Protective and risk factors in amateur equestrians and description of injury patterns: A retrospective data analysis and a case - control survey

Background In Switzerland there are about 150,000 equestrians. Horse related injuries, including head and spinal injuries, are frequently treated at our level I trauma centre. Objectives To analyse injury patterns, protective factors, and risk factors related to horse riding, and to define groups of safer riders and those at greater risk Methods We present a retrospective and a case-control survey at conducted a tertiary trauma centre in Bern, Switzerland. Injured equestrians from July 2000 - June 2006 were retrospectively classified by injury pattern and neurological symptoms. Injured equestrians from July-December 2008 were prospectively collected using a questionnaire with 17 variables. The same questionnaire was applied in non-injured controls. Multiple logistic regression was performed, and combined risk factors were calculated using inference trees. Results Retrospective survey A total of 528 injuries occured in 365 patients. The injury pattern revealed as follows: extremities (32%: upper 17%, lower 15%), head (24%), spine (14%), thorax (9%), face (9%), pelvis (7%) and abdomen (2%). Two injuries were fatal. One case resulted in quadriplegia, one in paraplegia. Case-control survey 61 patients and 102 controls (patients: 72% female, 28% male; controls: 63% female, 37% male) were included. Falls were most frequent (65%), followed by horse kicks (19%) and horse bites (2%). Variables statistically significant for the controls were: Older age (p = 0.015), male gender (p = 0.04) and holding a diploma in horse riding (p = 0.004). Inference trees revealed typical groups less and more likely to suffer injury. Conclusions Experience with riding and having passed a diploma in horse riding seem to be protective factors. Educational levels and injury risk should be graded within an educational level-injury risk index.

Occurrence of systemic hypertension in dogs with acute kidney injury and treatment with amlodipine besylate

OBJECTIVES: To describe the occurrence of systemic hypertension in dogs with acute kidney injury and the efficacy of amlodipine besylate for its treatment. METHODS: This retrospective study included 52 dogs with acute kidney injury (2007 to 2008) grouped based on the use of amlodipine in their treatment. Systemic blood pressure was measured with an oscillometric device at admission, before, during, and after amlodipine therapy. RESULTS: Occurrence of systolic systemic hypertension (>/=160 mmHg) and severe systolic systemic hypertension (>/=180 mmHg) was 37% and 15% at admission and increased with hospitalisation to 81% and 62%, respectively. Twenty-two dogs were treated with amlodipine, at a median daily dosage of 0.38 mg/kg (interquartile range 0.28 to 0.49) divided in one to two applications per day. Amlodipine therapy was associated with a decrease in systolic systemic blood pressure of 24 mmHg (12 to 34) and a correction of severe systemic hypertension in 10 of 11 dogs within 24 hours. Overall, 73% of the dogs survived with a significantly lower proportion of survivors in treated compared to non-treated dogs (59% versus 83%, respectively, P=0.05). CLINICAL SIGNIFICANCE: Results of this study reveal that systemic hypertension is common in canine acute kidney injury and that treatment with amlodipine is beneficial in reducing systemic hypertension. The potential effect of amlodipine on global outcome requires prospective assessment.

A 13-year analysis from Switzerland of non-fatal sledging (sledding or tobogganing) injuries

INTRODUCTION: Winter sports have evolved from an upper class activity to a mass industry. Especially sledging regained popularity at the start of this century, with more and more winter sports resorts offering sledge runs. This study investigated the rates of sledging injuries over the last 13 years and analysed injury patterns specific for certain age groups, enabling us to make suggestions for preventive measures. METHODS: We present a retrospective analysis of prospectively collected data. From 1996/1997 to 2008/2009, all patients involved in sledging injuries were recorded upon admission to a Level III trauma centre. Injuries were classified into body regions according to the Abbreviated Injury Scale (AIS). The Injury Severity Score (ISS) was calculated. Patients were stratified into 7 age groups. Associations between age and injured body region were tested using the chi-squared test. The slope of the linear regression with 95% confidence intervals was calculated for the proportion of patients with different injured body regions and winter season. RESULTS: 4956 winter sports patients were recorded. 263 patients (5%) sustained sledging injuries. Sledging injury patients had a median age of 22 years (interquartile range [IQR] 14-38 years) and a median ISS of 4 (IQR 1-4). 136 (51.7%) were male. Injuries (AIS≥2) were most frequent to the lower extremities (n=91, 51.7% of all AIS≥2 injuries), followed by the upper extremities (n=48, 27.3%), the head (n=17, 9.7%), the spine (n=7, 4.0%). AIS≥2 injuries to different body regions varied from season to season, with no significant trends (p>0.19). However, the number of patients admitted with AIS≥2 injuries increased significantly over the seasons analysed (p=0.031), as did the number of patients with any kind of sledging injury (p=0.004). Mild head injuries were most frequent in the youngest age group (1-10 years old). Injuries to the lower extremities were more often seen in the age groups from 21 to 60 years (p<0.001). CONCLUSION: Mild head trauma was mainly found in very young sledgers, and injuries to the lower extremities were more frequent in adults. In accordance with the current literature, we suggest that sledging should be performed in designated, obstacle-free areas that are specially prepared, and that children should always be supervised by adults. The effect of routine use of helmets and other protective devices needs further evaluation, but it seems evident that these should be obligatory on official runs.

Neuronal expression of the ubiquitin ligase Nedd4-2 in rat dorsal root ganglia: modulation in the spared nerve injury model of neuropathic pain

Neuronal hyperexcitability following peripheral nerve lesions may stem from altered activity of voltage-gated sodium channels (VGSCs), which gives rise to allodynia or hyperalgesia. In vitro, the ubiquitin ligase Nedd4-2 is a negative regulator of VGSC α-subunits (Na(v)), in particular Na(v)1.7, a key actor in nociceptor excitability. We therefore studied Nedd4-2 in rat nociceptors, its co-expression with Na(v)1.7 and Na(v)1.8, and its regulation in pathology. Adult rats were submitted to the spared nerve injury (SNI) model of neuropathic pain or injected with complete Freund's adjuvant (CFA), a model of inflammatory pain. L4 dorsal root ganglia (DRG) were analyzed in sham-operated animals, seven days after SNI and 48 h after CFA with immunofluorescence and Western blot. We observed Nedd4-2 expression in almost 50% of DRG neurons, mostly small and medium-sized. A preponderant localization is found in the non-peptidergic sub-population. Additionally, 55.7 ± 2.7% and 55.0 ± 3.6% of Nedd4-2-positive cells are co-labeled with Na(v)1.7 and Na(v)1.8 respectively. SNI significantly decreases the proportion of Nedd4-2-positive neurons from 45.9 ± 1.9% to 33.5 ± 0.7% (p<0.01) and the total Nedd4-2 protein to 44% ± 0.13% of its basal level (p<0.01, n=4 animals in each group, mean ± SEM). In contrast, no change in Nedd4-2 was found after peripheral inflammation induced by CFA. These results indicate that Nedd4-2 is present in nociceptive neurons, is downregulated after peripheral nerve injury, and might therefore contribute to the dysregulation of Na(v)s involved in the hyperexcitability associated with peripheral nerve injuries.

Non-coding keratin variants associate with liver fibrosis progression in patients with hemochromatosis

Background Keratins 8 and 18 (K8/K18) are intermediate filament proteins that protect the liver from various forms of injury. Exonic K8/K18 variants associate with adverse outcome in acute liver failure and with liver fibrosis progression in patients with chronic hepatitis C infection or primary biliary cirrhosis. Given the association of K8/K18 variants with end-stage liver disease and progression in several chronic liver disorders, we studied the importance of keratin variants in patients with hemochromatosis. Methods The entire K8/K18 exonic regions were analyzed in 162 hemochromatosis patients carrying homozygous C282Y HFE (hemochromatosis gene) mutations. 234 liver-healthy subjects were used as controls. Exonic regions were PCR-amplified and analyzed using denaturing high-performance liquid chromatography and DNA sequencing. Previously-generated transgenic mice overexpressing K8 G62C were studied for their susceptibility to iron overload. Susceptibility to iron toxicity of primary hepatocytes that express K8 wild-type and G62C was also assessed. Results We identified amino-acid-altering keratin heterozygous variants in 10 of 162 hemochromatosis patients (6.2%) and non-coding heterozygous variants in 6 additional patients (3.7%). Two novel K8 variants (Q169E/R275W) were found. K8 R341H was the most common amino-acid altering variant (4 patients), and exclusively associated with an intronic KRT8 IVS7+10delC deletion. Intronic, but not amino-acid-altering variants associated with the development of liver fibrosis. In mice, or ex vivo, the K8 G62C variant did not affect iron-accumulation in response to iron-rich diet or the extent of iron-induced hepatocellular injury. Conclusion In patients with hemochromatosis, intronic but not exonic K8/K18 variants associate with liver fibrosis development.

Immediate and delayed transplantation of mesenchymal stem cells improve muscle force after skeletal muscle injury in rats

Mesenchymal stem cell (MSC) therapy is a promising approach for regaining muscle function after trauma. Prior to clinical application, the ideal time of transplantation has to be determined. We investigated the effects of immediate and delayed transplantation. Sprague-Dawley rats received a crush trauma to the left soleus muscle. Treatment groups were transplanted locally with 2 × 10(6) autologous MSCs, either immediately or 7 days after trauma. Saline was used as sham therapy. Contraction force tests and histological analyses were performed 4 weeks after injury. GFP-labelled MSCs were followed after transplantation. The traumatized soleus muscles of the sham group displayed a reduction of twitch forces to 36 ± 17% and of tetanic forces to 29 ± 11% of the non-injured right control side, respectively. Delayed MSC transplantation resulted in a significant improvement of contraction maxima in both stimulation modes (twitch, p = 0.011; tetany, p = 0.014). Immediate transplantation showed a significant increase in twitch forces to 59 ± 17% (p = 0.043). There was no significant difference in contraction forces between muscles treated by immediate and delayed cell transplantation. We were able to identify MSCs in the interstitium of the injured muscles up to 4 weeks after transplantation. Despite the fundamental differences of the local environment, which MSCs encounter after transplantation, similar results could be obtained with respect to functional muscle regeneration. We believe that transplanted MSCs residing in the interstitial compartment evolve their regenerative capabilities through paracrine pathways. Our data suggest a large time window of the therapeutical measures.

Attenuation of myocardial reperfusion injury in pigs by Mirococept, a membrane-targeted complement inhibitor derived from human CR1

OBJECTIVES: Membrane-targeted application of complement inhibitors may ameliorate ischemia/reperfusion (I/R) injury by directly targeting damaged cells. We investigated whether Mirococept, a membrane-targeted, myristoylated peptidyl construct derived from complement receptor 1 (CR1) could attenuate I/R injury following acute myocardial infarction in pigs. METHODS: In a closed-chest pig model of acute myocardial infarction, Mirococept, the non-tailed derivative APT154, or vehicle was administered intracoronarily into the area at risk 5 min pre-reperfusion. Infarct size, cardiac function and inflammatory status were evaluated. RESULTS: Mirococept targeted damaged vasculature and myocardium, significantly decreasing infarct size compared to vehicle, whereas APT154 had no effect. Cardioprotection correlated with reduced serum troponin I and was paralleled by attenuated local myocardial complement deposition and tissue factor expression. Myocardial apoptosis (TUNEL-positivity) was also reduced with the use of Mirococept. Local modulation of the pro-inflammatory and pro-coagulant phenotype translated to improved left ventricular end-diastolic pressure, ejection fraction and regional wall motion post-reperfusion. CONCLUSIONS: Local modification of a pro-inflammatory and pro-coagulant environment after regional I/R injury by site-specific application of a membrane-targeted complement regulatory protein may offer novel possibilities and insights into potential treatment strategies of reperfusion-induced injury.

Course of psychological variables in whiplash injury--a 2-year follow-up with age, gender and education pair-matched patients

This study evaluated the course of psychological variables during a 2-year follow-up in patients after common whiplash of the cervical spine. From a sample of 117 non-selected patients with common whiplash (investigated on average 7.2 +/- 4.2 days after trauma) a total of 21 suffered trauma-related symptoms over 2 years following initial injury. These patients (symptomatic group) were compared with 21 age, gender and education pair-matched patients, who showed complete recovery from trauma-related symptoms during the 2-year follow-up (asymptomatic group). Both groups underwent standardised testing procedures (i.e., Freiburg Personality Inventory and Well-Being Scale) at referral, and at 3, 6 and 24 months. In the symptomatic group during follow-up no significant changes in rating of neck pain or headache were found. Significant differences between the groups and significant deviation of scores over time were found on the Well-Being and Nervousness Scales. There was a lack of significant difference between the groups on the Depression Scale, indicating a possible somatic basis for changes in psychological functioning in the investigated sample. With regard to scales of Extraversion or Neuroticism, there were neither significant differences between the groups nor significant deviation over time. These results highlight that patients' psychological problems are rather a consequence than a cause of somatic symptoms in whiplash.

The role of purinergic signaling in the liver and in transplantation: effects of extracellular nucleotides on hepatic graft vascular injury, rejection and metabolism

Extracellular nucleotides (e.g. ATP, UTP, ADP) are released by activated endothelium, leukocytes and platelets within the injured vasculature and bind specific cell-surface type-2 purinergic (P2) receptors. This process drives vascular inflammation and thrombosis within grafted organs. Importantly, there are also vascular ectonucleotidases i.e. ectoenzymes that hydrolyze extracellular nucleotides in the blood to generate nucleosides (viz. adenosine). Endothelial cell NTPDase1/CD39 has been shown to critically modulate levels of circulating nucleotides. This process tends to limit the activation of platelet and leukocyte expressed P2 receptors and also generates adenosine to reverse inflammatory events. This vascular protective CD39 activity is rapidly inhibited by oxidative reactions, such as is observed with liver ischemia reperfusion injury. In this review, we chiefly address the impact of these signaling cascades following liver transplantation. Interestingly, the hepatic vasculature, hepatocytes and all non-parenchymal cell types express several components co-ordinating the purinergic signaling response. With hepatic and vascular dysfunction, we note heightened P2- expression and alterations in ectonucleotidase expression and function that may predispose to progression of disease. In addition to documented impacts upon the vasculature during engraftment, extracellular nucleotides also have direct influences upon liver function and bile flow (both under physiological and pathological states). We have recently shown that alterations in purinergic signaling mediated by altered CD39 expression have major impacts upon hepatic metabolism, repair mechanisms, regeneration and associated immune responses. Future clinical applications in transplantation might involve new therapeutic modalities using soluble recombinant forms of CD39, altering expression of this ectonucleotidase by drugs and/or using small molecules to inhibit deleterious P2-mediated signaling while augmenting beneficial adenosine-mediated effects within the transplanted liver.

ENHANCING COMMUNICATION THROUGH SUCCESSFUL REPAIR: EXAMINING FLUENCY AND MECHANISMS FOR SYNTACTIC PROGRESS IN APHASIC AND NON-APHASIC SPEECH

The fields of Rhetoric and Communication usually assume a competent speaker who is able to speak well with conscious intent; however, what happens when intent and comprehension are intact but communicative facilities are impaired (e.g., by stroke or traumatic brain injury)? What might a focus on communicative success be able to tell us in those instances? This project considers this question in examining communication disorders through identifying and analyzing patterns of (dis) fluent speech between 10 aphasic and 10 non-aphasic adults. The analysis in this report is centered on a collection of data provided by the Aphasia Bank database. The database’s collection protocol guides aphasic and non-aphasic participants through a series of language assessments, and for my re-analysis of the database’s transcripts I consider communicative success is and how it is demonstrated during a re-telling of the Cinderella narrative. I conducted a thorough examination of a set of participant transcripts to understand the contexts in which speech errors occur, and how (dis) fluencies may follow from aphasic and non-aphasic participant’s speech patterns. An inductive mixed-methods approach, informed by grounded theory, qualitative, and linguistic analyses of the transcripts functioned as a means to balance the classification of data, providing a foundation for all sampling decisions. A close examination of the transcripts and the codes of the Aphasia Bank database suggest that while the coding is abundant and detailed, that further levels of coding and analysis may be needed to reveal underlying similarities and differences in aphasic vs. non-aphasic linguistic behavior. Through four successive levels of increasingly detailed analysis, I found that patterns of repair by aphasics and non-aphasics differed primarily in degree rather than kind. This finding may have therapeutic impact, in reassuring aphasics that they are on the right track to achieving communicative fluency.

Non-robotic thoracoscopic internal mammary artery preparation in the pig. A training model

Notwithstanding non-robotic, thoracoscopic preparation of the internal mammary artery (IMA) is a difficult surgical task, an appropriate experimental training model is lacking. We evaluated the young domestic pig for this purpose. Four domestic female pigs (30-40 kg body weight) were used for this study. Bilateral thoracoscopic preparation of the IMA was carried out under continuous, pressure controlled CO(2) insufflation. A 30 degrees rigid thoracoscope was inserted through a 10-mm port in the 5th/6th intercostal space (ICS) dorsally to the posterior axillary line. The dissection instrument (Ultracision Harmonic Scalpel) was inserted (5-mm port) in the 7th ICS at the posterior axillary line and the endo-forceps (5-mm port) in the 5th ICS at the posterior axillary line. Thoracoscopic IMA preparation in pig resulted more difficult than in man. A total of seven IMAs were prepared in their full intrathoracic length. A change in the preparation technique (lateral detachment of the endothoracic muscle) improved the safety of the procedure, allowing all four respective IMAs to be prepared safely, while the initial technique ensued an injury for 2 out of 3 vessels. The described young domestic pig model is suitable for experimental training of bilateral thoracoscopic IMA preparation.

Comparison of two non-bronchoscopic methods for evaluating inflammation in patients with acute hypoxaemic respiratory failure

INTRODUCTION: The simple bedside method for sampling undiluted distal pulmonary edema fluid through a normal suction catheter (s-Cath) has been experimentally and clinically validated. However, there are no data comparing non-bronchoscopic bronchoalveolar lavage (mini-BAL) and s-Cath for assessing lung inflammation in acute hypoxaemic respiratory failure. We designed a prospective study in two groups of patients, those with acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) and those with acute cardiogenic lung edema (ACLE), designed to investigate the clinical feasibility of these techniques and to evaluate inflammation in both groups using undiluted sampling obtained by s-Cath. To test the interchangeability of the two methods in the same patient for studying the inflammation response, we further compared mini-BAL and s-Cath for agreement of protein concentration and percentage of polymorphonuclear cells (PMNs). METHODS: Mini-BAL and s-Cath sampling was assessed in 30 mechanically ventilated patients, 21 with ALI/ARDS and 9 with ACLE. To analyse agreement between the two sampling techniques, we considered only simultaneously collected mini-BAL and s-Cath paired samples. The protein concentration and polymorphonuclear cell (PMN) count comparisons were performed using undiluted sampling. Bland-Altman plots were used for assessing the mean bias and the limits of agreement between the two sampling techniques; comparison between groups was performed by using the non-parametric Mann-Whitney-U test; continuous variables were compared by using the Student t-test, Wilcoxon signed rank test, analysis of variance or Student-Newman-Keuls test; and categorical variables were compared by using chi-square analysis or Fisher exact test. RESULTS: Using protein content and PMN percentage as parameters, we identified substantial variations between the two sampling techniques. When the protein concentration in the lung was high, the s-Cath was a more sensitive method; by contrast, as inflammation increased, both methods provided similar estimates of neutrophil percentages in the lung. The patients with ACLE showed an increased PMN count, suggesting that hydrostatic lung edema can be associated with a concomitant inflammatory process. CONCLUSIONS: There are significant differences between the s-Cath and mini-BAL sampling techniques, indicating that these procedures cannot be used interchangeably for studying the lung inflammatory response in patients with acute hypoxaemic lung injury.

Free abdominal fluid without obvious solid organ injury upon CT imaging: an actual problem or simply over-diagnosing?

Whereas a non-operative approach for hemodynamically stable patients with free intraabdominal fluid in the presence of solid organ injury is generally accepted, the presence of free fluid in the abdomen without evidence of solid organ injury not only presents a challenge for the treating emergency physician but also for the surgeon in charge. Despite recent advances in imaging modalities, with multi-detector computed tomography (CT) (with or without contrast agent) usually the imaging method of choice, diagnosis and interpretation of the results remains difficult. While some studies conclude that CT is highly accurate and relatively specific at diagnosing mesenteric and hollow viscus injury, others studies deem CT to be unreliable. These differences may in part be due to the experience and the interpretation of the radiologist and/or the treating physician or surgeon.A search of the literature has made it apparent that there is no straightforward answer to the question what to do with patients with free intraabdominal fluid on CT scanning but without signs of solid organ injury. In hemodynamically unstable patients, free intraabdominal fluid in the absence of solid organ injury usually mandates immediate surgical intervention. For patients with blunt abdominal trauma and more than just a trace of free intraabdominal fluid or for patients with signs of peritonitis, the threshold for a surgical exploration - preferably by a laparoscopic approach - should be low. Based on the available information, we aim to provide the reader with an overview of the current literature with specific emphasis on diagnostic and therapeutic approaches to this problem and suggest a possible algorithm, which might help with the adequate treatment of such patients.

Non-selective cutaneous sensory neurectomy as an alternative treatment for auto-mutilation lesion following arthrodesis in three dogs

OBJECTIVE: To describe an alternative method for the treatment of non-responsive self-mutilation injuries in three dogs after carpal/tarsal arthrodesis. STUDY DESIGN: Case series ANIMALS: Two dogs with carpal injury and one dog with tarsal injury treated by arthrodesis METHODS: All dogs developed self-mutilation injuries due to licking and/or chewing of the toes within 21-52 days of surgery. Clinical signs did not resolve within one week after conservative treatment with wound debridement and protective bandages. Following general anaesthesia, a deep horseshoe-shaped skin incision, including the subdermal tissue, was performed proximal to the self-mutilation injury transecting the sensory cutaneous afferent nerves. The skin incision was closed with simple interrupted sutures. RESULTS: All wounds healed without complication. Self-mutilation resolved completely within 24 hours after surgery in all dogs. No recurrence was observed (5 months to 3 years). CONCLUSION: Non-selective cutaneous sensory neurectomy may lead to resolution of self-mutilation following arthrodesis in dogs. CLINICAL RELEVANCE: Failure of conservative treatment in self-mutilation injuries often leads to toe or limb amputation as a last resort. The technique described in this case series is a simple procedure that should be considered prior to amputation. The outcome of this procedure in dogs self-multilating due to neurological or behavioral disturbances unrelated to carpal or tarsal arthrodesis is not known.

Inhibition of Fas-associated death domain-containing protein (FADD) protects against myocardial ischemia/reperfusion injury in a heart failure mouse model

AIM As technological interventions treating acute myocardial infarction (MI) improve, post-ischemic heart failure increasingly threatens patient health. The aim of the current study was to test whether FADD could be a potential target of gene therapy in the treatment of heart failure. METHODS Cardiomyocyte-specific FADD knockout mice along with non-transgenic littermates (NLC) were subjected to 30 minutes myocardial ischemia followed by 7 days of reperfusion or 6 weeks of permanent myocardial ischemia via the ligation of left main descending coronary artery. Cardiac function were evaluated by echocardiography and left ventricular (LV) catheterization and cardiomyocyte death was measured by Evans blue-TTC staining, TUNEL staining, and caspase-3, -8, and -9 activities. In vitro, H9C2 cells transfected with ether scramble siRNA or FADD siRNA were stressed with chelerythrin for 30 min and cleaved caspase-3 was assessed. RESULTS FADD expression was significantly decreased in FADD knockout mice compared to NLC. Ischemia/reperfusion (I/R) upregulated FADD expression in NLC mice, but not in FADD knockout mice at the early time. FADD deletion significantly attenuated I/R-induced cardiac dysfunction, decreased myocardial necrosis, and inhibited cardiomyocyte apoptosis. Furthermore, in 6 weeks long term permanent ischemia model, FADD deletion significantly reduced the infarct size (from 41.20 ± 3.90% in NLC to 26.83 ± 4.17% in FADD deletion), attenuated myocardial remodeling, improved cardiac function and improved survival. In vitro, FADD knockdown significantly reduced chelerythrin-induced the level of cleaved caspase-3. CONCLUSION Taken together, our results suggest FADD plays a critical role in post-ischemic heart failure. Inhibition of FADD retards heart failure progression. Our data supports the further investigation of FADD as a potential target for genetic manipulation in the treatment of heart failure.