Airway management in acute tetraplegics: a retrospective study

The objective of this study was to develop an evidence-based airway management protocol for patients with acute tetraplegia. The method consisted of an analysis of the medical records of patients (September 1997–December 2002) with a spinal cord injury and a neurological deficit less than 8 weeks old. Of the 175 patients, 72 (41, 14%) were tracheotomised. This was influenced by the origin of the paralysis, Frankel score, and number of cervical spine operations, accompanying injuries and accompanying illnesses. Tracheotomy did not affect the duration of treatment, duration of ventilation or length of stay in the intensive care unit. The need for a tracheotomy was able to be predicted in 73.31% with neurological level, Frankel score and severity of accompanying injuries. In patients with acute tetraplegia, primary tracheotomy is indicated in sub C1–C3 with Frankel stage A/B, sub C4–C6 with Frankel stage A/B with trauma and accompanying injuries/accompanying illnesses, and in patients with complex cervical spine trauma that requires a combined surgical approach. In other patients, an attempt at extubation should be made

A key role for mitochondrial gatekeeper pyruvate dehydrogenase in oncogene-induced senescence

In response to tenacious stress signals, such as the unscheduled activation of oncogenes, cells can mobilize tumour suppressor networks to avert the hazard of malignant transformation. A large body of evidence indicates that oncogene-induced senescence (OIS) acts as such a break, withdrawing cells from the proliferative pool almost irreversibly, thus crafting a vital pathophysiological mechanism that protects against cancer. Despite the widespread contribution of OIS to the cessation of tumorigenic expansion in animal models and humans, we have only just begun to define the underlying mechanism and identify key players. Although deregulation of metabolism is intimately linked to the proliferative capacity of cells and senescent cells are thought to remain metabolically active, little has been investigated in detail about the role of cellular metabolism in OIS. Here we show, by metabolic profiling and functional perturbations, that the mitochondrial gatekeeper pyruvate dehydrogenase (PDH) is a crucial mediator of senescence induced by BRAFV600E, an oncogene commonly mutated in melanoma and other cancers. BRAFV600E-induced senescence was accompanied by simultaneous suppression of the PDH-inhibitory enzyme pyruvate dehydrogenase kinase 1 (PDK1) and induction of the PDH-activating enzyme pyruvate dehydrogenase phosphatase 2 (PDP2). The resulting combined activation of PDH enhanced the use of pyruvate in the tricarboxylic acid cycle, causing increased respiration and redox stress. Abrogation of OIS, a rate-limiting step towards oncogenic transformation, coincided with reversion of these processes. Further supporting a crucial role of PDH in OIS, enforced normalization of either PDK1 or PDP2 expression levels inhibited PDH and abrogated OIS, thereby licensing BRAFV600E-driven melanoma development. Finally, depletion of PDK1 eradicated melanoma subpopulations resistant to targeted BRAF inhibition, and caused regression of established melanomas. These results reveal a mechanistic relationship between OIS and a key metabolic signalling axis, which may be exploited therapeutically

Mid- to long-term outcome of instrumented anterior cervical fusion for subaxial injuries

The management of patients with subaxial cervical injuries lacks consensus, particularly in regard to the decision which surgical approach or combination of approaches to use and which approach yields the best clinical outcome in the distinct injury. The trauma literature is replete with reports of surgical techniques, complications and gross outcome assessment in heterogeneous samples. However, data on functional and clinical outcome using validated outcome measures are scanty. Therefore, the authors performed a study on plated anterior cervical decompression and fusion for unstable subaxial injuries with focus on clinical outcome. For the purpose of a strongly homogenous subgroup of patients with subaxial injuries without spinal cord injuries, robust criteria were applied that were fulfilled by 28 patients out of an original series of 131 subaxial injuries. Twenty-six patients subjected to 1- and 2-level fusions without having spinal cord injury could be surveyed after a mean of 5.5 years (range 16–128 months). The cervical spine injury severity score averaged 9.6. Cross-sectional outcome assessment included validated outcome measures (Neck pain disability index, Cervical Spine Outcome Questionnaire, SF-36), the investigation of construct failure and successful surgical outcome were defined by strict criteria, the reconstruction and maintenance of local and total cervical lordosis, adjacent-segment degeneration and intervertebral motion, and the fusion-rate using an interobserver assessment. Self-rated clinical outcome was excellent or good in 81% of patients and moderate or poor in 19% that corresponded to the results of the validated outcome measures. Results of the NPDI averaged 12.4 ± 12.7% (0–40). With the SF-36 mean physical and mental component summary scores were 47.0 ± 9.8 (18.2–59.3) and 52.2 ± 12.4 (14.6–75.3), respectively. Using merely non-constrained plates, construct failure was observed in 31% of cases and loss of local lordosis, expressed as a mean injury angle of 14°, postoperative angle of −5.5° and follow-up angle of −1°, was significant. However, total cervical lordosis was within the limits of normalcy (−24.3° ± 13.3) and fusion-rate was 88.5%. The progression of adjacent-level degeneration was shown to be significantly influenced by a decreased plate-to-disc-distance. Adjacent-level intervertebral motion was not altered due to the adjacent fusion, but reduced in the presence of advanced adjacent-level degeneration. Patients were more likely to maintain a high satisfaction level if they succeeded to maintain segmental lordosis (<0°), had a solid fusion, an increased plate-to-disc distance, and if they were judged to have a successful surgical outcome that included the absence of construct failure and reconstruction of lordosis within ±1 SD of normalcy. Using validated outcome vehicles the interdependencies between radiographical, functional and clinical outcome parameters could be substantiated with statistically significant correlations. The use of validated outcome vehicles in a subgroup of patients with plated anterior cervical fusions for subaxial injuries is recommended. With future studies, it enables objective comparison of surgical techniques and related radiographical, functional and clinical outcome