Remote Ischemic Preconditioning Protects the Brain Against Injury After Hypothermic Circulatory Arrest

Background-Ischemic preconditioning (IPC) is a mechanism protecting tissues from injury during ischemia and reperfusion. Remote IPC (RIPC) can be elicited by applying brief periods of ischemia to tissues with ischemic tolerance, thus protecting vital organs more susceptible to ischemic damage. Using a porcine model, we determined whether RIPC of the limb is protective against brain injury caused by hypothermic circulatory arrest (HCA).Methods and Results-Twelve piglets were randomized to control and RIPC groups. RIPC was induced in advance of cardiopulmonary bypass by 4 cycles of 5 minutes of ischemia of the hind limb. All animals underwent cardiopulmonary bypass followed by 60 minutes of HCA at 18 degrees C. Brain metabolism and electroencephalographic activity were monitored for 8 hours after HCA. Assessment of neurological status was performed for a week postoperatively. Finally, brain tissue was harvested for histopathological analysis.Study groups were balanced for baseline and intraoperative parameters. Brain lactate concentration was significantly lower (P < 0.0001, ANOVA) and recovery of electroencephalographic activity faster (P < 0.05, ANOVA) in the RIPC group. RIPC had a beneficial effect on neurological function during the 7-day follow-up (behavioral score; P < 0.0001 versus control, ANOVA). Histopathological analysis demonstrated a significant reduction in cerebral injury in RIPC animals (injury score; mean [interquartile range]: control 5.8 [3.8 to 7.5] versus RIPC 1.5 [0.5 to 2.5], P < 0.001, t test).Conclusions-These data demonstrate that RIPC protects the brain against HCA-induced injury, resulting in accelerated recovery of neurological function. RIPC might be neuroprotective in patients undergoing surgery with HCA and improve long-term outcomes. Clinical trials to test this hypothesis are warranted. (Circulation. 2011; 123: 714-721.

Requirements and special considerations for drug trials with children across six jurisdictions: 1. Clinical trial application review in the regulatory approval process.

BackgroundConducting clinical trials (CTs) with children presents several challenges. A major challenge is the need to enrol participants at multiple sites across different jurisdictions. Regardless of whether the trials involve children, adults, or both, CTs need to meet separate Competent Authority (CA) requirements to proceed in each participating country. This work, undertaken by the Working Group (WG) on International Collaborations at the European Network of Pediatric Research at the European Medicines Agency (Enpr-EMA) aims to describe the regulatory requirements including any specific to pediatrics, as well as current or upcoming changes across six jurisdictions-the European Union (EU), United Kingdom (UK), United States of America (USA), Canada, Japan, and Australia.MethodsAn open questionnaire developed by the WG and directed at both the CA and the national pediatric clinical trial networks arranged by jurisdictions.ResultsA synopsis of the current legislative and regulatory requirements for CTs applications, application submission processes and application requirements is presented for each of the six jurisdictions. Requirements were found to be mostly consistent across jurisdictions. No difference was found in processes for CTs submission, review, and authorization for pediatric CTs vs. CTs in adults. However, there are additional Ethics Committee/Institutional Review Board requirements for clinical trials including children. Some jurisdictions are considering adopting a risk-based approach, inspired by the Organization of Economic Co-operation and Development (OECD) recommendations on Governance. Changes currently or soon to be implemented in some jurisdictions are also described.ConclusionsRegulators from the jurisdictions represented in this WG are collaborating to facilitate regulatory harmonization and foster international alignment of pediatric CTs. By interacting with their respective regulatory bodies and developing expertise in their jurisdiction's regulatory requirements, national pediatric networks can support both academic and industry sponsors in navigating the regulatory process for CTs

Do Treatment Policies for Proximal Humerus Fractures Differ among Three Nordic Countries and Estonia? Results of a Survey Study

Background and Purpose: Proximal humerus fractures are common fragility injuries. The incidence of these fractures has been estimated to be 82–105 per 105 person-years. Treatment of this fracture, especially in the elderly, is controversial. Our study group published a systematic review of the available literature and concluded that non-operative methods are favored over operative methods in three- and four-part fractures. The aim of this multinational study was to compare treatment policies for proximal humerus fractures among the Nordic countries and Estonia. Materials and Methods: The study was conducted as a questionnaire-based survey, using the Internet-based program, Webropol® ( webropol.com ). The questionnaire link was sent to the surgeons responsible for treating proximal humerus fractures in major public hospitals in Estonia, Finland, Norway, and Sweden. Questionnaire included questions regarding the responder’s hospital, patient characteristics, and examinations taken before decision making. Clinical part included eight example patient cases with treatment options. Results: Of the 77 recipients of the questionnaire, 59 responded; consequently, the response rate was 77%. Based on the eight presented displaced fracture examples, in both Estonia and Norway and in Finland, 41% and 38%, respectively, preferred surgical treatment with locking plate. In Sweden, the percentage was 28%. The pre- and post-operative protocols showed a similarity in all participant countries. Conclusion: Our survey revealed a remarkable uniformity in the current practice of operative treatments and rehabilitation for proximal humerus fractures in the participant countries. </jats:sec

Onko olkapään kiertäjäkalvosimen repeämän hoitopaikka kuntosali vai leikkaussali?

Tiivistelmä Olkapään kiertäjäkalvosimen repeämä voi syntyä jänteen rappeuman, äkillisen tapaturman tai näiden yhdistelmän seurauksena. Suurin osa on oireettomia eikä tarvitse hoitoa. Tyypillisiä oireita ovat levossa tai rasituksessa esiintyvä kipu sekä liikelaajuuksien ja voimien pieneneminen. Diagnostiikka perustuu kliiniseen tutkimukseen ja röntgenkuvaukseen. Kaikututkimus tai magneettikuvaus saattavat olla tarpeen. Rappeumaperäisen repeämän ensilinjan hoito on konservatiivinen. Kirurgista hoitoa tarvitaan lähinnä tapaturman jälkeen