Incidence and characteristics of severe exercise-associated collapse at the world's largest half-marathon

Background Whilst many health benefits are associated with regular exercise, medical complications may occur during higher-intensity activities, such as long distance running contests. The most common complication is collapse. However, the incidence and characteristics of these collapses are not very well studied. Method This is a retrospective study of severe collapse, defined as a patient in need of advanced medical care after a collapse, during the large Gothenburg's half marathon, Goteborgsvarvet. The study included 230,501 competitors during the study-period of 5 years (20132017) with data being collected from medical race tents and using ambulance data. Vital signs, treatment and blood gas samples were noted and analyzed. Results The incidence of severe collapse was 1.53 per 1000 starting runners. The average age for patients was 34 years old and no difference in incidence were seen between male and female runners. The typical collapsed runner presented with tachycardia, normal systolic blood pressure, elevated body temperature and metabolic acidosis. The most common medical encounter was exercise-associated collapse. Conclusion The incidence of severe collapse was similar to findings in other studies, even though this study was set in different part of the world. Typical characteristics of a collapsed runner were identified providing new information which could be beneficial in the medical planning of larger running competitions and future preventative interventions. Importantly, life threatening conditions seem uncommon; no case of hyponatremia and only two cases of hypoglycemia were seen

Efficacy and safety of dexanabinol in severe traumatic brain injury : results of a phase III randomised, placebo-controlled, clinical trial

Background Traumatic brain injury is a major cause of death and disability. We sought to assess the safety and efficacy of dexanabinol, a synthetic cannabinoid analogue devoid of psychotropic activity, in severe traumatic brain injury. Methods 861 patients with severe traumatic brain injury admitted to 86 specialist centres from 15 countries were included in a multi-centre, placebo-controlled, phase III trial. Patients were randomised to receive a single intravenous 150 mg dose of dexanabinol or placebo within 6 h of injury. The primary outcome was the extended Glasgow outcome scale assessed at 6 months, with the point of dichotomisation into unfavourable versus favourable outcome differentiated by baseline prognostic risk. Prespecified subgroup analyses were defined by injury severity, recruitment rate, and time to dosing. Secondary analysis included control of intracranial pressure and quality of life. Analysis were prespecified in the protocol and the statistical analysis plan. This study is registered with ClinicalTrials.gov, number NCT00129857. Findings 846 patients were included in the efficacy analysis. The extended Glasgow outcome scale at 6 months did not differ between groups; 215 (50%) patients in the dexanabinol group and 214 (51%) patients in the placebo group had an unfavourable outcome (odds ratio for a favourable response 1.04; 95% CI 0.79-1.36). Improvements in the control of intracranial pressure or quality of life were not recorded and subgroup analysis showed no indication of differential treatment effects. Dexanabinol was not associated with hepatic, renal, or cardiac toxic effects. Interpretation Dexanabinol is safe, but is not efficacious in the treatment of traumatic brain injury

A Novel Mitogen-Activated Protein Kinase Phosphatase Is an Important Negative Regulator of Lipopolysaccharide-Mediated c-Jun N-Terminal Kinase Activation in Mouse Macrophage Cell Lines

We have isolated a cDNA homologous to known dual-specificity phosphatases from a mouse macrophage cDNA library and termed it MKP-M (for mitogen-activated protein kinase phosphatase isolated from macrophages). Three other presumed splice variant isoforms have also been identified for MKP-M. The longest and most abundant mRNA contains an open reading frame corresponding to 677 amino acids and produces an 80-kDa protein. The deduced amino acid sequence of MKP-M is most similar to those of hVH-5 (or mouse M3/6) and VHP1, a Caenorhabditis elegans tyrosine phosphatase. It includes an N-terminal rhodanase homology domain, the extended active-site sequence motif (V/L)X(V/I)HCXAG(I/V)SRSXT(I/V)XXAY(L/I)M (where X is any amino acid), and a C-terminal PEST sequence. Northern blot analysis revealed a dominant MKP-M mRNA species of approximately 5.5 kb detected ubiquitously among all tissues examined. MKP-M was constitutively expressed in mouse macrophage cell lines, and its expression levels were rapidly increased by lipopolysaccharide (LPS) stimulation but not by tumor necrosis factor alpha (TNF-α), gamma interferon, interleukin-2 (IL-2), or IL-15 stimulation. Immunocytochemical analysis showed MKP-M to be present within cytosol. When expressed in COS7 cells, MKP-M blocks activation of mitogen-activated protein kinases with the selectivity c-Jun N-terminal kinase (JNK) ≫ p38 = extracellular signal-regulated kinase. Furthermore, expression of a catalytically inactive form of MKP-M in a mouse macrophage cell line increased the intensity and duration of JNK activation and TNF-α secretion after LPS stimulation, suggesting that MKP-M is at least partially responsible for the desensitization of LPS-mediated JNK activation and cytokine secretion in macrophages