ABSTRACT
Introduction: Calcium use during cardiac arrest has conflicting results in terms of efficacy. Therefore, we performed a systematic review evaluating the role of calcium administration in cardiac arrest. Methods: We searched PubMed, Cochrane, and EMBASE for studies comparing calcium administration versus no calcium administration during cardiac arrest. The study was prospectively registered in PROSPERO (CRD42022316641) adhering to PRISMA guideline recommendations. The primary outcome was return of spontaneous circulation (ROSC) or survival at one hour. The secondary outcomes included survival to discharge or at 30 days, and favorable neurologic outcomes at 30 and 90 days. We planned to perform a random-effects meta-analysis of low risk of bias studies. We evaluated risk of bias with RoB-2 and ROBINS-I. Results: We identified 1,921 articles and included ten studies with 2509 patients. We were not able to perform a meta-analysis with low-risk of bias studies as only one study was found to be at low-risk of bias. However, for the primary outcome, the three RCTs included showed no benefit with calcium administration during cardiac arrest for ROSC. For the secondary outcomes, based on the most recent study and lower risk of bias, there was a neutral effect for survival to discharge or at 30 days and neurologic outcomes at 30 days. However, there was unfavorable neurologic outcomes at 90 days. Conclusion: Based on our results, calcium administration in cardiac arrests shows no benefit and can cause harm. Further studies on this matter are likely not advisable.
ABSTRACT
A peripheral nerve injury results in disruption of the fiber that usually protects axons from the surrounding environment. Severed axons from the proximal nerve stump are capable of regenerating, but axons are exposed to a completely new environment. Regeneration recruits cells that produce and deposit key molecules, including growth factor proteins and fibrils in the extracellular matrix (ECM), thus changing the chemical and geometrical environment. The regenerating axons thus surf on a newly remodeled micro-landscape. Strategies to enhance and control axonal regeneration and growth after injury often involve mimicking the extrinsic cues that are found in the natural nerve environment. Indeed, nano- and micropatterned substrates have been generated as tools to guide axons along a defined path. The mechanical cues of the substrate are used as guides to orient growth or change the direction of growth in response to impediments or cell surface topography. However, exactly how axons respond to biophysical information and the dynamics of axonal movement are still poorly understood. Here we use anisotropic, groove-patterned substrate topography to direct and enhance sensory axonal growth of whole mouse dorsal root ganglia (DRG) transplanted ex vivo. Our results show significantly enhanced and directed growth of the DRG sensory fibers on the hemi-3D topographic substrates compared to a 0 nm pitch, flat control surface. By assessing the dynamics of axonal movement in time-lapse microscopy, we found that the enhancement was not due to increases in the speed of axonal growth, but to the efficiency of growth direction, ensuring axons minimize movement in undesired directions. Finally, the directionality of growth was reproduced on topographic patterns fabricated as fully 3D substrates, potentially opening new translational avenues of development incorporating these specific topographic feature sizes in implantable conduits in vivo.
