Electroclinical and Multimodality Neuroimaging Characteristics and Predictors of Post-Surgical Outcome in Focal Cortical Dysplasia Type IIIa

Focal cortical dysplasia (FCD) type IIIa is an easily ignored cause of intractable temporal lobe epilepsy. This study aimed to analyze the clinical, electrophysiological, and imaging characteristics in FCD type IIIa and to search for predictors associated with postoperative outcome in order to identify potential candidates for epilepsy surgery. We performed a retrospective review including sixty-six patients with FCD type IIIa who underwent resection for drug-resistant epilepsy. We evaluated the clinical, electrophysiological, and neuroimaging features for potential association with seizure outcome. Univariate and multivariate analyses were conducted to explore their predictive role on the seizure outcome. We demonstrated that thirty-nine (59.1%) patients had seizure freedom outcomes (Engel class Ia) with a median postsurgical follow-up lasting 29.5 months. By univariate analysis, duration of epilepsy (less than 12 years) (p = 0.044), absence of contralateral insular lobe hypometabolism on PET/MRI (pLog-rank = 0.025), and complete resection of epileptogenic area (pLog-rank = 0.004) were associated with seizure outcome. The incomplete resection of the epileptogenic area (hazard ratio = 2.977, 95% CI 1.218–7.277, p = 0.017) was the only independent predictor for seizure recurrence after surgery by multivariate analysis. The results of past history, semiology, electrophysiological, and MRI were not associated with seizure outcomes. Carefully included patients with FCD type IIIa through a comprehensive evaluation of their clinical, electrophysiological, and neuroimaging characteristics can be good candidates for resection. Several preoperative factors appear to be predictive of the postoperative outcome and may help in optimizing the selection of ideal candidates to benefit from epilepsy surgery.

A comparative analysis of anatomical variations of popliteal artery and its branches in concomitant aneurysmal disease

Objectives Open or endovascular treatment of popliteal artery aneurysms (PAAs) is still debated. Data about the popliteal artery anatomy and its branches are essential to plan a surgical approach. The aim of this study was to report the anatomical variations of the popliteal artery and its branches in a population with aneurysmal disease and compare them with a standard population with non-aneurysmal disease. Methods A retrospective review of consecutive patients who underwent surgical PAA repair in our center between January 2011 and December 2020 was performed. One-hundred-forty-six limbs in 128 patients underwent PAA treatment (Group 1). Computed tomography angiography images using a 128-section configuration were reviewed for anatomical variations of the popliteal artery and its branches. A control population of 178 limbs in 89 patients with non-aneurysmal disease was used to compare the outcomes (Group 2). All limbs were classified according to Kim’s classification. The two groups were analyzed and compared by means of nonparametric Pearson chi-square test. Results Both groups were homogeneous in terms of demographics, risk factors, and clinical presentation. In Group 1, the limbs with PAA were classified as type IA, 133 (91.1%); type IB, 2 (1.4%); type IC, 0; type IIA1, 1 (0.7%); type IIA2, 1 (0.7%); type IIB, 4 (2.7%); type IIC, 0; type IIIA, 3 (2.1%); type IIIB, 0; and type IIIC, 2 (1.4%). In Group 2 the limbs with non-aneurysmal disease were classified as type IA, 163 (91.6%); type IB, 5 (2.8%); type IC, 1 (0.6%); type IIA1, 1 (0.6%); type IIA2, 3 (1.7%); type IIB, 2 (1.1%); type IIC, 0; type IIIA, 3 (1.7%); type IIIB, 0; and type IIIC, 0. No difference in terms of anatomy of the popliteal artery and its branches was found between the two groups ( P = NS). Conclusions Knowledge of anatomical variations of the popliteal artery and its branches is mandatory in case of the surgical approach. Anatomy in PAA patients is not different. Studies with larger population size are needed to validate these outcomes.

An International, Multicenter Retrospective Observational Study to Assess Technical Success and Clinical Outcomes of Patients Treated with an Endovascular Aneurysm Sealing Device for Type III Endoleak

Introduction: Type III endoleaks post-endovascular aortic aneurysm repair (EVAR) warrant treatment because they increase pressure within the aneurysm sac leading to increased rupture risk. The treatment may be difficult with regular endovascular devices. Endovascular aneurysm sealing (EVAS) might provide a treatment option for type III endoleaks, especially if located near the flow divider. This study aims to analyze clinical outcomes of EVAS for type III endoleaks after EVAR. Methods: This is an international, retrospective, observational cohort study including data from 8 European institutions. Results: A total of 20 patients were identified of which 80% had a type IIIb endoleak and the remainder (20%) a type IIIa endoleak. The median time between EVAR and EVAS was 49.5 months (28.5–89). Mean AAA diameter prior to EVAS revision was 76.6±19.9 mm. Technical success was achieved in 95%, 1 patient had technical failure due to a postoperative myocardial infarction resulting in death. Mean follow-up was 22.8±15.2 months. During follow-up 1 patient had a type Ia endoleak, and 1 patient had a new type IIIa endoleak at an untreated location. There were 5 patients with aneurysm growth. Five patients underwent AAA-related reinterventions indications being: growth with type II endoleak (n=3), type Ia endoleak (n=1), and iliac aneurysm (n=1). At 1-year follow-up, the freedom from clinical failure was 77.5%, freedom from all-cause mortality 94.7%, freedom from aneurysm-related mortality 95%, and freedom from aneurysm-related reinterventions 93.8%. Conclusion: The EVAS relining can be safely performed to treat type III endoleaks with an acceptable technical success rate, a low 30-day mortality rate and no secondary ruptures at short-term follow-up. The relatively low clinical success rates, related to reinterventions and AAA enlargement, highlight the need for prolonged follow-up.

Ultrasonographic characteristics and outcome of Type III umbilical-portal-systemic venous shunt

Aims: According to a novel in-utero classification termed “umbilical-portal-systemic venous shunt (UPSVS)” recently proposed for an abnormal umbilical, portal and ductal venous system, the portal-systemic shunt belongs to type III UPSVS. This study was designed to examine the ultrasonographic characteristics and outcome of type III UPSVS.Material and methods: All cases of Type III UPSVS diagnosed at our department from April 2016 to December 2020 were retrospectively studied.Results: Seventeen patients with type III UPSVS including 12 type IIIa and 5 IIIb cases were identified. Sonography showed a shunt between the inferior left portal vein and the left hepatic vein in all type IIIa cases. Three cases of type IIIb had a combination of another shunt (2 with type I and one with type IIIa). Integrate intrahepatic portal vein system was not seen in those 2 cases of type IIIb combined with type I UPSVS, leading to termination of pregnancy (TOP). TOP occurred in 4 patients with type IIIa as requested by the parents. Two cases (type IIIa and type IIIb each) underwent surgical procedure for the closure of the shunt. Spontaneous complete closure in 4 type IIIa cases and partial closure in one type IIIb case occurred during a period of 3-16 months.Conclusions: The majority of patients had type IIIa UPSVS presenting a good outcome. The lack of integrate intrahepatic portal vein system was the main reason for TOP in patients with type IIIb UPSVS. These data suggest the UPSVS classification is a useful tool for a prognosis prediction of type III UPSVS.

CRISPR-Associated Primase-Polymerases are implicated in prokaryotic CRISPR-Cas adaptation

CRISPR-Cas pathways provide prokaryotes with acquired “immunity” against foreign genetic elements, including phages and plasmids. Although many of the proteins associated with CRISPR-Cas mechanisms are characterized, some requisite enzymes remain elusive. Genetic studies have implicated host DNA polymerases in some CRISPR-Cas systems but CRISPR-specific replicases have not yet been discovered. We have identified and characterised a family of CRISPR-Associated Primase-Polymerases (CAPPs) in a range of prokaryotes that are operonically associated with Cas1 and Cas2. CAPPs belong to the Primase-Polymerase (Prim-Pol) superfamily of replicases that operate in various DNA repair and replication pathways that maintain genome stability. Here, we characterise the DNA synthesis activities of bacterial CAPP homologues from Type IIIA and IIIB CRISPR-Cas systems and establish that they possess a range of replicase activities including DNA priming, polymerisation and strand-displacement. We demonstrate that CAPPs operonically-associated partners, Cas1 and Cas2, form a complex that possesses spacer integration activity. We show that CAPPs physically associate with the Cas proteins to form bespoke CRISPR-Cas complexes. Finally, we propose how CAPPs activities, in conjunction with their partners, may function to undertake key roles in CRISPR-Cas adaptation.