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1.
Neurosurgery ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38747605

RESUMO

BACKGROUND AND OBJECTIVES: Vein of Galen malformation (VOGM), the result of arteriovenous shunting between choroidal and/or subependymal arteries and the embryologic prosencephalic vein, is among the most severe cerebrovascular disorders of childhood. We hypothesized that in situ analysis of the VOGM lesion using endoluminal tissue sampling (ETS) is feasible and may advance our understanding of VOGM genetics, pathogenesis, and maintenance. METHODS: We collected germline DNA (cheek swab) from patients and their families for genetic analysis. In situ VOGM "endothelial" cells (ECs), defined as CD31+ and CD45-, were obtained from coils through ETS during routine endovascular treatment. Autologous peripheral femoral ECs were also collected from the access sheath. Single-cell RNA sequencing of both VOGM and peripheral ECs was performed to demonstrate feasibility to define the transcriptional architecture. Comparison was also made with a published normative cerebrovascular transcriptome atlas. A subset of VOGM ECs was reserved for future DNA sequencing to assess for somatic and second-hit mutations. RESULTS: Our cohort contains 6 patients who underwent 10 ETS procedures from arterial and/or venous access during routine VOGM treatment (aged 12 days to ∼6 years). No periprocedural complications attributable to ETS occurred. Six unique coil types were used. ETS captured 98 ± 88 (mean ± SD; range 17-256) experimental ECs (CD31+ and CD45-). There was no discernible correlation between cell yield and coil type or route of access. Single-cell RNA sequencing demonstrated hierarchical clustering and unique cell populations within the VOGM EC compartment compared with peripheral EC controls when annotated using a publicly available cerebrovascular cell atlas. CONCLUSION: ETS may supplement investigations aimed at development of a molecular-genetic taxonomic classification scheme for VOGM. Moreover, results may eventually inform the selection of personalized pharmacologic or genetic therapies for VOGM and cerebrovascular disorders more broadly.

2.
J Neurosurg ; : 1-8, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38701528

RESUMO

OBJECTIVE: This study was conducted to investigate the impact of antiplatelet administration in the periprocedural period on the occurrence of thromboembolic complications (TECs) in patients undergoing treatment using the Woven EndoBridge (WEB) device for intracranial wide-necked bifurcation aneurysms. The primary objective was to assess whether the use of antiplatelets in the pre- and postprocedural phases reduces the likelihood of developing TECs, considering various covariates. METHODS: A retrospective multicenter observational study was conducted within the WorldWideWEB Consortium and comprised 38 academic centers with endovascular treatment capabilities. Univariable and multivariable logistic regression analyses were performed to determine the association between antiplatelet use and TECs, adjusting for covariates. Missing predictor data were addressed using multiple imputation. RESULTS: The study comprised two cohorts: one addressing general thromboembolic events and consisting of 1412 patients, among whom 103 experienced TECs, and another focusing on symptomatic thromboembolic events and comprising 1395 patients, of whom 50 experienced symptomatic TECs. Preprocedural antiplatelet use was associated with a reduced likelihood of overall TECs (OR 0.32, 95% CI 0.19-0.53, p < 0.001) and symptomatic TECs (OR 0.49, 95% CI 0.25-0.95, p = 0.036), whereas postprocedural antiplatelet use showed no significant association with TECs. The study also revealed additional predictors of TECs, including stent use (overall: OR 4.96, 95% CI 2.38-10.3, p < 0.001; symptomatic: OR 3.24, 95% CI 1.26-8.36, p = 0.015), WEB single-layer sphere (SLS) type (overall: OR 0.18, 95% CI 0.04-0.74, p = 0.017), and posterior circulation aneurysm location (symptomatic: OR 18.43, 95% CI 1.48-230, p = 0.024). CONCLUSIONS: The findings of this study suggest that the preprocedural administration of antiplatelets is associated with a reduced likelihood of TECs in patients undergoing treatment with the WEB device for wide-necked bifurcation aneurysms. However, postprocedural antiplatelet use did not show a significant impact on TEC occurrence.

3.
Childs Nerv Syst ; 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38506930

RESUMO

INTRODUCTION: Pediatric non-galenic pial arteriovenous fistulas (pAVFs) are rare vascular malformations that are characterized by a pial arterial-venous connection without an intervening capillary bed. Outcomes and treatment strategies for pAVFs are highly individualized, owing to the rarity of the disease and lack of large-scale data guiding optimal treatment approaches. METHODS: We performed a systematic review of pediatric patients (< 18 years at diagnosis) diagnosed with a pAVF by digital subtraction angiogram (DSA). The demographics, treatment modalities, and outcomes were documented for each patient and clinical outcome data was collected. Descriptive information stratified by outcome scores were classified as follows: 1 = excellent (no deficit and full premorbid activity), 2 = good (mild deficit and full premorbid activity), 3 = fair (moderate deficit and impaired activity), 4 = poor (severe deficit and dependent on others), 5 = death. RESULTS: A total of 87 studies involving 231 patients were identified. Median age at diagnosis was 3 years (neonates to 18 years). There was slight male preponderance (55.4%), and 150 subjects (81.1%*) experienced excellent outcomes after treatment. Of the 189 patients treated using endovascular approaches, 80.3% experienced excellent outcomes and of the 15 patients surgically treated subjects 75% had an excellent outcome. The highest rate of excellent outcomes was achieved in patients treated with Onyx (95.2%) and other forms of EvOH (100%). High output heart failure and comorbid vascular lesions tended to result in worse outcomes, with only 54.2% and 68% of subjects experiencing an excellent outcome, respectively. *Outcomes were reported in only 185 patients. CONCLUSION: pAVFs are rare lesions, necessitating aggregation of patient data to inform natural history and optimal treatment strategies. This review summarizes the current literature on pAVF in children, where children presenting with heart failure as a result of high flow through the lesion were less likely to experience an excellent outcome. Prospective, large-scale studies would further characterize pediatric pAVFs and enable quantitative analysis of outcomes to inform best treatment practices.

4.
Neurosurg Rev ; 47(1): 116, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38483647

RESUMO

BACKGROUND: The Woven EndoBridge (WEB) devices have been used for treating wide neck bifurcation aneurysms (WNBAs) with several generational enhancements to improve clinical outcomes. The original device dual-layer (WEB DL) was replaced by a single-layer (WEB SL) device in 2013. This study aimed to compare the effectiveness and safety of these devices in managing intracranial aneurysms. METHODS: A multicenter cohort study was conducted, and data from 1,289 patients with intracranial aneurysms treated with either the WEB SL or WEB DL devices were retrospectively analyzed. Propensity score matching was utilized to balance the baseline characteristics between the two groups. Outcomes assessed included immediate occlusion rate, complete occlusion at last follow-up, retreatment rate, device compaction, and aneurysmal rupture. RESULTS: Before propensity score matching, patients treated with the WEB SL had a significantly higher rate of complete occlusion at the last follow-up and a lower rate of retreatment. After matching, there was no significant difference in immediate occlusion rate, retreatment rate, or device compaction between the WEB SL and DL groups. However, the SL group maintained a higher rate of complete occlusion at the final follow-up. Regression analysis showed that SL was associated with higher rates of complete occlusion (OR: 0.19; CI: 0.04 to 0.8, p = 0.029) and lower rates of retreatment (OR: 0.12; CI: 0 to 4.12, p = 0.23). CONCLUSION: The WEB SL and DL devices demonstrated similar performances in immediate occlusion rates and retreatment requirements for intracranial aneurysms. The SL device showed a higher rate of complete occlusion at the final follow-up.


Assuntos
Embolização Terapêutica , Procedimentos Endovasculares , Aneurisma Intracraniano , Humanos , Resultado do Tratamento , Aneurisma Intracraniano/cirurgia , Aneurisma Intracraniano/etiologia , Embolização Terapêutica/efeitos adversos , Pontuação de Propensão , Estudos Retrospectivos , Estudos de Coortes , Procedimentos Endovasculares/efeitos adversos
5.
Nat Commun ; 15(1): 2558, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38519509

RESUMO

Encapsulins are self-assembling protein nanocompartments capable of selectively encapsulating dedicated cargo proteins, including enzymes involved in iron storage, sulfur metabolism, and stress resistance. They represent a unique compartmentalization strategy used by many pathogens to facilitate specialized metabolic capabilities. Encapsulation is mediated by specific cargo protein motifs known as targeting peptides (TPs), though the structural basis for encapsulation of the largest encapsulin cargo class, dye-decolorizing peroxidases (DyPs), is currently unknown. Here, we characterize a DyP-containing encapsulin from the enterobacterial pathogen Klebsiella pneumoniae. By combining cryo-electron microscopy with TP and TP-binding site mutagenesis, we elucidate the molecular basis for cargo encapsulation. TP binding is mediated by cooperative hydrophobic and ionic interactions as well as shape complementarity. Our results expand the molecular understanding of enzyme encapsulation inside protein nanocompartments and lay the foundation for rationally modulating encapsulin cargo loading for biomedical and biotechnological applications.


Assuntos
Proteínas de Bactérias , Peroxidase , Proteínas de Bactérias/metabolismo , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/metabolismo , Microscopia Crioeletrônica , Peroxidases/metabolismo
6.
MicroPubl Biol ; 20242024.
Artigo em Inglês | MEDLINE | ID: mdl-38545437

RESUMO

The anticancer drug Gefitinib is a tyrosine kinase inhibitor with selectivity for the Epidermal Growth Factor Receptor (EGFR/ErbB1). As the C. elegans EGF receptor LET-23 shares notable structural homology over its kinase domain with human EGFR, we wished to examine whether Gefitinib treatment can interfere with LET-23-dependent processes. We show that Gefitinib disrupts C. elegans stress-induced sleep (SIS) but does not impact EGF overexpression-induced sleep nor vulva induction. These findings indicate that Gefitinib does not interfere with LET-23 signaling and impairs SIS through an off-target mechanism.

7.
J Neurointerv Surg ; 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38238006

RESUMO

BACKGROUND: The Woven EndoBridge (WEB) device is frequently used for the treatment of intracranial aneurysms. Postoperative management, including the use of aspirin, varies among clinicians and institutions, but its impact on the outcomes of the WEB has not been thoroughly investigated. METHODS: This was a retrospective, multicenter study involving 30 academic institutions in North America, South America, and Europe. Data from 1492 patients treated with the WEB device were included. Patients were categorized into two groups based on their postoperative use of aspirin (aspirin group: n=1124, non-aspirin group: n=368). Data points included patient demographics, aneurysm characteristics, procedural details, complications, and angiographic and functional outcomes. Propensity score matching (PSM) was applied to balance variables between the two groups. RESULTS: Prior to PSM, the aspirin group exhibited significantly higher rates of modified Rankin scale (mRS) mRS 0-1 and mRS 0-2 (89.8% vs 73.4% and 94.1% vs 79.8%, p<0.001), lower rates of mortality (1.6% vs 8.6%, p<0.001), and higher major compaction rates (13.4% vs 7%, p<0.001). Post-PSM, the aspirin group showed significantly higher rates of retreatment (p=0.026) and major compaction (p=0.037) while maintaining its higher rates of good functional outcomes and lower mortality rates. In the multivariable regression, aspirin was associated with higher rates of mRS 0-1 (OR 2.166; 95% CI 1.16 to 4, p=0.016) and mRS 0-2 (OR 2.817; 95% CI 1.36 to 5.88, p=0.005) and lower rates of mortality (OR 0.228; 95% CI 0.06 to 0.83, p=0.025). However, it was associated with higher rates of retreatment (OR 2.471; 95% CI 1.11 to 5.51, p=0.027). CONCLUSIONS: Aspirin use post-WEB treatment may lead to better functional outcomes and lower mortality but with higher retreatment rates. These insights are crucial for postoperative management after WEB procedures, but further studies are necessary for validation.

8.
Childs Nerv Syst ; 40(1): 197-204, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37864710

RESUMO

BACKGROUND: Dural arteriovenous fistulas (dAVF) are arteriovenous shunts in communication with the dural vasculature in the brain or spine. Apart from single-center series, risk factors and treatment outcomes for pediatric dAVFs are largely undescribed. METHODS: We performed a systematic literature review of pediatric (< 18 years at diagnosis) intracranial and spinal dAVF according to PRISMA guidelines. We queried PubMed, CINAHL, SCOPUS, and Embase databases without time/date restriction. Search strings included a variety of MeSH keywords relating to dural AV fistulas in combination with MeSH keywords related to pediatric cases (see Appendix). Manuscripts describing patients diagnosed with dural sinus malformations or pial AVF were excluded. RESULTS: We identified 61 studies describing 69 individual patients. Overall, dAVF were more common in males (55.1%) with a mean age of diagnosis (5.17 ± 4.42 years). Approximately 20.2% of patients presented with cardiovascular disease (CVD), and 31.9% were discovered incidentally on neuroimaging studies. Transverse-sigmoid junction was the most common location (17.3%). Ninety-three percent (64 patients) were treated, most commonly using endovascular embolization (68.1%) followed by surgery (8.7%) and radiosurgery (2.9%). Almost half (43.8%) of dAVFs were completely obliterated. Of the 64 procedures, there were 19 neurological complications (29.7%) of varying severity where 12.5% were considered transient (i.e., pseudomeningocele) and 17.2% permanent (i.e., mortality secondary to acute sinus thrombosis, etc.). CONCLUSION: There is a paucity of information on pediatric dAVFs. This systematic review summarizes the published cases of dAVFs in the pediatric population. While the rate of missing data is high, there is publication bias, and precise details regarding complications are difficult to ascertain, this review serves as a descriptive summary of pediatric dAVFs.


Assuntos
Fístula Arteriovenosa , Malformações Vasculares do Sistema Nervoso Central , Embolização Terapêutica , Radiocirurgia , Masculino , Humanos , Criança , Lactente , Pré-Escolar , Resultado do Tratamento , Embolização Terapêutica/métodos , Malformações Vasculares do Sistema Nervoso Central/diagnóstico por imagem , Malformações Vasculares do Sistema Nervoso Central/terapia , Fístula Arteriovenosa/diagnóstico por imagem , Fístula Arteriovenosa/terapia , Fístula Arteriovenosa/etiologia
9.
J Neurosurg ; 140(4): 1071-1079, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37862717

RESUMO

OBJECTIVE: The Woven EndoBridge (WEB) device is an intrasaccular flow disruptor designed for wide-necked bifurcation aneurysms. These aneurysms may require the use of a concomitant stent. The objective of this study was to determine the clinical and radiological outcomes of patients undergoing stent-assisted WEB treatment. In addition, the authors also sought to determine the predictors of a concomitant stent in aneurysms treated with the WEB device. METHODS: The data for this study were taken from the WorldWideWEB Consortium, an international multicenter cohort including patients treated with the WEB device. Aneurysms were classified into two groups based on treatment: stent-assisted WEB and WEB device alone. The authors compared clinical and radiological outcomes of both groups. Univariable and multivariable binary logistic regression analyses were performed to determine factors that predispose to stent use. RESULTS: The study included 691 intracranial aneurysms (31 with stents and 660 without stents) treated with the WEB device. The adequate occlusion status did not differ between the two groups at the latest follow-up (83.3% vs 85.6%, p = 0.915). Patients who underwent stenting had more thromboembolic (32.3% vs 6.5%, p < 0.001) and procedural (16.1% vs 3.0%, p < 0.001) complications. Aneurysms treated with a concomitant stent had wider necks, greater heights, and lower dome-to-neck ratios. Increasing neck size was the only significant predictor for stent use. CONCLUSIONS: This study demonstrates that there is no difference in the degree of aneurysm occlusion between the two groups; however, complications were more frequent in the stent group. In addition, a wider aneurysm neck predisposes to stent assistance in WEB-treated aneurysms.


Assuntos
Embolização Terapêutica , Procedimentos Endovasculares , Aneurisma Intracraniano , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgia , Resultado do Tratamento , Estudos Retrospectivos , Stents
10.
bioRxiv ; 2023 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-37790520

RESUMO

Encapsulins are self-assembling protein nanocompartments capable of selectively encapsulating dedicated cargo proteins, including enzymes involved in iron storage, sulfur metabolism, and stress resistance. They represent a unique compartmentalization strategy used by many pathogens to facilitate specialized metabolic capabilities. Encapsulation is mediated by specific cargo protein motifs known as targeting peptides (TPs), though the structural basis for encapsulation of the largest encapsulin cargo class, dye-decolorizing peroxidases (DyPs), is currently unknown. Here, we characterize a DyP-containing encapsulin from the enterobacterial pathogen Klebsiella pneumoniae. By combining cryo-electron microscopy with TP mutagenesis, we elucidate the molecular basis for cargo encapsulation. TP binding is mediated by cooperative hydrophobic and ionic interactions as well as shape complementarity. Our results expand the molecular understanding of enzyme encapsulation inside protein nanocompartments and lay the foundation for rationally modulating encapsulin cargo loading for biomedical and biotechnological applications.

11.
Interv Neuroradiol ; : 15910199231185804, 2023 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-37769315

RESUMO

BACKGROUND: Studies during the COVID-19 pandemic have demonstrated an association between COVID-19 virus infection and the development of acute ischemic stroke, particularly large vessel occlusion (LVO). Studying the characteristics and immunohistochemistry of retrieved stroke emboli during mechanical thrombectomy for LVO may offer insights into the pathogenesis of LVO in COVID-19 patients. We examined retrieved COVID-19 emboli from the STRIP, EXCELLENT, and RESTORE registries and compared their characteristics to a control group. METHODS: We identified COVID-positive LVO patients from the STRIP, RESTORE, and EXCELLENT studies who underwent mechanical thrombectomy. These patients were matched to a control group controlling for stroke etiology based on Trial of Org 10172 in Acute Stroke Treatment criteria. All clots were stained with Martius Scarlet Blue (MSB) along with immunohistochemistry for interleukin-6 (IL-6), C-reactive protein (CRP), von Willebrand factor (vWF), CD66b, fibrinogen, and citrullinated Histone H3. Clot composition was compared between groups. RESULTS: Nineteen COVID-19-positive patients and 38 controls were included. COVID-19-positive patients had a significantly higher percentage of CRP and vWF. There was no difference in IL-6, fibrin, CD66b, or citrullinated Histone H3 between groups. Based on MSB staining, there was no statistically significant difference regarding the percentage of red blood cells, white blood cells, fibrin, and platelets. CONCLUSIONS: Our study found higher concentrations of CRP and vWF in retrieved clots of COVID-19-positive stroke patients compared to COVID-19-negative controls. These findings support the potential role of systemic inflammation as indicated by elevated CRP and endothelial injury as indicated by elevated vWF as precipitating factors in thrombus development in these patients.

12.
J Neurointerv Surg ; 2023 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-37479480

RESUMO

BACKGROUND: Medium vessel occlusions (MeVOs) comprise a large proportion of all stroke events. We performed a multicenter study of MIVI Q catheters, a novel design that optimizes suction forces without an increase in lumen diameter, for the treatment of MeVOs, aiming to evaluate its efficacy and safety. METHODS: Databases of two US and two UK centers were retrospectively reviewed for MeVO patients (M2-M3, anterior cerebral artery (ACA), or posterior cerebral artery (PCA)) treated with Q catheters. Outcomes were assessed as successful recanalization (modified Thrombolysis in Cerebral Infarction (mTICI) score ≥2b), first pass effect (FPE), and modified FPE (mFPE) as single pass achieving mTICI ≥2c and mTICI≥2b, respectively, and 90 day modified Rankin Scale (mRS) score. RESULTS: 69 patients were included (median age 71 years, IQR 56-82.5; 52.2% men). Median National Institutes of Health Stroke Scale (NIHSS) score at admission was 14, and Alberta Stroke Program Early CT Score (ASPECTS) was 9. Primary (without large vessel occlusion (LVO)) and secondary (with LVO) MeVOs represented 47.8% and 52.2% of cases, respectively. Q catheters used were Q3 (47.8%), Q4 (33.3%), Q5 (10.1%), and Q6 (8.7%). mTICI≥2b was achieved in 92.8% of patients, with FPE in 47.8%, and mFPE in 68.1%. Two (2.9%) intraprocedural complications (symptomatic intracranial hemorrhage) occurred. 50% (27/54) achieved an mRS score of ≤2 at the 90 day follow-up. The median NIHSS at admission was significantly higher in secondary than in primary MeVOs (19.5 vs 12, P=0.009). The rate of mRS ≤2 at 90 days was significantly higher in primary than in secondary MeVOs (77.3% vs 31.3%, P=0.002). CONCLUSIONS: Treatment of MeVO patients with Q catheters resulted in optimal angiographic and clinical outcomes. Although angiographic results were similar between primary and secondary MeVOs, the former had less severe presenting NIHSS and better outcomes at 90 days than the latter.

13.
Ultrasound Med Biol ; 49(8): 1892-1900, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37271680

RESUMO

OBJECTIVE: Focused ultrasound (FUS) has become a non-invasive option for some surgical procedures, including tumor ablation and thalamotomy. Extension of magnetic resonance (MR) imaging-guided focused ultrasound for ablation of slowly perfused cerebrovascular lesions requires a novel treatment monitoring method that does not rely on thermometry or high-frequency Doppler methods. The goal of this study was to evaluate the sensitivity and specificity of strain estimates based on MR acoustic radiation force imaging (MR-ARFI) for differentiation of solids and liquids. METHODS: Strain fields were estimated in gelatin-based tissue-mimicking focused ultrasound phantoms on the basis of apparent displacement fields measured by MR-ARFI. MR-ARFI and diffusion-weighted imaging (DWI) measurements were made before and after FUS-induced heating to evaluate the performance of displacement, strain and apparent diffusion coefficient (ADC) measurements for the discrimination of solid and liquid phases. RESULTS: As revealed by receiver operating characteristic analyses, axial normal strain and shear strain components performed significantly better than axial displacement measurements alone when predicting whether a gelatin had melted. Additional measurements must be made to estimate certain strain components, so this trade-off must be considered when developing clinical strategies. ADC had the best overall performance, but DWI is vulnerable to signal dropouts and susceptibility artifacts near cerebrovascular lesions, so this metric may have limited clinical applicability. CONCLUSION: Strain components based on MR-ARFI apparent displacement measurements perform better than apparent displacement measurements alone at discriminating between solids and liquids. These methods are applicable to FUS treatment monitoring and evaluation of mechanical tissue properties in vivo.


Assuntos
Gelatina , Ablação por Ultrassom Focalizado de Alta Intensidade , Imageamento por Ressonância Magnética/métodos , Imagem de Difusão por Ressonância Magnética , Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Ondas Ultrassônicas
14.
J Mater Chem B ; 11(20): 4377-4388, 2023 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-37158413

RESUMO

Encapsulins are a recently discovered class of prokaryotic self-assembling icosahedral protein nanocompartments measuring between 24 and 42 nm in diameter, capable of selectively encapsulating dedicated cargo proteins in vivo. They have been classified into four families based on sequence identity and operon structure, and thousands of encapsulin systems have recently been computationally identified across a wide range of bacterial and archaeal phyla. Cargo encapsulation is mediated by the presence of specific targeting motifs found in all native cargo proteins that interact with the interior surface of the encapsulin shell during self-assembly. Short C-terminal targeting peptides (TPs) are well documented in Family 1 encapsulins, while more recently, larger N-terminal targeting domains (TDs) have been discovered in Family 2. The modular nature of TPs and their facile genetic fusion to non-native cargo proteins of interest has made cargo encapsulation, both in vivo and in vitro, readily exploitable and has therefore resulted in a range of rationally engineered nano-compartmentalization systems. This review summarizes current knowledge on cargo protein encapsulation within encapsulins and highlights select studies that utilize TP fusions to non-native cargo in creative and useful ways.


Assuntos
Bactérias , Proteínas de Bactérias , Humanos , Proteínas de Bactérias/metabolismo , Bactérias/metabolismo
15.
Biomacromolecules ; 24(3): 1388-1399, 2023 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-36796007

RESUMO

Encapsulins are microbial protein nanocages capable of efficient self-assembly and cargo enzyme encapsulation. Due to their favorable properties, including high thermostability, protease resistance, and robust heterologous expression, encapsulins have become popular bioengineering tools for applications in medicine, catalysis, and nanotechnology. Resistance against physicochemical extremes like high temperature and low pH is a highly desirable feature for many biotechnological applications. However, no systematic search for acid-stable encapsulins has been carried out, while the influence of pH on encapsulin shells has so far not been thoroughly explored. Here, we report on a newly identified encapsulin nanocage from the acid-tolerant bacterium Acidipropionibacterium acidipropionici. Using transmission electron microscopy, dynamic light scattering, and proteolytic assays, we demonstrate its extreme acid tolerance and resilience against proteases. We structurally characterize the novel nanocage using cryo-electron microscopy, revealing a dynamic five-fold pore that displays distinct "closed" and "open" states at neutral pH but only a singular "closed" state under strongly acidic conditions. Further, the "open" state exhibits the largest pore in an encapsulin shell reported to date. Non-native protein encapsulation capabilities are demonstrated, and the influence of external pH on internalized cargo is explored. Our results expand the biotechnological application range of encapsulin nanocages toward potential uses under strongly acidic conditions and highlight pH-responsive encapsulin pore dynamics.


Assuntos
Bactérias , Proteínas de Bactérias , Proteínas de Bactérias/química , Microscopia Crioeletrônica , Bactérias/metabolismo , Biotecnologia , Nanotecnologia
16.
J Neurointerv Surg ; 15(9): 844-850, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35868856

RESUMO

BACKGROUND: The Woven EndoBridge (WEB) device is a novel intrasaccular flow disruptor tailored for bifurcation aneurysms. We aim to describe the degree of aneurysm occlusion at the latest follow-up, and the rate of complications of aneurysms treated with the WEB device stratified according to rupture status. METHODS: Our data were taken from the WorldWideWeb Consortium, an international multicenter cohort including patients treated with the WEB device. Aneurysms were classified into two groups: ruptured and unruptured. We compared clinical and radiologic outcomes of both groups. Propensity score matching (PSM) was done to match according to age, gender, bifurcation, location, prior treatment, neck, height, dome width, daughter sac, incorporated branch, pretreatment antiplatelets, and last imaging follow-up. RESULTS: The study included 676 patients with 691 intracranial aneurysms (529 unruptured and 162 ruptured) treated with the WEB device. The PSM analysis had 55 pairs. In both the unmatched (85.8% vs 84.3%, p=0.692) and matched (94.4% vs 83.3%, p=0.066) cohorts there was no significant difference in the adequate occlusion rate at the last follow-up. Likewise, there were no significant differences in both ischemic and hemorrhagic complications between the two groups. There was no documented aneurysm rebleeding after WEB device implantation. CONCLUSION: There was no significant difference in both the radiologic outcomes and complications between unruptured and ruptured aneurysms. Our findings support the feasibility of treatment of ruptured aneurysms with the WEB device.


Assuntos
Aneurisma Roto , Embolização Terapêutica , Procedimentos Endovasculares , Aneurisma Intracraniano , Humanos , Resultado do Tratamento , Procedimentos Endovasculares/métodos , Estudos Retrospectivos , Aneurisma Roto/diagnóstico por imagem , Aneurisma Roto/cirurgia , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgia , Embolização Terapêutica/métodos
17.
Interv Neuroradiol ; 29(2): 183-188, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35234073

RESUMO

Background: Mural type vein of Galen malformation (mVOGM) is a congenital high flow arteriovenous shunt between choroidal arteries and the prosencephalic vein of Markowski leading to heart failure and hydrovenous disorder in children. Embolizing fistulous connections can be challenging and typically requires adjunctive techniques such as induced hypotension, balloon-assisted flow control, and creation of a coil basket. These maneuvers add time, complexity, and unpredictability. Rapid ventricular pacing (RVP) has been proposed as an alternative strategy with fewer drawbacks, but has not been well studied. The approach involves catheterizing the right ventricle with a pacing catheter connected to a temporary external pacemaker. Prior to embolization, RVP is initiated to lower cardiac output. Following embolization, pacing is discontinued, and the heart returns to sinus rhythm. Methods: We performed RVP in five mVOGM patients from 4/2020 through 7/2021. Accounting for multiple procedures, RVP was utilized in ten cases and twenty-six pedicles. Results: Ventricular capture was achieved in all instances and was well tolerated, without arrhythmia. Casting the arterial pedicle with liquid embolic immediately adjacent to, or traversing, the fistulous point was achieved in 9/10 cases. There were no procedural complications. In 1 case, creation of a coil basket in the venous pouch was required to achieve a stable arterial cast Conclusions: This report describes the largest case series utilizing RVP in mVOGM. The technique appears safe and well tolerated.


Assuntos
Fístula Arteriovenosa , Embolização Terapêutica , Malformações da Veia de Galeno , Criança , Humanos , Ventrículos do Coração , Malformações da Veia de Galeno/diagnóstico por imagem , Malformações da Veia de Galeno/terapia , Embolização Terapêutica/métodos , Procedimentos Cirúrgicos Vasculares , Veias
18.
J Neurointerv Surg ; 15(6): 558-565, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35483912

RESUMO

BACKGROUND: The Woven EndoBridge (WEB) device has Food and Drug Administration approval for treatment of wide-necked intracranial bifurcation aneurysms. The WEB device has been shown to result in adequate occlusion in bifurcation aneurysms overall, but its usefulness in the individual bifurcation locations has been evaluated separately only in few case series, which were limited by small sample sizes. OBJECTIVE: To compare angiographic and clinical outcomes after treatment of bifurcation aneurysms at various locations, including anterior communicating artery (AComA), anterior cerebral artery (ACA) bifurcation distal to AComA, basilar tip, internal carotid artery (ICA) bifurcation, and middle cerebral artery (MCA) bifurcation aneurysms using the WEB device. METHODS: A retrospective cohort analysis was conducted at 22 academic institutions worldwide to compare treatment outcomes of patients with intracranial bifurcation aneurysms using the WEB device. Data include patient and aneurysm characteristics, procedural details, angiographic and functional outcomes, and complications. RESULTS: A total of 572 aneurysms were included. MCA (36%), AComA (35.7%), and basilar tip (18.9%) aneurysms were most common. The rate of adequate aneurysm occlusion was significantly higher for basilar tip (91.6%) and ICA bifurcation (96.7%) aneurysms and lower for ACA bifurcation (71.4%) and AComA (80.6%) aneurysms (p=0.04). CONCLUSION: To our knowledge, this is the most extensive study to date that compares the treatment of different intracranial bifurcation aneurysms using the WEB device. Basilar tip and ICA bifurcation aneurysms showed significantly higher rates of aneurysm occlusion than other locations.


Assuntos
Doenças das Artérias Carótidas , Embolização Terapêutica , Procedimentos Endovasculares , Aneurisma Intracraniano , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/terapia , Doenças das Artérias Carótidas/terapia
19.
Transl Stroke Res ; 14(4): 455-464, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36066701

RESUMO

Several studies have shown promising outcomes of the Woven EndoBridge (WEB) device for the treatment of wide-necked intracranial bifurcation aneurysms. This is a multicenter study attempts to explore the changes in trends and treatment outcomes over time for WEB embolization of intracranial aneurysms. The WorldWideWEB consortium is a retrospective multicenter collaboration of data from international centers spanning from January 2011 and June 2021, with no limitations on aneurysm location or rupture status. Both bifurcation and sidewall aneurysms were included. These patients were stratified based on treatment year into five treatment intervals: 2011-2015 (N = 66), 2016-2017 (N = 77), 2018 (N = 66), 2019 (N = 300), and 2020-2021 (N = 173). Patient characteristics and angiographic and clinical outcomes were compared between these time intervals. This study comprised 671 patients (median age 61.4 years; 71.2% female) with 682 intracranial aneurysms. Over time, we observed an increasing tendency to treat patients presenting with ruptured aneurysms and aneurysms with smaller neck, diameter, and dome widths. Furthermore, we observed a trend towards more off-label use of the WEB for sidewall aneurysms and increased adoption of transradial access for WEB deployment. Moreover, the proportion of patients with adequate WEB occlusion immediately and at last follow-up was significantly higher in more recent year cohorts, as well as lower rates of compaction and retreatment. Mortality and complications did not differ over time. This learning curve study suggests improved experience using the WEB for the treatment of intracranial aneurysms and has yielded higher rates of adequate occlusion over time.


Assuntos
Embolização Terapêutica , Procedimentos Endovasculares , Aneurisma Intracraniano , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgia , Resultado do Tratamento , Estudos Retrospectivos
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