism. This selection spans the whole ALOX5 gene range and includes all variants with reported functional associations. A gene structure analysis in DNAs from 187 healthy unrelated Caucasians revealed two haploblocks, one in the promoter and one spanning six SNPs from rs3740107G>A in intron 6 to rs2229136A>G in exon 13. The five-repeat genotype was the most frequent Sp1/Egr1 promoter tandem repeat variant (allelic frequency 84%). These assays and analyses provide a solid basis for future assessments of the genetic modulation of leukotriene production.

Midterm results after operatively stabilised shoulder dislocations in elderly patients.

Anterior shoulder dislocation is frequently seen in young patients. The therapeutic regime in elderly patients after shoulder dislocation is less clearly defined. The aim of this study was to compare the clinical benefit of operative stabilisation following anterior shoulder dislocation in young versus elderly patients. Seventy-two patients with anterior shoulder dislocations were allocated into two groups. Group 1 (> 40 years of age) consisted of 23 patients, and group 2 (< 40 years of age) consisted of 49 patients. Operative stabilisation resulted in a significant reduction in recurrence rate in both groups. However, the clinical functional results measured by the Constant score, Rowe score and disabilities of the arm, shoulder and hand (DASH) score revealed significantly better outcomes in the younger (group 2) than in the older group (group 1). These results indicate that while operative stabilisation is equally effective in reducing recurrent shoulder dislocation in the elderly functional outcomes are not as good as in younger patients.

Periprosthetic humeral fractures after shoulder arthroplasty: operative management and functional outcome.

BACKGROUND: Currently, little information is available on functional outcome of periprosthetic humeral fractures after shoulder arthroplasty. This investigation aimed to evaluate functional and radiological outcome and patients' satisfaction following this type of injury treated by open reduction and internal fixation. METHODS: Retrospective chart analysis of patients treated at two level-I trauma centers. Patients were examined clinically and radiologically. Additionally, functional outcome was assessed using the established DASH-questionnaire and standardized examination for calculation of the Constant score. RESULTS: Five out of six patients showed complete fracture consolidation with satisfying functional results (mean follow up time 62 weeks). One patient showed major complications with poor outcome. DASH and Constant scores were comparable to those described after primary shoulder arthroplasty. CONCLUSIONS: Periprosthetic humeral fractures after shoulder arthroplasty can be treated by angular stable plating with low complication rates and acceptable results.

Role of lung contusions on posttraumatic inflammatory response and organ dysfunction in traumatized patients.

BACKGROUND: Multiple trauma is often accompanied by lung contusion leading to secondary pulmonary inflammation and organ dysfunction. The particular role of lung contusions on the systemic inflammatory response remains unclear. Therefore, the aim of the present study was to compare the degree of lung contusion with markers of inflammation and multiple organ failure (MOF) in trauma patients. METHODS: According to the Injury Severity Score (ISS), 45 patients were assigned to a low (< 25 points) and a high ISS group (> 25 points), respectively. Both groups were subdivided into minor and major lung injury groups as defined by computed tomography (CT) scan. Plasma levels of interleukin 6 (IL-6), interleukin 8 (IL-8), tumor necrosis factor (TNF) receptors, C-reactive protein (CRP), and polymorphonuclear (PMN) elastase were assessed, as well as the Murray lung score (MLS) and the MOF score. RESULTS: Patients with low ISS present moderate activation of inflammation which is not influenced by the degree of lung contusion. In contrast, patients with a high ISS develop significant posttraumatic inflammation and MOF. Patients with high ISS and severe lung contusions present significantly higher MLS and MOF scores. Interestingly, patients of the high ISS group without severe lung contusions develop a similar degree of MLS and MOF only after 5 days following the traumatic insult. However, the initial plasma levels of IL-6 and IL-8 differ significantly in this group. CONCLUSION: Our data show that severe lung contusions contributes to an immediate onset of posttraumatic inflammation in severely traumatized patients, resulting in MOF, while in severely injured patients without lung contusion, this development requires up to 5 days.

Influence of surgical experience on accuracy of acetabular cup positioning in total hip arthroplasty.

Acetabular cup positioning with respect to inclination and anteversion is important in total hip arthroplasty. Positioning affects wear, range of motion, dislocation, and aseptic loosening and is essential for the prognosis after surgery. In this study, we sought to determine the accuracy of surgeons' cup positioning and to test for any differences in accuracy among surgeons with different levels of surgical experience. Using a lateral transgluteal approach, 2 groups of surgeons with different levels of surgical experience positioned 85 cups. Fifty-nine percent of the cups were outside the safe zone of Lewinnek. There was no significant difference between the 2 groups.

Adjustment of pelvispinal parameters preserves the constant gravity line position.

There is a high variance in sagittal morphology and complaints between different subjects suffering from spinal disorders. Sagittal spinal alignment and clinical presentation are not closely related. Different parameters have been used to describe the pelvispinal morphology based on standing lateral radiographs. We conducted a study using radiography of the lumbar spine combined with force platform data to examine the correlation between pelvispinal parameters and the gravity line position. Fifty consecutive patients with a mean age of 55 years (18-84 years) were compared to normal controls. Among patients we found a statistically significant correlation between the following spinal parameters: lumbar lordosis and sacral slope (r=0.77; P<0.001), sacral slope and pelvic incidence (r=0.72; P<0.001) and pelvic tilt and overhang (r=-0.93; P<0.001). In patients and controls, the gravity line position was found to be located at 60 and 61%, respectively, of the foot length measured from the great toe, ranging from 53 to 69%, when corrected for the individual foot length. The results indicate that subjects with and without spinal disorders have their gravity line position localised within a very small range despite the high variability for lumbar lordosis and pelvic tilt.