Molecular and biophysical mechanisms behind the enhancement of lung surfactant function during controlled therapeutic hypothermia.

Therapeutic hypothermia (TH) enhances pulmonary surfactant performance in vivo by molecular mechanisms still unknown. Here, the interfacial structure and the composition of lung surfactant films have been analysed in vitro under TH as well as the molecular basis of its improved performance both under physiological and inhibitory conditions. The biophysical activity of a purified porcine surfactant was tested under slow and breathing-like dynamics by constrained drop surfactometry (CDS) and in the captive bubble surfactometer (CBS) at both 33 and 37 °C. Additionally, the temperature-dependent surfactant activity was also analysed upon inhibition by plasma and subsequent restoration by further surfactant supplementation. Interfacial performance was correlated with lateral structure and lipid composition of films made of native surfactant. Lipid/protein mixtures designed as models to mimic different surfactant contexts were also studied. The capability of surfactant to drastically reduce surface tension was enhanced at 33 °C. Larger DPPC-enriched domains and lower percentages of less active lipids were detected in surfactant films exposed to TH-like conditions. Surfactant resistance to plasma inhibition was boosted and restoration therapies were more effective at 33 °C. This may explain the improved respiratory outcomes observed in cooled patients with acute respiratory distress syndrome and opens new opportunities in the treatment of acute lung injury.

Voluntary femoro-tibial subluxations: a benign differential diagnosis in the snapping knee of a child.

PURPOSE: Voluntary femoro-tibial subluxation is a rare entity predominantly found in pretoddlers. It presents as a dynamic phenomenon with uni- or bilateral audible snapping of the knee, often in a context of fatigue or irritation at the end of the day. The aim of the study was to observe the evolution and recovery in these patients. METHODS: Ten children were included. Other causes of dislocating joints and pathologies with snapping of the lateral meniscus were excluded from this study. Six-week immobilisation with a splint at 70° of knee flexion was primarily recommended to all patients. RESULTS: The mean age at onset of symptoms was 10 months. Forty percent of the patients presented with bilateral symptoms. Clinically, four patients were hyperlax. In all patients, subluxations could be reproduced passively by rotating the foot externally and advancing the internal tibial plateau anteriorly. Three of the patients were treated with a dorsal splint and experienced significantly less or cessation of symptoms. Two patients underwent surgery, one for a concomitant anterior cruciate ligament (ACL) rupture and meniscus tear that worsened the symptoms, another for concomitant patella dislocation and a meniscus tear. One patient's parents refused treatment and four patients experienced less symptoms at the time of consultation and were not immobilized. Except for the two patients undergoing surgeries, no sequelae were observed. In general, the symptoms got less frequent when the patient began to walk. CONCLUSION: Voluntary femoro-tibial subluxation in children is a rare and benign condition that often resolves spontaneously without sequelae. The risk of meniscus tear should, however, be considered if subluxations do not cease. LEVEL OF EVIDENCE: IV.

Current trends in tendinopathy: consensus of the ESSKA basic science committee. Part II: treatment options.

The treatment of painful chronic tendinopathy is challenging. Multiple non-invasive and tendon-invasive methods are used. When traditional non-invasive treatments fail, the injections of platelet-rich plasma autologous blood or cortisone have become increasingly favored. However, there is little scientific evidence from human studies supporting injection treatment. As the last resort, intra- or peritendinous open or endoscopic surgery are employed even though these also show varying results. This ESSKA basic science committee current concepts review follows the first part on the biology, biomechanics and anatomy of tendinopathies, to provide a comprehensive overview of the latest treatment options for tendinopathy as reported in the literature.

[Ramp lesions : Tips and tricks in diagnostics and therapy]. / Rampenläsionen : Tipps und Tricks in Diagnostik und Therapie.

There is an increasing biomechanical and anatomical understanding of the different types of meniscal lesions. Lesions of the posterior part of the medial meniscus in the meniscosynovial area have recently received increased attention. They generally occur in association with anterior cruciate ligament (ACL) injuries. They are often missed ("hidden lesions") due to the fact that they cannot be seen by routine anterior arthroscopic inspection. Furthermore, meniscosynovial lesions play a role in anteroposterior knee laxity and, as such, they may be a cause of failure of ACL reconstruction or of postoperative persistent laxity. Little information is available regarding their cause with respect to injury mechanism, natural history, biomechanical implications, healing potential and treatment options. This article presents an overview of the currently available knowledge of these ramp lesions, their possible pathomechanism, classification, biomechanical relevance as well as repair techniques.

Current trends in tendinopathy: consensus of the ESSKA basic science committee. Part I: biology, biomechanics, anatomy and an exercise-based approach.

Chronic tendinopathies represent a major problem in the clinical practice of sports orthopaedic surgeons, sports doctors and other health professionals involved in the treatment of athletes and patients that perform repetitive actions. The lack of consensus relative to the diagnostic tools and treatment modalities represents a management dilemma for these professionals. With this review, the purpose of the ESSKA Basic Science Committee is to establish guidelines for understanding, diagnosing and treating this complex pathology.

There is no such thing like a single ACL injury: Profiles of ACL-injured patients.

BACKGROUND: Current ACL registries rarely include non-operatively treated patients thus delivering an incomplete picture of the ACL-injured population. The aim of this study was to get an image of the population and treatment decision of an intrahospital registry. Our hypotheses were that patient-specific subtypes can be identified and that the percentage of operated patients differs between them. MATERIAL AND METHODS: Three hundred and forty-six operated and non-operated patients were included from March 2011 to December 2013. Standardized questionnaires allowed for data collection on gender, age, sports practice and previous ACL injuries. Chi-square tests allowed to compare these parameters between genders and age groups. A cluster analysis was computed to determine profiles of patients with similar characteristics. RESULTS: Three age groups were considered (I: ≤20; II: 21-35; III: ≥36 years). For males, the highest frequency of injuries was noted in group II with a greater proportion of injuries compared to females. In group III, more females were injured than males. Before injury, 54% patients were involved in competitive sports. Males were more likely to be injured in pivoting/contact sports before 35 and females during recreational skiing after 35. Twenty-one percent of the patients had had a previous ACL injury. The percentage of surgical treatment was superior to 80% in patients under 35 years involved in competitive sports, of 60-80% for those not involved in competitive sports and inferior to 60% for patients above 35 years. DISCUSSION: Systematic data collection allowed to identify specific subtypes of ACL-injured patient according to gender, age, previous ACL injury and preinjury level of practice. The decision-making process for or against ACL reconstructions at time of presentation depended on these characteristics. Consideration of these parameters will serve as a basis for an individualized treatment approach and a better understanding of patients at risk for ACL injuries. LEVEL OF EVIDENCE: III.

Combined anterior and rotational knee laxity measurements improve the diagnosis of anterior cruciate ligament injuries.

PURPOSE: This study analysed whether associating the side-to-side difference in displacement and the slope of the load-displacement curve of anterior and rotational knee laxity measurements would improve the instrumental diagnosis of anterior cruciate ligament (ACL) ruptures and help to detect different types of ACL tears. METHODS: Anterior and rotational knee laxity was measured in 128 patients with an arthroscopically confirmed ACL injury and 104 healthy controls. Side-to-side differences were determined for three variables in anterior laxity: anterior displacement at 200 N (ATD200), primary compliance from 30 to 50 N (PCA) and secondary compliance from 100 to 200 N (SCA). Furthermore, four variables in rotational laxity were considered: internal and external rotation at 5 N m (IR5/ER5) and compliance from 2 to 5 N m (C IR/C ER). Receiver operating characteristic curves allowed to determine thresholds, specificities and sensitivities to detect ACL lesions, based on single variables considered and combinations thereof. RESULTS: Sensitivity and specificity reached, respectively, 75 and 95 % for ATD200 (threshold: 1.2 mm) and 38 and 95 % for IR5 (threshold: 3.2°). If either two out of the three variables were positive for anterior laxity or both IR5 and C IR were positive, 81 % of patients were identified without a false positive. All patients for whom ATD200 was >3.7 mm, PCA > 48 µm/N or SCA > 17.5 µm/N had ACL remnants that were either totally resorbed or healed on the posterior cruciate ligament. CONCLUSION: Combined instrumented anterior and rotational knee laxity measurements have excellent diagnostic value for ACL injury, provided that several measurements be considered concomitantly. LEVEL OF EVIDENCE: Diagnostic study, Level III.

[Acquired and repeated factor VII deficiency during two infectious episodes: a case report]. / Déficit acquis et répété en facteur VII au cours d'épisodes infectieux : à propos d'un cas.

We described the management of a patient with acquired and severe FVII deficiency appeared during two infections outbreaks. This case report focused on both biological diagnosis and treatment of the F VII deficiency.

Fracture risk increases after diagnosis of breast or other cancers in postmenopausal women: results from the Women's Health Initiative.

SUMMARY: Risk for falls and fractures increases after breast cancer or other cancer diagnosis in postmenopausal women. Factors other than falls may be the major causes for the increased fracture risk. INTRODUCTION: Cancer treatment and prognosis may have detrimental effects on bone health. However, there is a lack of prospective investigations on fracture risk among incident cancer cases. METHODS: In this study, postmenopausal women (N = 146,959) from the Women's Health Initiative prospective cohort, who had no cancer history at baseline, were followed for up to 9 years and classified into no cancer, incident breast cancer (BC) and incident other cancer (OC) groups. The main outcomes measured were incident fractures and falls before and after cancer diagnosis. Hazards ratios (HR) and 95% confidence intervals (CI) were computed from Cox proportional hazards model. RESULTS: While hip fracture risk before a cancer diagnosis was similar between the no cancer and cancer groups, hip fracture risk was significantly higher after BC diagnosis (HR = 1.55, CI = 1.13-2.11) and the elevated risk was even more notable after OC diagnosis (HR = 2.09, CI = 1.65-2.65). Risk of falls also increased after BC (HR = 1.15, CI = 1.06-1.25) or OC diagnosis (HR = 1.27, CI = 1.18-1.36), but could not fully explain the elevated hip fracture risk. Incident clinical vertebral and total fractures were also significantly increased after OC diagnosis (p < 0.05). CONCLUSIONS: Postmenopausal women have significantly elevated risks for falls and fractures after a cancer diagnosis. The causes for this increased risk remained to be investigated.

[Perioperative anticoagulation management for prosthetic heart valves]. / Gestion en période périopératoire de l'anticoagulation des valves prothétiques cardiaques.

OBJECTIVES: The practices and the guidelines over the perioperative management of the anticoagulation of patients with cardiac valves prothesis are the object of no consensual attitude. The thrombotic risk over the time is well known. It depends of the type or the location on the valve, of their associations and the age of the patient. In the perioperative period, the antithrombotic treatment must be interrupted according to the surgical haemorrhagic risk. STUDY DESIGN: Short review. RESULTS: Only patients, without associated risk factor, carriers of bioprosthesis from more than 3 months, can be maintained only under antiplatelets agents. In others situations, the caution imposes a bridge of anticoagulants from 48 to 72 hours with unfractionated heparin (subcutaneous at home, intravenous at the hospital). Low molecular weight heparin has no commercial authorization in this indication. The resumption of the anticoagulation by unfractionated heparin in postoperative period must be the most premature possible after the decrease of the surgical bleeding. The relay by vitamin K antagonists has to be made over 48 to 72 hours. Within the framework of the urgency, the surgical haemorrhagic risk is weak for an INR <1.5. According to the urgency of the surgery, a treatment by vitamin K (if the delay is over 12 hours) or by prothrombinic complex allows to correct this INR. The identification of thrombotic complications requires a particular attention. In the postoperative period, as soon as there is suspicion of thrombosis, clinical manifestations must be consolidated by the practice of a transoesophageal echography, which only confirm the diagnosis.

[Monitoring of heparin therapy during extracorporeal bypass: what are the remaining questions?]. / Surveillance de l'anticoagulation des circulations extracorporelles par l'héparine non fractionnée: quels sont les problèmes non résolus?

Cardiac surgery with extracorporeal circulation induces major alterations of haemostasis and requires high level of anticoagulation, usually achieved by unfractionated heparin infusion. Optimization of anticoagulant regimen, through adapted biological monitoring, can probably improve postoperative course, at least for postoperative haemostatic status. Despite increasing knowledge on extracorporeal circulation-induced haemostatic abnormalities and the development of new biological devices for heparin monitoring, the optimal level of anticoagulation remains matter of debate, as well as the monitoring procedures. This critical review presents the current available data on heparin anticoagulation and monitoring in this specific context, and underlines the pending issues about anticoagulation management during extracorporeal bypass.

Immediate hypersensitivity to chlorhexidine: literature review.

Chlorhexidine, an antiseptic belonging to family of biguanides, is used extensively in the medical and surgical environment. Late onset hypersensitivity and eczema occur regularly and are well documented events. Conversely, immediate hypersensitivity, sometimes taking the form of acute urticaria that can result in anaphylactic shock, is rarer. These manifestations can occur during contact of the skin or mucosa with chlorhexidine. Out of the fifty case reports of chlorhexidine-related anaphylaxis published worldwide over the past ten years, fifteen occurred during surgery. Signs generally appear from 15 to 45 minutes after the start of anesthesia. If there is any suspicion of immediate allergy to chlorhexidine, prick-tests or even intradermal reaction (IDR) techniques are highly recommended. In the event of confirmed allergy to chlorhexidine, strict eviction is required, bearing in mind that over a hundred medicinal products currently on the French market contain chlorhexidine.

Platelet function point-of-care tests in post-bypass cardiac surgery: are they relevant?

BACKGROUND: Platelet dysfunction is an important cause of excessive bleeding after cardiac surgery. We assessed two platelet function point-of-care tests: the platelet function analyser (PFA-100) and the Hemostatus(TM) in patients with and without excessive bleeding after cardiac surgery with cardiopulmonary bypass. METHODS: Mediastinal chest tube drainage (MCTD) was measured for the first 6 h in the intensive care unit (ICU). Haematology and coagulation tests were done on arrival in the ICU, and when excessive bleeding occurred (MCTD >1 ml kg(-1) h(-1)) or after 3 h. RESULTS: Eighteen patients bled excessively and 27 had normal MCTD. Hemostatus measurements were prolonged in those with excessive bleeding compared with the normal group. The times for PFA-100 adenosine diphosphate (ADP) and epinephrine were 91 vs 71 s (P=0.004) and 155 vs 114 s (P=0.02) in the bleeding and normal group s, respectively. None of the Hemostatus or PFA-100 values correlated with total MCTD. Depending on the agonist used, maximum aggregation was 33-81% and 52-86% in bleeding and normal groups, respectively. Only poor correlations were found between PFA-100 epinephrine and maximum aggregation in response to ADP (r=-0.52, P=0.03) or to collagen (r=-0.48, P=0.04). CONCLUSION: Patients bleeding excessively in the ICU had abnormal measurements in point-of-care tests without a dramatic decrease in aggregation. Except for patients with increased risk of postbypass bleeding, point-of-care tests are not useful for routine use after cardiac surgery.

Segregation of leading-edge and uropod components into specific lipid rafts during T cell polarization.

Redistribution of specialized molecules in migrating cells develops asymmetry between two opposite cell poles, the leading edge and the uropod. We show that acquisition of a motile phenotype in T lymphocytes results in the asymmetric redistribution of ganglioside GM3- and GM1-enriched raft domains to the leading edge and to the uropod, respectively. This segregation to each cell pole parallels the specific redistribution of membrane proteins associated to each raft subfraction. Our data suggest that raft partitioning is a major determinant for protein redistribution in polarized T cells, as ectopic expression of raft-associated proteins results in their asymmetric redistribution, whereas non-raft-partitioned mutants of these proteins are distributed homogeneously in the polarized cell membrane. Both acquisition of a migratory phenotype and SDF-1alpha-induced chemotaxis are cholesterol depletion-sensitive. Finally, GM3 and GM1 raft redistribution requires an intact actin cytoskeleton, but is insensitive to microtubule disruption. We propose that membrane protein segregation not only between raft and nonraft domains but also between distinct raft subdomains may be an organizational principle that mediates redistribution of specialized molecules needed for T cell migration.

Latex hypersensitivity in spinal cord injured adult patients.

Latex hypersensitivity is a major cause of anaphylaxis during anaesthesia. Patients with spina bifida, health care or rubber industry workers have been considered at risk for latex sensitization. By analogy, the existence of other at-risk subsets of patients with latex exposure due to frequent surgical procedures has been suggested. The aim of this study was to evaluate the prevalence of latex sensitization in a cohort of adult patients with spinal cord injury and repeated latex exposure. Forty-two adult patients with spinal cord injury were studied and retrospectively compared to a group of 30 children with spina bifida evaluated using a similar protocol. Patients were administered a questionnaire concerning history of latex hypersensitivity, atopy, and surgical procedures. Latex sensitivity was investigated by skin prick-tests and latex-specific IgE assay. The search for atopy was based on in vivo and in vitro tests against a panel of environmental allergens. No chronic spinal cord injured patient had a history of latex allergy. When compared with spina bifida, the number of surgical procedures was not statistically different. Although not significantly different, the prevalence of atopy was higher in spina bifida patients. The high level of latex sensitization in spina bifida patients contrasted sharply with the absence of sensitization observed on both skin and in vitro tests in patients with spinal cord injury (P<0.0001). This study confirms that adult patients with chronic neurologic defects resulting from spinal cord injury exhibit a low risk of latex sensitization. These results suggest that considering adult patients with repeated surgical procedures as a group at risk for latex sensitization because of a high degree of latex exposure should be re-examined.