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1.
Cancers (Basel) ; 16(7)2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38611105

RESUMO

Spinal meningiomas are the most common intradural, extramedullary tumor in adults, yet the least common entity when accounting for all meningiomas spanning the neuraxis. While traditionally considered a benign recapitulation of their intracranial counterpart, a paucity of knowledge exists regarding the differences between meningiomas arising from these two anatomic compartments in terms of histopathologic subtypes, molecular tumor biology, surgical principles, long-term functional outcomes, and recurrence rates. To date, advancements at the bench have largely been made for intracranial meningiomas, including the discovery of novel gene targets, DNA methylation profiles, integrated diagnoses, and alternative systemic therapies, with few exceptions reserved for spinal pathology. Likewise, evolving clinical research offers significant updates to our understanding of guiding surgical principles, intraoperative technology, and perioperative patient management for intracranial meningiomas. Nonetheless, spinal meningiomas are predominantly relegated to studies considering non-specific intradural extramedullary spinal tumors of all histopathologic types. The aim of this review is to comprehensively report updates in both basic science and clinical research regarding intraspinal meningiomas and to provide illustrative case examples thereof, thereby lending a better understanding of this heterogenous class of central nervous system tumors.

2.
Neurosurg Focus ; 55(4): E5, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37778049

RESUMO

OBJECTIVE: The optimal perioperative management of antithrombotic therapy (ATT) in patients requiring urgent neurosurgical intervention for subdural hematoma (SDH) is poorly understood. The delicate equilibrium of effective hemostasis while preventing thrombosis is complex and relies on numerous factors such as indication for and type of ATT, medical comorbidities, and extent of neurological injury. This study aimed to analyze the impact of ATT and reversal strategies on surgical outcomes to highlight current challenges in the management of these high-risk patients. METHODS: The authors performed a retrospective surgical cohort analysis of 100 patients undergoing urgent SDH evacuation at a level I trauma center between March 2020 and May 2021. The patients were first stratified into two cohorts based on preoperative ATT use and then further segregated by receipt of reversal agents. Statistical analysis included the chi-square test, Welch two-sample t-test, and multivariate logistic regression. The primary outcome was mortality. Secondary endpoints included radiographic SDH reexpansion, revision surgery, improvement in preoperative neurological deficits, and incidence of thromboembolism. A crossover cohort was secondarily analyzed in patients for whom ATT was interrupted for a minimum duration equal to effective drug metabolism. Finally, ATT reinitiation patterns were examined. RESULTS: Of 100 patients, 48% received ATT, 54.2% of whom were given reversal agents. ATT use was significantly associated with decreased rates of postoperative neurological improvement (p = 0.023) with trends toward increased mortality (p = 0.078), SDH reexpansion (p = 0.12), and need for revision surgery (p = 0.10). Patient crossover revealed a 4 times greater likelihood of death in patients without ATT interruption prior to surgery (p = 0.040) without an observable impact on secondary outcomes. ATT reversal contributed no improvement in outcomes other than a decreased intensive care unit length of stay when adjusted for in-hospital mortality (p = 0.014). The rate of postoperative thromboembolism following ATT reversal was 11.5%. ATT reinitiation was highly variable, occurring in 59.5% of patients, with median times of 17 and 15 days for antiplatelets and anticoagulants, respectively. CONCLUSIONS: Use of preoperative ATT portends poor clinical outcomes following nonelective SDH evacuation regardless of attempts to reverse these medications with replacement blood products. This study further reinforces the critical need for judicious use of ATT and optimization of reversal strategies in high-risk patient populations as best guided by multidisciplinary teams and evolving clinical practice guidelines.


Assuntos
Fibrinolíticos , Tromboembolia , Humanos , Fibrinolíticos/uso terapêutico , Estudos Retrospectivos , Hematoma Subdural/diagnóstico por imagem , Hematoma Subdural/tratamento farmacológico , Hematoma Subdural/cirurgia , Craniotomia/efeitos adversos
3.
Neurosurg Focus ; 55(3): E8, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37657101

RESUMO

OBJECTIVE: Cervical spondylotic myelopathy (CSM) is a common clinical degenerative disease treated with anterior cervical discectomy and fusion (ACDF), which seriously impacts quality of life and causes severe disability. The objective of the study was to determine the effect of different characteristics of the neurological deficit found in myelopathic patients undergoing ACDFs on hospital cost, length of stay (LOS), and discharge location. METHODS: This is a retrospective review of ACDF cases performed at a single institution by multiple surgeons from 2011 to 2017. Patient symptomatology, complications, comorbidities, demographics, surgical time, LOS, and discharge location were collected. Patients with readmissions or reoperations were excluded. Symptoms evaluated were based on clinical diagnosis, Japanese Orthopaedic Association classification, Ranawat grade, and Cooper scales. Symptoms were further grouped using principal component analysis. Cost was defined as surgical episode hospital stay costs plus outpatient clinic costs plus discharge disposition cost. Multivariate linear regression models were created to evaluate correlations with outcomes. The primary outcome was total 90-day hospital costs. Secondary outcomes were discharge location and LOS. RESULTS: A total of 250 patients were included in the analyses. Discharge location, neuromonitoring use, number of surgical vertebral levels, cage use, LOS, surgical time, having a complication, and sex were all found to be predictive of total 90-day costs. Myelopathic symptomatology was not found to be associated with increased 90-day costs (p ≥ 0.131) when correcting for these other factors. Lower-extremity functionality was found to be associated with increased LOS (p < 0.0001). Upper-extremity myelopathy was found to be associated with increased discharge location needs (p < 0.0001). CONCLUSIONS: Cervical myelopathy was not found to be predictive of total 90-day costs using symptomatology based on multiple myelopathy grading systems. Lower-extremity functionality was, however, found to predict LOS, while upper-extremity myelopathy was found to predict increased discharge location needs. This implies that preoperative deficits from myelopathy should not be considered in a bundled payment system; however, certain myelopathic symptoms should be considered when determining the cost of care.


Assuntos
Custos Hospitalares , Alta do Paciente , Humanos , Tempo de Internação , Qualidade de Vida , Discotomia
4.
Front Med (Lausanne) ; 10: 1197061, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37575987

RESUMO

Long COVID is characterized by persistent symptoms beyond 3-months of severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) infection that last for at least 2 months and cannot be explained by an alternative diagnosis. Autonomic, immunologic, endothelial, and hypercoagulation are implicated as possible mechanisms of long COVID symptoms. Despite recognition of the public health challenges posed by long COVID, the current understanding of the pathophysiological underpinnings is still evolving. In this narrative review, we explore the long-term effects of SARS-CoV-2 infection on T cell activation such as autoimmune disorders and endothelial cell dysfunction involving vascular impairments within pulmonary and renal architecture. We have described how endothelial dysfunction and vascular abnormalities may underscore findings of exercise intolerance by way of impaired peripheral oxygen extraction in individuals with long COVID.

5.
J Am Coll Radiol ; 20(9): 836-841, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37454752

RESUMO

Artificial intelligence (AI) continues to show great potential in disease detection and diagnosis on medical imaging with increasingly high accuracy. An important component of AI model creation is dataset development for training, validation, and testing. Diverse and high-quality datasets are critical to ensure robust and unbiased AI models that maintain validity, especially in traditionally underserved populations globally. Yet publicly available datasets demonstrate problems with quality and inclusivity. In this literature review, the authors evaluate publicly available medical imaging datasets for demographic, geographic, genetic, and disease representation or lack thereof and call for an increase emphasis on dataset development to maximize the impact of AI models.


Assuntos
Inteligência Artificial , Radiologia , Radiografia , Viés
6.
Lancet Respir Med ; 11(9): 791-803, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37348524

RESUMO

BACKGROUND: There is a clinical need for therapeutics for COVID-19 patients with acute hypoxemic respiratory failure whose 60-day mortality remains at 30-50%. Aviptadil, a lung-protective neuropeptide, and remdesivir, a nucleotide prodrug of an adenosine analog, were compared with placebo among patients with COVID-19 acute hypoxaemic respiratory failure. METHODS: TESICO was a randomised trial of aviptadil and remdesivir versus placebo at 28 sites in the USA. Hospitalised adult patients were eligible for the study if they had acute hypoxaemic respiratory failure due to confirmed SARS-CoV-2 infection and were within 4 days of the onset of respiratory failure. Participants could be randomly assigned to both study treatments in a 2 × 2 factorial design or to just one of the agents. Participants were randomly assigned with a web-based application. For each site, randomisation was stratified by disease severity (high-flow nasal oxygen or non-invasive ventilation vs invasive mechanical ventilation or extracorporeal membrane oxygenation [ECMO]), and four strata were defined by remdesivir and aviptadil eligibility, as follows: (1) eligible for randomisation to aviptadil and remdesivir in the 2 × 2 factorial design; participants were equally randomly assigned (1:1:1:1) to intravenous aviptadil plus remdesivir, aviptadil plus remdesivir matched placebo, aviptadil matched placebo plus remdesvir, or aviptadil placebo plus remdesivir placebo; (2) eligible for randomisation to aviptadil only because remdesivir was started before randomisation; (3) eligible for randomisation to aviptadil only because remdesivir was contraindicated; and (4) eligible for randomisation to remdesivir only because aviptadil was contraindicated. For participants in strata 2-4, randomisation was 1:1 to the active agent or matched placebo. Aviptadil was administered as a daily 12-h infusion for 3 days, targeting 600 pmol/kg on infusion day 1, 1200 pmol/kg on day 2, and 1800 pmol/kg on day 3. Remdesivir was administered as a 200 mg loading dose, followed by 100 mg daily maintenance doses for up to a 10-day total course. For participants assigned to placebo for either agent, matched saline placebo was administered in identical volumes. For both treatment comparisons, the primary outcome, assessed at day 90, was a six-category ordinal outcome: (1) at home (defined as the type of residence before hospitalisation) and off oxygen (recovered) for at least 77 days, (2) at home and off oxygen for 49-76 days, (3) at home and off oxygen for 1-48 days, (4) not hospitalised but either on supplemental oxygen or not at home, (5) hospitalised or in hospice care, or (6) dead. Mortality up to day 90 was a key secondary outcome. The independent data and safety monitoring board recommended stopping the aviptadil trial on May 25, 2022, for futility. On June 9, 2022, the sponsor stopped the trial of remdesivir due to slow enrolment. The trial is registered with ClinicalTrials.gov, NCT04843761. FINDINGS: Between April 21, 2021, and May 24, 2022, we enrolled 473 participants in the study. For the aviptadil comparison, 471 participants were randomly assigned to aviptadil or matched placebo. The modified intention-to-treat population comprised 461 participants who received at least a partial infusion of aviptadil (231 participants) or aviptadil matched placebo (230 participants). For the remdesivir comparison, 87 participants were randomly assigned to remdesivir or matched placebo and all received some infusion of remdesivir (44 participants) or remdesivir matched placebo (43 participants). 85 participants were included in the modified intention-to-treat analyses for both agents (ie, those enrolled in the 2 x 2 factorial). For the aviptadil versus placebo comparison, the median age was 57 years (IQR 46-66), 178 (39%) of 461 participants were female, and 246 (53%) were Black, Hispanic, Asian or other (vs 215 [47%] White participants). 431 (94%) of 461 participants were in an intensive care unit at baseline, with 271 (59%) receiving high-flow nasal oxygen or non-invasive ventiliation, 185 (40%) receiving invasive mechanical ventilation, and five (1%) receiving ECMO. The odds ratio (OR) for being in a better category of the primary efficacy endpoint for aviptadil versus placebo at day 90, from a model stratified by baseline disease severity, was 1·11 (95% CI 0·80-1·55; p=0·54). Up to day 90, 86 participants in the aviptadil group and 83 in the placebo group died. The cumulative percentage who died up to day 90 was 38% in the aviptadil group and 36% in the placebo group (hazard ratio 1·04, 95% CI 0·77-1·41; p=0·78). The primary safety outcome of death, serious adverse events, organ failure, serious infection, or grade 3 or 4 adverse events up to day 5 occurred in 146 (63%) of 231 patients in the aviptadil group compared with 129 (56%) of 230 participants in the placebo group (OR 1·40, 95% CI 0·94-2·08; p=0·10). INTERPRETATION: Among patients with COVID-19-associated acute hypoxaemic respiratory failure, aviptadil did not significantly improve clinical outcomes up to day 90 when compared with placebo. The smaller than planned sample size for the remdesivir trial did not permit definitive conclusions regarding safety or efficacy. FUNDING: National Institutes of Health.


Assuntos
COVID-19 , Insuficiência Respiratória , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , COVID-19/complicações , SARS-CoV-2 , Resultado do Tratamento , Tratamento Farmacológico da COVID-19 , Insuficiência Respiratória/tratamento farmacológico , Insuficiência Respiratória/etiologia , Oxigênio
7.
Cureus ; 15(5): e39535, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37366461

RESUMO

INTRODUCTION: Spine trauma is a common pathology that frequently requires neurosurgical intervention. Few studies have examined short-segment, 360-degree stabilization of traumatic thoracolumbar fractures. METHODS: A retrospective review was completed of adult and pediatric patients who underwent surgical correction for thoracolumbar fractures between December 2011 and December 2021. RESULTS: Forty patients met the inclusion criteria. The majority of patients presented with an American Spinal Injury Association (ASIA) score of D (n = 11) or E (n = 21). The most common level of injury was L1 (n = 20). The average length of stay was 11.7 days. Postoperatively, two patients had pulmonary emboli or deep venous thrombosis, and two had surgical site infections. Most patients were discharged to home (n = 21) or acute rehab (n = 14). The fusion rate at six months was 97.5%. Neurologically, all patients regained ambulation by >18 months follow-up. For the ASIA scale, most had a score of D (n = 4) or E (n = 32) at six months. The same trend was observed with the Frankel score, where most patients had either D (n = 5) or E (n = 31), improving to only two having a score of D at >18 months. CONCLUSIONS: Corpectomy followed by posterior fusion has a number of biomechanical benefits. This construct permits circumferential decompression, larger surface area for fusion, improved reconstitution of vertebral body height, reduced kyphosis, and an overall shorter segment. This results in fewer levels needing to be fused while enabling the greatest changes of successful fusion.

8.
J Clin Pathw ; 9(1): 22-28, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37360010

RESUMO

The Department of Veterans Health Affairs (VHA) has launched 22 multispecialty post-COVID-19 clinics across the US for the growing number of veterans experiencing long-term sequelae after acute COVID-19 infection. While evidence-based treatments for this syndrome are under investigation, there is a critical need to establish and disseminate clinical pathways (CPWs) based on knowledge and experience gained in those clinics. This VHA CPW is intended to guide primary care clinicians who care for patients experiencing dyspnea and/or cough during post-COVID-19 syndrome (PCS), which includes symptoms and abnormalities persisting or present beyond 12 weeks of the onset of acute COVID-19. This effort will help guide and standardize the care of veterans across the VHA, improve health outcomes, and effectively utilize health care resources. This article summarizes our stepwise diagnostic approach for patients presenting with PCS dyspnea and/or cough in primary care; it also highlights teleconsultation and telerehabilitation as opportunities to reach those in rural areas or with transportation barriers and improve reach for specialized services.

9.
Ultrasound J ; 14(1): 47, 2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36517635

RESUMO

BACKGROUND: Shock management requires quick and reliable means to monitor the hemodynamic effects of fluid resuscitation. Point-of-care ultrasound (POCUS) is a relatively quick and non-invasive imaging technique capable of capturing cardiac output (CO) variations in acute settings. However, POCUS is plagued by variable operator skill and interpretation. Artificial intelligence may assist healthcare professionals obtain more objective and precise measurements during ultrasound imaging, thus increasing usability among users with varying experience. In this feasibility study, we compared the performance of novice POCUS users in measuring CO with manual techniques to a novel automation-assisted technique that provides real-time feedback to correct image acquisition for optimal aortic outflow velocity measurement. METHODS: 28 junior critical care trainees with limited experience in POCUS performed manual and automation-assisted CO measurements on a single healthy volunteer. CO measurements were obtained using left ventricular outflow tract (LVOT) velocity time integral (VTI) and LVOT diameter. Measurements obtained by study subjects were compared to those taken by board-certified echocardiographers. Comparative analyses were performed using Spearman's rank correlation and Bland-Altman matched-pairs analysis. RESULTS: Adequate image acquisition was 100% feasible. The correlation between manual and automated VTI values was not significant (p = 0.11) and means from both groups underestimated the mean values obtained by board-certified echocardiographers. Automated measurements of VTI in the trainee cohort were found to have more reproducibility, narrower measurement range (6.2 vs. 10.3 cm), and reduced standard deviation (1.98 vs. 2.33 cm) compared to manual measurements. The coefficient of variation across raters was 11.5%, 13.6% and 15.4% for board-certified echocardiographers, automated, and manual VTI tracing, respectively. CONCLUSIONS: Our study demonstrates that novel automation-assisted VTI is feasible and can decrease variability while increasing precision in CO measurement. These results support the use of artificial intelligence-augmented image acquisition in routine critical care ultrasound and may have a role for evaluating the response of CO to hemodynamic interventions. Further investigations into artificial intelligence-assisted ultrasound systems in clinical settings are warranted.

10.
Fed Pract ; 39(7): 310-314, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36425345

RESUMO

Background: Global initiatives to mitigate COVID-19 transmission have shifted health system priorities to management of patients with prolonged long COVID symptoms. To better meet the needs of patients, clinicians, and systems, a learning health system approach can use rapid-cycle methods to integrate data and real-world experience to iteratively evaluate and adapt models of long COVID care. Observations: Employees in the Veterans Health Administration formed a multidisciplinary workgroup. We sought to develop processes to learn more about this novel long COVID syndrome and innovative long COVID care models that can be applied within and outside of our health care system. We describe our workgroup processes and goals to create a mechanism for cross-facility communication, identify gaps in care and research, and cocreate knowledge on best practices for long COVID care delivery. Conclusions: The learning health system approach will be critical in reimagining health care service delivery after the COVID-19 pandemic.

11.
Am J Crit Care ; 30(6): e99-e107, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34719712

RESUMO

BACKGROUND: Detecting delirium with standardized assessment tools such as the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) is important, but such detection is frequently hampered by poor documentation and inappropriate "unable to assess" responses (in noncomatose patients). OBJECTIVE: To identify patient, clinical, and workplace factors that may impede or facilitate appropriate delirium assessment through use of the CAM-ICU, specifically documentation and inappropriate "unable to assess" responses. METHODS: An electronic health record-based data set was used to quantify CAM-ICU documentation and inappropriate "unable to assess" responses during 24 months. Associated patient (eg, age), clinical (eg, diagnosis), and workplace (eg, geographic location within the ICU, shift) factors were evaluated with multivariable regression. RESULTS: Of 28 586 CAM-ICU documentation opportunities, 66% were documented; 16% of documentations in alert or lightly sedated patients had inappropriate "unable to assess" responses. Night shift was associated with lower CAM-ICU documentation rates (P = .001), whereas physical restraints and location on side B (rather than side A) of the ICU were associated with higher documentation rates (P < .05 for both). Age older than 80 years, non-White race, intubation, and physical restraints were associated with more inappropriate "unable to assess" responses (all P < .05), as was infusion of propofol, midazolam, dexmedetomidine, or fentanyl (all P < .05). CONCLUSION: Data from electronic health records can identify patient, clinical, and workplace factors associated with CAM-ICU documentation and inappropriate "unable to assess" responses, which can help target quality improvement efforts related to delirium assessment.


Assuntos
Delírio , Cuidados de Enfermagem , Idoso de 80 Anos ou mais , Delírio/diagnóstico , Documentação , Humanos , Unidades de Terapia Intensiva , Restrição Física
12.
Cureus ; 13(6): e15365, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34239796

RESUMO

During the COVID-19 pandemic, many patients are hospitalized, and those suffering from in-hospital cardiac arrest (IHCA) have been previously reported to have poor outcomes. This is a single-center, retrospective, observational study conducted at the Veterans Affairs Medical Center, Washington, DC, USA. The inclusion criteria were: patients admitted to the hospital with a diagnosis of COVID-19 who underwent cardiopulmonary resuscitation (CPR) for IHCA. Patients were labeled as COVID-19 positive based on a laboratory-confirmed positive polymerase chain reaction test. Patients with do-not-resuscitate (DNR) orders, those who were made comfort care, or enrolled in hospice were excluded. The study was approved by the hospital's institutional review board. A total of 155 patients with COVID-19 infection were admitted; 145/155 (93.5%) admitted to the medical floor and 10/155 (6.5%) to the medical intensive care unit (MICU). 36/145 (24.8%) floor patients were upgraded to MICU. Of the 46 patients treated in MICU, 17/46 (36.9%) were excluded for DNR status. From the remaining 29/46 (63.1%) patients, 19/29 (65.5%) patients survived, and 10/29 (34.5%) patients had IHCA. All 10/10 (100%) died after CPR without return of spontaneous circulation (ROSC). The initial rhythm was non-shockable in all patients, with pulseless electrical activity (PEA) in 7/10 (70%) and asystole in 3/10 (30%) patients. Patients with COVID-19 infection who had an IHCA and underwent CPR had a 0% survival at our hospital. Discussions on advanced care options, especially CPR, with COVID-19 patients and their families, are important as the overall prognosis after CPR for IHCA is poor.

13.
Cureus ; 12(11): e11486, 2020 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-33329982

RESUMO

While hemorrhage is commonly encountered in various intracranial tumors, it is relatively rare in benign meningiomas. We present an interesting case report of a 75-year-old male who fell during intoxication, sustaining right frontal cranial trauma, coincidentally directly overlying a previously undiagnosed right frontal meningioma. He experienced an acute neurological decline and was found to have an intracranial hematoma, causing significant mass effect and herniation. Based on the radiographic appearance, an underlying neoplasm with significant edema was suspected. Intraoperatively, the hematoma and mass were successfully evacuated, and post-operative pathology confirmed the presence of a World Health Organization Grade I meningioma with a microcystic and angiomatous pattern. We speculate on the mechanism of injury and hemorrhage in this patient through review of the literature and discussion of medical and pathological risk factors.

14.
Clin Neurol Neurosurg ; 184: 105406, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31302381

RESUMO

OBJECTIVE: In response to rising national health expenditures, the Patient Protection and Affordable Care Act (ACA) was passed in 2010, with major provisions implemented in 2014. Due to increasing concerns about workload and compensation among neurosurgeons, we evaluated trends in neurosurgical reimbursement, productivity and compensation before and after the implementation of the major provisions of the ACA. PATIENTS AND METHODS: Results from Neurosurgery Executives' Resource Value and Education Society (NERVES) annual surveys were collected, representing data from 2011 to 2016. Responses from different practice settings across the six years were categorized into groups, and inverse variance-weighted averaging was performed within the frameworks of a one-way ANOVA model with year. Data from 2011 to 2013 and 2014-2016 were analyzed similarly for differences among practice setting and region. RESULTS: The NERVES survey response rates ranged from 20% to 36%. Median values for compensation decreased by 3.66%, 6.42%, and 10.34% within private, hospital, and academic practices respectively after 2014 although these trends did not reach statistical significance. Median work RVUs had a trend to decrease by 5.67%, 13.08%, and 19.44% within private, hospital, and academic practices respectively after 2014. Academic practices showed statistically significant decreases in annual total RVUs, total gross charges and collections. CONCLUSION: These data demonstrate neurosurgical reimbursement and productivity have trended down during a time that increases in productivity and reimbursement were predicted. This phenomenon is most notable in academic practices compared to private or hospital based practices. Prospective analyses of the impact of healthcare policy reform on neurosurgical productivity are urgently needed.


Assuntos
Planos de Pagamento por Serviço Prestado/economia , Planos de Pagamento por Serviço Prestado/tendências , Neurocirurgiões/economia , Neurocirurgiões/tendências , Procedimentos Neurocirúrgicos/economia , Procedimentos Neurocirúrgicos/tendências , Inquéritos e Questionários , Feminino , Humanos , Masculino , Patient Protection and Affordable Care Act/economia , Patient Protection and Affordable Care Act/tendências , Sociedades Médicas/economia , Sociedades Médicas/tendências
15.
J Mol Cell Cardiol ; 123: 26-37, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30138628

RESUMO

Acto-myosin cross-bridge kinetics are important for beat-to-beat regulation of cardiac contractility; however, physiological and pathophysiological mechanisms for regulation of contractile kinetics are incompletely understood. Here we explored whether thin filament-mediated Ca2+ sensitization influences cross-bridge kinetics in permeabilized, osmotically compressed cardiac muscle preparations. We used a murine model of hypertrophic cardiomyopathy (HCM) harboring a cardiac troponin C (cTnC) Ca2+-sensitizing mutation, Ala8Val in the regulatory N-domain. We also treated wild-type murine muscle with bepridil, a cTnC-targeting Ca2+ sensitizer. Our findings suggest that both methods of increasing myofilament Ca2+ sensitivity increase cross-bridge cycling rate measured by the rate of tension redevelopment (kTR); force per cross-bridge was also enhanced as measured by sinusoidal stiffness and I1,1/I1,0 ratio from X-ray diffraction. Computational modeling suggests that Ca2+ sensitization through this cTnC mutation or bepridil accelerates kTR primarily by promoting faster cross-bridge detachment. To elucidate if myofilament structural rearrangements are associated with changes in kTR, we used small angle X-ray diffraction to simultaneously measure myofilament lattice spacing and isometric force during steady-state Ca2+ activations. Within in vivo lattice dimensions, lattice spacing and steady-state isometric force increased significantly at submaximal activation. We conclude that the cTnC N-domain controls force by modulating both the number and rate of cycling cross-bridges, and that the both methods of Ca2+ sensitization may act through stabilization of cTnC's D-helix. Furthermore, we propose that the transient expansion of the myofilament lattice during Ca2+ activation may be an additional factor that could increase the rate of cross-bridge cycling in cardiac muscle. These findings may have implications for the pathophysiology of HCM.


Assuntos
Cálcio/metabolismo , Contração Miocárdica , Miocárdio/metabolismo , Miofibrilas/metabolismo , Troponina C/metabolismo , Algoritmos , Animais , Sinalização do Cálcio , Cardiomiopatia Hipertrófica/genética , Cardiomiopatia Hipertrófica/metabolismo , Cardiomiopatia Hipertrófica/patologia , Cardiomiopatia Hipertrófica/fisiopatologia , Modelos Animais de Doenças , Feminino , Humanos , Contração Isométrica , Cinética , Masculino , Camundongos , Modelos Moleculares , Modelos Teóricos , Mutação , Miocárdio/química , Miofibrilas/química , Ligação Proteica , Conformação Proteica , Domínios e Motivos de Interação entre Proteínas , Relação Estrutura-Atividade , Troponina C/química , Troponina C/genética
16.
Otol Neurotol ; 35(3): 519-25, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23988997

RESUMO

HYPOTHESIS: Flexible electrode interaction with intracochlear structures in a noise-damaged region of the cochlea can lead to measureable electrophysiologic changes. BACKGROUND: An emerging goal in cochlear implantation is preservation of residual hearing subsequently allowing for combined electric and acoustic stimulation (EAS). However, residual hearing is at least partially lost in most patients as a result of electrode insertion. A gerbil model was used to examine changes to acoustically evoked cochlear potentials during simulated cochlear implantation. METHODS: Gerbils were partially deafened by noise exposure to mimic residual hearing in human cochlear implant candidates. After 1 month, round window and intracochlear recordings during flexible electrode insertion were made in response to 1 kHz tone burst stimuli at 80 dB SPL. After the insertion, the cochleas were histologically examined for hair cell loss because of the noise exposure and trauma because of the electrode insertion. RESULTS: Anatomic damage from the flexible electrode was not observable in most cases. However, insertions caused response declines that were, on average, greater than the controls, although some losses were similar to the controls. The CM was more sensitive than the CAP for detecting cochlear disturbance. CONCLUSION: Because response reductions occurred in the absence of anatomic damage, disturbances in the fluid at the base appear to affect responses from the apex. The losses were less than in previous experiments where the basilar membrane was penetrated.


Assuntos
Cóclea/fisiopatologia , Implante Coclear , Eletrodos Implantados , Potenciais Evocados Auditivos/fisiologia , Perda Auditiva Provocada por Ruído/fisiopatologia , Janela da Cóclea/fisiopatologia , Estimulação Acústica , Animais , Cóclea/cirurgia , Implantes Cocleares , Estimulação Elétrica , Fenômenos Eletrofisiológicos , Gerbillinae , Perda Auditiva Provocada por Ruído/cirurgia , Testes Auditivos , Janela da Cóclea/cirurgia
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