Bi-allelic variants in the ESAM tight-junction gene cause a neurodevelopmental disorder associated with fetal intracranial hemorrhage.

The blood-brain barrier (BBB) is an essential gatekeeper for the central nervous system and incidence of neurodevelopmental disorders (NDDs) is higher in infants with a history of intracerebral hemorrhage (ICH). We discovered a rare disease trait in thirteen individuals, including four fetuses, from eight unrelated families associated with homozygous loss-of-function variant alleles of ESAM which encodes an endothelial cell adhesion molecule. The c.115del (p.Arg39Glyfs∗33) variant, identified in six individuals from four independent families of Southeastern Anatolia, severely impaired the in vitro tubulogenic process of endothelial colony-forming cells, recapitulating previous evidence in null mice, and caused lack of ESAM expression in the capillary endothelial cells of damaged brain. Affected individuals with bi-allelic ESAM variants showed profound global developmental delay/unspecified intellectual disability, epilepsy, absent or severely delayed speech, varying degrees of spasticity, ventriculomegaly, and ICH/cerebral calcifications, the latter being also observed in the fetuses. Phenotypic traits observed in individuals with bi-allelic ESAM variants overlap very closely with other known conditions characterized by endothelial dysfunction due to mutation of genes encoding tight junction molecules. Our findings emphasize the role of brain endothelial dysfunction in NDDs and contribute to the expansion of an emerging group of diseases that we propose to rename as "tightjunctionopathies."

Necrotizing enterocolitis in premature infants at different gestation ages.

OBJECTIVE: Aim: To compare X-ray signs in different gestational and body weight groups of patients with NEC. PATIENTS AND METHODS: Materials and Methods: We conducted a retrospective study, enrolling 52 preterm newborns with symptoms of NEC regardless of onset time, who underwent treatment at Neonatal Intensive Care Units in Municipal Non-commercial enterprise "City Children Hospital №2", Odesa. The patients were split into 3 clinical groups: very preterm newborns (VPN), moderately preterm newborns (MPN), and moderately preterm newborns with intrauterine growth restriction (MPN+IUGR). RESULTS: Results: In the VPN group NEC was diagnosed at stage II (58,82±12,30) % and III (41,18±12,30) % by Bell MJ, р>0,05. In the group MPN+IUGR, NEC stage II (33,33±14,21) % and stage III (66,66 ±14,21) %, р>0,05, were equally observed. In the MPN group, NEC was diagnosed at stage I (41,67±10,28) % and II (58,33±10,28) %, р>0,05, without prevalence of any. Also only localized forms were observed. In VPN, we observed localized forms in most cases, while diffuse forms were diagnosed in (11,76±8,05) % cases, р<0,05. In the MPN+IUGR group, we found diffuse form of the NEC in half of the cases - (50,00±15,08) %. In the VPN and MPN+IUGR groups, NEC developed at 13,23±0,39 and 14,33±1,19 days, respectively. However, in MPN without IUGR, NEC developed at 17,75±0,55 days, significantly later than in the MPN+IUGR group, р<0,05. CONCLUSION: Conclusions: We have described distinct features of NEC in MPN with IUGR. Compared to MPN without IUGR, NEC had more severe course and earlier manifestation in such neonates.

RV size may predict death in unstable patients with PE.

BACKGROUND: Pulmonary emboli (PE) is a life threatening condition that discovered in many patients only "post mortem". Sub massive and massive PE that led to hemodynamic collapse characterized by right ventricular (RV) dysfunction, leading to a higher risk of death. OBJECTIVES: To assess the ability to predict in hospital death of patients with acute PE, using a non-gated computed tomography pulmonary angiography (CTPA), based on the dimensions of the right ventricle. METHODS: A retrospective study that analyzed CTPA images of patients admitted with acute PE during the years 2012-2017. The cohort study included 300 patients with documented acute PE, among them 255 hospitalized in medical (non-intensive care unit) wards, 45 were hospitalized in an intensive care unit (ICU). RESULTS: Among the 45 patients admitted to the ICU 8% died. Larger RV diameters predicted mortality (OR = 10.14, 95% CI [1.09-93.86]) as well as lower systolic and diastolic blood pressure measurements (p = 0.001 and 0.01). Among the 255 patients admitted to the Internal Medicine Ward 7% died. Older age (p = 0.028), sepsis and cancer (both p < 0.001), high WBCs count (p < 0.001), and renal failure (p < 0.001) predicted death. Lower blood pressure (systolic and diastolic) (p < 0.001, 0.008), older age (p < 0.007), sepsis (p < 0.001), cancer (p = 0.006), higher WBCs count (p < 0.001), and impaired renal function (p < 0.001) predicted death in patients admitted with acute PE. CONCLUSIONS: Clinical parameters and hematological parameters could predict death of patients admitted with acute PE. RV diameter, measured by the non-ECG gated CTPA, had an additive predictive value for patients who admitted to the ICU.

High Mitral Annulus Calcium Score in Pre-Operative Chest Computerized Tomography and Adverse Outcomes in Mitral Valve Surgery.

BACKGROUND: Severe mitral annulus calcification (MAC) is believed to bear high operative and post-operative risk during mitral valve replacement (MVR) surgery, including longer surgery time, post-surgical valvular leaks and increased rate of embolic phenomena. We hypothesized that quantification of mitral calcium in pre-operative chest computerized tomography (CCT), performed to assess aortic root before cross-clamping may help in risk assessment of adverse intraoperative and postoperative outcomes in patients undergoing MVR. METHODS: We included patients who underwent MVR between the years 2015 and 2018 at Poriya medical center. Preoperative CCT was performed using Philips iCT 256 and Agatston mitral annulus calcium score (MACS) was retrospectively calculated using Philips Intellispace portal version 8.0. Patients were divided into MACS quintiles; 1-3 quintiles were grouped (Low MACS) and compared to the 4-5 quintiles (High MACS) group for demographic, clinical operative and post-operative parameters. RESULTS: A total of 66 patients had MVR, out of which 61% were males, with mean age of 64±9. Concomitant coronary or valvular procedures were done in 60% of patients. The median MACS was 43. High MACS (≥854) was not associated with longer bypass or cross clamp times. No differences in the MVR results were found between the groups. There were 6 post-operative embolic events; 1 mesenteric and 5 cerebral, which were not associated with MACS. CONCLUSION: MACS did not seem to be related to adverse outcomes in MVR. Due to a low event rate and probable pre-selection of patients without extreme mitral annulus calcifications our results should be confirmed in larger prospective study.