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1.
J Am Chem Soc ; 146(15): 10489-10497, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38584354

RESUMO

We describe the synthesis and characterization of a versatile platform for gold functionalization, based on self-assembled monolayers (SAMs) of distal-pyridine-functionalized N-heterocyclic carbenes (NHC) derived from bis(NHC) Au(I) complexes. The SAMs are characterized using polarization-modulation infrared reflectance-absorption spectroscopy, surface-enhanced Raman spectroscopy, and X-ray photoelectron spectroscopy. The binding mode is examined computationally using density functional theory, including calculations of vibrational spectra and direct comparisons to the experimental spectroscopic signatures of the monolayers. Our joint computational and experimental analyses provide structural information about the SAM binding geometries under ambient conditions. Additionally, we examine the reactivity of the pyridine-functionalized SAMs toward H2SO4 and W(CO)5(THF) and verify the preservation of the introduced functionality at the interface. Our results demonstrate the versatility of N-heterocyclic carbenes as robust platforms for on-surface acid-base and ligand exchange reactions.

2.
J Huntingtons Dis ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38578897

RESUMO

Background: Huntington's disease (HD) is a neurodegenerative disease that presents families with significant numbers of stressful events. However, relatively little empirical research has characterized the stressors encountered by members of HD-affected families and their correlations with psychological symptoms. Objective: This study examined frequencies of specific stressors in HD patients and at-risk individuals and the correlates of these stressors with demographics, disease characteristics, and symptoms of depression and anxiety. Methods: HD patients (n = 57) and at-risk individuals (n = 81) completed the Responses to Stress Questionnaire -Huntington's Disease Version to assess HD-related stressors. Participants completed measures of depression and anxiety symptoms. Patient health records were accessed to obtain information related to disease characteristics. Results: Patients endorsed a mean number of 5.05 stressors (SD = 2.74) out of the 10-item list. Demographics were not related to total stressors, but disease characteristics were significantly related to specific stressors. At-risk individuals endorsed a mean number of 3.20 stressors (SD = 2.65) out of the 11-item list. Age and sex were significantly related to specific stressors. Total number of stressors was significantly related to depression (ß=0.67, p <  0.001) and anxiety symptoms (ß=0.58, p <  0.001) in patients and at-risk individuals (ß=0.35, p = 0.003 and ß=0.32, p = 0.006, respectively). Conclusions: hese findings emphasize the significant burden of stress experienced by HD patients and at-risk individuals. We highlight a need for more specific stress-based measures and psychosocial support interventions for HD-affected families.

3.
Ther Innov Regul Sci ; 58(3): 443-455, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38528279

RESUMO

Conducting clinical trials (CTs) has become increasingly costly and complex in terms of designing and operationalizing. These challenges exist in running CTs on novel therapies, particularly in oncology and rare diseases, where CTs increasingly target narrower patient groups. In this study, we describe external control arms (ECA) and other relevant tools, such as virtualization and decentralized clinical trials (DCTs), and the ability to follow the clinical trial subjects in the real world using tokenization. ECAs are typically constructed by identifying appropriate external sources of data, then by cleaning and standardizing it to create an analysis-ready data file, and finally, by matching subjects in the external data with the subjects in the CT of interest. In addition, ECA tools also include subject-level meta-analysis and simulated subjects' data for analyses. By implementing the recent advances in digital health technologies and devices, virtualization, and DCTs, realigning of CTs from site-centric designs to virtual, decentralized, and patient-centric designs can be done, which reduces the patient burden to participate in the CTs and encourages diversity. Tokenization technology allows linking the CT data with real-world data (RWD), creating more comprehensive and longitudinal outcome measures. These tools provide robust ways to enrich the CT data for informed decision-making, reduce the burden on subjects and costs of trial operations, and augment the insights gained for the CT data.


Assuntos
Ensaios Clínicos como Assunto , Desenvolvimento de Medicamentos , Humanos , Projetos de Pesquisa
4.
Gynecol Oncol Rep ; 52: 101339, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38435347

RESUMO

Objectives: To determine the cost of two surgical treatment approaches for vulvar Paget's disease and model the cost-effectiveness considering differences in recurrence and reoperation over time. Methods: We assessed cost-effectiveness between excision guided by Mohs micrographic surgery (MMS-E) and traditional wide local excision (WLE). We examined billing data from patients with vulvar Paget's disease who underwent MMS-E (cases, n = 24, 2018-2022) or WLE (controls, n = 64, 1990-2020). We created typical treatment bundles incorporating physician-administered services and facility costs standardized to Medicare reimbursements in 2022 United States Dollars (USD). The primary measure of effectiveness was disease-free years of life. A secondary analysis estimated quality-adjusted life years (QALY). A Markov model simulated treatment pathways over a 10-year time horizon. Transition probabilities were based on institutional recurrence rates (3-year RR 6.7 % for MMS-E vs 34.1 % for WLE). We used a willingness-to-pay threshold of 100,000 USD per QALY. Results: The cost of a single surgical episode was 34,664 USD for MMS-E and 14,969 USD for WLE. In the setting of lower recurrence rates with MMS-E, the incremental cost was 12,789 USD per disease-free year gained. A secondary analysis incorporating QALY showed an incremental cost of 72,820 USD per QALY. Conclusions: MMS-E appears to be a cost-effective treatment for vulvar Paget's disease compared to historic standard of care. Our ability to estimate quality of life gained by avoiding disease recurrence was limited by scant data for this rare condition; thus, future studies incorporating health utility values are needed to facilitate a more comprehensive analysis.

5.
eNeuro ; 11(3)2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38514185

RESUMO

The internal globus pallidus (GPi) is a major source of tonic GABAergic inhibition to the motor thalamus. In parkinsonism, the firing rate of GPi neurons is increased, and their pattern switches from a tonic to a burst mode, two pathophysiological changes associated with increased GABAergic pallidothalamic activity. In this study, we used high-resolution 3D electron microscopy to demonstrate that GPi terminals in the parvocellular ventral anterior nucleus (VApc) and the centromedian nucleus (CM), the two main GPi-recipient motor thalamic nuclei in monkeys, undergo significant morphometric changes in parkinsonian monkeys including (1) increased terminal volume in both nuclei; (2) increased surface area of synapses in both nuclei; (3) increased number of synapses/GPi terminals in the CM, but not VApc; and (4) increased total volume, but not number, of mitochondria/terminals in both nuclei. In contrast to GPi terminals, the ultrastructure of putative GABAergic nonpallidal terminals was not affected. Our results also revealed striking morphological differences in terminal volume, number/area of synapses, and volume/number of mitochondria between GPi terminals in VApc and CM of control monkeys. In conclusion, GABAergic pallidothalamic terminals are endowed with a high level of structural plasticity that may contribute to the development and maintenance of the abnormal increase in pallidal GABAergic outflow to the thalamus in the parkinsonian state. Furthermore, the evidence for ultrastructural differences between GPi terminals in VApc and CM suggests that morphologically distinct pallidothalamic terminals from single pallidal neurons may underlie specific physiological properties of pallidal inputs to VApc and CM in normal and diseased states.


Assuntos
Elétrons , Núcleos Intralaminares do Tálamo , Neurônios/fisiologia , Globo Pálido , Microscopia Eletrônica
6.
ACS Catal ; 14(5): 2883-2896, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38449532

RESUMO

The catalytic dehydrogenation of substituted alkenones on noble metal catalysts supported on carbon (Pt/C, Pd/C, Rh/C, and Ru/C) was investigated in an organic phase under inert conditions. The dehydrogenation and semihydrogenation of the enone starting materials resulted in aromatic compounds (primary products), saturated cyclic ketones (secondary products), and cyclic alcohols (minor products). Pd/C exhibits the highest catalytic activity, followed by Pt/C and Rh/C. Aromatic compounds remain the primary products, even in the presence of hydrogen donors. Joint experimental and theoretical analyses showed that the four catalytic materials stabilize a common dienol intermediate on the metal surfaces, formed by keto-enol tautomerization. This intermediate subsequently forms aromatic products upon dehydrogenation. The binding orientation of the enone reactants on the catalytic surface is strongly metal-dependent, as the M-O bond distance changes substantially according to the metal. The longer M-O bonds (Pt: 2.84 Å > Pd: 2.23 Å > Rh: 2.17 Å > Ru: 2.07 Å) correlate with faster reaction rates and more favorable keto-enol tautomerization, as shorter distances correspond to a more stabilized starting material. Tautomerization is shown to occur via a stepwise surface-assisted pathway. Overall, each of the studied metals exhibits a distinct balance of enthalpy and entropy of activation (ΔH°‡, ΔS°‡), offering unique possibilities in the realm of enone dehydrogenation reactions that can be achieved by suitable selection of catalytic materials.

8.
Pharmacogenomics J ; 24(2): 4, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38360955

RESUMO

CYP3A5 genetic variants are associated with tacrolimus metabolism. Controversy remains on whether CYP3A4 increased [*1B (rs2740574), *1 G (rs2242480)] and decreased function [*22 (rs35599367)] genetic variants provide additional information. This retrospective cohort study aims to address whether tacrolimus dose-adjusted trough concentrations differ between combined CYP3A (CYP3A5 and CYP3A4) phenotype groups. Heart transplanted patients (n = 177, between 2008 and 2020) were included and median age was 54 years old. Significant differences between CYP3A phenotype groups in tacrolimus dose-adjusted trough concentrations were found in the early postoperative period and continued to 6 months post-transplant. In CYP3A5 nonexpressers, carriers of CYP3A4*1B or *1 G variants (Group 3) compared to CYP3A4*1/*1 (Group 2) patients were found to have lower tacrolimus dose-adjusted trough concentrations at 2 months. In addition, significant differences were found among CYP3A phenotype groups in the dose at discharge and time to therapeutic range while time in therapeutic range was not significantly different. A combined CYP3A phenotype interpretation may provide more nuanced genotype-guided TAC dosing in heart transplant recipients.


Assuntos
Transplante de Coração , Tacrolimo , Adulto , Humanos , Pessoa de Meia-Idade , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Imunossupressores/uso terapêutico , Estudos Retrospectivos , Polimorfismo de Nucleotídeo Único , Fenótipo , Genótipo , Transplante de Coração/efeitos adversos , Transplantados
9.
Artigo em Inglês | MEDLINE | ID: mdl-38311626

RESUMO

Individuals with Tourette syndrome (TS) have poorer quality of life (QoL) than their peers, yet factors contributing to poor QoL in this population remain unclear. Research to date has predominantly focused on the impact of tics and psychiatric symptoms on QoL in TS samples. The aim of this cross-sectional, multi-informant study was to identify psychosocial variables that may impact adolescent QoL in TS. Thirty-eight adolescents aged 13 to 17 with TS and 28 age-matched controls participated with a caregiver. No group differences were found on QoL, although the TS group reported reduced QoL compared to population normative data. In the TS group, reduced QoL was associated with lower self-esteem, poorer family functioning, higher stress, and greater depression and anxiety; QoL was unrelated to tic severity. In regression analyses, after adjusting for covariates, family functioning was the strongest predictor of QoL. These results emphasize the need to further explore the influence of psychosocial factors, particularly family functioning, on QoL in adolescents with TS.

10.
Neurosurgery ; 94(3): 630-642, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37967154

RESUMO

BACKGROUND AND OBJECTIVES: Stereotactic radiosurgery (SRS) has been an attractive treatment modality for both cranial and spinal hemangioblastomas, especially for multiple lesions commonly associated with von Hippel-Lindau (VHL) disease. This study aims to provide the largest long-term analysis of treatment efficacy and adverse effects of SRS for cranial and spinal hemangioblastomas at a single institution. METHODS: We evaluated the clinical and radiological outcomes of patients with hemangioblastomas treated with CyberKnife SRS at our institute from 1998 to 2022. The follow-up data were available for 135 hemangioblastomas in 35 patients. Twenty-eight patients had 123 hemangioblastomas associated with VHL, and 7 had 12 sporadic hemangioblastomas. The median age was 36 years, and the median tumor volume accounted for 0.4 cc. The SRS was administered with the median single-fraction equivalent dose of 18 Gy to the 77% median isodose line. RESULTS: At a median follow-up of 57 months (range: 3-260), only 20 (16.2%) of the VHL-associated and 1 (8.3%) sporadic hemangioblastomas progressed. The 5-year local tumor control rate was 91.3% for all hemangioblastomas, 91.7% among the sporadic lesions, and 92.9% in patients with VHL. SRS improved tumor-associated symptoms of 98 (74.8%) of 131 symptomatic hemangioblastomas, including headache, neck pain, dizziness, visual disturbances, dysesthesia, ataxia, motor impairment, seizures, and dysphagia. Two patients developed radiation necrosis (5.7%), and 1 of them required surgical resection. CONCLUSION: SRS is a safe and effective treatment option for patients with hemangioblastomas in critical locations, such as the brainstem, cervicomedullary junction, and spinal cord, and in patients with multiple hemangioblastomas associated with VHL disease.


Assuntos
Hemangioblastoma , Radiocirurgia , Neoplasias da Medula Espinal , Doença de von Hippel-Lindau , Humanos , Adulto , Hemangioblastoma/cirurgia , Hemangioblastoma/complicações , Hemangioblastoma/patologia , Radiocirurgia/efeitos adversos , Estudos Retrospectivos , Doença de von Hippel-Lindau/complicações , Doença de von Hippel-Lindau/diagnóstico , Doença de von Hippel-Lindau/cirurgia , Resultado do Tratamento , Neoplasias da Medula Espinal/radioterapia , Neoplasias da Medula Espinal/cirurgia , Seguimentos
11.
Biol Psychiatry ; 95(3): 256-265, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37567334

RESUMO

BACKGROUND: Patients with stimulant use disorder experience high rates of relapse. While neurobehavioral mechanisms involved in initiating drug use have been studied extensively, less research has focused on relapse. METHODS: To assess motivational processes involved in relapse and diagnosis, we acquired functional magnetic resonance imaging responses to nondrug (monetary) gains and losses in detoxified patients with stimulant use disorder (n = 68) and community control participants (n = 42). In a prospective multimodal design, we combined imaging of brain function, brain structure, and behavior to longitudinally track subsequent risk for relapse. RESULTS: At the 6-month follow-up assessment, 27 patients remained abstinent, but 33 had relapsed. Patients with blunted anterior insula (AIns) activity during loss anticipation were more likely to relapse, an association that remained robust after controlling for potential confounds (i.e., craving, negative mood, years of use, age, and gender). Lower AIns activity during loss anticipation was associated with lower self-reported negative arousal to loss cues and slower behavioral responses to avoid losses, which also independently predicted relapse. Furthermore, AIns activity during loss anticipation was associated with the structural coherence of a tract connecting the AIns and the nucleus accumbens, as was functional connectivity between the AIns and nucleus accumbens during loss processing. However, these neurobehavioral responses did not differ between patients and control participants. CONCLUSIONS: Taken together, the results of the current study show that neurobehavioral markers predicted relapse above and beyond conventional self-report measures, with a cross-validated accuracy of 72.7%. These findings offer convergent multimodal evidence that implicates blunted avoidance motivation in relapse to stimulant use and may therefore guide interventions targeting individuals who are most vulnerable to relapse.


Assuntos
Encéfalo , Transtornos Relacionados ao Uso de Substâncias , Humanos , Estudos Prospectivos , Encéfalo/diagnóstico por imagem , Motivação , Doença Crônica , Imageamento por Ressonância Magnética , Recidiva , Antecipação Psicológica/fisiologia , Recompensa
12.
J Neurosurg Spine ; 40(4): 485-497, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38157539

RESUMO

OBJECTIVE: Leiomyosarcoma (LMS) is a rare, aggressive soft-tissue sarcoma that seldom spreads to the bone. The spine can be either the site of LMS osseous metastases or the primary tumor site. The optimal treatment option for spinal LMS is still unclear. The authors present a cohort of patients with spinal LMS treated with either upfront surgery or upfront CyberKnife stereotactic radiosurgery (SRS). METHODS: The authors retrospectively studied the clinical and radiological outcomes of 17 patients with spinal LMS treated at their institution between 2004 and 2020. Either surgery or SRS was used as the upfront treatment. The clinical and radiological outcomes were assessed. A systematic review of the literature was also conducted. RESULTS: Of the 17 patients (20 spinal lesions), 12 (70.6%) were female. The median patient age was 61 years (range 41-80 years). Ten patients had upfront surgery for their spinal lesions, and 7 had upfront CyberKnife radiosurgery. The median follow-up was 11 months (range 0.3-130 months). The median overall survival (OS) for the entire cohort was 13 months (range 0.3-97 months). In subgroup analysis, the median OS was lower for the surgical group (13 months, range 0.3-50 months), while the median OS for the SRS group was 15 months (range 5-97 months) (p = 0.5). Forty percent (n = 4) of those treated with surgery presented with local recurrence at a median of 6.7 months (range 0.3-36 months), while only 14% (n = 1) of those treated with CyberKnife radiosurgery had local recurrence after 5 months. Local tumor control (LTC) rates at the 6-, 12-, and 18-month follow-ups were 72%, 58%, and 43%, respectively, for the SRS group and 40%, 30%, and 20%, respectively, for the surgery group (p < 0.05). The literature review included 35 papers with 70 patients harboring spinal LMS; only 2 patients were treated with SRS. The literature review confirms the clinical and radiological outcomes of the surgical group, while data on SRS are anecdotal. CONCLUSIONS: The authors present the largest series in the literature of spinal LMS and the first on SRS for spinal LMS. This study shows that LTC is statistically significantly better in patients receiving upfront SRS instead of surgery. The OS does not appear different between the two groups.


Assuntos
Neoplasias Encefálicas , Leiomiossarcoma , Radiocirurgia , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Masculino , Estudos Retrospectivos , Seguimentos , Leiomiossarcoma/diagnóstico por imagem , Leiomiossarcoma/radioterapia , Leiomiossarcoma/cirurgia , Resultado do Tratamento
13.
J Neurooncol ; 165(2): 373-379, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37955759

RESUMO

PURPOSE: Belzutifan is a Hypoxia Inducible Factor 2-alpha inhibitor approved in 2021 by the FDA for the treatment of renal cell carcinoma (RCC) in patients with Von-Hippel Landau (VHL) disease. These patients can also present with central nervous system (CNS) hemangioblastomas (HBs). We aim to study the effectiveness and adverse effects of belzutifan for CNS HBs, by reporting our preliminary institutional experience. METHODS: We present a series of VHL patients with CNS HBs undergoing treatment with belzutifan for RCC. All the included patients met the RECIST inclusion criteria. The clinical and radiological outcome measures included: Objective response rate (ORR), time-to-response (TTR), adverse events (AE), and patient response. Patient response was classified as partial response (PR), complete response (CR), progressive disease (PD), or stable disease (SD). RESULTS: Seven patients with 25 HBs were included in our study. A belzutifan dose of 120 mg/day PO was administered for a median of 13 months (range 10-17). Median follow up time was 15 months (range 10-24). An ORR of 71% was observed. The median TTR was 5 months (range: 1-10). None of the patients showed CR, while 5 patients (71.4%) showed PR and 2 (28.5%) showed SD. Among patients with SD the maximum tumor response was 20% [increase/decrease] of the lesion diameter. All the patients experienced decreased hemoglobin concentration, fatigue, and dizziness. None of the patients experienced severe anemia (grade 3-4 CTCAE). CONCLUSION: Belzutifan appears to be an effective and safe treatment for CNS hemangioblastoma in VHL patients. Further clinical trials to assess the long-term effectiveness of the medication are required.


Assuntos
Carcinoma de Células Renais , Neoplasias do Sistema Nervoso Central , Hemangioblastoma , Neoplasias Renais , Doença de von Hippel-Lindau , Humanos , Hemangioblastoma/tratamento farmacológico , Hemangioblastoma/patologia , Estudos Retrospectivos , Doença de von Hippel-Lindau/complicações , Doença de von Hippel-Lindau/tratamento farmacológico , Doença de von Hippel-Lindau/patologia , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Sistema Nervoso Central/patologia , Proteína Supressora de Tumor Von Hippel-Lindau
14.
Dermatol Online J ; 29(4)2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37921814

RESUMO

Sickle cell disease is a monogenic hemoglobinopathy that results in the abnormal production of hemoglobin S, which yields the characteristic sickle-shaped red blood cells. Sickle cell vaso-occlusive crisis is a painful complication of sickle cell disease caused by red blood cell entrapment within the microcirculation. The resulting tissue ischemia triggers a secondary inflammatory process involved in the pathogenesis of varying inflammatory skin conditions. Chronic leg ulcers are the most common skin presentation in sickle cell disease. A 58-year-old woman with sickle cell disease presented with systemic edematous plaques with the most notable involvement of her bilateral legs, which exhibited reticulated purpuric patches with central pallor. We report a case highlighting an unusual presentation of livedo racemosa as the presenting sign in a patient with sickle cell disease in vaso-occlusive crisis.


Assuntos
Anemia Falciforme , Livedo Reticular , Humanos , Feminino , Pessoa de Meia-Idade , Livedo Reticular/etiologia , Anemia Falciforme/complicações , Dor/etiologia
15.
Front Physiol ; 14: 1266292, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37929211

RESUMO

Healthy bone adjusts its traits in an exceptionally coordinated, compensatory process. Recent advancements in skeletal imaging via High-Resolution Peripheral Quantitative Computed Tomography (HR-pQCT) allows for the in vivo 3-dimensional and longitudinal quantification of bone density, microarchitecture, geometry, and parameters of mechanical strength in response to varying strain stimuli including those resulting from exercise or military training. Further, the voxel size of 61 microns has the potential to capture subtle changes in human bone in as little as 8 weeks. Given the typical time course of bone remodeling, short-term detection of skeletal changes in bone microstructure and morphology is indicative of adaptive bone formation, the deposition of new bone formation, uncoupled from prior resorption, that can occur at mechanistically advantageous regions. This review aims to synthesize existing training-induced HR-pQCT data in three distinct populations of healthy adults excluding disease states, pharmacological intervention and nutritional supplementation. Those included are: 1) military basic or officer training 2) general population and 3) non-osteoporotic aging. This review aims to further identify similarities and contrasts with prior modalities and cumulatively interpret results within the scope of bone functional adaptation.

16.
J Card Fail ; 2023 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-37907147

RESUMO

BACKGROUND: Transplantation of hearts from hepatitis C virus (HCV)-positive donors has increased substantially in recent years following development of highly effective direct-acting antiviral therapies for treatment and cure of HCV. Although historical data from the pre-direct-acting antiviral era demonstrated an association between HCV-positive donors and accelerated cardiac allograft vasculopathy (CAV) in recipients, the relationship between the use of HCV nucleic acid test-positive (NAT+) donors and the development of CAV in the direct-acting antiviral era remains unclear. METHODS AND RESULTS: We performed a retrospective, single-center observational study comparing coronary angiographic CAV outcomes during the first year after transplant in 84 heart transplant recipients of HCV NAT+ donors and 231 recipients of HCV NAT- donors. Additionally, in a subsample of 149 patients (including 55 in the NAT+ cohort and 94 in the NAT- cohort) who had serial adjunctive intravascular ultrasound examination performed, we compared development of rapidly progressive CAV, defined as an increase in maximal intimal thickening of ≥0.5 mm in matched vessel segments during the first year post-transplant. In an unadjusted analysis, recipients of HCV NAT+ hearts had reduced survival free of CAV ≥1 over the first year after heart transplant compared with recipients of HCV NAT- hearts. After adjustment for known CAV risk factors, however, there was no significant difference between cohorts in the likelihood of the primary outcome, nor was there a difference in development of rapidly progressive CAV. CONCLUSIONS: These findings support larger, longer-term follow-up studies to better elucidate CAV outcomes in recipients of HCV NAT+ hearts and to inform post-transplant management strategies.

17.
Cureus ; 15(8): e44455, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37664337

RESUMO

Introduction Glioblastoma (GBM) is the most common malignant adult brain tumor and is invariably fatal. The standard treatment for GBM involves resection where possible, followed by chemoradiation per Stupp's protocol. We frequently use stereotactic radiosurgery (SRS) as a single-fraction treatment for small (volume ≤ 1cc) nodular recurrent GBM to the contrast-enhancing target on T1 MRI scan. In this paper, we aimed to evaluate the safety and efficacy of SRS for patients with contrast-enhancing satellite nodules in recurrent GBM. Methods This retrospective study analyzed the clinical and radiological outcomes of five patients who underwent CyberKnife (Accuray Inc., Sunnyvale, California) SRS at the institute between 2013 and 2022. Results From 96 patients receiving SRS for GBM, five (four males, one female; median age 53) had nine distinct new satellite lesions on MRI, separate from their primary tumor beds. Those nine lesions were treated with a median margin dose of 20 Gy in a single fraction. The three-, six, and 12-month local tumor control rates were 77.8%, 66.7%, and 26.7%, respectively. Median progression-free survival (PFS) was seven months, median overall survival following SRS was 10 months, and median overall survival (OS) was 35 months. Interestingly, the only lesion that did not show radiological progression was separate from the T2-fluid attenuated inversion recovery (FLAIR) signal of the main tumor. Conclusion Our SRS treatment outcomes for recurrent GBM satellite lesions are consistent with existing findings. However, in a unique case, a satellite nodule distinct from the primary tumor's T2-FLAIR signal and treated with an enlarged target volume showed promising control until the patient's demise. This observation suggests potential research avenues, given the limited strategies for 'multicentric' GBM lesions.

18.
Natl Sci Rev ; 10(10): nwad176, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37671331

RESUMO

It has long been established that plastic flow in the asthenosphere interacts constantly with the overlying lithosphere and plays a pivotal role in controlling the occurrence of geohazards such as earthquakes and volcanic eruptions. Unfortunately, accurately characterizing the direction and lateral extents of the mantle flow field is notoriously difficult, especially in oceanic areas where deployment of ocean bottom seismometers (OBSs) is expensive and thus rare. In this study, by applying shear wave splitting analyses to a dataset recorded by an OBS array that we deployed between mid-2019 and mid-2020 in the South China Sea (SCS), we show that the dominant mantle flow field has a NNW-SSE orientation, which can be attributed to mantle flow extruded from the Tibetan Plateau by the ongoing Indian-Eurasian collision. In addition, the results suggest that E-W oriented flow fields observed in South China and the Indochina Peninsula do not extend to the central SCS.

19.
Optom Vis Sci ; 100(9): 654-660, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37585731

RESUMO

SIGNIFICANCE: Traumatic optic neuropathy is an uncommon but devastating cause of vision loss after injury to the head. Soccer players may have a heightened risk because of the game's emphasis on heading the ball, a technique in which a player hits the soccer ball with his/her head. PURPOSE: This article reviews the case of an avid soccer player with traumatic optic neuropathy that occurred after numerous soccer ball headings during a game. This article also (1) provides a summary of the pathophysiology and epidemiology of traumatic optic neuropathy, (2) reviews the current literature on head and eye injuries in soccer, and (3) discusses biomechanical differences in orbital structure throughout aging, which may predispose older patients to traumatic optic neuropathy. CASE REPORT: We present the case of a 62-year-old male patient who reported to the clinic, after repeated subconcussive soccer ball headers the previous day, with symptoms of blurred vision and "seeing stars" in the right eye and a right inferior visual field impairment. Physical examination, subsequent laboratory work, and neurologic consults implicated traumatic optic neuropathy as the primary diagnosis, and halting soccer playing resulted in symptom improvement. CONCLUSIONS: Although not commonly encountered in soccer players, the potential for traumatic optic neuropathy exists. Older athletes may be predisposed because of morphological changes of the orbit. Future direction may look to further investigate hazards promoting traumatic optic neuropathy in older athletes and determine possible protections against injury.


Assuntos
Concussão Encefálica , Traumatismos do Nervo Óptico , Futebol , Baixa Visão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atletas , Concussão Encefálica/complicações , Concussão Encefálica/diagnóstico , Cabeça , Traumatismos do Nervo Óptico/complicações , Futebol/lesões , Futebol/fisiologia
20.
ASAIO J ; 69(11): 984-992, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37549669

RESUMO

There are minimal data on the use of venoarterial extracorporeal membrane life support (VA-ECLS) in adult congenital heart disease (ACHD) patients presenting with cardiogenic shock (CS). This study sought to describe the population of ACHD patients with CS who received VA-ECLS in the Extracorporeal Life Support Organization (ELSO) Registry. This was a retrospective analysis of adult patients with diagnoses of ACHD and CS in ELSO from 2009-2021. Anatomic complexity was categorized using the American College of Cardiology/American Heart Association 2018 guidelines. We described patient characteristics, complications, and outcomes, as well as trends in mortality and VA-ECLS utilization. Of 528 patients who met inclusion criteria, there were 32 patients with high-complexity anatomy, 196 with moderate-complexity anatomy, and 300 with low-complexity anatomy. The median age was 59.6 years (interquartile range, 45.8-68.2). The number of VA-ECLS implants increased from five implants in 2010 to 81 implants in 2021. Overall mortality was 58.3% and decreased year-by-year (ß= -2.03 [95% confidence interval, -3.36 to -0.70], p = 0.007). Six patients (1.1%) were bridged to heart transplantation and 21 (4.0%) to durable ventricular assist device. Complications included cardiac arrhythmia/tamponade (21.6%), surgical site bleeding (17.6%), cannula site bleeding (11.4%), limb ischemia (7.4%), and stroke (8.7%). Utilization of VA-ECLS for CS in ACHD patients has increased over time with a trend toward improvement in survival to discharge.


Assuntos
Oxigenação por Membrana Extracorpórea , Cardiopatias Congênitas , Humanos , Adulto , Pessoa de Meia-Idade , Choque Cardiogênico/etiologia , Choque Cardiogênico/terapia , Oxigenação por Membrana Extracorpórea/efeitos adversos , Estudos Retrospectivos , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/cirurgia , Sistema de Registros
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