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1.
World Neurosurg ; 185: 224, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38401755

RESUMEN

Cystic craniopharyngiomas of the third ventricle can be challenging to treat because complete resection of the cyst wall can be associated with hypothalamic dysfunction and minimal rostral displacement of the optic chiasm leads to a small endonasal operative corridor. Various methods to overcome the frequent recurrences have been described, such as intracystic bleomycin or catheter placement, with mixed results.1-12 In Video 1, we describe a simple cystocisternal fenestration technique with preservation of the rostral cyst wall via an endoscopic endonasal approach where the solid portion of the tumor is resected, and the inferior wall of the cyst is opened into the prepontine cistern and the superior wall of the cyst and adjacent third ventricle are preserved. This allows for ventricular pressure to collapse the cyst cavity in the postoperative period. In select patients where safe complete resection of a cystic craniopharyngioma is prohibitive, this may provide a durable treatment and can be performed through a small endonasal corridor below a nondisplaced optic chiasm.


Asunto(s)
Craneofaringioma , Neuroendoscopía , Neoplasias Hipofisarias , Tercer Ventrículo , Humanos , Craneofaringioma/cirugía , Craneofaringioma/diagnóstico por imagen , Neoplasias Hipofisarias/cirugía , Neoplasias Hipofisarias/diagnóstico por imagen , Tercer Ventrículo/cirugía , Neuroendoscopía/métodos , Neoplasias del Ventrículo Cerebral/cirugía , Neoplasias del Ventrículo Cerebral/diagnóstico por imagen , Seno Esfenoidal/cirugía , Masculino
2.
NPJ Digit Med ; 6(1): 92, 2023 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-37217691

RESUMEN

In machine learning (ML), association patterns in the data, paths in decision trees, and weights between layers of the neural network are often entangled due to multiple underlying causes, thus masking the pattern-to-source relation, weakening prediction, and defying explanation. This paper presents a revolutionary ML paradigm: pattern discovery and disentanglement (PDD) that disentangles associations and provides an all-in-one knowledge system capable of (a) disentangling patterns to associate with distinct primary sources; (b) discovering rare/imbalanced groups, detecting anomalies and rectifying discrepancies to improve class association, pattern and entity clustering; and (c) organizing knowledge for statistically supported interpretability for causal exploration. Results from case studies have validated such capabilities. The explainable knowledge reveals pattern-source relations on entities, and underlying factors for causal inference, and clinical study and practice; thus, addressing the major concern of interpretability, trust, and reliability when applying ML to healthcare, which is a step towards closing the AI chasm.

3.
Clin Neurol Neurosurg ; 227: 107625, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36870088

RESUMEN

BACKGROUND: The retrosigmoid craniotomy is a versatile surgical approach to the cerebellopontine angle though cerebrospinal fluid leak remains a concern, with a reported prevalence of 0-22 %. A host of closure materials and strategies have been proposed to achieve a watertight dural closure to varying degrees of success. We review our series of keyhole retrosigmoid craniotomies and describe our simple, standardized method of closure without watertight dural closure. METHODS: A retrospective review of all retrosigmoid craniotomies performed by the senior author was completed. Closure was achieved by placing an oversized piece of gelatin in the subdural space. The dura is grossly approximated. An oversized sheet of collagen matrix is placed as an overlay followed by gelatin sponge in the craniectomy defect held in place with titanium mesh. The superficial layers are approximated. The skin is closed with a running sub-cuticular suture followed by skin glue. Patient demographics, cerebrospinal fluid leak risk factors, and surgical outcomes were determined. RESULTS: A total of 114 patients were included. There was one case (0.9 %) of CSF leak, which resolved with placement of a lumbar drain for 5 days. The patient had one defined risk factor (morbid obesity, BMI 41.0 kg/m2). CONCLUSIONS: Obtaining a watertight dural layer closure has been the generally accepted strategy in preventing CSF leaks in a traditional retrosigmoid approach. In keyhole retrosigmoid approaches it may not be necessary by utilizing a simple gelfoam bolstered collagen matrix onlay technique potentially improving outcome measures including operative time.


Asunto(s)
Pérdida de Líquido Cefalorraquídeo , Gelatina , Humanos , Pérdida de Líquido Cefalorraquídeo/cirugía , Craneotomía/métodos , Duramadre/cirugía , Procedimientos Neuroquirúrgicos/efectos adversos , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos
4.
Neurol Clin ; 40(2): 375-389, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35465881

RESUMEN

Intraoperative neuromonitoring encompasses a variety of different modalities in which different neuropathways are monitored either continuously or at defined time points throughout a neurosurgical procedure. Surgical morbidity can be mitigated with careful patient selection and thoughtful implementation of the appropriate neuromonitoring modalities through the identification of eloquent areas or early detection of iatrogenic pathway disruption. Modalities covered in this article include somatosensory and motor evoked potentials, electromyography, electroencephalography, brainstem auditory evoked responses, and direct cortical stimulation.


Asunto(s)
Potenciales Evocados Somatosensoriales , Monitoreo Intraoperatorio , Electromiografía , Potenciales Evocados Motores/fisiología , Potenciales Evocados Somatosensoriales/fisiología , Humanos , Monitoreo Intraoperatorio/métodos , Procedimientos Neuroquirúrgicos/métodos
5.
Brain Struct Funct ; 226(8): 2481-2487, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34254165

RESUMEN

The interthalamic adhesion (IA) is a midline structure connecting the two thalami. Though it has been studied for centuries its exact function remains elusive. Early studies had noted its peculiar absence even among some healthy individuals. Population studies have investigated the differences in prevalence of IA in pathologic conditions and healthy controls. However, there is a general lack of consensus on IA prevalence in the healthy population. Understanding the true prevalence is critical in providing context for future studies, as well as uncovering further clues regarding IA's function. We systematically reviewed the existing literature to evaluate the prevalence of IA. The average prevalence among reviewed studies was higher than previously reported, at 87.3%. Studies utilizing magnetic resonance imaging rather than cadaveric specimens reported higher rates of IA prevalence. A higher prevalence among females was noted throughout the literature that persisted regardless of acquisition modality utilized.


Asunto(s)
Encéfalo , Tálamo , Encéfalo/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética , Prevalencia , Tálamo/diagnóstico por imagen
6.
Korean J Neurotrauma ; 17(1): 48-53, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33981643

RESUMEN

Surgical management of elevated intracranial pressures due to stroke or traumatic brain injury has classically been through decompressive craniectomy (DC). There is significant morbidity associated with DC including subdural hygromas, syndrome of the trephined, and the need for subsequent cranioplasty. Alternative techniques including the hinged and floating craniotomy have shown promise though can still suffer from complications associated with an unsecured bone flap. We report a case in which a patient who presented with an acute subdural hematoma and associated midline shift that was successfully treated with decompression via thinning and re-securing of the bone flap in a "split-thickness decompression."

7.
World Neurosurg ; 151: 70-76, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33878464

RESUMEN

OBJECTIVE: Unique challenges can present in the treatment of small to mid-sized meningiomas that arise from the region of the anterior most aspect of the falx cerebri including its junction with the anterior skull base, what we call the far frontal region. Although this region of the anterior skull base is considered in the surgical approach of olfactory groove meningiomas invading this space, important differences exist between these tumors and those of the far frontal region. METHODS: Toward refining surgical selection, our cadaveric study details a minimally invasive keyhole superior interhemispheric approach to the far frontal region and 2 illustrative cases show the feasibility of this approach. RESULTS: Our cadaveric study defines 5 steps of the approach from the incision, craniectomy, dural opening, approaching the skull base and ipsilateral exposure, and finally falcine resection and bilateral skull base exposure. Two illustrative cases with the approach confirmed visualization of the full extent of tumor and gross total resection with preservation of the unaffected olfactory bulb. CONCLUSIONS: To the best of our knowledge, our anatomic study is distinctively unique in quantifying the working distance of the keyhole superior interhemispheric exposure and refining visualization of the far frontal region. We discuss these benefits and limitations (i.e., substantial involvement of tumor beyond midline) and differences with large meningiomas of the olfactory groove and far frontal region with significant posterior or lateral extension for which conventional exposures are appropriate.


Asunto(s)
Craneotomía/métodos , Neoplasias Meníngeas/cirugía , Meningioma/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Procedimientos Neuroquirúrgicos/métodos , Neoplasias de la Base del Cráneo/cirugía , Anciano , Cadáver , Femenino , Humanos , Neoplasias Meníngeas/diagnóstico por imagen , Meningioma/diagnóstico por imagen , Persona de Mediana Edad , Neoplasias de la Base del Cráneo/diagnóstico por imagen
8.
Sci Rep ; 11(1): 5688, 2021 03 11.
Artículo en Inglés | MEDLINE | ID: mdl-33707478

RESUMEN

Machine Learning has made impressive advances in many applications akin to human cognition for discernment. However, success has been limited in the areas of relational datasets, particularly for data with low volume, imbalanced groups, and mislabeled cases, with outputs that typically lack transparency and interpretability. The difficulties arise from the subtle overlapping and entanglement of functional and statistical relations at the source level. Hence, we have developed Pattern Discovery and Disentanglement System (PDD), which is able to discover explicit patterns from the data with various sizes, imbalanced groups, and screen out anomalies. We present herein four case studies on biomedical datasets to substantiate the efficacy of PDD. It improves prediction accuracy and facilitates transparent interpretation of discovered knowledge in an explicit representation framework PDD Knowledge Base that links the sources, the patterns, and individual patients. Hence, PDD promises broad and ground-breaking applications in genomic and biomedical machine learning.

9.
ACS Cent Sci ; 7(2): 345-354, 2021 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-33655072

RESUMEN

The maintenance of therapeutic glycoproteins within the circulatory system is associated, in large part, with the integrity of sialic acids as terminal sugars on the glycans. Glycoprotein desialylation, either by spontaneous cleavage or through host sialidases, leads to protein clearance, mainly through the liver. Thus, the installation of minimally modified sialic acids that are hydrolysis-resistant yet biologically equivalent should lead to increased circulatory half-lives and improved pharmacokinetic profiles. Here we describe the chemoenzymatic synthesis of CMP-sialic acid sugar donors bearing fluorine atoms at the 7-position, starting from the corresponding 4-deoxy-4-fluoro-N-acetylhexosamine precursors. For the derivative with natural stereochemistry we observe efficient glycosyl transfer by sialyltransferases, along with improved stability of the resultant 7-fluorosialosides toward spontaneous hydrolysis (3- to 5-fold) and toward cleavage by GH33 sialidases (40- to 250-fold). Taking advantage of the rapid transfer of 7-fluorosialic acid by sialyltransferases, we engineered the O-glycan of Interferon α-2b and the N-glycans of the therapeutic glycoprotein α1-antitrypsin. Studies of the uptake of the glyco-engineered α1-antitrypsin by HepG2 liver cells demonstrated the bioequivalence of 7-fluorosialic acid to sialic acid in suppressing interaction with liver cell lectins. In vivo pharmacokinetic studies reveal enhanced half-life of the protein decorated with 7-fluorosialic acid relative to unmodified sialic acid in the murine circulatory system. 7-Fluorosialylation therefore offers considerable promise as a means of prolonging circulatory half-lives of glycoproteins and may pave the way toward biobetters for therapeutic use.

10.
Surg Neurol Int ; 12: 13, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33500828

RESUMEN

BACKGROUND: Metastatic nonsmall cell lung cancer (NSCLC) to the pituitary (NSCLC-PitM) is rare and often presents with visual field deficits. Surgical resection for the decompression of the optic apparatus has been the treatment of choice in such cases. Osimertinib is a third-generation tyrosine kinase inhibitor (TKI) approved for the treatment of patients with NSCLC with an epithelial growth factor receptor (EGFR) mutation though its role in the treatment of NSCLC-PitM that remains unclear. We present a case of NSCLC-PitM with optic chiasm compression and visual deficits that were successfully treated with osimertinib alone without surgical intervention. CASE DESCRIPTION: A 43-year-old male presented with pleuritic chest pain, fatigue, and visual deficits found to have NSCLC and a sellar mass with suprasellar extension and optic chiasm compression. Visual field testing demonstrated associated visual field deficits. Molecular testing was positive for EGFR exon 19 deletion. The patient was started on osimertinib with complete resolution of pituitary lesion and visual deficits at 4 weeks. CONCLUSION: Osimertinib is a third-generation EGFR-TKI that has demonstrated promising results among patients with metastatic EGFR-mutated NSCLC. While surgery is the mainstay of treatment in patients with a sellar mass, optic compression, and visual deficits, those with EGFR-mutated NSCLC-PitM may benefit from early initiation of such systemic therapies, rather than surgical intervention, with good ophthalmologic results.

11.
BMC Med Inform Decis Mak ; 21(1): 16, 2021 01 09.
Artículo en Inglés | MEDLINE | ID: mdl-33422088

RESUMEN

BACKGROUND: Statistical data analysis, especially the advanced machine learning (ML) methods, have attracted considerable interest in clinical practices. We are looking for interpretability of the diagnostic/prognostic results that will bring confidence to doctors, patients and their relatives in therapeutics and clinical practice. When datasets are imbalanced in diagnostic categories, we notice that the ordinary ML methods might produce results overwhelmed by the majority classes diminishing prediction accuracy. Hence, it needs methods that could produce explicit transparent and interpretable results in decision-making, without sacrificing accuracy, even for data with imbalanced groups. METHODS: In order to interpret the clinical patterns and conduct diagnostic prediction of patients with high accuracy, we develop a novel method, Pattern Discovery and Disentanglement for Clinical Data Analysis (cPDD), which is able to discover patterns (correlated traits/indicants) and use them to classify clinical data even if the class distribution is imbalanced. In the most general setting, a relational dataset is a large table such that each column represents an attribute (trait/indicant), and each row contains a set of attribute values (AVs) of an entity (patient). Compared to the existing pattern discovery approaches, cPDD can discover a small succinct set of statistically significant high-order patterns from clinical data for interpreting and predicting the disease class of the patients even with groups small and rare. RESULTS: Experiments on synthetic and thoracic clinical dataset showed that cPDD can 1) discover a smaller set of succinct significant patterns compared to other existing pattern discovery methods; 2) allow the users to interpret succinct sets of patterns coming from uncorrelated sources, even the groups are rare/small; and 3) obtain better performance in prediction compared to other interpretable classification approaches. CONCLUSIONS: In conclusion, cPDD discovers fewer patterns with greater comprehensive coverage to improve the interpretability of patterns discovered. Experimental results on synthetic data validated that cPDD discovers all patterns implanted in the data, displays them precisely and succinctly with statistical support for interpretation and prediction, a capability which the traditional ML methods lack. The success of cPDD as a novel interpretable method in solving the imbalanced class problem shows its great potential to clinical data analysis for years to come.


Asunto(s)
Algoritmos , Aprendizaje Automático , Interpretación Estadística de Datos , Humanos
12.
World Neurosurg ; 146: e467-e472, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33130137

RESUMEN

OBJECTIVE: Meningiomas of the anterior clinoid process (ACP) present significant surgical challenges given their anatomic relation to critical neurovascular structures. Routine anterior clinoidectomy is often described as a critical step in the resection of these tumors to reduce recurrence and improve visual outcomes. Anterior clinoidectomy, however, is not without risk and its benefits have not been clearly delineated. We present the outcomes of our series of surgically managed ACP meningiomas in which an anterior clinoidectomy was not routinely employed. METHODS: A retrospective review of all ACP meningiomas operated on between August 1997 and March 2019 was conducted. Patients with a recurrent tumor or with <6 months of follow-up were excluded. Resection was typically carried out via a frontotemporal craniotomy followed by intradural removal of the tumor. Anterior clinoidectomy was only performed if hyperostosis of the ACP caused mass effect on the optic nerve. RESULTS: Twenty-nine patients were included in this study. Anterior clinoidectomy was performed in 3 patients (10.3%). Gross total resection was achieved in 22 patients (75.9%). Of the 21 patients (72.4%) who presented with visual deficits, vision improved in 18 patients (85.7%) and worsened in 2 (9.5%). Tumor recurrence occurred in 5 patients (17.2%) at a mean follow-up of 64.9 months. Perioperative morbidity was 10.3%. Permanent morbidity and mortality were 6.9% (vision deterioration) and 0%, respectively. CONCLUSIONS: Resection of ACP meningiomas without routine anterior clinoidectomy minimizes potential risk while achieving gross total resection, recurrence, and visual improvement rates comparable with those in previously reported series.


Asunto(s)
Craneotomía , Neoplasias Meníngeas/cirugía , Meningioma/cirugía , Recurrencia Local de Neoplasia/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Craneotomía/métodos , Femenino , Humanos , Masculino , Neoplasias Meníngeas/patología , Meningioma/patología , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Procedimientos Neuroquirúrgicos/métodos , Nervio Óptico/cirugía , Base del Cráneo/cirugía , Hueso Esfenoides/cirugía , Resultado del Tratamiento
13.
World Neurosurg ; 145: 5-12, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32891837

RESUMEN

BACKGROUND: Tuberculum sellae meningiomas are challenging tumors often compressing the optic apparatus and involving the optic canals. Traditional approaches provide wide exposure, but optic canal access can remain difficult. Endonasal approaches offer a less invasive option that allows access to the medial optic canals, but larger tumors can still be challenging along with a higher risk of postoperative spinal fluid leak. We present the use of a keyhole superior interhemispheric approach for tuberculum sellae meningioma resection. METHODS: Five patients with tuberculum sellae meningioma who underwent a keyhole superior interhemispheric approach were retrospectively reviewed. Preoperative tumor volumes, visual outcomes, extent of resection, pathologic grading, perioperative complications, recurrence rates, operative times, and hospital length of stays were analyzed. RESULTS: The average age of the patients was 68.6 ± 7.7 years old (range 57-78). Average tumor volume was 8 ± 1.8 cm3. All patients had a gross total resection. Three out of 5 patients had World Health Organization grade 1 meningioma, and the other 2 had World Health Organization grade 2 meningioma. There were no recurrences over an average follow-up of 18.6 months (range 1-44). On preoperative visual assessment, 9 out of 10 eyes (90%) had a deficit. Postoperative visual assessment found 9 out of 9 eyes with preoperative deficits had improvement (100%). There were no perioperative or postoperative complications. CONCLUSIONS: The keyhole superior interhemispheric approach provides a transcranial alternative that allows excellent exposure of the vasculature and both optic canals, resulting in good extents of resection and recovery of vision.


Asunto(s)
Meningioma/cirugía , Procedimientos Neuroquirúrgicos/métodos , Silla Turca/cirugía , Neoplasias de la Base del Cráneo/cirugía , Hueso Esfenoides/cirugía , Anciano , Craneotomía , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Neuroendoscopía , Tempo Operativo , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Resultado del Tratamiento
14.
Surg Neurol Int ; 11: 410, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33365173

RESUMEN

BACKGROUND: Postoperative cerebral venous sinus thrombosis (pCVST) after resection of cerebellopontine angle and posterior fossa tumor resections occur almost exclusively in the lateral venous sinuses and are generally asymptomatic. Thrombus extension and involvement of the superior sagittal sinus (SSS) - a serious and potentially devastating complication - are rarely described and, as such, successful treatment for which is still poorly understood. We report a case of pCVST involving the SSS after translabyrinthine approach for resection of a metastatic neuroendocrine tumor (NET), and the first that was successfully treated with anticoagulation therapy. CASE DESCRIPTION: A 40-year-old man presented with headaches, diminished right-sided hearing, and ataxia was found to have a large right-sided cerebellopontine angle (CPA) lesion with extra-axial and possible intraparenchymal invasion. A retrosigmoid craniotomy for debulking and diagnosis was undertaken. Postoperative imaging revealed patent venous sinuses. Pathology confirmed NET. Further imaging revealed a likely pancreatic primary lesion. The patient then underwent subsequent translabyrinthine approach for definitive surgical resection. Postoperative imaging again revealed patent venous sinuses. The patient subsequently developed headaches on postoperative day 10 and was found to have pCVST involving the ipsilateral internal jugular to the SSS. The patient was started on therapeutic heparin with significant improvement in pCVST and symptoms. CONCLUSION: Extensive pCVST involving the SSS after CPA and posterior fossa tumor resections is extremely rare. Initial management with anticoagulation can yield promising results and should be initiated early in the clinical course unless otherwise contraindicated.

15.
Curr Pain Headache Rep ; 24(12): 80, 2020 Dec 17.
Artículo en Inglés | MEDLINE | ID: mdl-33331965

RESUMEN

PURPOSE OF REVIEW: The purpose of this review is to evaluate the current evidence on ultrasound-guided ilioinguinal nerve blocks for ilioinguinal neuralgia post hernia surgery. METHODS: A literature search was performed to find all relevant case reports, case series, prospective or retrospective cohort studies, and randomized controlled trials (RCTs) where ultrasound-guided or landmark-based ilioinguinal nerve blocks were used for ilioinguinal neuralgia post-inguinal hernia surgery. RECENT FINDINGS: A total of six studies were identified with suitable data for inclusion. Three studies were retrospective, two studies were prospective, and one study was a randomized controlled trial. A total of 133 subjects were enrolled across these studies. Approximately 55-70% had a beneficial analgesic response to treatment. No major complications were reported in these studies. Ultrasound- and landmark-based ilioinguinal nerve blocks are safe and effective for pain relief post inguinal hernia surgery. Although there were two studies that did not show a statically significant difference in both techniques, the ultrasound-guided injection has the advantage of direct visualization of pathology, more accurate needle placement, and decreased risks of intravascular injections.


Asunto(s)
Hernia , Herniorrafia/efectos adversos , Neuralgia/terapia , Dolor Postoperatorio/terapia , Hernia/diagnóstico por imagen , Humanos , Neuralgia/diagnóstico por imagen , Neuralgia/etiología , Dolor Postoperatorio/diagnóstico por imagen , Dolor Postoperatorio/etiología , Estudios Prospectivos , Estudios Retrospectivos
16.
World Neurosurg ; 144: 143-147, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32891848

RESUMEN

BACKGROUND: Cerebrospinal fluid (CSF) leaks in the lateral recess of the sphenoid sinus (LRSS) are typically spontaneous in nature and require surgical repair. Endoscopic endonasal approaches have become the mainstay of CSF leak repair in the LRSS, though they remain technically challenging and place the vidian nerve (VN) and sphenopalatine artery (SPA) at risk. Here we present a lateral paraorbital approach (LPOA) as a minimally invasive transcranial VN and SPA sparing alternative for LRSS CSF leak repairs. CASE DESCRIPTION: A 41-year-old African American woman presented with headaches and was found to have a spontaneous CSF leak in the LRSS. A LPOA was used to repair the CSF leak. An incision was made along the frontal process of zygoma (FPZ). Removal of the overhanging portion of the FPZ while sparing the lateral orbital rim and retraction of the temporalis muscle allowed for a tangential approach to the LRSS. A small encephalocele was seen and resected; the defect was identified and repaired with onlay DuraGen (Integra LifeSciences, Princeton, NJ) and Dura Repair (J&J Medical Devices, New Brunswick, NJ). There were no postoperative complications or recurrence of CSF leak. CONCLUSIONS: The LPOA can be a useful alternative approach to the LRSS for CSF leak repair. The lateral-to-medial approach to defects in this area provides a shorter working distance while avoiding critical neurovascular structures.


Asunto(s)
Pérdida de Líquido Cefalorraquídeo/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Procedimientos Neuroquirúrgicos/métodos , Órbita/cirugía , Seno Esfenoidal/cirugía , Adulto , Arterias Cerebrales/cirugía , Encefalocele/cirugía , Femenino , Cefalea/etiología , Humanos , Cirugía Endoscópica por Orificios Naturales , Obesidad Mórbida/complicaciones , Hueso Esfenoides/cirugía , Resultado del Tratamiento
17.
J Virol ; 94(19)2020 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-32669328

RESUMEN

The "shock and kill" strategy predicates that virus reactivation in latently infected cells is required to eliminate the human immunodeficiency virus (HIV) reservoir. In a recent study, we showed robust and persistent induction of plasma viremia in antiretroviral therapy (ART)-treated simian immunodeficiency virus-infected rhesus macaques (RMs) undergoing CD8α depletion and treated with the interleukin-15 (IL-15) superagonist N-803 (J. B. McBrien et al., Nature 578:154-159, 2020, https://doi.org/10.1038/s41586-020-1946-0). Of note, in that study we used an antibody targeting CD8α, thereby depleting NK cells, NKT cells, and γδ T cells, in addition to CD8+ T cells. In the current proof-of-concept study, we tested whether virus reactivation can be induced by administration of N-803 to simian-human chimeric immunodeficiency virus-infected, ART-treated RMs that are selectively depleted of CD8+ T cells via the CD8ß-targeting antibody CD8b255R1. CD8ß depletion was performed in five SHIVSF162P3-infected RMs treated with ART for 12 months and with plasma viremia consistently below 3 copies/ml. All animals received four weekly doses of N-803 starting at the time of CD8b255R1 administration. The induction of detectable plasma viremia was observed in three out of five RMs, with the level of virus reactivation seemingly correlated with the frequency of CD8+ T cells following CD8ß depletion as well as the level of virus reactivation observed when the same animals underwent CD8α depletion and N-803 administration after 24 weeks of ART. These data indicate that CD8ß depletion and N-803 administration can induce virus reactivation in SHIVSF162P3-infected RMs despite suboptimal depletion of CD8+ T cells and profound ART-induced suppression of virus replication, confirming a critical role for these cells in suppressing virus production and/or reactivation in vivo under ART.IMPORTANCE The "shock and kill" HIV cure strategy attempts to reverse and eliminate the latent viral infection that prevents eradication of the virus. Latency-reversing agents tested in clinical trials to date have failed to affect the HIV viral reservoir. IL-15 superagonist N-803, currently involved in a clinical trial for HIV cure, was recently shown by our laboratory to induce robust and persistent induction of plasma viremia during ART in three in vivo animal models of HIV infection. These results suggest a substantial role for CD8+ lymphocytes in suppressing the latency reversal effect of N-803 by promoting the maintenance of viral latency. In this study, we tested whether the use of a CD8ß-targeting antibody, which would specifically deplete CD8+ T cells, would yield similar levels of virus reactivation. We observed the induction of plasma viremia, which correlated with the efficacy of the CD8 depletion strategy.


Asunto(s)
Antirretrovirales/farmacología , Antígenos CD8/inmunología , Infecciones por VIH/inmunología , Interleucina-15/inmunología , Síndrome de Inmunodeficiencia Adquirida del Simio/inmunología , Virus de la Inmunodeficiencia de los Simios/efectos de los fármacos , Virus de la Inmunodeficiencia de los Simios/inmunología , Animales , Antirretrovirales/uso terapéutico , Linfocitos T CD8-positivos/inmunología , Modelos Animales de Enfermedad , VIH/efectos de los fármacos , Células Asesinas Naturales/efectos de los fármacos , Depleción Linfocítica , Macaca mulatta , Carga Viral , Viremia/virología , Latencia del Virus/efectos de los fármacos , Replicación Viral/efectos de los fármacos
18.
Surg Neurol Int ; 11: 99, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32494378

RESUMEN

BACKGROUND: Endoscopic endonasal transclival approaches provide direct access to the ventral skull base allowing the treating of clival and paraclival pathology without the manipulation of the brain or neurovascular structures. Postoperative spinal fluid leak, however, remains a challenge and various techniques have been described to reconstruct the operative defect. The "gasket seal" has been well-described, but has anatomic challenges when applied to clival defects. We describe a modification of this technique for use in endonasal transclival approaches. METHODS: Two patients who underwent an endoscopic endonasal transclival approach for tumor resection with an intraoperative spinal fluid leak underwent a modified "gasket seal" closure technique for skull base reconstruction. RESULTS: A 71-year-old woman with a petroclival meningioma and a 22 year old with a clival chordoma underwent endoscopic endonasal transclival resection with the modified repair. No new postoperative deficits occurred and no postoperative spinal fluid leak was seen with a follow-up of 17 and 23 months, respectively. CONCLUSION: We describe the successful use of a simple, low risk, and technique modification of the "gasket seal" technique adapted to the clivus that allows for hard reconstruction and facilitates placement of the nasoseptal flap.

19.
Surg Neurol Int ; 11: 31, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32257557

RESUMEN

BACKGROUND: Basilar apex (BX) aneurysms are surgically challenging due to their anatomic location, need to traverse neurovascular structures, and proximity to multiple perforator arteries. Surgical approaches often require extensive bone resection and neurovascular manipulation. Visualization of low-lying BX aneurysms is typically obscured by the posterior clinoid and upper clivus and poses a unique challenge. Subtemporal or anterolateral approaches with a posterior clinoidectomy are often required to achieve adequate exposure, though these maneuvers can add invasiveness, risk, and morbidity to the procedure. Endoscopes and, more recently, fluoroscopic angiography capable endoscopes offer the possibility of providing improved visualization with less exposure allowing for minimally invasive clipping. CASE DESCRIPTION: We present the case of a 42-year-old female with incidentally found 5 mm middle cerebral artery and 5 mm BX aneurysms. She underwent a minimally invasive supraorbital keyhole craniotomy for the clipping of both aneurysms. While the posterior clinoid obstructed the necessary visualization for the BX aneurysm, use of endoscopy and endoscopic fluoroscopic angiography allowed for safe and successful clipping without the need for a posterior clinoidectomy. CONCLUSION: This represents the first reported case of a BX aneurysm clipping through a minimally invasive keyhole craniotomy using endoscopic indocyanine green video angiography. Use of endoscopic indocyanine green angiography, combined with keyhole endoscopic approaches, allows for safe minimally invasive clipping of challenging posterior circulation aneurysms.

20.
World Neurosurg ; 133: e683-e689, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31568915

RESUMEN

OBJECTIVE: The middle fossa craniotomy for tegmen defect repair provides wide access. This approach often requires temporal lobe manipulation, lumbar drain placement, and longer recovery. We describe a keyhole middle fossa approach with a simple titanium skull base repair that allows for wide access with no temporal lobe manipulation and does not require lumbar drain placement, which results in a dramatic reduction in hospital length of stay. METHODS: A retrospective review was performed on 14 consecutive patients with spontaneous cerebrospinal fluid (CSF) otorrhea. Each patient underwent a keyhole middle fossa approach followed by multilayer dural repair with titanium mesh "gull wing" skull base reconstruction. Postoperative measures included operative time, length of hospital stay, CSF leak recurrence, and surgical complications (seizures, hemorrhage, aphasia, infection). RESULTS: The average age of the patients was 60.7 ± 12.7 years old, and average body mass index was 32.8 ± 7.9 kg/m2. Nine of the patients were female. The average operative time was 103 ± 32.8 minutes. The average hospital length of stay was 1.4 days. There were no cases of postoperative CSF otorrhea, meningitis, aphasia, or seizures. There were no recurrences over a mean follow-up of 20.3 months (range: 5-48 months). CONCLUSIONS: A minimally invasive keyhole middle fossa approach with a multilayer dural reconstruction including titanium mesh "gull wing" skull base repair provides a quick, effective treatment for a broad spectrum of tegmen defects and meningoencephaloceles. This exposure and reconstruction technique do not require the use of a lumbar drain and result in minimal hospitalization.


Asunto(s)
Fosa Craneal Media/cirugía , Craneotomía/métodos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Procedimientos de Cirugía Plástica/métodos , Adulto , Anciano , Placas Óseas , Otorrea de Líquido Cefalorraquídeo/cirugía , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Titanio
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