Transarterial embolization of vein of Galen aneurysmal malformation after unsuccessful stereotactic radiosurgery

The authors present three cases of vein of Galen aneurysmal malformations (VGAMs) diagnosed in infancy and submitted by the referring teams for stereotactic radiosurgery as the initial therapy (therapeutic doses ranging between 20–25 Gy and 40–50 Gy to the peak dose). After the conventional follow-up of 18–24 months, no change could be detected in the angioarchitecture of the lesions. All three cases were then referred for endovascular treatment and underwent embolization by the transarterial route using liquid adhesives (N-butyl cyanoacrylate). This resulted in complete anatomical exclusion of the lesion. Regardless of the theoretical efficiency of radiosurgery in the management of brain arteriovenous malformations, the present authors believe that transarterial embolization remains the treatment of choice in VGAMs. It offers a high rate of morphological cure and the best chances for normal neurocognitive development. The time required by radiosurgery to achieve a significant result is too long for developing and maturing brain and may not prevent the negative effects of the lesion, mainly in regard to hemo- and hydrodynamic disorders (atrophy, subcortical calcifications, etc.) created by the VGAM, thus leading to irreversible mental retardation.     

The incidence, timing, and predisposing factors of germinal matrix and intraventricular hemorrhage (GMH/IVH) in preterm neonates

Background Germinal matrix and intraventricular hemorrhage (GMH/IVH) is a known complication occurring in the first week of life in preterm neonates. However, the precise time of its occurrence and the ideal time to perform diagnostic imaging studies remain controversial. The purpose of this paper is to address these two issues in our patient population to allocate our resources to those at highest risk.Materials and methods This study included 282 premature newborns (under 37 weeks of gestation) that were admitted to our neonate ICU in a year’s time and screened for GMH/IVH. They were grouped in four categories according to their weight at birth, and according to their gestational age. All patients had a daily cranial ultrasound during the first week. It was then repeated once in the second week and once in the third.Results We found that the incidence of GMH/IVH among preterm neonates was 44.68%. It was inversely related to the weight and the age of the newborn. The onset of bleeding coordinated with the occurrence of hypoxia and respiratory distress requiring mechanical ventilation. The majorities occurred in the first 7 days of life; they were mostly grade I and II according to the Papule classification and silent for the most part. Complications were present in 41% of the survivors.     

Clinicopathological analysis of papillary thyroid cancer with PIK3CA alterations in a Middle Eastern population

CONTEXT: Genetic aberration in phosphatidylinositol 3-kinase (PI3K)/AKT pathway has been detected in numerous and diverse human cancers. PIK3CA, which encodes for the catalytic subunit of p110alpha of PI3K, is amplified in some cases of papillary thyroid cancer (PTC). Mutations in the PIK3CA have also been identified in thyroid cancers and, although relatively common in anaplastic thyroid carcinoma, are uncommon in PTC. OBJECTIVE: The objective of the study was to investigate genetic alterations like PIK3CA gene mutation, PIK3CA amplification, RAS, and RAF mutations and to further explore the relationship of these genetic alterations with various clinicopathological characteristics in Middle Eastern PTC. DESIGN: We used the fluorescence in situ hybridization technique for analysis of PIK3CA amplification from 536 PTC cases, and selected amplified samples were further validated by real-time quantitative PCR. Mutation analysis was done by direct DNA sequencing of PIK3CA, N2-RAS, and BRAF genes. RESULTS: PIK3CA amplification was seen in 265 of 499 PTC cases analyzed (53.1%); PIK3CA gene mutations in four of 207 PTC (1.9%); N2-RAS mutations in 16 of 265 PTC (6%); and BRAF mutations in 153 of 296 PTC (51.7%). N-RAS mutations were-associated with an early stage (P = 0.0465) and lower incidence of extrathyroidal extension (P = 0.027), whereas BRAF mutations were-associated with metastasis (P = 0.0274) and poor disease-free survival (P = 0.0121) in PTCs. CONCLUSION: A higher incidence of PIK3CA alterations and the possible synergistic effect of PIK3CA alterations and BRAF mutations suggest their major role in Middle Eastern PTC tumorigenesis and argue for therapeutic targeting of PI3K/AKT and MAPK pathways.     

A safeguard eliminates T cell receptor gene-modified autoreactive T cells after adoptive transfer

By transfer of T cell receptor (TCR) genes, antigen specificity of T cells can be redirected to target any antigen. Adoptive transfer of TCR-redirected T cells into patients has shown promising results. However, this immunotherapy bears the risk of autoreactive side effects if the TCR recognizes antigens on self-tissue. Here, we introduce a safeguard based on a TCR-intrinsic depletion mechanism to eliminate autoreactive TCR-redirected T cells in vivo. By the introduction of a 10-aa tag of the human c-myc protein into murine (OT-I, P14) and human (gp100) TCR sequences, we were able to deplete T cells that were transduced with these myc-tagged TCRs with a tag-specific antibody in vitro. T cells transduced with the modified TCR maintained equal properties compared with cells transduced with the wild-type receptor concerning antigen binding and effector function. More importantly, therapeutic in vivo depletion of adoptively transferred T cells rescued mice showing severe signs of autoimmune insulitis from lethal diabetes. This safeguard allows termination of adoptive therapy in case of severe side effects.     

Is membrane sweeping beneficial at the initiation of labor induction?

Objective: To determine whether cervical membrane sweeping during labor induction is beneficial.

Methods: Outcomes of labor after induction in pregnant women at term were compared in a randomized trial. Women were assigned to having their membranes “swept” or “not swept” at the initiation of labor induction.

Results: We recruited a total of 870 women of which 70 were excluded. There were 400 nullipara (Group A) [198 “swept”, 202 “not swept”] and 400 multiparas (Group B) (201 “swept” and 199 “not swept”]. Among group A who received intravaginal prostaglandin (PG) E₂, those who had simultaneous sweeping had significantly shorter mean induction-labor interval (12.9?±?1.3 versus 16.2?±?1.1 hours, p?=?0.046), lower mean dose of oxytocin (6.6?±?0.6 versus 10.11?±?1.4?mU/minute, p?=?0.01), and increased normal delivery rates (vaginal delivery 82.8% versus 58.6%, p?=?0.01). Sweeping also had a favorable effect on nulliparas who had ARM and received oxytocin alone (mean induction-labor interval 5.9?±?2.9 versus 10.9?±?2.6 hours p?=?0.04, mean maximum dose of oxytocin 9.8?±?1.1 versus 15.2?±?1.1?mU/min, p?=?0.01). These results were restricted to women with unfavorable cervix in Group A those who had membrane sweeping.

Conclusion: Membrane sweeping, has beneficial effects on labor and delivery, which is limited to nulliparas with unfavorable cervix requiring PGE₂ or Oxytocin alone.     

Effects of tissue-engineered articular disc implants on the biomechanical loading of the human temporomandibular joint in a three-dimensional finite element model

The purpose of this study was to evaluate biomechanical loading of the temporomandibular joint when using a biodegradable laminate implant to replace the articular disc and to test the hypothesis that the use of the implant reduces stress distribution in the condyle, implant, and glenoid fossa. A finite element model of a female human mandible, including the temporomandibular joint, which had two standard endosseous implants inserted bilaterally in the premolar region, was constructed from computed tomography scan images using a commercially available finite element software. The disc, condyle, and glenoid fossa were arbitrarily divided into five regions: the anterior, posterior, medial, lateral, and central. The disc was then replaced with a poly-L/DL-lactide biodegradable laminate. The finite element model was then used to predict principal and Von Mises stresses. The use of poly-L/DL-lactide implant resulted in remarkable reduction in Von Mises stresses (approximately threefold) in the anterior, central, and medial regions of the mandibular condyle in comparison with slight to moderate stress reductions in the corresponding regions of the implant and glenoid fossa. The mandibular condyle also demonstrated the largest total displacement in all directions followed by the implant and glenoid fossa. The use of an alloplastic implant such as the bioresorbable, poly-L/DL-lactide laminate to replace the articular disc reduces loading of the mandibular condyle rather than the implant and glenoid fossa. These findings lead to support the hypothesis that the mandibular condyle more likely functions as a shock absorber than the disc. The use of bioresorbable laminate implants might prove an efficient technique to replace the articular disc and promote normal function of the temporomandibular joint.     

Satisfaction with and adherence to warfarin treatment: A cross-sectional study among Sudanese patients

Background

Satisfaction with and adherence to oral anticoagulant treatment are important measures that decrease morbidity and mortality. Higher satisfaction and adherence to warfarin therapy was found to be associated among other factors with good International Normalized Ratio (INR) control.

The SARS-CoV-2 B.1.618 variant slightly alters the spike RBD–ACE2 binding affinity and is an antibody escaping variant: a computational structural perspective

Continuing reports of new SARS-CoV-2 variants have caused worldwide concern and created a challenging situation for clinicians. The recently reported variant B.1.618, which possesses the E484K mutation specific to the receptor-binding domain (RBD), as well as two deletions of Tyr145 and His146 at the N-terminal binding domain (NTD) of the spike protein, must be studied in depth to devise new therapeutic options. Structural variants reported in the RBD and NTD may play essential roles in the increased pathogenicity of this SARS-CoV-2 new variant. We explored the binding differences and structural-dynamic features of the B.1.618 variant using structural and biomolecular simulation approaches. Our results revealed that the E484K mutation in the RBD slightly altered the binding affinity through affecting the hydrogen bonding network. We also observed that the flexibility of three important loops in the RBD required for binding was increased, which may improve the conformational optimization and consequently binding of the new variant. Furthermore, we found that deletions of Tyr145 and His146 at the NTD reduced the binding affinity of the monoclonal antibody (mAb) 4A8, and that the hydrogen bonding network was significantly affected consequently. This data show that the new B.1.618 variant is an antibody-escaping variant with slightly altered ACE2–RBD affinity. Moreover, we provide insights into the binding and structural-dynamics changes resulting from novel mutations in the RBD and NTD. Our results suggest the need for further in vitro and in vivo studies that will facilitate the development of possible therapies for new variants such as B.1.618.

This study explored the binding patterns of the wild type and B.1.618 variant using which revealed that the B.1.618 variant possess a stronger binding affinity for the host ACE2 and escape the neutralizing antibodies.