Change in Pull-Out Force during Resorption of Magnesium Compression Screws for Osteosynthesis of Mandibular Condylar Fractures

Background: Magnesium has been used as degradable fixation material for osteosynthesis, but it seems that mechanical strength is still a current issue in these fixations. The aim of this study was to evaluate the axial pull-out force of compression headless screws made of magnesium alloy during their resorption. Methods: The tests included screws made for osteosynthesis of the mandible head: 2.2 mm diameter magnesium alloy MgYREZr (42 screws) and 2.5 mm diameter polylactic-co-glycolic acid (PLGA) (42 pieces, control). The screws were resorbed in Sørensen’s buffer for 2, 4, 8, 12, and 16 weeks, and force was measured as the screw was pulled out from the polyurethane block. Results: The force needed to pull the screw out was significantly higher for MgYREZr screws than for PLGA ones (p < 0.01). Within eight weeks, the pull-out force for MgYREZr significantly decreased to one third of its initial value (p < 0.01). The dynamics of this decrease were greater than those of the pull-out force for PLGA screws (p < 0.05). After these eight weeks, the values for metal and polymer screws equalized. It seems that the described reduction of force requires taking into account when using magnesium screws. This will provide more stable resorbable metallic osteosynthesis.     

The relationships among monocyte subsets,miRNAs and inflammatory cytokines in patients with acute myocardial infarction

Background

Acute myocardial infarction (AMI) causes irreversible myocardial damage and release of inflammatory mediators, including cytokines, chemokines and miRNAs. We aimed to investigate changes in the levels of cytokines (IL-6, TNF-α and IL-10), miRNAs profiles (miR-146 and miR-155) and distribution of different monocyte subsets (CD14++CD16-, CD14++CD16+, CD14+CD16++) in the acute and post-healing phases of AMI.

Pituitary Adenylate Cyclase-Activating Polypeptide Attenuates Brain Edema by Protecting Blood–Brain Barrier and Glymphatic System After Subarachnoid Hemorrhage in Rats

Brain edema is a vital contributor to early brain injury after subarachnoid hemorrhage (SAH), which is responsible for prolonged hospitalization and poor outcomes. Pharmacological therapeutic targets on edema formation have been the focus of research for decades. Pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to participate in neural development and brain injury. Here, we used PACAP knockout CRISPR to demonstrate that endogenous PACAP plays an endogenous neuroprotective role against brain edema formation after SAH in rats. The exogenous PACAP treatment provided both short- and long-term neurological benefits by preserving the function of the blood–brain barrier and glymphatic system after SAH. Pretreatment of inhibitors of PACAP receptors showed that the PACAP-involved anti-edema effect and neuroprotection after SAH was facilitated by the selective PACAP receptor (PAC1). Further administration of adenylyl cyclase (AC) inhibitor and sulfonylurea receptor 1 (SUR1) CRISPR activator suggested that the AC–cyclic adenosine monophosphate (cAMP)–protein kinase A (PKA) axis participated in PACAP signaling after SAH, which inhibited the expression of edema-related proteins, SUR1 and aquaporin-4 (AQP4), through SUR1 phosphorylation. Thus, PACAP may serve as a potential clinical treatment to alleviate brain edema in patients with SAH.Electronic supplementary materialThe online version of this article (10.1007/s13311-020-00925-3) contains supplementary material, which is available to authorized users.Key Words: Subarachnoid hemorrhage, brain edema, pituitary adenylate cyclase-activating polypeptide, blood–brain barrier, glymphatic system     

Systematic Review and Meta-Analysis of Diagnostic Test Accuracy Studies Evaluating Point-of-Care Tests of Coagulopathy in Cardiac Surgery

Treatment guidelines recommend the routine use of point-of-care diagnostic tests for coagulopathy in the management of cardiac surgery patients at risk of severe bleeding despite uncertainty as to their diagnostic accuracy. We performed a systematic review and meta-analysis of studies that evaluated the diagnostic accuracy of viscoelastometry, platelet function tests, and modified thromboelastography (TEG) tests, for coagulopathy in cardiac surgery patients. The reference standard included resternotomy for bleeding, transfusion of non-red cell components, or massive transfusion. We searched MEDLINE, EMBASE, CINAHL, and Clinical Trials.gov, from inception to June 2019. Study quality was assessed using QUADAS-2. Bivariate models were used to estimate summary sensitivity and specificity with (95% confidence intervals). All 29 studies (7440 participants) included in the data synthesis evaluated the tests as predictors of bleeding. No study evaluated their role in the management of bleeding. None was at low risk of bias. Four were judged as low concern regarding applicability. Pooled estimates of diagnostic accuracy were; Viscoelastic tests, 12 studies, sensitivity 0.61 (0.44, 0.76), specificity 0.83 (0.70, 0.91) with significant heterogeneity. Platelet function tests, 12 studies, sensitivity 0.63 (0.53, 0.72), specificity 0.75 (0.64, 0.84) with significant heterogeneity. TEG modification tests, 3 studies, sensitivity 0.80 (0.67, 0.89), specificity 0.76 (0.69, 0.82) with no evidence of heterogeneity. Studies reporting the highest values for sensitivity and specificity had important methodological limitations. In conclusion, we did not demonstrate predictive accuracy for commonly used point-of-care devices for coagulopathic bleeding in cardiac surgery. However, the certainty of the evidence was low.     

Genotype-phenotype correlation and molecular heterogeneity in pyruvate kinase deficiency

Pyruvate kinase (PK) deficiency is a rare recessive congenital hemolytic anemia caused by mutations in the PKLR gene. This study reports the molecular features of 257 patients enrolled in the PKD Natural History Study. Of the 127 different pathogenic variants detected, 84 were missense and 43 non-missense, including 20 stop-gain, 11 affecting splicing, five large deletions, four in-frame indels, and three promoter variants. Within the 177 unrelated patients, 35 were homozygous and 142 compound heterozygous (77 for two missense, 48 for one missense and one non-missense, and 17 for two non-missense variants); the two most frequent mutations were p.R510Q in 23% and p.R486W in 9% of mutated alleles. Fifty-five (21%) patients were found to have at least one previously unreported variant with 45 newly described mutations. Patients with two non-missense mutations had lower hemoglobin levels, higher numbers of lifetime transfusions, and higher rates of complications including iron overload, extramedullary hematopoiesis, and pulmonary hypertension. Rare severe complications, including lower extremity ulcerations and hepatic failure, were seen more frequently in patients with non-missense mutations or with missense mutations characterized by severe protein instability. The PKLR genotype did not correlate with the frequency of complications in utero or in the newborn period. With ICCs ranging from 0.4 to 0.61, about the same degree of clinical similarity exists within siblings as it does between siblings, in terms of hemoglobin, total bilirubin, splenectomy status, and cholecystectomy status. Pregnancy outcomes were similar across genotypes in PK deficient women. This report confirms the wide genetic heterogeneity of PK deficiency.