The Effects of IRL-1620 in Post-ischemic Brain Injury: A Systematic Review and Meta-analysis of Experimental Studies.

BACKGROUND: Sovateltide (IRL-1620), an endothelin B receptor agonist, has previously demonstrated neuroprotective and neuroregenerative effects in animal models of acute ischemic stroke. Recently, clinical trials indicated that it could also be effective in humans with stroke. Here, we systematically investigate whether IRL-1620 may be used for the treatment of ischemia-induced brain injury. METHODS: A systematic review was performed following the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. MEDLINE (PubMed) and Scopus databases were searched for eligible studies up to December 2022. The databases ClinicalTrials.gov and Pharmazz Inc. were screened for unpublished or ongoing trials. Only studies in English were evaluated for eligibility. Meta-analysis of the included studies was also conducted. RESULTS: Finally, seven studies were included in the review, all in animal rat models because of scarcity of clinical trials. Six studies, all in middle cerebral artery occlusion (MCAO) models, were selected for meta-analysis. In the two studies assessing mortality, no deaths were reported in the IRL-1620 group 24 h after MCAO, whereas the vehicle group had almost a five times higher mortality risk (risk ratio 5.3, 95% confidence interval 0.7-40.1, I2 = 0%). In all five studies evaluating outcome on day 7 after MCAO, IRL-1620 was associated with statistically significantly lower neurological deficit and improved motor performance compared with the vehicle. Infract volume, differentiation potential of neuronal progenitor cells, and mitochondrial fate also improved with IRL-1620 administration. CONCLUSIONS: According to the above, in animal MCAO models, IRL-1620 enhanced neurogenesis and neuroprotection and improved outcome. Future studies are needed to expand our understanding of its effects in human study participants with acute ischemic stroke as well as in other common causes of cerebral ischemia including cardiac arrest.

The Effects of Dexmedetomidine on Children Undergoing Magnetic Resonance Imaging: A Systematic Review and Meta-Analysis.

BACKGROUND: Magnetic Resonance Imaging (MRI) is a valuable diagnostic tool but often requires sedation to complete, especially in children. Dexmedetomidine (DEX) is an a2 agonist, for which there are experimental findings that support its potential neuroprotective effects. Given the potential risks of anesthetic drugs, we ran this study to examine DEX's effectiveness and cardiopulmonary safety as a sedative drug for children undergoing MRI. MATERIAL AND METHODS: Systematic research was conducted in PubMed, Google Scholar, Scopus and Cochrane databases for randomized controlled trials published between 2010 and 6th/2022 and involving children undergoing MRI who received DEX as sedative medication. The records which met the including criteria, after indexing via the PRISMA chart and assessing for bias, were processed, and a meta-analysis was carried out with the random effects method. RESULTS: Thirteen studies were included. Out of 6204 measurements obtained, in 4626, it was planned for the participants to only receive DEX (measure group) as an anesthetic drug throughout the procedure. The participants' mean age was 57 months (Ι2 = 4%, τ2 = 0.5317, p = 0.40). A total of 5.6% (95% CI: 0.6-14.1%, I2 = 98%, p < 0.01) of the patients needed a second dose of DEX. In total, 6% (95% CI: 1-15%, I2 = 93%, τ2 = 0.0454, p < 0.01) required the administration of another drug, besides DEX, to complete the imaging (sedation failure). The effectiveness of the only-DEX method was 99% (95% CI: 97.5-100%, I2 = 81%, τ2 = 0.0107, p < 0.01). The whole rate of adverse events was 15% (95% CI: 9.3-21.5%, I2 = 92%, p < 0.01). Hypotension was reported in 8.7% of the cases (95% CI: 3.1-16.4%, I2 = 84%, p < 0.01), hypertension in 1.1% (95% CI: 0-5.4%, I2 = 89%, p < 0.01), bradycardia in 10% (95% CI: 4-18%, I2 = 95%, p < 0.01) and desaturation in 1.2% (95% CI: 0-4%, I2 = 68%, p < 0.01). There was no statistically significant incidence in respiratory rate decrease (comparing the children who received DEX to their baseline). Five cases of vomiting and one of apnea were recorded. CONCLUSIONS: Given that DEX seems to be an effective as well as respiratory and hemodynamically safe drug, it may be a future spotlight in (pediatric) sedation for imaging procedures such as MRI.

A Global Assessment of Coagulation Profile and a Novel Insight into Adamts-13 Implication in Neonatal Sepsis.

Neonatal sepsis is a life-threatening condition associated with significant morbidity and mortality. Sepsis-induced coagulopathy is a well-recognized entity, signifying the strong cross-talk between inflammation and coagulation. The aim of the present study was to compare the coagulation profile between the acute phase of sepsis and recovery in term and preterm neonates. Additional comparisons to healthy neonates were undertaken. Levels of clotting, anti-clotting factors and ADAMTS-13 (A disintegrin and metalloprotease with thrombospondin type-1 motives), the cleaving protein of von Willebrand factor (VWF), were measured in 16 term and preterm neonates in the acute phase of infection and following recovery, as well as in 18 healthy neonates. Clotting times were prolonged, while levels of particular clotting factors were lower in the acute phase of infection compared to controls and recovery. On the other hand, levels of fibrinogen, factor VIII (FVIII) and VWF were significantly higher in the acute phase in comparison to controls and recovery, while they remained persistently higher in the infection group compared to controls. In regard to the anticlotting mechanism, a clear suppression was observed in septic neonates. ADAMTS-13 levels were significantly lower in the acute phase of infection in comparison to controls and recovery (p = 0.015 and 0.004, respectively), while a trend toward superimposed normalization was demonstrated post infection, as higher ADAMTS-13 levels were measured in recovered neonates compared to controls (p = 0.002). The coagulation profile is considerably deranged in neonatal sepsis. ADAMTS-13 deficiency in septic neonates is a novel finding with promising future implications, as ADAMTS-13 substitution may serve as a useful therapeutic option in neonatal sepsis, prompting further investigation in future studies.

Serum Activin A as Brain Injury Biomarker in the First Three Days of Life. A Prospective Case-Control Longitudinal Study in Human Premature Neonates.

Disruption of normal intrauterine brain development is a significant consequence of premature birth and may lead to serious complications, such as neonatal brain injury (NBI). This prospective case-control longitudinal study aimed at determining the levels and prognostic value of serum activin A during the first three days of life in human premature neonates which later developed NBI. It was conducted in a single tertiary hospital and eligible participants were live-born premature (<34 weeks) neonates. Each case (n = 29) developed NBI in the form of an intraventricular haemorrhage, or periventricular leukomalacia, and was matched according to birth weight and gestational age to one neonate with normal head ultrasound scans. Serum activin A levels in both groups showed a stable concentration during the first three days of life as no difference was observed within the two groups from the first to the third day. Neonates diagnosed with NBI had significantly higher activin A levels during the first two days of life compared to control neonates and its levels correlated to the severity of NBI during the second and third day of life. Although serum activin A on the second day was the best predictor for neonates at risk to develop NBI, the overall predictive value was marginally fair (area under the ROC-curve 69.2%). Activin A, in combination with other biomarkers, may provide the first clinically useful panel for the early detection of premature neonates at high risk of NBI.

S100B as a biomarker of brain injury in premature neonates. A prospective case - control longitudinal study.

BACKGROUND: Neonatal brain injury (NBI) is a serious adverse outcome in premature neonates. We sought to determine the levels and prognostic value of serum S100B during the first three days of life in premature neonates (<34 weeks) that later developed NBI in the form of either intraventricular hemorrhage (IVH) or periventricular leukomalacia (PVL). METHODS: This is a prospective case - control longitudinal study. Each case (n = 29) was matched according to birthweight and gestational age to one neonate with normal head ultrasound scans. RESULTS: Neonates with NBI, had significantly higher S100B concentration during the first three days of life. In both groups S100B was significantly higher on the first day when compared to the next two days of life showing a downwards trend. Serum S100B on the first day was the best predictor for adverse neonatal outcome such as death or II-IV IVH grade. A cut-off value of 10.51 ng/ml serum S100B performed a sensitivity of 100% and a specificity of 93.9% to predict adverse neonatal outcome. CONCLUSION: Further research on the predictive value of serum S100B regarding NBI in premature neonates is of great interest and may provide the first clinically useful biomarker for early detection of neonates at high risk.

Bilateral ectopic femoral testes: A rare cause of empty scrotum.

Empty scrotum is a relatively rare entity, with few cases reported in the literature, so far; if it coexists with bilateral ectopic femoral testes, it then constitutes an extremely rare congenital abnormality. We report a case of empty scrotum revealed at the first physical examination of a neonate. The scrotum appeared empty and no testes could be palpated in the scrotum or the inguinal canal. Two solitary, oval masses were palpable laterally of each hemiscrotum, close to femoral canal and the diagnosis of bilateral femoral ectopic testes was confirmed by the consultant pediatric surgeon.