Rate of Complications after Hip Fractures Caused by Prolonged Time-to-Surgery Depends on the Patient's Individual Type of Fracture and Its Treatment.

INTRODUCTION: Hip fractures are common injuries in the elderly and are usually treated with timely surgery. While severe postoperative complications are reported for up to 10% of patients, many studies identified predictive factors for the occurrence of complications postoperatively. A controversially discussed factor is "time-to-surgery". The aim of the study was to examine if time-to-surgery was associated with the occurrence of complications and if the complication rate differed between the patient individual fracture types of intracapsular on the one hand and extracapsular hip fractures on the other hand. We hypothesized that time-to-surgery had less impact on complications in intracapsular hip fractures compared to extracapsular ones, and therefore, guidelines should pay attention to the patient individual case scenario. MATERIALS AND METHODS: All patients who were admitted to the Department of Trauma and Orthopaedic Surgery of an academic teaching hospital for hip fracture surgery (n = 650) over a five-year period were included in the study. After the application of the exclusion criteria, such as periprosthetic or pathologic fractures, cases needed immediate surgical treatment, and after outlier adjustment, 629 cases remained in the study. Hip fractures were classified into intracapsular fractures (treated by hip arthroplasty) and extracapsular fractures (treated by intramedullary nailing osteosynthesis). The occurrence of severe complications in patients treated within 24 h was compared with patients treated later than 24 h after injury. For statistical evaluation, a multivariate logistic regression analysis was performed to investigate the impact of time-to-surgery interval on the occurrence of complications. RESULTS: Patients with an extracapsular fracture, which was treated with intramedullary nailing (44.5%), rarely suffered a serious complication when surgery was performed within 24 h after injury. However, when the interval of the time-to-surgery was longer than 24 h, the complication rate increased significantly (8.63% vs. 25.0%, p = 0.002). In contrast to this finding in patients with intracapsular fractures (55.5%), which were treated with cemented arthroplasty, complication rates did not depend on the 24 h interval (26.17% vs. 20.83%, p = 0.567). CONCLUSIONS: The occurrence of complications after surgical treatment of hip fractures is associated with the time interval between injury and surgery. A 24 h time interval between injury and surgical procedure seems to play a major role only in extracapsular fractures treated with osteosynthesis but not in intracapsular fractures treated with arthroplasty. Therefore, guidelines should take notice of the patient individual case scenario and, in particular, the individual hip fracture type.

Serum neurofilament light chain in COVID-19 and the influence of renal function.

COVID-19 is associated with various neurological symptoms. Serum neurofilament light chain (sNfL) is a robust marker for neuroaxonal injury. Recent studies have shown that elevated levels of sNfL are associated with unfavorable outcome in COVID-19 patients. However, neuroaxonal injury is rare in COVID-19, and renal dysfunction and hypoxia, both of which are known in severe COVID-19, can also increase sNfL levels. Thus, the meaning and mechanisms of sNfL elevation in COVID-19 patients remain unclear. We evaluated sNfL levels in 48 patients with COVID-19 (mean age = 63 years) and correlated them to clinical outcome, the form of oxygen therapy, and creatinine. Levels of sNfL were age adjusted and compared with normal values and z-scores. COVID-19 patients treated with nasal cannula had normal sNfL levels (mean sNfL = 19.6 pg/ml) as well as patients with high-flow treatment (mean sNfL = 40.8 pg/ml). Serum NfL levels were statistically significantly higher in COVID-19 patients treated with mechanical ventilation on intensive care unit (ICU) (mean sNfL = 195.7 pg/ml, p < 0.01). There was a strong correlation between sNfL elevation and unfavorable outcome in COVID-19 patients (p < 0.01). However, serum creatinine levels correlated directly and similarly with sNfL elevation and with unfavorable outcome in COVID-19 patients (p < 0.01). Additionally, multivariate analysis for serum creatinine and sNfL showed that both variables are jointly associated with clinical outcomes. Our results identify renal dysfunction as an important possible confounder for sNfL elevation in COVID-19. Thus, serum creatinine and renal dysfunction should be strongly considered in studies evaluating sNfL as a biomarker in COVID-19.

Outcome Comparison of Acute Respiratory Distress Syndrome (ARDS) in Patients with Trauma-Associated and Non-Trauma-Associated ARDS: A Retrospective 11-Year Period Analysis.

(1) Background: Acute respiratory distress syndrome (ARDS) is a rare complication in multiply injured patients. Due to the rarity of ARDS development after trauma, little is known about outcomes of patients with trauma-associated ARDS compared to patients with non-trauma-associated ARDS. (2) Methods: This retrospective analysis included n = 1038 ARDS patients admitted to the ARDS center of Charité-Universitätsmedizin Berlin between 2007 and 2018. Patients with trauma-associated ARDS (n = 62) were compared to patients with non-trauma-associated ARDS (n = 976). In a secondary analysis, patients from the group with non-trauma-associated ARDS were 1:1 nearest neighbor matched to patients with trauma-associated ARDS. The primary outcomes were 28-day in-hospital mortality, 60-day in-hospital mortality, and overall in-hospital mortality. (3) Results: Overall in-hospital mortality in trauma-associated ARDS was 29.0% compared to 40.5% in all patients with non-trauma-associated ARDS (p = 0.074). The in-hospital mortality rate in matched patients with non-trauma-associated ARDS (33.9%) was comparable to the trauma-associated ARDS cohort (p = 0.701). Kaplan-Meier curves indicated time-sensitive variations in 28-day and 60-day in-hospital survival. (4) Conclusion: Mortality was not different in patients with trauma-associated ARDS compared to patients with non-trauma-associated ARDS. Survival rate in the Kaplan-Meier curves stabilized after the critical initial phase and throughout the further 60-day period in patients with trauma-associated ARDS compared to patients with non-trauma-associated ARDS. Since this divergence was less pronounced in the matched cohort, it may be related to the younger age, fewer comorbidities, and lower ARDS severity in patients with trauma-associated ARDS. Patients with trauma-associated ARDS remain a very different cohort compared to patients with non-trauma-associated ARDS. Therefore, the outcome comparison is limited, even after matching.

Induction of severe hypoxemia and low lung recruitability for the evaluation of therapeutic ventilation strategies: a translational model of combined surfactant-depletion and ventilator-induced lung injury.

BACKGROUND: Models of hypoxemic lung injury caused by lavage-induced pulmonary surfactant depletion are prone to prompt recovery of blood oxygenation following recruitment maneuvers and have limited translational validity. We hypothesized that addition of injurious ventilation following surfactant-depletion creates a model of the acute respiratory distress syndrome (ARDS) with persistently low recruitability and higher levels of titrated "best" positive end-expiratory pressure (PEEP) during protective ventilation. METHODS: Two types of porcine lung injury were induced by lung lavage and 3 h of either protective or injurious ventilation, followed by 3 h of protective ventilation (N = 6 per group). Recruitment maneuvers (RM) and decremental PEEP trials comparing oxygenation versus dynamic compliance were performed after lavage and at 3 h intervals of ventilation. Pulmonary gas exchange function, respiratory mechanics, and ventilator-derived parameters were assessed after each RM to map the course of injury severity and recruitability. RESULTS: Lung lavage impaired respiratory system compliance (Crs) and produced arterial oxygen tensions (PaO2) of 84±13 and 80±15 (FIO2 = 1.0) with prompt increase after RM to 270-395 mmHg in both groups. After subsequent 3 h of either protective or injurious ventilation, PaO2/FIO2 was 104±26 vs. 154±123 and increased to 369±132 vs. 167±87 mmHg in response to RM, respectively. After additional 3 h of protective ventilation, PaO2/FIO2 was 120±15 vs. 128±37 and increased to 470±68 vs. 185±129 mmHg in response to RM, respectively. Subsequently, decremental PEEP titration revealed that Crs peaked at 36 ± 10 vs. 25 ± 5 ml/cm H2O with PEEP of 12 vs. 16 cmH2O, and PaO2/FIO2 peaked at 563 ± 83 vs. 334 ± 148 mm Hg with PEEP of 16 vs. 22 cmH2O in the protective vs. injurious ventilation groups, respectively. The large disparity of recruitability between groups was not reflected in the Crs nor the magnitude of mechanical power present after injurious ventilation, once protective ventilation was resumed. CONCLUSION: Addition of transitory injurious ventilation after lung lavage causes prolonged acute lung injury with diffuse alveolar damage and low recruitability yielding high titrated PEEP levels. Mimicking lung mechanical and functional characteristics of ARDS, this porcine model rectifies the constraints of single-hit lavage models and may enhance the translation of experimental research on mechanical ventilation strategies.

COVID-19 Patients Require Prolonged Extracorporeal Membrane Oxygenation Support for Survival Compared With Non-COVID-19 Patients.

To investigate the ICU survival of venovenous extracorporeal membrane oxygenation (ECMO) patients suffering from COVID-19-related acute respiratory distress syndrome (ARDS) versus ECMO patients without COVID-19 (non-COVID-19)-related ARDS. DESIGN: Preliminary analysis of data from two prospective ECMO trials and retrospective analysis of a cohort of ARDS ECMO patients. SETTING: Single-center ICU. PATIENTS: Adult ARDS ECMO patients, 16 COVID-19 versus 23 non-COVID-19 patients. Analysis of retrospective data from 346 adult ARDS ECMO patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: COVID-19 and non-COVID-19 ARDS patients did not differ with respect to preexisting disease or body mass index. ICU survival rate was 62% for COVID-19 ECMO patients and 70% for non-COVID-19 ECMO patients. COVID-19 ECMO survivors were supported with ECMO for a median of 43 days (interquartile range [IQR], 18-58 d) versus 16 days (IQR, 19-39 d; p = 0.03) for non-COVID-19 patients. The median duration of ECMO therapy for all ARDS patients between 2007 and 2018 was 15 days (IQR, 6-28 d). The subgroup of patients suffering from any viral pneumonia received ECMO support for a median of 16 days (IQR, 9-27 d), survivors of influenza pneumonia received ECMO support for 13 days (IQR, 7-25 d). CONCLUSIONS: COVID-19 patients required significant longer ECMO support compared with patients without COVID-19 to achieve successful ECMO weaning and ICU survival.

Timing, Outcome, and Risk Factors of Intracranial Hemorrhage in Acute Respiratory Distress Syndrome Patients During Venovenous Extracorporeal Membrane Oxygenation.

OBJECTIVES: Intracranial hemorrhage is a serious complication in patients receiving venovenous extracorporeal membrane oxygenation during treatment of the acute respiratory distress syndrome. We analyzed timing, outcome, and risk factors of intracranial hemorrhage in patients on venovenous extracorporeal membrane oxygenation. DESIGN: Retrospective cohort study. SETTING: Single acute respiratory distress syndrome referral center. PATIENTS: Patients receiving venovenous extracorporeal membrane oxygenation were identified from a cohort of 1,044 patients with acute respiratory distress syndrome. Patients developing an intracranial hemorrhage during venovenous extracorporeal membrane oxygenation therapy were compared with patients without evidence for intracranial hemorrhage. The primary objective was to assess the association of intracranial hemorrhage with 60-day mortality. Further objectives included the identification of risk factors for intracranial hemorrhage and the evaluation of clinical cutoff values. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 444 patients treated with venovenous extracorporeal membrane oxygenation, 49 patients (11.0% [95% CI, 8.3-14.4%]) developed an intracranial hemorrhage. The median time to intracranial hemorrhage occurrence was 4 days (95% CI, 2-7 d). Patients who developed an intracranial hemorrhage had a higher 60-day mortality compared with patients without intracranial hemorrhage (69.4% [54.4-81.3%] vs 44.6% [39.6-49.6%]; odds ratio 3.05 [95% CI, 1.54-6.32%]; p = 0.001). A low platelet count, a high positive end expiratory pressure, and a major initial decrease of Paco2 were identified as independent risk factors for the occurrence of intracranial hemorrhage. A platelet count greater than 100/nL and a positive end expiratory pressure less than or equal to 14 cm H2O during the first 7 days of venovenous extracorporeal membrane oxygenation therapy as well as a decrease of Paco2 less than 24 mm Hg during venovenous extracorporeal membrane oxygenation initiation were identified as clinical cutoff values to prevent intracranial hemorrhage (sensitivity 91% [95% CI, 82-99%], 94% [85-99%], and 67% [48-81%], respectively). CONCLUSIONS: Intracranial hemorrhage occurs early during venovenous extracorporeal membrane oxygenation and is a determinant for 60-day mortality. Appropriate adjustment of identified modifiable risk factors might lower the prevalence of intracranial hemorrhage during venovenous extracorporeal membrane oxygenation therapy.

Gender differences in blood transfusion strategy for patients with hip fractures - a retrospective analysis.

Background: In the last decades, transfusion therapy with allogenic blood has progressively shifted to a more restrictive approach. The current study analyzed the transfusion practice and transfusion-associated factors in a regional trauma center over the course of five years. Methods: Retrospective analysis of all patients undergoing surgery for hip fractures in a level 1 trauma center of an academic teaching hospital from 2010 to 2014 (n=650). The number of transfused packed red blood cells (PRBCs), preoperative Hb concentrations, and intensive care unit (ICU) and hospital length of stay (LOS) were analyzed. A logistic regression analysis was performed to evaluate transfusion and ICU LOS-associated risk factors. (Ethical Review Board approval: 2015-497-f-S). Results: From 2010 to 2014 the average number of PRBCs transfused per patient decreased continuously despite similar preoperative Hb levels. During the same period, ICU LOS increased while hospital LOS decreased. Advanced patient age, preoperative Hb concentrations, surgical complications, and ICU LOS were associated with increased transfusion requirements. Although preoperative Hb levels were lower, females received fewer PRBCs compared to males. Conclusion: Over the course of five years, a restrictive transfusion strategy was implemented within clinical practice in patients undergoing surgery for hip fractures. In parallel, a significant reduction in the hospital LOS and an increased ICU LOS was noted. Whether there is an association between increased ICU LOS and decreasing hospital LOS and whether there is a gender effect on transfusion requirements in patients with surgery for hip fractures should be subject to further research.

Transfusion of red blood cells does not impact progression-free and overall survival after surgery for ovarian cancer.

BACKGROUND: Allogeneic red blood cells (RBCs) have the potential to impact the immunosurveillance of the recipient and may therefore increase the risk of recurrence after cancer surgery. In this article the relationship between perioperative RBC transfusion and the risk of recurrence after ovarian cancer surgery is examined. STUDY DESIGN AND METHODS: This is a retrospective cohort analysis of a prospective database of patients who underwent surgery due to primary ovarian cancer between 2006 and 2014 and who had no residual disease after surgery. Patients who did and did not receive perioperative RBC transfusion were compared. The primary endpoint was progression-free survival (PFS). Propensity score matching (PSM) and Cox proportional hazards regression (CPH) was used to control for between-group differences of prognostic determinants. RESULTS: A total of 529 patients with a median follow-up of 51.4 months (95% CI, 46.1-56.5) were eligible for analysis. Of those, 408 patients (77.1%) received allogeneic, leukoreduced RBCs with a median of 4 units (IQR, 2-6) per patient. There was a strong selection bias of prognostic determinants between patients with and without transfusion. In unadjusted analysis, transfusion of RBCs was associated with an increased risk of cancer recurrence (hazard ratio [HR] of PFS 2.71 [95% CI, 1.94-3.77], p < 0.001). After bias reduction, transfusion of RBCs was no longer associated with an increased risk of cancer recurrence, neither in PSM-adjusted (HR 1.03 [95% CI, 0.59-1.80], p = 0.91), nor in multivariable CPH-adjusted analysis (HR 1.26 [95% CI, 0.85-1.86], p = 0.23). CONCLUSION: Perioperative transfusion of RBCs did not increase the risk of recurrence after ovarian cancer surgery.

Efficiency of platelet-rich plasma therapy in knee osteoarthritis does not depend on level of cartilage damage.

OBJECTIVES: Osteoarthritis of the knee is common and often leads to significant physical disability. While classic conservative therapeutic approaches aim for symptoms like pain and inflammation, procedures like the intraarticular application of hyaluronic acids (HA) or platelet-rich plasma (PRP) are thought to stimulate the endogenous HA production, stop catabolism of cartilage tissue, and promote tissue regeneration. To analyse whether the positive effects of PRP injections are associated with the level of cartilage damage, patient satisfaction with the treatment was correlated with the level of knee joint osteoarthritis quantified by MRI. METHODS: PRP was performed with a low-leukocyte autologous conditioned plasma (ACP) system in 59 patients. A pre-treatment MRI was performed and a Whole-Organ MRI Score (WORMS) was used to score the level of knee osteoarthritis by 14 features: integrity of the cartilage, affection of the bone marrow, subcortical cysts, bone attrition, osteophytes, integrity of the menisci and ligaments, presence of synovitis, loose bodies, and periarticular cysts. A multivariate analysis with ordinary least squares regressions was used. RESULTS: Although pain symptoms and severity of clinical osteoarthritis symptoms decreased, regression analysis could not detect a correlation between the degree of cartilage damage measured by the WORMS score and a positive response to PRP therapy. CONCLUSION: This study suggests that intraarticular injection of PRP might improve osteoarthritis symptoms and reduces the pain in patients suffering from osteoarthritis of the knee joint independent from the level of cartilage damages quantified by the whole-organ MRI scoring method WORMS.

Indicated trauma emergency department utilization - A comparison between patients' self-assessment and professional evaluation.

INTRODUCTION: Patient visits to emergency departments (EDs) increase in many countries. As a result, these facilities are often congested and the socioeconomic burden of growing workload is a well-known problem. In this study, patients' reasons attending an ED with non-emergent needs were analyzed. METHODS: From October 2015 to March 2016 patients (n = 499), attending the ED of an academic teaching hospital without referral from a General Practitioner (GP) were surveyed regarding circumstances of their visit, a self-assessment of illness-severity, and reasons for choosing the ED instead of a GP. Results were compared to responses of ED staff (n = 40). RESULTS: Most patients assessed their case as urgent (patients: 65% vs. ED staff: 28%, p < 0.001) and felt that their medical problem could not to be treated by a GP (74%). However, most patients ranked their injuries as mild (45.7%) or moderate (41.7%). Reasons to prefer an ED instead of a GP were not responded in 80.1% of cases. CONCLUSION: In contrast to the self-evaluation of patients, ED staff believed that a significant portion of medical problems could be treated by a GP. Understanding patient-centred reasons and the discrepancy between self-perceived emergencies and minor medical problems might help to reduce inappropriate ED-admissions.

Influence of Time to Surgery in Ankle Fractures on the Rate of Complications and Length of Stay - a Multivariate Analysis. / Der Einfluss des OP-Zeitpunktes bei Sprunggelenkfrakturen auf das Komplikationsrisiko und die Verweildauer ­ eine multivariate Analyse.

BACKGROUND: With an incidence of 9/1000 per year, ankle fracture is one of the most common skeletal injuries. It is currently unclear whether time to surgery affects the complication rate or the hospital length of stay and whether there are confounders in patient characteristics or comorbidities. MATERIAL AND METHODS: In a retrospective cohort study (n = 421), the risk of perioperative complications in patients with a primary operative fracture treatment within 6 hours of trauma was compared to a secondary surgical treatment. Furthermore, the influence of patient characteristics and comorbidities was examined in a multivariate regression analysis. RESULTS: In comparison to secondary therapy, there was no benefit of a surgical fracture treatment within 6 hours after trauma was detected with regard to the perioperative complication rate or the hospital length of stay. Advanced patient age and severe soft tissue damage were associated with prolonged hospital length of stay but not with an increased rate of local perioperative complications. CONCLUSION: The occurrence of severe local perioperative complications after surgical treatment of an ankle fracture is not associated with the time to surgery or covariates such as patient age or comorbidities. Current German guidelines for ankle fractures recommend surgical treatment within 6 - 8 hours, but these should be re-evaluated in further prospective randomised studies.

Biomechanics of common fixation devices for first tarsometatarsal joint fusion-a comparative study with synthetic bones.

BACKGROUND: Hallux valgus disease is a common deformity of the forefoot. There are currently more than 100 surgical approaches for operative treatment. Because hypermobility of the first tarsometatarsal joint is considered to be causal for hallux valgus disease, fusion of the tarsometatarsal joint is an upcoming surgical procedure. Despite the development of new and increasingly stable fixation devices like different locking plates, malunion rates have been reported in 5 to 15% of cases. METHODS: Biomechanical comparison of three commonly used fixation devices (a dorsal locking plate, a plantar locking plate, and an intramedullary fixation device) was performed by weight-bearing simulation tests on synthetic bones. Initial compression force and stiffness during simulation of postoperative weight-bearing were analysed. RESULTS: Fixation of the first tarsometatarsal joint with the plantar plate combination demonstrated a higher stiffness compared to fixation with the intramedullary implant or the medial locking plate. The intramedullary device provided the highest initial compression force. Failure was detected in the following ranking: (1) the angle-stable intramedullary fixation device, (2) the medial located plate, and (3) the plantar locking plate. CONCLUSION: The intramedullary device demonstrated the highest initial compression force of the three tested implants. The plantar locking plate showed the best overall stability during weight-bearing simulation. Further clinical research is necessary to analyse if the intramedullary fixation device needs a longer period of non-weight-bearing to reach a better non-union rate compared to the plantar locking plate.

Chronic Alcohol Consumption Inhibits Autophagy and Promotes Apoptosis in the Liver.

Background: Chronic alcohol consumption is a major cause of liver injury. However, the molecular mechanisms by which alcohol impairs hepatocellular function and induces cell death remain unclear. Macroautophagy (hereafter called 'autophagy') is a degradation pathway involved in the survival or death of cells during conditions of cellular stress. This study examines the effect of chronic alcohol consumption on hepatocellular autophagy in an animal model. Methods: During a 12-week period male Wistar rats were fed a Lieber-DeCarli diet containing 5% alcohol (EtOH group; n=10), or an isocaloric diet (control group; n=10). Hepatic expression of key regulatory autophagy proteins (e.g. Beclin-1, ATG-3, ATG-5, p62/SQSTM1 and LC3) were detected by real-time polymerase chain reaction and Western blot analysis. Markers of cellular stress and apoptotic cell death (e.g. HO-1, caspase-3, PARP-1 and Bcl-2) were determined, and levels of reduced and oxidized glutathione were measured. Results: Chronic alcohol consumption caused cellular and oxidative stress in the liver. Transcriptional and translational expression of Beclin-1 and ATG-5 was significantly impaired. The protein expression of LC3-I and LC3-II was significantly increased, while the ratio of LC3I/II remained unchanged in the EtOH group compared with controls. Hepatocellular expression of p62/SQSTM1 and markers of apoptotic cell death (such as cleaved caspase-3 and cleaved PARP-1) were significantly increased in the EtOH group indicating a disrupted autophagic flux and increased rate of apoptosis in the liver. Conclusions: In this model, chronic alcohol consumption impaired hepatocellular autophagy and induced apoptotic cell death. It appears that changes in autophagy might contribute to alcohol-induced structural and functional hepatocellular injury.

Angiotensin II type 2 receptor agonist Compound 21 attenuates pulmonary inflammation in a model of acute lung injury.

PURPOSE: Although the role of the angiotensin II type 2 (AT2) receptor in acute lung injury is not yet completely understood, a protective role of this receptor subtype has been suggested. We hypothesized that, in a rodent model of acute lung injury, stimulation of the AT2 receptor with the direct agonist Compound 21 (C21) might have a beneficial effect on pulmonary inflammation and might improve pulmonary gas exchange. MATERIALS AND METHODS: Male adult rats were divided into a treatment group that received pulmonary lavage followed by mechanical ventilation (LAV, n=9), a group receiving pulmonary lavage, mechanical ventilation, and direct stimulation of the AT2 receptor with C21 (LAV+C21, n=9), and a control group that received mechanical ventilation only (control, n=9). Arterial blood gas analysis was performed every 30 min throughout the 240-min observation period. Lung tissue and plasma samples were obtained at 240 min after the start of mechanical ventilation. Protein content and surface activity of bronchoalveolar lavage fluid were assessed and the wet/dry-weight ratio of lungs was determined. Transcriptional and translational regulation of pro- and antiinflammatory cytokines IL-1ß, tumor necrosis factor-alpha, IL-6, IL-10, and IL-4 was determined in lungs and in plasma. RESULTS: Pulmonary lavage led to a significant impairment of gas exchange, the formation of lung edema, and the induction of pulmonary inflammation. Protein content of lavage fluid was increased and contained washed-out surfactant. Direct AT2 receptor stimulation with C21 led to a significant inhibition of tumor necrosis factor-alpha and IL-6 expressions in the lungs, whereas the expressions of IL-1, IL-10, and IL-4 remained unchanged. During the 240-min observation period, AT2 receptor stimulation did not improve pulmonary gas exchange or lung edema. CONCLUSION: In this rodent model of acute lung injury after repeated pulmonary lavage, AT2 receptor stimulation attenuates pulmonary inflammation but does not improve gas exchange.

Intramedullary nailing in opening wedge high tibial osteotomy-in vitro test for validation of a method of fixation.

PURPOSE: Opening wedge high tibial osteotomy (HTO) as a treatment in unicompartimental osteoarthritis of the knee can significantly relieve pain and prevent or at least delay an early joint replacement. The fixation of the osteotomy has undergone development and refinements during the last years. The angle-stable plate fixator is currently one of the most commonly used plates in HTOs. The angular stable fixation between screws and the plate offers a high primary stability to retain the correction with early weight-bearing protocols. This surgical technique is performed as a standard of care and generally well tolerated by the patients. Nevertheless, some studies observed that many patients complained about discomfort related to the implant. METHODS: Therefore, the stability of two different intramedullary nails, a short implant used in humeral fractures and a long device used in tibial fractures for stabilization in valgus HTOs, was investigated as an alternative fixation technique. The plate fixator was defined as reference standard. Nine synthetic tibia models were standardly osteotomized and stabilized by one of the fixation devices. Axial compression was realized using a special testing machine and two protocols were performed: a multi-step fatigue test and a load-to-failure test. RESULTS: Overall motion, medial, and lateral displacements were documented. Fractures always occurred at the lateral cortex. Axial cyclic loading up to 800 N was tolerated by all implants without failure. The tibia nail provided highest fatigue strength under the load-to-failure conditions. CONCLUSIONS: The results suggest that intramedullary nailing might be used as an alternative concept in HTO.

Bone preserving level of osteotomy in short-stem total hip arthroplasty does not influence stress shielding dimensions - a comparing finite elements analysis.

BACKGROUND: The main objective of every new development in total hip arthroplasty (THA) is the longest possible survival of the implant. Periprosthetic stress shielding is a scientifically proven phenomenon which leads to inadvertent bone loss. So far, many studies have analysed whether implanting different hip stem prostheses result in significant preservation of bone stock. The aim of this preclinical study was to investigate design-depended differences of the stress shielding effect after implantation of a selection of short-stem THA-prostheses that are currently available. METHODS: Based on computerised tomography (CT), a finite elements (FE) model was generated and a virtual THA was performed with different stem designs of the implant. Stems were chosen by osteotomy level at the femoral neck (collum, partial collum, trochanter sparing, trochanter harming). Analyses were performed with previously validated FE models to identify changes in the strain energy density (SED). RESULTS: In the trochanteric region, only the collum-type stem demonstrated a biomechanical behaviour similar to the native femur. In contrast, no difference in biomechanical behaviour was found between partial collum, trochanter harming and trochanter sparing models. All of the short stem-prostheses showed lower stress-shielding than a standard stem. CONCLUSION: Based on the results of this study, we cannot confirm that the design of current short stem THA-implants leads to a different stress shielding effect with regard to the level of osteotomy. Somehow unexpected, we found a bone stock protection in metadiaphyseal bone by simulating a more distal approach for osteotomy. Further clinical and biomechanical research including long-term results is needed to understand the influence of short-stem THA on bone remodelling and to find the optimal stem-design for a reduction of the stress shielding effect.

Characterization of inflammation in a rat model of acute lung injury after repeated pulmonary lavage.

AIM OF THE STUDY: Repeated pulmonary lavage allows to reliably reproduce failure of gas exchange and major histological findings of acute lung injury (ALI). However, because the capacity of pulmonary lavage to induce pulmonary inflammation is not well established in rodents, this study aims to characterize the induction of pulmonary inflammation in a rat model of ALI. MATERIALS AND METHODS: Male adult rats were divided into a treatment group (n = 9) that received pulmonary lavage with consecutive mechanical ventilation, and a control group that received mechanical ventilation only (n = 9). Arterial blood gas analyses were performed every 30 min throughout the study. Pressure-volume curves, and lung tissue and plasma samples, were obtained at 240 min after the start of mechanical ventilation. Protein content and surface activity of bronchoalveolar lavage fluid was assessed. Transcriptional and translational regulation of pro- and anti-inflammatory cytokines IL-1ß, TNF-α, IL-6, and IL-10 was determined in lungs and plasma. Markers of cellular stress were measured in lung tissue. RESULTS: Pulmonary lavage significantly decreased lung compliance, induced hypoxia and hypercapnia, and mediated respiratory acidosis. Protein content of lavage fluid was significantly increased and contained washed out surfactant. Expression of IL-1ß, TNF-α, and IL-6 mRNA and protein expression of IL-1ß and TNF-α was significantly induced in lavaged lungs, without spillover into the systemic circulation. Markers of cellular stress were significantly upregulated in lavaged lungs. CONCLUSIONS: This model of ALI applied in rats can induce pulmonary inflammation. The model might be used to develop therapeutic strategies that target pulmonary inflammation in ALI.

Stimulation of the Angiotensin II AT2 Receptor is Anti-inflammatory in Human Lipopolysaccharide-Activated Monocytic Cells.

Recently, AT2 receptors have been discovered on the surface of human immunocompetent cells such as monocytes. Data on regulative properties of this receptor on the cellular immune response are poor. We hypothesized that direct stimulation of the AT2 receptor mediates anti-inflammatory responses in these cells. Human monocytic THP-1 and U937 cells were stimulated with lipopolysaccharide (LPS) and the selective AT2 receptor agonist Compound 21 (C21). Expression of pro- and anti-inflammatory cytokines IL-6, IL-10, tumor necrosis factor-α (TNFα), and IL-1ß were analyzed on both the transcriptional and the translational level over course of time. Treatment with C21 attenuated the expression of TNFα, IL-6, and IL-10 after LPS challenge in both cell lines in a time- and dose-dependent manner. We conclude that selective AT2 receptor stimulation acts anti-inflammatory in human monocytes. Modulation of cytokine response by AT2 receptor activation might be a beneficial and novel treatment concept in inflammatory conditions.