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1.
J Neurosurg ; : 1-15, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38875724

RESUMO

OBJECTIVE: This study summarizes medical device reports (MDRs) associated with adverse events for vagus nerve stimulation (VNS) devices indicated for epilepsy as reported by the Manufacturer and User Facility Device Experience (MAUDE) database of the US Food and Drug Administration. METHODS: The MAUDE database was surveyed for MDRs from November 2013 to September 2022 regarding VNS devices for epilepsy. Event descriptions, device problems, correlated patient consequences, and device models were grouped and analyzed in Python. Based on event description, revision surgeries and other unique events were identified. Revenue from VNS device sales was used to approximate growth in their use over time. RESULTS: A total of 21,448 MDRs met the inclusion criteria. High VNS impedance, the most prevalent device malfunction overall (17.0% of MDRs), was the most common factor for 18 of the 102 encountered patient problems and led to 1001 revision surgeries (3371 total revisions). Included in those 18 device malfunctions were 3 of the top 6 occurring patient problems: seizure recurrence (9.9% associated with high impedance; encompassed focal, absence, and grand mal subtypes), death (1.3%), and generalized pain (7.9%). The next 4 top cited device malfunctions-lead fracture (13.7% of MDRs), operational issue (6.6%), battery problem holding charge (4.2%), and premature end-of-life indicator (2.9%)-differed widely in their percentage of cases that did not impact patients (77.4%, 57.3%, 48.9%, and 92.2%, respectively), highlighting differing malfunction severities. Seizure recurrence, the most prevalent patient impact, was the outcome most associated with 32 of the 68 encountered device problems, including high impedance (12.8%), lead fracture (12.2%), operational issue (18.4%), battery problem holding charge (31.2%), and premature end-of-life indicator (8.9%), which comprised the top 5 occurring device problems. In general, MDRs spanned a diverse range including device age, hardware, software, and surgeon or manufacturer error. Trends were seen over time with declining annual MDRs coupled with a rise in the use of VNS devices as gauged by revenue growth. Shifting device and patient problem profiles were also seen in successive models, reflecting engineering updates. CONCLUSIONS: This study characterizes the most common and consequential side effects of VNS devices for epilepsy while clarifying likely causes. In addition, the outcomes of 68 distinct device malfunctions were identified, including many not ubiquitously present in literature, lending critical perspective to clinical practice.

2.
Cureus ; 16(5): e60648, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38903290

RESUMO

Persistent trigeminal artery (PTA) is the most common remnant of the primitive carotid-vertebrobasilar anastomoses, which typically form and obliterate during the early stages of human embryonic development. While PTA can be non-pathologic and is usually an incidental finding, it is also associated with various other vascular abnormalities, such as arteriovenous malformations and fistulae, but most commonly cerebral aneurysms. In these cases, aneurysms are usually reported in the anterior cerebral circulation or in the PTA trunk itself; to date, only one report exists of an associated aneurysm in the posterior circulation (basilar artery). These associated vascular pathologies are not only a source of morbidity and mortality but can also complicate subsequent endovascular treatment due to different flow patterns and increased vessel tortuosity. In this case report, we present the first reported case of PTA-associated aneurysm in the anterior inferior cerebellar artery and its resulting impact on the endovascular treatment of this aneurysm.

3.
Tetrahedron ; 1612024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38911481

RESUMO

The synthesis of cyclopropanes by the cyclization of allylic diazoesters is well-known. In prior studies toward the sesquiterpenoid euonyminol, we attempted to carry out an intramolecular cyclopropanation of an allylic diazoester containing an electronically-unbiased alkene embedded in a 6-oxa-bicyclo[3.2.1]-oct-3-ene skeleton. We obtained exclusively a product arising from 1,2-addition of oxygen and carbon (oxyalkylation) to the alkene. While oxyalkylation products have been reported when electron-rich alkenes (e.g. enol ethers) are employed, examples derived from electronically-unbiased alkenes are rare. Here, we establish that the oxyalkylation is general for a range of 6-oxa-bicyclo[3.2.1]-oct-3-ene substrates and show that these products form competitively in the cyclization of simpler α-diazo ß-ketoesters. Our data suggest increasing charge separation in the transition state for the addition promotes the oxyalkylation pathway.

5.
J Neurol Surg B Skull Base ; 85(3): 287-294, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38721365

RESUMO

Background Arterial compression of the trigeminal nerve at the root entry zone has been the long-attributed cause of compressive trigeminal neuralgia despite numerous studies reporting distal and/or venous compression. The impact of compression type on patient outcomes has not been fully elucidated. Objective We categorized vascular compression (VC) based on vessel and location of compression to correlate pain outcomes based on compression type. Methods A retrospective video review of 217 patients undergoing endoscopic microvascular decompression for trigeminal neuralgia categorizing VC into five distinct types, proximal arterial compression (VC1), proximal venous compression (VC2), distal arterial compression (VC3), distal venous compression (VC4), and no VC (VC5). VC type was correlated with postoperative pain outcomes at 1 month ( n = 179) and last follow-up (mean = 42.9 mo, n = 134). Results At 1 month and longest follow-up, respectively, pain was rated as "much improved" or "very much improved" in 89 69% of patients with VC1, 86.6 and 62.5% of patients with VC2, 100 and 87.5% of patients with VC3, 83 and 62.5% of patients with VC4, and 100 and 100% of patients with VC5. Multivariate analysis demonstrated VC4 as a significant negative of predictor pain outcomes at 1 month, but not longest follow-up, and advanced age as a significant positive predictor. Conclusion The degree of clinical improvement in all types of VC was excellent, but at longest follow-up VC type was not a significant predictor out outcome. However distal venous compression was significantly associated with worse outcomes at 1 month.

6.
Vascular ; : 17085381241247098, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38607337

RESUMO

BACKGROUND: Vascular surgical site infections have been reported with an overall incidence of 5-10% for patients undergoing arterial interventions and as high as 10-20% for lower-limb bypass grafting procedures. Given that vascular surgery patients are known to be at a higher risk of postoperative wound infections and other complications, our objective was to evaluate a potential method to reduce such complications. This study compares the rate of wound healing complications between incisional negative pressure wound therapy (NPWT) and conventional dressings in vascular surgery patients with infra-inguinal incisions. The primary endpoint is complete closure of the wound at the 2-week follow-up appointment. Secondary endpoints include frequency infections requiring antibiotics, need for wound revision, and wound dehiscence. METHODS: A prospective cohort study with retrospective control group was performed following infra-inguinal vascular surgeries for peripheral arterial disease at the Mount Carmel Health System. The patients included in this study were those who underwent a lower-extremity vascular procedure with primary closure of an incision distal to the groin between January 2014 and July 2018. Patients that had received an infra-inguinal incision with primary closure were included. Patients in the experimental group who had a Prevena Wound VAC were compared with a retrospectively obtained control arm treated with conventional dressings. Data regarding wound healing and complications, specifically infections and wound dehiscence, were obtained. RESULTS: A total of 201 patients were recruited in our study: 64 in the Prevena group and 137 in the control group. There was a significant reduction in the number of open wounds in the Prevena group compared to the control group at the 2-week follow-up (10.9% Prevena vs 33.6% control; p = .0005). When evaluated in aggregate, there was a statistically significant reduction in the number of patients who succumbed to any complication in the Prevena arm compared with traditional dressings (13 (20.3%) Prevena vs 72 (52.6%) control; p < .0001). CONCLUSION: The results of our study suggest there should be a significant consideration for the use of NPWT as a prophylactic measure to reduce the risk of wound complications of primarily closed infra-inguinal incisions in vascular surgery patients following common vascular procedures. Its use is particularly effective for patients at enhanced risk of infection, especially those with poor vascularization from BMI, smoking, and diabetes. This leads to decreased trends in antibiotic use, ED visits, readmissions, and surgical revisions, which translates to decreased utilization of hospital resources and economic burden.

7.
Neuroradiol J ; : 19714009241242642, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38565221

RESUMO

BACKGROUND AND PURPOSE: Perivascular spaces (PVS) are interstitial fluid-filled spaces surrounding blood vessels traversing the deep gray nuclei and white matter of the brain. These are commonly encountered on CT and MR imaging and are generally asymptomatic and of no clinical significance. However, occasional changes in the size of focal PVS, for example, when enlarging, may mimic pathologies including neoplasms and infections, hence potentially confounding radiological interpretation. Given these potential diagnostic issues, we sought to better characterize common clinical and imaging features of focal PVS demonstrating size fluctuations. MATERIALS AND METHODS: Upon institutional approval, we retrospectively identified 4 cases demonstrating PVS with size changes at our institution. To supplement our cases, we also performed a literature review, which identified an additional 14 cases. Their clinical and imaging data were analyzed to identify characteristic features. RESULTS: Of the 18 total cases (including the 4 institutional cases), 10 cases increased and 8 decreased in size. These focal PVS ranged from 0.4-4.5 cm in size. Whereas a decrease in size did not represent a diagnostic issue, focal increase in size of PVS led to concerning differential diagnoses in at least 30% of the radiology reports. These enlarging PVS were most found in the basal ganglia and temporal lobe, and in patients with previous brain radiation treatment. CONCLUSION: Focal size change of PVS can occur, especially years after brain radiation treatment. Being cognizant of this benign finding is important to consider in the differential diagnosis to avoid undue patient anxiety or unnecessary medical intervention.

8.
Artigo em Inglês | MEDLINE | ID: mdl-38521092

RESUMO

BACKGROUND AND PURPOSE: Interest in artificial intelligence (AI) and machine learning (ML) has been growing in neuroradiology, but there is limited knowledge on how this interest has manifested into research and specifically, its qualities and characteristics. This study aims to characterize the emergence and evolution of AI/ML articles within neuroradiology and provide a comprehensive overview of the trends, challenges, and future directions of the field. MATERIALS AND METHODS: We performed a bibliometric analysis of the American Journal of Neuroradiology; the journal was queried for original research articles published since inception (January 1, 1980) to December 3, 2022 that contained any of the following key terms: "machine learning," "artificial intelligence," "radiomics," "deep learning," "neural network," "generative adversarial network," "object detection," or "natural language processing." Articles were screened by 2 independent reviewers, and categorized into statistical modeling (type 1), AI/ML development (type 2), both representing developmental research work but without a direct clinical integration, or end-user application (type 3), which is the closest surrogate of potential AI/ML integration into day-to-day practice. To better understand the limiting factors to type 3 articles being published, we analyzed type 2 articles as they should represent the precursor work leading to type 3. RESULTS: A total of 182 articles were identified with 79% being nonintegration focused (type 1 n = 53, type 2 n = 90) and 21% (n = 39) being type 3. The total number of articles published grew roughly 5-fold in the last 5 years, with the nonintegration focused articles mainly driving this growth. Additionally, a minority of type 2 articles addressed bias (22%) and explainability (16%). These articles were primarily led by radiologists (63%), with most (60%) having additional postgraduate degrees. CONCLUSIONS: AI/ML publications have been rapidly increasing in neuroradiology with only a minority of this growth being attributable to end-user application. Areas identified for improvement include enhancing the quality of type 2 articles, namely external validation, and addressing both bias and explainability. These results ultimately provide authors, editors, clinicians, and policymakers important insights to promote a shift toward integrating practical AI/ML solutions in neuroradiology.

9.
J Neurosurg ; : 1-13, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38364220

RESUMO

OBJECTIVE: Recent studies have suggested that biologically effective dose (BED) is an important correlate of pain relief and sensory dysfunction after Gamma Knife radiosurgery (GKRS) for trigeminal neuralgia (TN). The goal of this study was to determine if BED is superior to prescription dose in predicting outcomes in TN patients undergoing GKRS as a first procedure. METHODS: This was a retrospective study of 871 patients with type 1 TN from 13 GKRS centers. Patient demographics, pain characteristics, treatment parameters, and outcomes were reviewed. BED was compared with prescription dose and other dosimetric factors for their predictive value. RESULTS: The median age of the patients was 68 years, and 60% were female. Nearly 70% of patients experienced pain in the V2 and/or V3 dermatomes, predominantly on the right side (60%). Most patients had modified BNI Pain Intensity Scale grade IV or V pain (89.2%) and were taking 1 or 2 pain medications (74.1%). The median prescription dose was 80 Gy (range 62.5-95 Gy). The proximal trigeminal nerve was targeted in 77.9% of cases, and the median follow-up was 21 months (range 6-156 months). Initial pain relief (modified BNI Pain Intensity Scale grades I-IIIa) was noted in 81.8% of evaluable patients at a median of 30 days. Of 709 patients who achieved initial pain relief, 42.3% experienced at least one pain recurrence after GKRS at a median of 44 months, with 49.0% of these patients undergoing a second procedure. New-onset facial numbness occurred in 25.3% of patients after a median of 8 months. Age ≥ 63 years was associated with a higher probability of both initial pain relief and maintaining pain relief. A distal target location was associated with a higher probability of initial and long-term pain relief, but also a higher incidence of sensory dysfunction. BED ≥ 2100 Gy2.47 was predictive of pain relief at 30 days and 1 year for the distal target, whereas physical dose ≥ 85 Gy was significant for the proximal target, but the restricted range of BED values in this subgroup could be a confounding factor. A maximum brainstem point dose ≥ 29.5 Gy was associated with a higher probability of bothersome facial numbness. CONCLUSIONS: BED and physical dose were both predictive of pain relief and could be used as treatment planning goals for distal and proximal targets, respectively, while considering maximum brainstem point dose < 29.5 Gy as a potential constraint for bothersome numbness.

10.
Neurosurgery ; 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38169310

RESUMO

BACKGROUND AND OBJECTIVES: Smartphone activity data recorded through high-fidelity accelerometry can provide accurate postoperative assessments of patient mobility. The "big data" available through smartphones allows for advanced analyses, yielding insight into patient well-being. This study compared rate of change in functional activity data between lumbar fusion (LF) and lumbar decompression (LD) patients to determine preoperative and postoperative course differences. METHODS: Twenty-three LF and 18 LD patients were retrospectively included. Activity data (steps per day) recorded in Apple Health, encompassing over 70 000 perioperative data points, was classified into 6 temporal epochs representing distinct functional states, including acute preoperative decline, immediate postoperative recovery, and postoperative decline. The daily rate of change of each patient's step counts was calculated for each perioperative epoch. RESULTS: Patients undergoing LF demonstrated steeper preoperative declines than LD patients based on the first derivative of step count data (P = .045). In the surgical recovery phase, LF patients had slower recoveries (P = .041), and LF patients experienced steeper postoperative secondary declines than LD patients did (P = .010). The rate of change of steps per day demonstrated varying perioperative trajectories that were not explained by differences in age, comorbidities, or levels operated. CONCLUSION: Patients undergoing LF and LD have distinct perioperative activity profiles characterized by the rate of change in the patient daily steps. Daily steps and their rate of change is thus a valuable metric in phenotyping patients and understanding their postsurgical outcomes. Prospective studies are needed to expand upon these data and establish causal links between preoperative patient mobility, patient characteristics, and postoperative functional outcomes.

11.
J Neurosurg ; 140(1): 210-217, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37486888

RESUMO

OBJECTIVE: Deep brain stimulation (DBS) is a rapidly growing surgical option for patients with drug-resistant epilepsy who are not candidates for resective/ablative surgery. Recent randomized controlled trials have demonstrated efficacy of DBS of the anterior nucleus of the thalamus (ANT), particularly in frontal or temporal epilepsy, whereas DBS of the centromedian (CM) nucleus appears to be most suitable in well-defined generalized epilepsy syndromes. At the authors' institution, DBS candidates who did not fit the populations represented in these trials were managed with DBS of multiple distinct targets, which included ANT, CM, and less-studied nuclei-i.e., mediodorsal nucleus, pulvinar, and subthalamic nucleus. The goal of this study was to present the authors' experience with these types of cases, and to motivate future investigations that can determine the long-term efficacy of multitarget DBS. METHODS: This single-center retrospective study of adult patients with drug-resistant epilepsy who underwent multitarget DBS was performed to demonstrate the feasibility and safety of this approach, and to present seizure outcomes. Patients in this cohort had epilepsy with features that were difficult to treat with DBS of the ANT or CM nucleus alone, including multifocal/multilobar, diffuse-onset, and/or posterior-onset seizures; or both generalized and focal seizures. RESULTS: Eight patients underwent DBS of 2-3 distinct thalamic/subthalamic nuclei. DBS was performed with 2 electrodes in each hemisphere. All leads in each patient were implanted with either frontal or parietal trajectories. There were no surgical complications. Among those with > 6 months of follow-up (n = 5; range 7-21 months), all patients were responders in terms of overall seizure frequency and/or convulsive seizure frequency (i.e., ≥ 50% reduction). Two patients had adverse stimulation effects, which resolved with further programming. CONCLUSIONS: Multitarget DBS is a procedurally feasible and safe treatment strategy to maximize outcomes in patients with complex epilepsy. The authors highlight their approach to inform future studies that are sufficiently powered to assess its efficacy.


Assuntos
Estimulação Encefálica Profunda , Epilepsia Resistente a Medicamentos , Epilepsia , Adulto , Humanos , Estudos Retrospectivos , Epilepsia/terapia , Epilepsia/etiologia , Epilepsia Resistente a Medicamentos/terapia , Convulsões/etiologia , Eletrodos Implantados/efeitos adversos
12.
J Neurosurg ; 140(3): 639-647, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37657095

RESUMO

OBJECTIVE: The use of magnetic resonance-guided focused ultrasound (MRgFUS) for the treatment of tremor-related disorders and other novel indications has been limited by guidelines advocating treatment of patients with a skull density ratio (SDR) above 0.45 ± 0.05 despite reports of successful outcomes in patients with a low SDR (LSDR). The authors' goal was to retrospectively analyze the sonication strategies, adverse effects, and clinical and imaging outcomes in patients with SDR ≤ 0.4 treated for tremor using MRgFUS. METHODS: Clinical outcomes and adverse effects were assessed at 3 and 12 months after MRgFUS. Outcomes and lesion location, volume, and shape characteristics (elongation and eccentricity) were compared between the SDR groups. RESULTS: A total of 102 consecutive patients were included in the analysis, of whom 39 had SDRs ≤ 0.4. No patient was excluded from treatment because of an LSDR, with the lowest being 0.22. Lesioning temperatures (> 52°C) and therapeutic ablations were achieved in all patients. There were no significant differences in clinical outcome, adverse effects, lesion location, and volume between the high SDR group and the LSDR group. SDR was significantly associated with total energy (rho = -0.459, p < 0.001), heating efficiency (rho = 0.605, p < 0.001), and peak temperature (rho = 0.222, p = 0.025). CONCLUSIONS: The authors' results show that treatment of tremor in patients with an LSDR using MRgFUS is technically possible, leading to a safe and lasting therapeutic effect. Limiting the number of sonications and adjusting the energy and duration to achieve the required temperature early during the treatment are suitable strategies in LSDR patients.


Assuntos
Crânio , Tremor , Humanos , Estudos Retrospectivos , Tremor/diagnóstico por imagem , Tremor/terapia , Cabeça , Espectroscopia de Ressonância Magnética
13.
J Neurosurg ; 140(1): 218-230, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37382356

RESUMO

A major goal of modern neurosurgery is the personalization of treatment to optimize or predict individual outcomes. One strategy in this regard has been to create whole-brain models of individual patients. Whole-brain modeling is a subfield of computational neuroscience that focuses on simulations of large-scale neural activity patterns across distributed brain networks. Recent advances allow for the personalization of these models by incorporating distinct connectivity architecture obtained from noninvasive neuroimaging of individual patients. Local dynamics of each brain region are simulated with neural mass models and subsequently coupled together, considering the subject's empirical structural connectome. The parameters of the model can be optimized by comparing model-generated and empirical data. The resulting personalized whole-brain models have translational potential in neurosurgery, allowing investigators to simulate the effects of virtual therapies (such as resections or brain stimulations), assess the effect of brain pathology on network dynamics, or discern epileptic networks and predict seizure propagation in silico. The information gained from these simulations can be used as clinical decision support, guiding patient-specific treatment plans. Here the authors provide an overview of the rapidly advancing field of whole-brain modeling and review the literature on neurosurgical applications of this technology.


Assuntos
Conectoma , Epilepsia , Humanos , Encéfalo/diagnóstico por imagem , Encéfalo/cirurgia , Encéfalo/patologia , Simulação por Computador , Conectoma/métodos , Neuroimagem , Rede Nervosa
14.
J Neurol Neurosurg Psychiatry ; 95(2): 167-170, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-37438098

RESUMO

BACKGROUND: The loss of the ability to swim following deep brain stimulation (DBS), although rare, poses a worrisome risk of drowning. It is unclear what anatomic substrate and neural circuitry underlie this phenomenon. We report a case of cervical dystonia with lost ability to swim and dance during active stimulation of globus pallidus internus. We investigated the anatomical underpinning of this phenomenon using unique functional and structural imaging analysis. METHODS: Tesla (3T) functional MRI (fMRI) of the patient was used during active DBS and compared with a cohort of four matched patients without this side effect. Structural connectivity mapping was used to identify brain network engagement by stimulation. RESULTS: fMRI during stimulation revealed significant (Pbonferroni<0.0001) stimulation-evoked responses (DBS ON

Assuntos
Estimulação Encefálica Profunda , Globo Pálido , Humanos , Globo Pálido/diagnóstico por imagem , Globo Pálido/fisiologia , Estimulação Encefálica Profunda/efeitos adversos , Estimulação Encefálica Profunda/métodos , Resultado do Tratamento , Imageamento por Ressonância Magnética
15.
J Neurol Neurosurg Psychiatry ; 95(2): 180-183, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-37722831

RESUMO

BACKGROUND: Given high rates of early complications and non-reversibility, refined targeting is necessitated for magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy for essential tremor (ET). Selection of lesion location can be informed by considering optimal stimulation area from deep brain stimulation (DBS). METHODS: 118 patients with ET who received DBS (39) or MRgFUS (79) of the ventral intermediate nucleus (VIM) underwent stimulation/lesion mapping, probabilistic mapping of clinical efficacy and normative structural connectivity analysis. The efficacy maps were compared, which depict the relationship between stimulation/lesion location and clinical outcome. RESULTS: Efficacy maps overlap around the VIM ventral border and encompass the dentato-rubro-thalamic tract. While the MRgFUS map extends inferiorly into the posterior subthalamic area, the DBS map spreads inside the VIM antero-superiorly. CONCLUSION: Comparing the efficacy maps of DBS and MRgFUS suggests a potential alternative location for lesioning, more antero-superiorly. This may reduce complications, without sacrificing efficacy, and individualise targeting. TRIAL REGISTRATION NUMBER: NCT02252380.


Assuntos
Estimulação Encefálica Profunda , Tremor Essencial , Humanos , Tremor Essencial/terapia , Imageamento por Ressonância Magnética , Tálamo/diagnóstico por imagem , Tálamo/cirurgia , Resultado do Tratamento , Tremor
16.
Nature ; 624(7990): 164-172, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38057571

RESUMO

Animal studies show aging varies between individuals as well as between organs within an individual1-4, but whether this is true in humans and its effect on age-related diseases is unknown. We utilized levels of human blood plasma proteins originating from specific organs to measure organ-specific aging differences in living individuals. Using machine learning models, we analysed aging in 11 major organs and estimated organ age reproducibly in five independent cohorts encompassing 5,676 adults across the human lifespan. We discovered nearly 20% of the population show strongly accelerated age in one organ and 1.7% are multi-organ agers. Accelerated organ aging confers 20-50% higher mortality risk, and organ-specific diseases relate to faster aging of those organs. We find individuals with accelerated heart aging have a 250% increased heart failure risk and accelerated brain and vascular aging predict Alzheimer's disease (AD) progression independently from and as strongly as plasma pTau-181 (ref. 5), the current best blood-based biomarker for AD. Our models link vascular calcification, extracellular matrix alterations and synaptic protein shedding to early cognitive decline. We introduce a simple and interpretable method to study organ aging using plasma proteomics data, predicting diseases and aging effects.


Assuntos
Envelhecimento , Biomarcadores , Doença , Saúde , Especificidade de Órgãos , Proteoma , Proteômica , Adulto , Humanos , Envelhecimento/sangue , Doença de Alzheimer/sangue , Biomarcadores/sangue , Encéfalo/metabolismo , Disfunção Cognitiva/sangue , Proteoma/análise , Aprendizado de Máquina , Estudos de Coortes , Progressão da Doença , Insuficiência Cardíaca/sangue , Matriz Extracelular/metabolismo , Sinapses/metabolismo , Calcificação Vascular/sangue , Coração
17.
Curr Biol ; 33(24): 5275-5287.e5, 2023 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-37924807

RESUMO

The human olfactory system has two discrete channels of sensory input, arising from olfactory epithelia housed in the left and right nostrils. Here, we asked whether the primary olfactory cortex (piriform cortex [PC]) encodes odor information arising from the two nostrils as integrated or distinct stimuli. We recorded intracranial electroencephalogram (iEEG) signals directly from PC while human subjects participated in an odor identification task where odors were delivered to the left, right, or both nostrils. We analyzed the time course of odor identity coding using machine-learning approaches and found that uni-nostril odor inputs to the ipsilateral nostril are encoded ∼480-ms faster than odor inputs to the contralateral nostril on average. During naturalistic bi-nostril odor sampling, odor information emerged in two temporally segregated epochs, with the first epoch corresponding to the ipsilateral and the second epoch corresponding to the contralateral odor representations. These findings reveal that PC maintains distinct representations of odor input from each nostril through temporal segregation, highlighting an olfactory coding scheme at the cortical level that can parse odor information across nostrils within the course of a single inhalation.


Assuntos
Córtex Olfatório , Percepção Olfatória , Córtex Piriforme , Humanos , Odorantes , Condutos Olfatórios , Olfato
18.
Lancet Reg Health Am ; 26: 100599, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37876670

RESUMO

Background: Deep brain stimulation (DBS) is an approved treatment option for Parkinson's Disease (PD), essential tremor (ET), dystonia, obsessive-compulsive disorder and epilepsy in the United States. There are disparities in access to DBS, and clear understanding of the contextual factors driving them is important. Previous studies aimed at understanding these factors have been limited by single indications or small cohort sizes. The aim of this study is to provide an updated and comprehensive analysis of DBS utilization for multiple indications to better understand the factors driving disparities in access. Methods: The United States based National Inpatient Sample (NIS) database was utilized to analyze the surgical volume and trends of procedures based on indication, using relevant ICD codes. Predictors of DBS use were analyzed using a logistic regression model. DBS-implanted patients in each indication were compared based on the patient-, hospital-, and outcome-related variables. Findings: Our analysis of 104,356 DBS discharges from 1993 to 2017 revealed that the most frequent indications for DBS were PD (67%), ET (24%), and dystonia (4%). Although the number of DBS procedures has consistently increased over the years, radiofrequency ablation utilization has significantly decreased to only a few patients per year since 2003. Negative predictors for DBS utilization in PD and ET cohorts included age increase and female sex, while African American status was a negative predictor across all cohorts. Significant differences in patient-, hospital-, and outcome-related variables between DBS indications were also determined. Interpretation: Demographic and socioeconomic-based disparities in DBS use are evident. Although racial disparities are present across all indications, other disparities such as age, sex, wealth, and insurance status are only relevant in certain indications. Funding: This work was supported by Alan & Susan Hudson Cornerstone Chair in Neurosurgery at University Health Network.

19.
Mov Disord ; 38(12): 2209-2216, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37811802

RESUMO

OBJECTIVE: Low-intensity transcranial focused ultrasound (TUS) is a novel method for neuromodulation. We aimed to study the feasibility of stimulating the bilateral primary motor cortices (M1) with accelerated theta-burst TUS (a-tbTUS) on neurophysiologic and clinical outcomes in Parkinson's disease (PD). METHODS: Patients were randomly assigned to receive active or sham a-tbTUS for the first visit and the alternate condition on the second visit, at least 10 days apart. a-tbTUS was administered in three consecutive sonications at 30-minute intervals. We used an accelerated protocol to produce an additive effect of stimulation. Patients were studied in the OFF-medication state. Transcranial magnetic stimulation (TMS)-elicited motor-evoked potentials (MEPs) were used to assess motor cortical excitability before and after TUS. Clinical outcomes after a-tbTUS administration were assessed using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS)-III. RESULTS: A total of 20 visits were conducted in 10 PD patients. Compared to the baseline, TMS-elicited MEP amplitudes significantly increased following active but not sham sonication (P = 0.0057). MEP amplitudes were also higher following a-tbTUS than sham sonication (P = 0.0064). There were no statistically significant changes in MDS-UPDRS-III scores with active or sham a-tbTUS. CONCLUSIONS: a-tbTUS increases motor cortex excitability and is a feasible non-invasive neuromodulation strategy in PD. Future studies should determine optimal dosing parameters and the durability of neurophysiologic and clinical outcomes in PD patients. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


Assuntos
Córtex Motor , Doença de Parkinson , Humanos , Doença de Parkinson/terapia , Projetos Piloto , Estimulação Magnética Transcraniana/métodos , Córtex Motor/fisiologia , Potencial Evocado Motor/fisiologia
20.
Transpl Int ; 36: 11552, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37663524

RESUMO

Although the association between post-transplant malignancy (PTM) and immunosuppressive therapy after organ transplantation has been studied, an integrated review of PTM after lung transplantation is lacking. We investigated the incidence and types of de novo PTM and its impact on survival following double lung transplantation (DLT). The incidence and type of PTM as well as the annual and cumulative risks of each malignancy after DLT were analyzed. The overall survival (OS) of recipients with or without PTM was compared by the Kaplan-Meier survival method and landmark analysis. There were 5,629 cases (23.52%) with 27 types of PTMs and incidences and OS varied according to the types of PTMs. The recipients with PTM showed a significantly longer OS than those without PTM (p < 0.001). However, while the recipients with PTM showed significantly better OS at 3, and 5 years (p < 0.001, p = 0.007), it was worse at the 10-year landmark time (p = 0.013). And the single PTM group showed a worse OS rate than the multiple PTM group (p < 0.001). This comprehensive report on PTM following DLT can help understand the risks and timing of PTM to improve the implementation of screening and treatment.


Assuntos
Terapia de Imunossupressão , Transplante de Pulmão , Neoplasias , Incidência , Risco , Terapia de Imunossupressão/efeitos adversos , Neoplasias/classificação , Neoplasias/epidemiologia , Neoplasias/mortalidade , Humanos , Masculino , Adulto , Pessoa de Meia-Idade
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