The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in maxillofacial trauma

In recent years, recombinant human bone morphogenetic protein-2 (rhBMP-2) has been introduced as a therapeutic option in the treatment of several congenital and acquired craniofacial defects. Although there have been promising clinical results, the international literature still lacks complete guidelines, including limits and indications for the use of rhBMP-2. The possible indications for rhBMP-2 in patients undergoing facial trauma are discussed in this article.     

Pre‐ischemia melatonin treatment alleviated acute neuronal injury after ischemic stroke by inhibiting endoplasmic reticulum stress‐dependent autophagy via PERK and IRE1 signalings

Melatonin has demonstrated a potential protective effect in central nervous system. Thus, it is interesting to determine whether pre‐ischemia melatonin administration could protect against cerebral ischemia/reperfusion (IR)‐related injury and the underlying molecular mechanisms. In this study, we revealed that IR injury significantly activated endoplasmic reticulum (ER) stress and autophagy in a middle cerebral artery occlusion mouse model. Pre‐ischemia melatonin treatment was able to attenuate IR‐induced ER stress and autophagy. In addition, with tandem RFP‐GFP‐LC3 adeno‐associated virus, we demonstrated pre‐ischemic melatonin significantly alleviated IR‐induced autophagic flux. Furthermore, we showed that IR induced neuronal apoptosis through ER stress related signalings. Moreover, IR‐induced autophagy was significantly blocked by ER stress inhibitor (4‐PBA), as well as ER‐related signaling inhibitors (PERK inhibitor, GSK; IRE1 inhibitor, 3,5‐dibromosalicylaldehyde). Finally, we revealed that melatonin significantly alleviated cerebral infarction, brain edema, neuronal apoptosis, and neurological deficiency, which were remarkably abolished by tunicamycin (ER stress activator) and rapamycin (autophagy activator), respectively. In summary, our study provides strong evidence that pre‐ischemia melatonin administration significantly protects against cerebral IR injury through inhibiting ER stress‐dependent autophagy. Our findings shed light on the novel preventive and therapeutic strategy of daily administration of melatonin, especially among the population with high risk of cerebral ischemic stroke.     

Primary anterior cruciate ligament reconstruction: perioperative considerations and complications

Anterior cruciate ligament (ACL) injuries are among the most commonly studied orthopaedic injuries. Despite having an excellent prognosis, complications do occur. The timely recognition and management of complications is imperative to ensure the success of reconstruction. Avoiding such complications requires thorough preoperative planning, proficient technical skills to properly manage intraoperative complications, and an extensive knowledge of possible postoperative complications.     

EFNS guidelines on diagnosis and management of neuromyelitis optica

Background and purpose: Neuromyelitis optica (NMO) or Devic′s disease is a rare inflammatory and demyelinating autoimmune disorder of the central nervous system (CNS) characterized by recurrent attacks of optic neuritis (ON) and longitudinally extensive transverse myelitis (LETM), which is distinct from multiple sclerosis (MS). The guidelines are designed to provide guidance for best clinical practice based on the current state of clinical and scientific knowledge. Search strategy: Evidence for this guideline was collected by searches for original articles, case reports and meta‐analyses in the MEDLINE and Cochrane databases. In addition, clinical practice guidelines of professional neurological and rheumatological organizations were studied. Results: Different diagnostic criteria for NMO diagnosis [Wingerchuk et al. Revised NMO criteria, 2006 and Miller et al. National Multiple Sclerosis Society (NMSS) task force criteria, 2008] and features potentially indicative of NMO facilitate the diagnosis. In addition, guidance for the work‐up and diagnosis of spatially limited NMO spectrum disorders is provided by the task force. Due to lack of studies fulfilling requirement for the highest levels of evidence, the task force suggests concepts for treatment of acute exacerbations and attack prevention based on expert opinion. Conclusions: Studies on diagnosis and management of NMO fulfilling requirements for the highest levels of evidence (class I–III rating) are limited, and diagnostic and therapeutic concepts based on expert opinion and consensus of the task force members were assembled for this guideline.     

Novel mutations in leukotriene C4 synthase and risk of cardiovascular disease based on genotypes from 50 000 individuals

Summary. Background: Atherosclerosis is an inflammatory condition where cysteinyl leukotrienes have been identified to play an important role. Furthermore, cysteinyl leukotrienes may also affect thrombus formation. Using prospective, cross‐sectional and case‐control designs, we tested the hypothesis that hitherto unknown genetic variation, likely to affect the function of leukotriene C₄ synthase, is associated with risk of venous thromboembolism, ischemic stroke and myocardial infarction. Methods and Results: Resequencing the gene coding for leukotriene C₄ synthase in an extreme risk population with more than 1500 individuals revealed 17 new mutations, of which four are likely to change protein function (211G>A (minor allele frequency, 0.0001), IVS3 + 1G>A (0.002), 374G>A (0.0006) and 451_453+10del (0.0007)). Based on genotyping 50 000 individuals, age and sex adjusted odds ratios for venous thromboembolism were 2.0 (95% CI, 1.3–3.5) for IVS3+1G>A heterozygotes vs. wild type, and 1.9 (1.5–2.7) for any mutation heterozygote vs. wild type. Corresponding values were 2.0 (1.3–3.2) and 1.5 (1.1–2.1) for ischemic stroke, and 1.0 (0.8–1.3) and 1.2 (1.0–1.4) for myocardial infarction. Conclusions: Four novel mutations that are likely to change the function of leukotriene C₄ synthase were associated with increased risk of venous thromboembolism and ischemic stroke. These findings need confirmation in other independent studies. In addition, the mechanism behind these findings deserves further investigation.     

Changes in lactate dehydrogenase are associated with central gray matter lesions in newborns with hypoxic-ischemic encephalopathy

Purpose: Biomarkers may predict neurological prognosis in infants with hypoxic-ischemic encephalopathy (HIE). We evaluated the relationship between serum lactate dehydrogenase (LDH) and brain magnetic resonance imaging (MRI), which predicts neurodevelopmental outcomes, in order to assess whether LDH levels are similarly predictive.

Materials and methods: Medical records were reviewed for infants with HIE and LDH levels were assessed on the first (LDH₁) and third (LDH₃) days following birth. Receiver operating characteristic curves were obtained in relation to central gray matter hypoxic-ischemic lesions.

Results: Of 92 patients, 52 (56.5%) had hypoxic-ischemic lesions on brain MRI, and 21 of these infants (40.4%) had central gray matter lesions. LDH₁ and LDH₃ did not differ; however, the percentage change (ΔLDH%) was significantly higher in infants with central gray matter lesions (36.9% versus 6.6%, p?=?0.006). With cutoffs of 187 (IU/L, ΔLDH) and 19.4 (%, ΔLDH%), the sensitivity, specificity, positive predictive value and negative predictive value were 71.4, 69.0, 40.5 and 89.1%, respectively. The relative risk was 5.57 (p?=?0.001).

Conclusion: Changes in serum LDH may be a useful biomarker for predicting future neurodevelopmental prognosis in infants with HIE.