Identification and Characterization of Thiamine Diphosphate-Dependent Lyases with an Unusual CDG Motif.

The thiamine diphosphate (ThDP)-binding motif, characterized by the canonical GDG(X)24-27N sequence, is highly conserved among ThDP-dependent enzymes. We investigated a ThDP-dependent lyase (JanthE from Janthinobacterium sp. HH01) with an unusual cysteine (C458) replacing the first glycine of this motif. JanthE exhibits a high substrate promiscuity and accepts long aliphatic α-keto acids as donors. Sterically hindered aromatic aldehydes or non-activated ketones are acceptor substrates, giving access to a variety of secondary and tertiary alcohols as carboligation products. The crystal structure solved at a resolution of 1.9 Šreveals that C458 is not primarily involved in cofactor binding as previously thought for the canonical glycine. Instead, it coordinates methionine 406, thus ensuring the integrity of the active site and the enzyme activity. In addition, we have determined the long-sought genuine tetrahedral intermediates formed with pyruvate and 2-oxobutyrate in the pre-decarboxylation states and deciphered the atomic details for their stabilization in the active site. Collectively, we unravel an unexpected role for the first residue of the ThDP-binding motif and unlock a family of lyases that can perform valuable carboligation reactions.

Early Surgical Resection of Left Atrial Myxoma After Thromboembolic Stroke.

We present a case report of a five-year-old male with acute ischemic stroke who underwent successful mechanical endovascular thrombectomy and early surgical resection of left atrial myxoma two days after onset of stroke symptoms without additional neurological sequelae.

Continuous direct intraarterial treatment of meningitis-induced vasospasm in a pediatric patient: illustrative case.

BACKGROUND: Bacterial meningitis-induced ischemic stroke continues to cause significant long-term complications in pediatric patients. The authors present a case of severe right internal carotid artery terminus and M1 segment vasospasm in a 9-year-old with an infected cholesteatoma, which was refractory to multiple intraarterial treatments with verapamil and milrinone. This is the first report of continuous intraarterial antispasmodic treatment in a pediatric patient as well as the first report of continuous treatment in an awake and extubated patient. OBSERVATIONS: Arterial narrowing was successfully treated by continuous direct intraarterial administration of both a calcium channel blocker (verapamil) and a phosphodiesterase-3 inhibitor (milrinone). The patient recovered remarkably well and was discharged home with no neurological deficit (National Institutes of Health Stroke Scale score 0) and ambulatory without assistance after 22 days. The authors report a promising outcome of this technique performed in a pediatric patient. LESSONS: This represents a novel treatment option for the prevention of stroke in pediatric bacterial meningitis. Continuous, direct intraarterial administration of antispasmodic medications can successfully prevent long-term neurological deficit in pediatric meningitis-associated vasospasm. The described method has the potential to significantly improve outcomes in severe pediatric meningitis-associated vasospasm.

Systematic Review and Case of Thrombectomy for Pediatric Stroke Due to Myxoma Embolism.

BACKGROUND: Stroke presentation secondary to a cardiac myxoma thromboembolism is rare in the pediatric population. Because of such rarity, the reported cases in the literature are primarily case reports. Additionally, general pediatric stroke management lacks evidence-based guidelines because of its low incidence and lack of clinical trials. In pediatric strokes identified from a cardiac myxoma, the incidence favors boys with the classical presentation of unilateral weakness and aphasia. We present a pediatric patient who presented with strokelike symptoms secondary to an intracranial embolus from a previously undiagnosed cardiac myxoma. METHODS: We performed a systematic review by searching PubMed, Google Scholar, Web of Science, and Embase databases for cases of pediatric myxoma causing stroke (n = 2431) and identified 19 reported uses of surgical management in treating pediatric patients who present with stroke symptoms secondary to a cardiac myxoma thromboembolism. RESULTS: The most common imaging modality was magnetic resonance imaging in 42% of cases, computed tomography in 36.8%, followed by computed tomography angiography in 31.6% of cases. Of these 19 children treated with procedures, 36.8% of pediatric patients aged between 4 and 14 years underwent neurosurgery (n = 7). CONCLUSIONS: We describe an urgent mechanical thrombectomy and share preoperative and postoperative images and pathology slides confirming a stroke from myxoma origin. We provide added insight in the safe use of mechanical thrombectomy as treatment for pediatric strokes secondary to a thromboembolism.

Preoperative planning with three-dimensional CT vs. three-dimensional magnetic resonance imaging does not change surgical management for shoulder instability.

Background: This study aims to determine the effect of time and imaging modality (three-dimensional (3D) CT vs. 3D magnetic resonance imaging (MRI)) on the surgical procedure indicated for shoulder instability. The hypothesis is there will be no clinical difference in procedure selection between time and imaging modality. Methods: Eleven shoulder surgeons were surveyed with the same ten shoulder instability clinical scenarios at three time points. All time points included history of present illness, musculoskeletal exam, radiographs, and standard two-dimensional MRI. To assess the effect of imaging modality, survey 1 included 3D MRI while survey 2 included a two-dimensional and 3D CT scan. To assess the effect of time, a retest was performed with survey 3 which was identical to survey 2. The outcome measured was whether surgeons made a "major" or "minor" surgical change between surveys. Results: The average major change rate was 14.1% (standard deviation: 7.6%). The average minor change rate was 12.6% (standard deviation: 7.5%). Between survey 1 to the survey 2, the major change rate was 15.2%, compared to 13.1% when going from the second to the third survey (P = .68). The minior change rate between the first and second surveys was 12.1% and between the second to third interview was 13.1% (P = .8). Discussion: The findings suggest that the major factor related to procedural changes was time between reviewing patient information. Furthermore, this study demonstrates that there remains significant intrasurgeon variability in selecting surgical procedures for shoulder instability. Lastly, the findings in this study suggest that 3D MRI is clinically equivalent to 3D CT in guiding shoulder instability surgical management. Conclusion: This study demonstrates that there is significant variability in surgical procedure selection driven by time alone in shoulder instability. Surgical decision making with 3D MRI was similar to 3D CT scans and may be used by surgeons for preoperative planning.

Multicenter early United States feasibility study and periprocedural safety of LVIS EVO for the treatment of unruptured intracranial aneurysms.

BACKGROUND: Stent development has focused recently on low-profile, self-expandable stents compatible with 0.0165 inch microcatheters. The LVIS EVO is the second-generation version of the Low-Profile Visualized Intraluminal Support (LVIS) with improved visibility and resheathability. The LVIS EVO underwent a limited premarket release (PMR) in December 2023. This study aims to report the early safety and feasibility experience with the LVIS EVO stent for the treatment of intracranial aneurysms in the United States (US). METHODS: This was a multicenter, retrospective, observational study evaluating patients who underwent treatment of an intracranial aneurysm with an LVIS EVO stent after the limited PMR. All physicians who had placed an LVIS EVO stent were asked to input their cases after institutional review board approval was obtained. The data were then sent to a single center for analysis. Any patient aged 18 years or older who underwent treatment of an intracranial aneurysm with a LVIS EVO stent in the US was included from the initial PMR in December 2023 until April 2024. Patient age (or ≤90 years old), sex, preoperative modified Rankin Scale (mRS), aneurysm location, aneurysm measurements, and information about preoperative antiplatelet management were all collected. Data on periprocedural complications, 30-day mortality, discharge mRS, and length of stay were also collected. RESULTS: Some 53 patients with 55 aneurysms underwent treatment with the LVIS EVO stent at 15 institutions. All aneurysms were unruptured. The most common location was the anterior communicating artery (35%) followed by the middle cerebral artery bifurcation (31%). All patients were on dual antiplatelet therapy. The average aneurysm size was 5.2 mm with a neck size of 3.7 mm. The smallest distal parent vessel size was 1.2 mm and 36% of stents were deployed in distal parent vessels <2 mm. All (100%) cases had successful deployment and the stent was repositioned in 10% of cases. A single stent was utilized in 91% of cases. Coils were placed in 48 cases (87.2%) and a microcatheter was jailed in 98% of those cases. Immediate Raymond Roy (RR) Class I occlusion was obtained in 33%, Class II in 22%, Class IIIa in 37%, and Class IIIb in 8% of cases. There were no delayed thromboembolic or hemorrhagic complications. CONCLUSIONS: The LVIS EVO is a braided, self-expanding, retrievable stent with enhanced visibility and smaller cell size. The drawn filled tube (DFT) technology results in improved visibility of the stent, allowing for more controlled stent positioning and visualization of vessel wall apposition. All cases in our series had complete neck coverage and good wall apposition. There were no thromboembolic or hemorrhagic complications.

Mid-term safety and efficacy in small intracranial aneurysm coiling: results from TARGET® nano prospective independent core lab adjudicated multicenter registry.

Background: The primary objective is to evaluate the safety and effectiveness of Stryker second generation Target® Nano Coils in the treatment of ruptured and unruptured small (<7 mm) intracranial aneurysms. Methods: The TARGET Registry is a prospective, two-arm study with independent medical event monitoring and core-lab adjudication. This paper describes the second arm of the TARGET registry. Patients with de novo intracranial aneurysms were embolized with 2nd generation TARGET Nano coils in 12 US centers. The primary efficacy outcome was adequate aneurysm occlusion (RR occlusion grade I-II) on follow-up. Primary safety outcome was treatment-related morbidity and mortality. Secondary outcomes included aneurysm packing density immediately post-procedure, immediate adequate occlusion, aneurysm re-access rate, retreatment rate and clinical outcomes using modified ranking scale. A secondary analysis investigated the influence of using Nano-predominant coils (≥2/3 of total coil-length) vs. non-Nano-predominant coils (<2/3 of total length). Results: 150 patients with 155 aneurysms met the inclusion and exclusion criteria. (31%) patients with ruptured and (69%) with unruptured aneurysms were treated using TARGET coils. Median age was 58.8 (SD 12.7), 74.7% were females, and 80% were Caucasians. Mean follow-up was 5.23 (SD 2.27) months. Peri-procedural mortality was seen in 2.0% of patients. Good outcome at discharge (mRS 0-2) was seen in 81.3% of the cohort. The median packing density (SD) was 29.4% (14.9). Mid-term complete/near complete occlusion rate was seen in 96% of aneurysms and complete obliteration was seen in 75.2% of aneurysms. Patients treated predominantly with Nano coils had higher PD (32.6% vs. 26.1%, p < 0.001). There was no significant difference in clinical and angiographic outcomes. The mid-term mRS0-2 was achieved in 106/109 (97.2%) patients. All-cause mortality was 5/115 (4.3%). Conclusion: In the multicenter TARGET Registry, 75.8% of aneurysms achieved mid-term complete occlusion, and 96% achieved complete/near complete occlusion with excellent independent functional outcome.

The Enterprise stent still useful after all these years.

BACKGROUND: The Enterprise stent (Codman Neuro, Massachusetts, USA) received Food and Drug Administration (FDA) approval in 2007 for stent-assisted coiling (SAC). Since its introduction, newer stents and devices for aneurysm treatment have been developed resulting in a shift in the utilization of this stent from SAC to other off-label indications. OBJECTIVE: To describe our experience with the Enterprise stent being used for SAC and other off-label indications. METHODS: This is a multi-center retrospective review of the use of the Enterprise stent between 2018 and 2023. All patients in which the Enterprise stent was successfully deployed were included in the study. RESULTS: Our study cohort comprised of 194 patients, mostly females (n = 112, 57.7%), with a mean age of 63.2 years ± 14.3. The Enterprise stent was used for SAC in only 24 (12.4%) patients and was used for rescue stenting in stroke in 101 patients (52.1%), treatment of intracranial stenosis in 53 patients (27.3%), treatment of in-stent stenosis in 1 patient (0.5%), and for treatment of dissections in 15 patients (7.7%). From 2018 to 2023, the use of Enterprise stents for SAC significantly decreased (p < 0.0001) while the use of Enterprise stents for non-SAC purposes was insignificantly variable (p = 0.05). CONCLUSION: Our study shows that the Enterprise stent remains a reliable tool in neuroendovascular procedures, even if its original intended use has been supplanted by other devices.

Cystic nephroma and DICER1 mutations: report of a hitherto unreported mutation / Nefroma quístico e mutações DICER1: relato de uma nova mutação

ABSTRACT Paediatric cystic nephroma is a neoplasm of uncertain pathogenesis characterized by a multilocular architecture that develops in children. Some cases may be sporadic, and others may present a familial association, together with other neoplasms, as part of a DICER1 syndrome. We present a case of a paediatric cystic nephroma with an unreported DICER1 mutation and explore the differential diagnosis mainly with cystic partially differentiated nephroblastoma.

RESUMO Nefroma quístico pediátrico é uma neoplasia de patogênese incerta caracterizada por uma arquitetura multilocular, que ocorre maioritariamente em crianças. Alguns casos podem ser esporádicos e outros podem apresentar associação familiar, juntamente com outras neoplasias, constituindo a síndrome DICER1. Apresentamos o caso de um nefroma quístico pediátrico com uma mutação do gene DICER1 não reportada na literatura e exploramos o diagnóstico diferencial, principalmente com o nefroblastoma quístico parcialmente diferenciado.