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1.
Clin Oral Investig ; 27(5): 2097-2107, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37022530

RESUMO

OBJECTIVES: Currently available reports on mandibular transverse growth are limited to two-dimensional images and cross-sectional studies. The objective of this study was to examine transverse growth of the mandibular body in untreated growing individuals during the mixed dentition stage using longitudinal three-dimensional imaging. METHODS: CBCT images of 25 (13 females and 12 males) untreated subjects at two time points were analyzed. The average age was 9.1 years at T1 and 11.3 years at T2. Mandibular segmentation and superimposition were performed to obtain linear and angular measurements at different axial levels. RESULTS: At the superior (mental foramen) axial level, transverse growth between the buccal surfaces gradually increased from the premolars to the ramus. At the inferior axial level, significant transverse growth differences were detected between the ramus and the dentition regions. In contrast, between the lingual surfaces, both superior and inferior levels showed minimal change in the region under the dentition and a significant amount of resorption in the ramus region. This difference between buccal and lingual surface changes led to a mandibular body angulation change in the premolar and molar regions. In contrast, the overall mandibular body angulation measured from the posterior-most border of the mandible to the symphysis remained the same. Differences were detected between males and females, with males tending to exhibit greater transverse growth in the ramus region at the inferior level. CONCLUSIONS: The mandibular body exhibited different transverse growth patterns at different axial levels. Differences were also found between genders. CLINICAL RELEVANCE: An in-depth understanding of craniofacial growth and development is crucial to diagnosis and treatment planning. The current study provides additional insight into the transverse growth of the mandible.


Assuntos
Tomografia Computadorizada de Feixe Cônico Espiral , Humanos , Masculino , Feminino , Criança , Estudos Transversais , Dente Molar , Dente Pré-Molar/diagnóstico por imagem , Mandíbula/diagnóstico por imagem , Tomografia Computadorizada de Feixe Cônico
2.
Stroke ; 52(11): e710-e714, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34619982

RESUMO

Background and Purpose: Since the publication of ARUBA trial (A Randomized Trial of Unruptured Brain Arteriovenous Malformations), outcomes in treated and untreated patients with unruptured arteriovenous malformation have been thoroughly compared. However, no prior analysis of ARUBA patients has sought to identify risk factors for perioperative stroke. Improved understanding of risks within the ARUBA cohort will help clinicians apply the study's findings in a broader context. Methods: The National Institute of Neurological Disorders and Stroke database was queried for all data relating to ARUBA patients, including demographics, interventions undertaken, and timing of stroke. Retrospective cohort analysis was performed with the primary outcome of perioperative stroke in patients who underwent endovascular intervention, and stroke risk was modeled with multivariate analysis. Results: A total of 64 ARUBA patients were included in the analysis. One hundred and fifty-ninth interventions were performed, and 26 (16%) procedures resulted in stroke within 48 hours of treatment. Posterior cerebral artery supply (adjusted odds ratio, 4.42 [95% CI, 1.23­15.9], P=0.02) and Spetzler-Martin grades 2 and 3 arteriovenous malformation (adjusted odds ratio, 7.76 [95% CI, 1.20­50.3], P=0.03; 9.64 [95% CI, 1.36­68.4], P=0.04, respectively) were associated with increased perioperative stroke risk in patients who underwent endovascular intervention. Patients treated in the United States or Germany had a significantly lower stroke risk than patients treated in other countries (adjusted odds ratio, 0.18 [95% CI, 0.04­0.82], P=0.02). Conclusions: Knowing patient and lesion characteristics that increase risk during endovascular treatment can better guide clinicians managing unruptured brain arteriovenous malformation. Our analysis suggests risk of perioperative stroke is dependent on Spetzler-Martin grade and posterior-circulation arterial supply. Differences in regional treatment paradigms may also affect stroke risk.


Assuntos
Fístula Arteriovenosa/cirurgia , Procedimentos Endovasculares/efeitos adversos , Malformações Arteriovenosas Intracranianas/cirurgia , Acidente Vascular Cerebral/etiologia , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
3.
Stroke ; 52(11): e715-e719, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34517765

RESUMO

Background and Purpose: Epidemiological studies have shown racial and ethnic minorities to have higher stroke risk and worse outcomes than non-Hispanic Whites. In this cohort study, we analyzed the STAR (Stroke Thrombectomy and Aneurysm Registry) database, a multi-institutional database of patients who underwent mechanical thrombectomy for acute large vessel occlusion stroke to determine the relationship between mechanical thrombectomy outcomes and race. Methods: Patients who underwent mechanical thrombectomy between January 2017 and May 2020 were analyzed. Data included baseline characteristics, vascular risk factors, complications, and long-term outcomes. Functional outcomes were assessed with respect to Hispanic status delineated as non-Hispanic White (NHW), non-Hispanic Black (NHB), or Hispanic patients. Multivariate analysis was performed to identify variables associated with unfavorable outcome or modified Rankin Scale ≥3 at 90 days. Results: Records of 2115 patients from the registry were analyzed. Median age of Hispanic patients undergoing mechanical thrombectomy was 60 years (72­84), compared with 63 years (54­74) for NHB, and 71 years (60­80) for NHW patients (P<0.001). Hispanic patients had a higher incidence of diabetes (41%; P<0.001) and hypertension (82%; P<0.001) compared with NHW and NHB patients. Median procedure time was shorter in Hispanics (36 minutes) compared to NHB (39 minutes) and NHW (44 minutes) patients (P<0.001). In multivariate analysis, Hispanic patients were less likely to have favorable outcome (odds ratio, 0.502 [95% CI, 0.263­0.959]), controlling for other significant predictors (age, admission National Institutes Health Stroke Scale, onset to groin time, number of attempts, procedure time). Conclusions: Hispanic patients are less likely to have favorable outcome at 90 days following mechanical thrombectomy compared to NHW or NHB patients. Further prospective studies are required to validate our findings.


Assuntos
AVC Isquêmico/etnologia , AVC Isquêmico/cirurgia , Trombectomia/métodos , Resultado do Tratamento , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Hispânico ou Latino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros
4.
Neurosurg Focus ; 47(1): E3, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31389675

RESUMO

Endothelial cell (EC) dysfunction is known to contribute to cerebral aneurysm (CA) pathogenesis. Evidence shows that damage or injury to the EC layer is the first event in CA formation. The mechanisms behind EC dysfunction in CA disease are interrelated and include hemodynamic stress, hazardous nitric oxide synthase (NOS) activity, oxidative stress, estrogen imbalance, and endothelial cell-to-cell junction compromise. Abnormal variations in hemodynamic stress incite pathological EC transformation and inflammatory zone formation, ultimately leading to destruction of the vascular wall and aneurysm dilation. Hemodynamic stress activates key molecular pathways that result in the upregulation of chemotactic cytokines and adhesion molecules, leading to inflammatory cell recruitment and infiltration. Concurrently, oxidative stress damages EC-to-EC junction proteins, resulting in interendothelial gap formation. This further promotes leukocyte traffic into the vessel wall and the release of matrix metalloproteinases, which propagates vascular remodeling and breakdown. Abnormal hemodynamic stress and inflammation also trigger adverse changes in NOS activity, altering proper EC mediation of vascular tone and the local inflammatory environment. Additionally, the vasoprotective hormone estrogen modulates gene expression that often suppresses these harmful processes. Crosstalk between these sophisticated pathways contributes to CA initiation, progression, and rupture. This review aims to outline the complex mechanisms of EC dysfunction in CA pathogenesis.


Assuntos
Endotélio Vascular/patologia , Aneurisma Intracraniano/patologia , Animais , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Endotélio Vascular/metabolismo , Hemodinâmica , Humanos , Aneurisma Intracraniano/metabolismo , Óxido Nítrico Sintase/metabolismo , Estresse Oxidativo , Estresse Fisiológico
5.
Neurosurg Focus ; 47(1): E20, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31261125

RESUMO

Cerebral aneurysm rupture is a devastating event resulting in subarachnoid hemorrhage and is associated with significant morbidity and death. Up to 50% of individuals do not survive aneurysm rupture, with the majority of survivors suffering some degree of neurological deficit. Therefore, prior to aneurysm rupture, a large number of diagnosed patients are treated either microsurgically via clipping or endovascularly to prevent aneurysm filling. With the advancement of endovascular surgical techniques and devices, endovascular treatment of cerebral aneurysms is becoming the first-line therapy at many hospitals. Despite this fact, a large number of endovascularly treated patients will have aneurysm recanalization and progression and will require retreatment. The lack of approved pharmacological interventions for cerebral aneurysms and the need for retreatment have led to a growing interest in understanding the molecular, cellular, and physiological determinants of cerebral aneurysm pathogenesis, maturation, and rupture. To this end, the use of animal cerebral aneurysm models has contributed significantly to our current understanding of cerebral aneurysm biology and to the development of and training in endovascular devices. This review summarizes the small and large animal models of cerebral aneurysm that are being used to explore the pathophysiology of cerebral aneurysms, as well as the development of novel endovascular devices for aneurysm treatment.


Assuntos
Modelos Animais de Doenças , Aneurisma Intracraniano/patologia , Modelos Biológicos , Aneurisma Roto/cirurgia , Animais , Cães , Embolização Terapêutica , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgia , Camundongos , Coelhos , Ratos , Suínos
6.
ScientificWorldJournal ; 2019: 7403104, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31186620

RESUMO

Mechanical thrombectomy (MT) has become the standard treatment for large vessel occlusion (LVO) in acute ischemic stroke (AIS). Few studies have investigated long-term outcomes for AIS treated with MT. Therefore, a pooled meta-analysis using data from randomized clinical trials (RCT) was performed to assess for long-term clinical outcomes. A systematic literature search was conducted on 27 September 2017, by searching the English literature in the Cochrane Library, MEDLINE, and Embase for RCTs investigating long-term outcomes (greater than standard 3-month timepoint) of endovascular intervention versus medical management for patients with AIS. The study was carried out according to PRISMA guidelines and random effects analysis was carried out to account for heterogeneity. Three trials were included: IMS III, MR CLEAN, and REVASCAT, comprising a total of 1,362 patients. Long-term clinical outcomes were available for 1-year follow-up in IMS III and REVASCAT and at 2 years in MR CLEAN. Functional independence at long-term follow-up favored endovascular stroke intervention (OR 1.51; p = 0.02). When stratified by LVO inclusion criteria, greater endovascular functional independence benefits were observed (OR 1.85; p = 0.0005). There was a significant difference between the 2 arms in favor of endovascular therapy for the quality of life at long-term follow-up (mean difference 0.11; p = 0.0002). No difference in mortality at long-term follow-up was observed (OR 0.82; p = 0.12). We conclude that endovascular therapy results in favorable outcomes at long-term follow-up for patients with acute ischemic stroke compared to standard medical treatment alone and that the 90-day timepoint offers a fair representation of the long-term outcomes.


Assuntos
Trombólise Mecânica , Acidente Vascular Cerebral/cirurgia , Trombectomia , Ensaios Clínicos como Assunto , Gerenciamento Clínico , Humanos , Trombólise Mecânica/métodos , Estudos Multicêntricos como Assunto , Razão de Chances , Prognóstico , Medição de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/mortalidade , Trombectomia/métodos
7.
PLoS Comput Biol ; 11(12): e1004608, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26680762

RESUMO

The epileptic network is characterized by pathologic, seizure-generating 'foci' embedded in a web of structural and functional connections. Clinically, seizure foci are considered optimal targets for surgery. However, poor surgical outcome suggests a complex relationship between foci and the surrounding network that drives seizure dynamics. We developed a novel technique to objectively track seizure states from dynamic functional networks constructed from intracranial recordings. Each dynamical state captures unique patterns of network connections that indicate synchronized and desynchronized hubs of neural populations. Our approach suggests that seizures are generated when synchronous relationships near foci work in tandem with rapidly changing desynchronous relationships from the surrounding epileptic network. As seizures progress, topographical and geometrical changes in network connectivity strengthen and tighten synchronous connectivity near foci-a mechanism that may aid seizure termination. Collectively, our observations implicate distributed cortical structures in seizure generation, propagation and termination, and may have practical significance in determining which circuits to modulate with implantable devices.


Assuntos
Epilepsia/fisiopatologia , Modelos Neurológicos , Neocórtex/fisiopatologia , Rede Nervosa/fisiopatologia , Convulsões/fisiopatologia , Transmissão Sináptica , Potenciais de Ação , Simulação por Computador , Humanos , Inibição Neural
9.
World Neurosurg ; 2023 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-37201791

RESUMO

OBJECTIVE: We report a unique case of a suspected recurrent intracranial epidermoid cyst (EDC) that was found on pathology to have undergone malignant transformation to squamous cell carcinoma (SCC) approximately 25 years after initial resection. Additionally, we performed a systematic review including 94 studies reporting intracranial EDC to SCC transformation. METHODS: Ninety-four studies were included in our systematic review. PubMed, Scopus, Cochrane Central, and EMBASE were searched in April 2020 for studies regarding histologically confirmed SCC arising within an EDC. Kaplan-Meier estimations were used to estimate time to event including survival, and log rank tests were used to test for significance. All analyses were conducted using STATA 14.1 (StataCorp, College Station, Texas, USA); tests were two-sided, and statistical significance was defined using the alpha threshold of 0.05. RESULTS: The overall median time to transformation was 60 months (95% confidence interval {CI}, 12-96). Transformation time was significantly shorter in the no surgery group (10 months, 95% CI undefined) versus the other 2 groups (60 months, 95% CI, 12-72 in surgery only and 70 months, 95% CI, 9-180 in surgery + adjuvant therapy group, both P < 0.01). Overall survival was significantly longer in the surgery + adjuvant therapy group (13 months, 95% CI, 9-24) versus the other 2 groups (3 months, 95% CI, 1-7 in surgery only and 6 months, 95% CI, 1-12 in the no surgery group, both P < 0.01). CONCLUSIONS: We report a rare case of delayed malignant transformation of an intracranial EDC to SCC, occurring nearly 25 years after initial resection. Transformation time in the no-surgery group was statistically significantly shorter as compared to the surgery only and surgery + adjuvant therapy groups. Overall survival was statistically significantly higher in the surgery + adjuvant therapy group as compared to the surgery only and no surgery groups.

10.
Neurosurgery ; 92(1): 205-212, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36519864

RESUMO

BACKGROUND: Dural arteriovenous fistulas (dAVFs) located at craniocervical junction are extremely rare (1%-2% of intracranial/spinal dAVFs). Their angio-architectural complexity renders endovascular embolization to be challenging given multiple small feeders with risk of embolysate reflux into vertebral artery and limited transvenous access. The available literature discussing microsurgery for these lesions is limited to few case reports. OBJECTIVE: To report a multicenter experience assessing microsurgery safety/efficacy. METHODS: Prospectively maintained registries at 13 North American centers were queried to identify craniocervical junction dAVFs treated with microsurgery (2006-2021). RESULTS: Thirty-eight patients (median age 59.5 years, 44.7% female patients) were included. The most common presentation was subarachnoid/intracranial hemorrhage (47.4%) and myelopathy (36.8%) (92.1% of lesions Cognard type III-V). Direct meningeal branches from V3/4 vertebral artery segments supplied 84.2% of lesions. All lesions failed (n = 5, 13.2%) or were deemed inaccessible/unsafe to endovascular treatment. Far lateral craniotomy was the most used approach (94.7%). Intraoperative angiogram was performed in 39.5% of the cases, with angiographic cure in 94.7% of cases (median imaging follow-up of 9.2 months) and retreatment rate of 5.3%. Favorable last follow-up modified Rankin Scale of 0 to 2 was recorded in 81.6% of the patients with procedural complications of 2.6%. CONCLUSION: Craniocervical dAVFs represent rare entity of lesions presenting most commonly with hemorrhage or myelopathy because of venous congestion. Microsurgery using a far lateral approach provides robust exposure and visualization for these lesions and allows obliteration of the arterialized draining vein intradurally as close as possible to the fistula point. This approach was associated with a high rate of angiographic cure and favorable clinical outcomes.


Assuntos
Malformações Vasculares do Sistema Nervoso Central , Embolização Terapêutica , Doenças da Medula Espinal , Hemorragia Subaracnóidea , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Malformações Vasculares do Sistema Nervoso Central/diagnóstico por imagem , Malformações Vasculares do Sistema Nervoso Central/cirurgia , Malformações Vasculares do Sistema Nervoso Central/complicações , Doenças da Medula Espinal/cirurgia , Embolização Terapêutica/métodos , Artéria Vertebral/diagnóstico por imagem , Artéria Vertebral/cirurgia , Artéria Vertebral/patologia , Hemorragia Subaracnóidea/complicações
11.
J Neurointerv Surg ; 15(9): 903-908, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35944975

RESUMO

BACKGROUND: Anterior cranial fossa dural arteriovenous fistulas (ACF-dAVFs) are aggressive vascular lesions. The pattern of venous drainage is the most important determinant of symptoms. Due to the absence of a venous sinus in the anterior cranial fossa, most ACF-dAVFs have some degree of drainage through small cortical veins. We describe the natural history, angiographic presentation and outcomes of the largest cohort of ACF-dAVFs. METHODS: The CONDOR consortium includes data from 12 international centers. Patients included in the study were diagnosed with an arteriovenous fistula between 1990-2017. ACF-dAVFs were selected from a cohort of 1077 arteriovenous fistulas. The presentation, angioarchitecture and treatment outcomes of ACF-dAVF were extracted and analyzed. RESULTS: 60 ACF-dAVFs were included in the analysis. Most ACF-dAVFs were symptomatic (38/60, 63%). The most common symptomatic presentation was intracranial hemorrhage (22/38, 57%). Most ACF-dAVFs drained through cortical veins (85%, 51/60), which in most instances drained into the superior sagittal sinus (63%, 32/51). The presence of cortical venous drainage predicted symptomatic presentation (OR 9.4, CI 1.98 to 69.1, p=0.01). Microsurgery was the most effective modality of treatment. 56% (19/34) of symptomatic patients who were treated had complete resolution of symptoms. Improvement of symptoms was not observed in untreated symptomatic ACF-dAVFs. CONCLUSION: Most ACF-dAVFs have a symptomatic presentation. Drainage through cortical veins is a key angiographic feature of ACF-dAVFs that accounts for their malignant course. Microsurgery is the most effective treatment. Due to the high risk of bleeding, closure of ACF-dAVFs is indicated regardless of presentation.


Assuntos
Fístula Arteriovenosa , Malformações Vasculares do Sistema Nervoso Central , Embolização Terapêutica , Humanos , Fossa Craniana Anterior/diagnóstico por imagem , Fossa Craniana Anterior/cirurgia , Angiografia , Resultado do Tratamento , Malformações Vasculares do Sistema Nervoso Central/diagnóstico por imagem , Malformações Vasculares do Sistema Nervoso Central/cirurgia , Hemorragias Intracranianas/terapia , Fístula Arteriovenosa/terapia
12.
Neurosurgery ; 2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-38095434

RESUMO

BACKGROUND AND OBJECTIVES: Anecdotal cases of rapidly progressing dementia in patients with dural arteriovenous fistulas (dAVFs) have been reported in small series. However, large series have not characterized these dAVFs. We conducted an analysis of the largest cohort of dAVFs presenting with cognitive impairment (dAVFs-CI), aiming to provide a detailed characterization of this subset of dAVFs. METHODS: Patients with dAVFs-CI were analyzed from the CONDOR Consortium, a multicenter repository comprising 1077 dAVFs. A propensity score matching analysis was conducted to compare dAVFs-CI with Borden type II and type III dAVFs without cognitive impairment (controls). Logistic regression was used to identify angiographic characteristics specific to dAVFs-CI. Furthermore, post-treatment outcomes were analyzed. RESULTS: A total of 60 patients with dAVFs-CI and 60 control dAVFs were included. Outflow obstruction leading to venous hypertension was observed in all dAVFs-CI. Sinus stenosis was significantly associated with dAVFs-CI (OR 2.85, 95% CI: 1.16-7.55, P = .027). dAVFs-CI were more likely to have a higher number of arterial feeders (OR 1.56, 95% CI 1.22-2.05, P < .001) and draining veins (OR 2.05, 95% CI 1.05-4.46, P = .004). Venous ectasia increased the risk of dAVFs-CI (OR 2.38, 95% CI 1.13-5.11, P = .024). A trend toward achieving asymptomatic status at follow-up was observed in patients with successful closure of dAVFs (OR 2.86, 95% CI 0.85-9.56, P = .09). CONCLUSION: Venous hypertension is a key angiographic feature of dAVFs-CI. Moreover, these fistulas present at a mean age of 58 years-old, and exhibit a complex angioarchitecture characterized by an increased number of arteriovenous connections and stenosed sinuses. The presence of venous ectasia further exacerbates the impaired drainage and contributes to the development of dAVFs-CI. Notably, in certain cases, closure of the dAVF has the potential to reverse symptoms.

13.
Neurosurg Focus Video ; 6(2): V13, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36284999

RESUMO

Petroclival meningiomas are challenging lesions that can be treated with several surgical approaches. The authors present a 66-year-old woman with a 1.6-cm left petroclival meningioma that was initially observed and then radiated after it grew 8 years later. Despite radiation, the tumor continued to grow to 4 cm; therefore, the patient was referred to the authors' institution. A left anterior petrosal (Kawase) approach was performed. Postoperatively, the patient had transient cranial nerve IV and VI palsy that improved. The case presentation, surgical anatomy, operative technique, postoperative course, and different surgical approaches are reviewed. The patient gave verbal consent for participating in the surgical video. The video can be found here: https://stream.cadmore.media/r10.3171/2022.1.FOCVID21259.

14.
Front Neurol ; 13: 1028290, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36408512

RESUMO

Autoimmune encephalitis (AE) frequently presents with seizures in the acute setting. Seizures are often refractory to anti-seizure medications (ASM) but have been shown to be responsive to immunomodulatory therapies. A subset of patients with AE continues to have refractory epilepsy, recently named "autoimmune-associated epilepsy (AAE)," for years after the acute AE presentation. Optimal treatment for AAE has not been determined. Furthermore, the efficacy of neuromodulation and immunotherapy has not been well established in AAE. Here, we report a patient with probable autoantibody negative AE who initially presented with new onset refractory status epilepticus (NORSE). After his acute presentation, he continued to have frequent seizures that were refractory to four ASMs at therapeutic doses. A responsive neurostimulation (RNS®, NeuroPace) system was implanted for diagnostic and therapeutic purposes, with minimal change in seizure frequency. Due to continued frequent seizures despite ASMs and neurostimulation, he underwent a trial of immunotherapy consisting of high-dose intravenous (IV) corticosteroids and intravenous immunoglobulin (IVIG). Despite the addition of immunotherapy to his treatment regimen, the patient experienced no significant clinical or electrographic change in seizure frequency. This case does not support the use of immunotherapy for treatment of AAE and illustrates the need for consensus guidelines in the management of patients with AAE. Further, the use of electrocorticography (ECoG) data provided an objective surrogate measure of seizure frequency; this may support the role for early neuromodulation in the management of AAE.

15.
Gigascience ; 122022 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-38096477

RESUMO

BACKGROUND: Melaleuca quinquenervia (broad-leaved paperbark) is a coastal wetland tree species that serves as a foundation species in eastern Australia, Indonesia, Papua New Guinea, and New Caledonia. While extensively cultivated for its ornamental value, it has also become invasive in regions like Florida, USA. Long-lived trees face diverse pest and pathogen pressures, and plant stress responses rely on immune receptors encoded by the nucleotide-binding leucine-rich repeat (NLR) gene family. However, the comprehensive annotation of NLR encoding genes has been challenging due to their clustering arrangement on chromosomes and highly repetitive domain structure; expansion of the NLR gene family is driven largely by tandem duplication. Additionally, the allelic diversity of the NLR gene family remains largely unexplored in outcrossing tree species, as many genomes are presented in their haploid, collapsed state. RESULTS: We assembled a chromosome-level pseudo-phased genome for M. quinquenervia and described the allelic diversity of plant NLRs using the novel FindPlantNLRs pipeline. Analysis reveals variation in the number of NLR genes on each haplotype, distinct clustering patterns, and differences in the types and numbers of novel integrated domains. CONCLUSIONS: The high-quality M. quinquenervia genome assembly establishes a new framework for functional and evolutionary studies of this significant tree species. Our findings suggest that maintaining allelic diversity within the NLR gene family is crucial for enabling responses to environmental stress, particularly in long-lived plants.

16.
J Cereb Blood Flow Metab ; 42(10): 1827-1839, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35673992

RESUMO

Inflammation plays an important role in the pathogenesis of stroke. The differential expression of inflammatory and angiogenic factors in thrombi and plasma remain undefined. In this observational cohort study, we evaluated angiogenic factors and inflammatory cytokines, in cerebral thrombi, local cerebral plasma (CP), and peripheral plasma (PP) in patients with acute ischemic stroke. Protein analysis of thrombi, CP and PP were used to measure angiogenic and inflammatory proteins using electrochemiluminescence. Our data indicate that VEGF-A, VEGF-C, bFGF, IL-4, IL-13, IL-1ß, IL-2, IL-8, IL-16, IL-6 and IL-12p70 were higher in the thrombi of acute ischemic stroke patients than in the CP and PP of stroke patients. Moreover, the protein levels of GM-CSF were lower in the PP than in the CP and the clot. Moreover, VEGF-D, Flt-1, PIGF, TIE-2, IL-5, TNF-ß, IL-15, IL-12/IL-23p40, IFN-γ and IL-17A were higher in PP and CP than in thrombi. Our results show that cytokines mediating the inflammatory response and proteins involved in angiogenesis are differentially expressed in thrombi within the cerebral and peripheral circulations. These data highlight the importance of identifying new biomarkers in different compartments of the circulatory system and in thrombi that may be used for the diagnosis and treatment of stroke patients.


Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Indutores da Angiogênese , Biomarcadores , Estudos de Coortes , Citocinas/metabolismo , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos , Humanos , Interleucina-12 , Interleucina-13 , Interleucina-15 , Interleucina-16 , Interleucina-17 , Interleucina-2 , Interleucina-4 , Interleucina-5 , Interleucina-6 , Interleucina-8 , Linfotoxina-alfa , Fator de Crescimento Placentário , Fator A de Crescimento do Endotélio Vascular , Fator C de Crescimento do Endotélio Vascular , Fator D de Crescimento do Endotélio Vascular
17.
Mol Ecol Resour ; 22(5): 1836-1854, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35016262

RESUMO

Telopea speciosissima, the New South Wales waratah, is an Australian endemic woody shrub in the family Proteaceae. Waratahs have great potential as a model clade to better understand processes of speciation, introgression and adaptation, and are significant from a horticultural perspective. Here, we report the first chromosome-level genome for T. speciosissima. Combining Oxford Nanopore long-reads, 10x Genomics Chromium linked-reads and Hi-C data, the assembly spans 823 Mb (scaffold N50 of 69.0 Mb) with 97.8% of Embryophyta BUSCOs "Complete". We present a new method in Diploidocus (https://github.com/slimsuite/diploidocus) for classifying, curating and QC-filtering scaffolds, which combines read depths, k-mer frequencies and BUSCO predictions. We also present a new tool, DepthSizer (https://github.com/slimsuite/depthsizer), for genome size estimation from the read depth of single-copy orthologues and estimate the genome size to be approximately 900 Mb. The largest 11 scaffolds contained 94.1% of the assembly, conforming to the expected number of chromosomes (2n = 22). Genome annotation predicted 40,158 protein-coding genes, 351 rRNAs and 728 tRNAs. We investigated CYCLOIDEA (CYC) genes, which have a role in determination of floral symmetry, and confirm the presence of two copies in the genome. Read depth analysis of 180 "Duplicated" BUSCO genes using a new tool, DepthKopy (https://github.com/slimsuite/depthkopy), suggests almost all are real duplications, increasing confidence in the annotation and highlighting a possible need to revise the BUSCO set for this lineage. The chromosome-level T. speciosissima reference genome (Tspe_v1) provides an important new genomic resource of Proteaceae to support the conservation of flora in Australia and further afield.


Assuntos
Cromossomos , Proteaceae , Austrália , Tamanho do Genoma , Anotação de Sequência Molecular , New South Wales , Proteaceae/genética
18.
World Neurosurg ; 168: e297-e308, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36198364

RESUMO

OBJECTIVE: The purpose of this study is to retrospectively evaluate the clinical and surgical outcomes of a large surgical series of vestibular schwannoma from North America over 20 years. METHODS: After institutional review board approval a retrospective review of the senior author's personal case logs to identify patients who had operations for vestibular schwannoma was performed. The clinical notes, operative record, preoperative and postoperative imagings, and long-term clinical follow-up notes were evaluated. RESULTS: A total of 415 patients who underwent 420 surgeries were identified from the years 1998-2021. The average length of follow-up was 3 years and 9 months. Overall, at last follow-up the rate of "good" facial nerve outcomes (House-Brackmann [HB] score I and II) was 86% and "poor" facial nerve outcomes (HB III-VI) was 14%. The amount of cerebellopontine angle extension (P = 0.023), tumor volume (P = 0.015), facial nerve consistency (P < 0.001), preoperative HB score (P < 0.001), and FN stimulation threshold at the end of the procedure (P < 0.001) were correlated to facial nerve function at the last follow-up. CONCLUSIONS: This study represents one of the largest recently reported surgical series of vestibular schwannoma in North American literature with available long term follow-up. Facial nerve outcomes correlated with cerebellopontine angle extension, tumor volume, facial nerve stimulation threshold, facial nerve consistency, preoperative facial nerve function, and history of a prior resection. Tumor recurrence remains significantly higher after subtotal resection. We believe the data supports a continuation of a strategy of general intent of gross total resection, greatly modifiable by intraoperative findings and judgment.


Assuntos
Neuroma Acústico , Humanos , Neuroma Acústico/diagnóstico por imagem , Neuroma Acústico/cirurgia , Nervo Facial/diagnóstico por imagem , Nervo Facial/cirurgia , Seguimentos , Estudos Retrospectivos , Procedimentos Neurocirúrgicos/efeitos adversos , Procedimentos Neurocirúrgicos/métodos , Resultado do Tratamento , Recidiva Local de Neoplasia/cirurgia , Complicações Pós-Operatórias/cirurgia
19.
J Neurosurg ; 136(4): 951-961, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-34507282

RESUMO

OBJECTIVE: Cranial dural arteriovenous fistulas (dAVFs) are rare lesions, hampering efforts to understand them and improve their care. To address this challenge, investigators with an established record of dAVF investigation formed an international, multicenter consortium aimed at better elucidating dAVF pathophysiology, imaging characteristics, natural history, and patient outcomes. This report describes the design of the Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) and includes characterization of the 1077-patient cohort. METHODS: Potential collaborators with established interest in the field were identified via systematic review of the literature. To ensure uniformity of data collection, a quality control process was instituted. Data were retrospectively obtained. RESULTS: CONDOR comprises 14 centers in the United States, the United Kingdom, the Netherlands, and Japan that have pooled their data from 1077 dAVF patients seen between 1990 and 2017. The cohort includes 359 patients (33%) with Borden type I dAVFs, 175 (16%) with Borden type II fistulas, and 529 (49%) with Borden type III fistulas. Overall, 852 patients (79%) presented with fistula-related symptoms: 427 (40%) presented with nonaggressive symptoms such as tinnitus or orbital phenomena, 258 (24%) presented with intracranial hemorrhage, and 167 (16%) presented with nonhemorrhagic neurological deficits. A smaller proportion (224 patients, 21%), whose dAVFs were discovered incidentally, were asymptomatic. Many patients (85%, 911/1077) underwent treatment via endovascular embolization (55%, 587/1077), surgery (10%, 103/1077), radiosurgery (3%, 36/1077), or multimodal therapy (17%, 184/1077). The overall angiographic cure rate was 83% (758/911 treated), and treatment-related permanent neurological morbidity was 2% (27/1467 total procedures). The median time from diagnosis to follow-up was 380 days (IQR 120-1038.5 days). CONCLUSIONS: With more than 1000 patients, the CONDOR registry represents the largest registry of cranial dAVF patient data in the world. These unique, well-annotated data will enable multiple future analyses to be performed to better understand dAVFs and their management.


Assuntos
Malformações Vasculares do Sistema Nervoso Central , Embolização Terapêutica , Malformações Vasculares do Sistema Nervoso Central/diagnóstico por imagem , Malformações Vasculares do Sistema Nervoso Central/patologia , Malformações Vasculares do Sistema Nervoso Central/terapia , Estudos de Coortes , Embolização Terapêutica/métodos , Humanos , Estudos Retrospectivos , Resultado do Tratamento
20.
J Neurosurg ; 136(4): 971-980, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-34507300

RESUMO

OBJECTIVE: There is a reported elevated risk of cerebral aneurysms in patients with intracranial dural arteriovenous fistulas (dAVFs). However, the natural history, rate of spontaneous regression, and ideal treatment regimen are not well characterized. In this study, the authors aimed to describe the characteristics of patients with dAVFs and intracranial aneurysms and propose a classification system. METHODS: The Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) database from 12 centers was retrospectively reviewed. Analysis was performed to compare dAVF patients with (dAVF+ cohort) and without (dAVF-only cohort) concomitant aneurysm. Aneurysms were categorized based on location as a dAVF flow-related aneurysm (FRA) or a dAVF non-flow-related aneurysm (NFRA), with further classification as extra- or intradural. Patients with traumatic pseudoaneurysms or aneurysms with associated arteriovenous malformations were excluded from the analysis. Patient demographics, dAVF anatomical information, aneurysm information, and follow-up data were collected. RESULTS: Of the 1077 patients, 1043 were eligible for inclusion, comprising 978 (93.8%) and 65 (6.2%) in the dAVF-only and dAVF+ cohorts, respectively. There were 96 aneurysms in the dAVF+ cohort; 10 patients (1%) harbored 12 FRAs, and 55 patients (5.3%) harbored 84 NFRAs. Dural AVF+ patients had higher rates of smoking (59.3% vs 35.2%, p < 0.001) and illicit drug use (5.8% vs 1.5%, p = 0.02). Sixteen dAVF+ patients (24.6%) presented with aneurysm rupture, which represented 16.7% of the total aneurysms. One patient (1.5%) had aneurysm rupture during follow-up. Patients with dAVF+ were more likely to have a dAVF located in nonconventional locations, less likely to have arterial supply to the dAVF from external carotid artery branches, and more likely to have supply from pial branches. Rates of cortical venous drainage and Borden type distributions were comparable between cohorts. A minority (12.5%) of aneurysms were FRAs. The majority of the aneurysms underwent treatment via either endovascular (36.5%) or microsurgical (15.6%) technique. A small proportion of aneurysms managed conservatively either with or without dAVF treatment spontaneously regressed (6.2%). CONCLUSIONS: Patients with dAVF have a similar risk of harboring a concomitant intracranial aneurysm unrelated to the dAVF (5.3%) compared with the general population (approximately 2%-5%) and a rare risk (0.9%) of harboring an FRA. Only 50% of FRAs are intradural. Dural AVF+ patients have differences in dAVF angioarchitecture. A subset of dAVF+ patients harbor FRAs that may regress after dAVF treatment.


Assuntos
Malformações Vasculares do Sistema Nervoso Central , Embolização Terapêutica , Aneurisma Intracraniano , Malformações Vasculares do Sistema Nervoso Central/complicações , Malformações Vasculares do Sistema Nervoso Central/diagnóstico por imagem , Malformações Vasculares do Sistema Nervoso Central/epidemiologia , Embolização Terapêutica/métodos , Humanos , Aneurisma Intracraniano/complicações , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/terapia , Avaliação de Resultados em Cuidados de Saúde , Estudos Retrospectivos
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