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1.
J Dent ; 145: 104939, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38521237

RESUMO

OBJECTIVES: To measure the impact of superimposition methods and the designated comparison area on accuracy analyses of dentate models using an ISO-recommended 3-dimensional (3D) metrology-grade inspection software (Geomagic Control X; 3D Systems; Rock Hill, South Carolina; USA). MATERIALS AND METHODS: A dentate maxillary typodont scanned with a desktop scanner (E4; 3 Shape; Copenhagen; Denmark) and an intraoral scanner (Trios 4; 3 Shape; Copenhagen; Denmark) was used as reference. Eight groups were created based on the core features of each superimposition method: landmark-based alignment (G1); partial area-based alignment (G2); entire tooth area-based alignment (G3); double alignment combining landmark-based alignment with entire tooth area-based alignment (G4); double alignment combining partial area-based alignment with entire tooth area-based alignment (G5); initial automated quick pre-alignment (G6); initial automated precise pre-alignment (G7); and entire model area-based alignment (G8). Diverse variations of each alignment and two regions for accuracy analyses (teeth surface or full model surface) were tested, resulting in a total of thirty-two subgroups (n = 18). The alignment accuracy between experimental and reference meshes was quantified using root mean square (RMS) error as trueness and its repeatability as precision. The descriptive statistics, a factorial repeated measures analysis of variance (ANOVA) and a post hoc Tuckey multiple comparison tests were used to analyze the trueness, and precision (α = 0.05). RESULTS: A total of 576 superimpositions were performed. The unique partial area-based superimposition method demonstrated the least precise alignment and was the sole group to exhibit a significant difference (p<.001). Automated initial pre-alignments demonstrated similar accuracy to other superimposition methods (p>.05). Double alignments did not result in accuracy improvement (p>.05). The designated comparison area displayed differences in both trueness (p<.001) and precision (p<.001), leading to an overall discrepancy of 8 ± 4 µm between selecting the teeth surface or full model surface. CONCLUSIONS: The superimposition method choice within the tested software did not impact accuracy analyses, except when the alignment relies on a unique and reduced area, such as the palatal rugae, a single tooth, or three adjacent teeth on one side. CLINICAL SIGNIFICANCE: The superimposition method choice within the tested ISO-recommended 3D inspection software did not impact accuracy analyses.


Assuntos
Processamento de Imagem Assistida por Computador , Imageamento Tridimensional , Modelos Dentários , Software , Humanos , Imageamento Tridimensional/métodos , Processamento de Imagem Assistida por Computador/métodos , Pontos de Referência Anatômicos , Reprodutibilidade dos Testes , Maxila/anatomia & histologia , Dente/anatomia & histologia , Dente/diagnóstico por imagem
2.
World Neurosurg ; 184: e659-e673, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38342172

RESUMO

BACKGROUND: Giant pituitary adenomas (GPAs) are defined as tumors with ≥40 mm in any maximum diameter, and these tend to invade multiple intracranial compartments. Hence, treatment remains a surgical challenge. OBJECTIVE: To describe the clinical and surgical outcomes of the endoscopic endonasal approach (EEA) for GPA in a pituitary referral center in Latin America and to analyze associated predictive factors. METHODS: 37 patients with histologically-confirmed GPA treated solely through the EEA between a 2-year period were included. Preoperative and postoperative clinical and neuroimaging findings; surgical morbidity and mortality; and binary logistic regression analysis to assess predictive factors were analyzed. RESULTS: Preoperative visual impairment prevalence was 97.3%. Mean tumor volume was 32 cc and gross total resection rate was 40.5%. Favorable visual acuity and visual fields outcome rate was 75% and 82.9%, respectively. In the multivariate analysis, bilateral cavernous sinus invasion (P = 0.018) and postoperative cerebrospinal fluid (CSF) leak (P = 0.036) were associated with an unfavorable visual acuity outcome, while radiation therapy (P = 0.035) was for visual fields. Similarly, intraoperative CSF leak was a predictive factor for postoperative CSF leak (10.8%) (P = 0.042) and vascular injury (13.5%) (P = 0.048). CONCLUSIONS: In this first Mexican clinical series, we demonstrated that the EEA is a safe and effective technique for GPA, although early diagnosis and prompt intervention may promote further visual function preservation without significant endocrine morbidity.


Assuntos
Adenoma , Doenças da Hipófise , Neoplasias Hipofisárias , Humanos , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/cirurgia , Neoplasias Hipofisárias/complicações , Adenoma/diagnóstico por imagem , Adenoma/cirurgia , Adenoma/complicações , Nariz/cirurgia , Complicações Pós-Operatórias/epidemiologia , Resultado do Tratamento , Estudos Retrospectivos
4.
J Neurol ; 271(4): 1515-1535, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37906325

RESUMO

The recent success of anti-CD20 monoclonal antibody therapies in the treatment of multiple sclerosis (MS) has highlighted the role of B cells in the pathogenesis of MS. In people with MS, the inflammatory characteristics of B-cell activity are elevated, leading to increased pro-inflammatory cytokine release, diminished anti-inflammatory cytokine production and an accumulation of pathogenic B cells in the cerebrospinal fluid. Rituximab, ocrelizumab, ofatumumab, ublituximab and BCD-132 are anti-CD20 therapies that are either undergoing clinical development, or have been approved, for the treatment of MS. Despite CD20 being a common target for these therapies, differences have been reported in their mechanistic, pharmacological and clinical characteristics, which may have substantial clinical implications. This narrative review explores key characteristics of these therapies. By using clinical trial data and real-world evidence, we discuss their mechanisms of action, routes of administration, efficacy (in relation to B-cell kinetics), safety, tolerability and convenience of use. Clinicians, alongside patients and their families, should consider the aspects discussed in this review as part of shared decision-making discussions to improve outcomes and health-related quality of life for people living with MS.


Assuntos
Antineoplásicos , Esclerose Múltipla , Humanos , Esclerose Múltipla/tratamento farmacológico , Qualidade de Vida , Anticorpos Monoclonais/farmacologia , Rituximab/uso terapêutico , Antineoplásicos/uso terapêutico , Citocinas
5.
Cancer Med ; 12(14): 15612-15627, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37317676

RESUMO

BACKGROUND: Patients' lack of knowledge about their own disease may function as a barrier to shared decision-making and well-being. This study aimed to evaluate the impact of written educational materials on breast cancer patients. METHODS: This multicenter, parallel, unblinded, randomized trial included Latin American women aged ≥18 years with a recent breast cancer diagnosis yet to start systemic therapy. Participants underwent randomization in a 1:1 ratio to receive a customizable or standard educational brochure. The primary objective was accurate identification of molecular subtype. Secondary objectives included identification of clinical stage, treatment options, participation in decision-making, perceived quality of information received, and illness uncertainty. Follow-up occurred at 7-21 and 30-51 days post-randomization. CLINICALTRIALS: gov identifier: NCT05798312. RESULTS: One hundred sixty-five breast cancer patients with a median age of 53 years and 61 days from diagnosis were included (customizable: 82; standard: 83). At first available assessment, 52%, 48%, and 30% identified their molecular subtype, disease stage, and guideline-endorsed systemic treatment strategy, respectively. Accurate molecular subtype and stage identification were similar between groups. Per multivariate analysis, customizable brochure recipients were more likely to identify their guideline-recommended treatment modalities (OR: 4.20,p = 0.001). There were no differences between groups in the perceived quality of information received or illness uncertainty. Customizable brochure recipients reported increased participation in decision-making (p = 0.042). CONCLUSIONS: Over one third of recently diagnosed breast cancer patients are incognizant of their disease characteristics and treatment options. This study demonstrates a need to improve patient education and shows that customizable educational materials increase patients' understanding of recommended systemic therapies according to individual breast cancer characteristics.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Folhetos , Tomada de Decisão Compartilhada
6.
Brain Res ; 1804: 148242, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36646367

RESUMO

Alzheimer's dementia (AD) is a neurodegenerative disorder that causes memory loss and dementia in older adults. Intracellular accumulation of Aß causes an imbalance in the oxidative status and cognitive dysfunctions. Besides oxidative stress and loss of memory, Alzheimer's patients show dysfunction of the circadian rhythms. The objective of this work was to evaluate the consequences of an intracerebroventricular injection of Aß (1-42) on temporal patterns of cognitive performance, as well as on lipid peroxidation, protein oxidation and total antioxidant capacity levels, in the rat temporal cortex. Holtzman male rats from control and Aß-injected groups were used in this study. We found that MDA, protein carbonyls and total antioxidant capacity levels displayed day-night oscillations in the rat temporal cortex and spatial memory performance also varied rhythmically. An intracerebroventricular injection of Aß (1-42) modified temporal patterns of cognitive performance as well as daily profiles of parameters of oxidative stress. Thus, elevated levels of Aß aggregates induces alterations in daily rhythmicity of parameters of oxidative stress and, consequently, would affect cellular clock activity, affecting the spatial memory performance in the AD.


Assuntos
Doença de Alzheimer , Ratos , Masculino , Animais , Doença de Alzheimer/metabolismo , Antioxidantes/metabolismo , Peptídeos beta-Amiloides/metabolismo , Memória Espacial , Ratos Wistar , Lobo Temporal/metabolismo , Cognição , Estresse Oxidativo , Ratos Sprague-Dawley , Fragmentos de Peptídeos/metabolismo , Modelos Animais de Doenças
7.
J Eur Acad Dermatol Venereol ; 37(1): 154-159, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36017740

RESUMO

BACKGROUND: To date, little is known about the prevalence of itch in multiple sclerosis (MS) and its characteristics. OBJECTIVES: In this cross-sectional study, we assessed the prevalence, intensity and characteristics of chronic pruritus in MS patients and its effect on quality-of-life and association with MS symptoms, clinical signs, comorbidities and MRI findings. METHODS: MS patients presenting to an outpatient neurology clinic were asked about their current symptoms. Those who experienced chronic pruritus were administered the Standardized Itch Questionnaire and Itch Quality of Life forms. All patients' medical records were reviewed. Patients with any medical conditions associated with chronic itch were excluded. RESULTS: Seventy-seven total MS patients were included, and 27 (35%) reported pruritus. The average itch NRS severity was 5.42 (range 0-10). The most affected body parts were the extremities, face or scalp, and trunk. Itch was characterized as acute (74%), paroxysmal (59%) and tingling (55%). Heat (52%) was the most common aggravating factor, while cold temperatures had no effect. Compared with MS patients without itch, itch patients reported more fatigue (77% vs 44%, p = 0.004), heat sensitivity (48% vs 20%, p = 0.0177), cognitive impairment (62% vs 26%, p = 0.0029) and depression or anxiety (48% vs 16%, p = 0.0063). Additionally, itch patients had more T2 hyperintensities in the posterior cervical cord and anterior pons/ventromedial medulla (74.1% vs 46.0%, p = 0.018 and 29.6% vs 8.0%, p = 0.020, respectively). Finally, T2 hyperintensities in the anterior pons/ventromedial medulla were strongly associated with itch localized to the face or scalp (OR 11.3, 95% CI 1.6-78.6, p = 0.025). CONCLUSION: MS patients experience paroxysmal neuropathic pruritus that is most frequently localized to the extremities, face or scalp. Patients with itch were more likely to have MS-related comorbidities and demyelinating lesions in the spinal cord or brainstem.


Assuntos
Esclerose Múltipla , Qualidade de Vida , Humanos , Estudos Transversais , Esclerose Múltipla/complicações , Índice de Gravidade de Doença , Prurido/epidemiologia , Prurido/etiologia , Prurido/diagnóstico
8.
Mundo saúde (Impr.) ; 47: e13572022, 2023.
Artigo em Inglês, Português | LILACS-Express | LILACS | ID: biblio-1418459

RESUMO

A morte faz parte do quotidiano da vida dos enfermeiros, principalmente quando lidam com pacientes em situação crítica. A forma como percecionam a morte pode ser relevante para uma prestação de cuidados humanizados. Objetivo: identificar quais os sentimentos de estudantes de um programa de mestrado perante a morte e a sua influência na prestação de cuidados a pacientes críticos. Método: Trata-se de uma pesquisa de abordagem qualitativa, aprovada pela comissão de ética da Universidade (Doc11/CE/2018 de 09/04/2018). Realizaram-se entrevistas a 11 estudantes, processadas por análise de conteúdo. Resultados: os principais sentimentos associados à morte dos pacientes foram: impotência, frustração/revolta, tristeza/angústia, aceitação, alívio e distanciamento. Conclusão: os estudantes criam barreiras emocionais para gerir o sofrimento dos pacientes com que lidam, sendo importante que estas não comprometam a qualidade dos cuidados. Os sentimentos dos estudantes perante a morte influenciam positivamente o cuidado ao paciente crítico, pois as vivências e experiência de vida permitem-lhes prestá-los com mais serenidade


Death is part of nurses' daily lives, especially when they deal with patients in critical situations. The way they perceive death may be relevant for providing humanized care. Objective: to identify the feelings of students of a master's program towards death and its influence on care provided to critical patients. Method: This is a study with a qualitative approach, approved by the ethics committee of the University (Doc11/CE/2018 of 09/04/2018). Interviews were carried out with 11 students, processed by content analysis. Results: the main feelings associated with the death of patients were: impotence, frustration/revolt, sadness/anguish, acceptance, relief, and distancing. Conclusion: students create emotional barriers to manage the suffering of the patients they deal with, and it is important that these do not compromise the quality of care. Students' feelings towards death positively influence critical patient care, as their experiences and life experience allow them to provide care more calmly.

9.
PLoS One ; 17(12): e0279132, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36548255

RESUMO

The Major Histocompatibility Complex (MHC) makes the largest genetic contribution to multiple sclerosis (MS) susceptibility, with 32 independent effects across the region explaining 20% of the heritability in European populations. Variation is high across populations with allele frequency differences and population-specific risk alleles identified. We sought to identify MHC-specific MS susceptibility variants and assess the effect of ancestral risk modification within 2652 Latinx and Hispanic individuals as well as 2435 Black and African American individuals. We have identified several novel susceptibility alleles which are rare in European populations including HLA-B*53:01, and we have utilized the differing linkage disequilibrium patterns inherent to these populations to identify an independent role for HLA-DRB1*15:01 and HLA-DQB1*06:02 on MS risk. We found a decrease in Native American ancestry in MS cases vs controls across the MHC, peaking near the previously identified MICB locus with a decrease of ~5.5% in Hispanics and ~0.4% in African Americans. We have identified several susceptibility variants, including within the MICB gene region, which show global ancestry risk modification and indicate ancestral differences which may be due in part to correlated environmental factors. We have also identified several susceptibility variants for which MS risk is modified by local ancestry and indicate true ancestral genetic differences; including HLA-DQB1*06:02 for which MS risk for European allele carriers is almost two times the risk for African allele carriers. These results validate the importance of investigating MS susceptibility at an ancestral level and offer insight into the epidemiology of MS phenotypic diversity.


Assuntos
Predisposição Genética para Doença , Complexo Principal de Histocompatibilidade , Esclerose Múltipla , Humanos , Alelos , Frequência do Gene , Haplótipos , Cadeias HLA-DRB1/genética , Desequilíbrio de Ligação , Complexo Principal de Histocompatibilidade/genética , Esclerose Múltipla/etnologia , Esclerose Múltipla/genética , Risco , População Europeia/genética , População Africana/genética
11.
Neurol Ther ; 11(2): 741-758, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35284994

RESUMO

INTRODUCTION: The SARS-CoV-2 pandemic necessitated better understanding of the impact of disease-modifying therapies on COVID-19 outcomes and vaccination. We report characteristics of COVID-19 cases and vaccination status in ofatumumab-treated relapsing multiple sclerosis (RMS) patients. METHODS: COVID-19 data analyzed were from the ongoing, open-label, long-term extension phase 3b ALITHIOS study from December 2019 (pandemic start) and post-marketing cases from August 2020 (ofatumumab first approval) up to 25 September 2021. COVID-19 cases, severity, seriousness, outcomes, vaccination status, and breakthrough infection were evaluated. RESULTS: As of 25 September 2021, 245 of 1703 patients (14.4%) enrolled in ALITHIOS receiving ofatumumab (median exposure: 2.45 years) reported COVID-19 (confirmed: 210; suspected: 35). Most COVID-19 was of mild (44.1%) or moderate (46.5%) severity, but 9% had severe/life-threatening COVID-19. There were 24 serious cases (9.8%) with 23 patients hospitalized; 22 recovered and 2 died. At study cut-off, 241 patients (98.4%) had recovered or were recovering or had recovered with sequelae and 2 (0.8%) had not recovered. Ofatumumab was temporarily interrupted in 39 (15.9%) patients. Before COVID-19 onset, IgG levels were within the normal range in all COVID-19-affected patients, while IgM was < 0.4 g/l in 23 (9.4%) patients. No patient had a reinfection. Overall, 559 patients were vaccinated (full, 476; partial, 74; unspecified, 9). Breakthrough infection was reported in 1.5% (7/476) patients, and 11 reported COVID-19 after partial vaccination. As of 25 September 2021, the Novartis Safety Database (~ 4713 patient-treatment years) recorded 90 confirmed COVID-19 cases receiving ofatumumab. Most cases were non-serious (n = 80), and ten were serious (1 medically significant, 9 hospitalized, 0 deaths). Among 36 of 90 cases with outcomes reported, 30 recovered and 6 did not recover. CONCLUSION: COVID-19 in RMS patients on ofatumumab was primarily of mild/moderate severity and non-serious in these observational data. Most recovered from COVID-19 without treatment interruption. Two people died with COVID-19. Breakthrough COVID-19 despite being fully/partially vaccinated was uncommon.

12.
Cancer Manag Res ; 14: 1075-1085, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35300062

RESUMO

Purpose: The aim of this study is to evaluate the oncological care during the first state of national emergency due to the COVID-19 pandemic in several public cancer hospitals in Peru. Materials and Methods: A multicentric cross-sectional descriptive study was conducted by interviewing adult cancer patients diagnosed and treated between January 2019 and February 2020 from 18 hospitals. This study was carried out in September 2020, the last month of the first state of national emergency. Demographic and clinical characteristics were evaluated, including COVID-19 status and cancer treatment features. Results: A total of 1472 patients were included; the median age was 55 years (range 19-97). Most patients (85.8%, n = 1263) had solid neoplasia, 13.5% (n = 198) hematologic neoplasia, and 0.7% (n = 11) others. SARS-CoV-2 infection was confirmed in 8.6% (n = 126), 1.2% (n = 18) were probable, 1.6% (n = 24) suspected, and 88.6% (n = 1304) negative cases. Overall, 51.6% of patients (n = 759) had cancer treatment delays, 42.5% (n = 626) changed treatment delivery (endovenous to oral systemic therapy), and 12.6% (n = 185) of cases cancer therapy was discontinued. In total, 10.3% (n = 117) of patients whose disease was controlled or in remission, experienced progression of disease during the state of emergency. A total of 6.7% (n = 98) of patients died, of whom 73.5% (n = 72) died from disease progression; 18.4% (n = 18) from SARS-CoV-2 infection and 8.1% (n = 8) from undetermined causes. Patients with hematological malignancies [hazard ratio (HR): 5.11 (95% confidence interval (CI): 1.99-13.07)] and no response to therapy before the onset of the pandemic [5.01 (1.44-17.42)] had an increased risk of death among COVID-19 infected individuals, whereas advanced clinical stage [5.09 (2.37-10.95)] and discontinuation of treatment [3.66 (1.97-6.78)] were risk factors among non-COVID-19 patients. Conclusion: Our study suggests that the COVID-19 pandemic has an adverse impact on the outcomes of Peruvian cancer patients. In our cohort, cancer mortality was higher than COVID-19 disease mortality.

13.
Neurochem Int ; 154: 105277, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35007657

RESUMO

Alzheimer's disease (AD) is the most common form of dementia characterized by a gradual impairment in cognitive functions. Recent research have shown that TNF-α is a proinflammatory cytokine implicated in the pathogenesis of neurodegenerative diseases, such as AD. Besides cognitive deficit, AD patients show alterations in their circadian rhythms. The objective of this work was to investigate the effects of an intracerebroventricular injection of Aß aggregates on temporal patterns of cognitive functions and on daily rhythms of Aß, TNFα, BMAL1 and RORα protein levels in the rat prefrontal cortex. Four-month-old males Holtzman rats were used in this study. Groups were defined as: control and Aß-injected rats. Rats were maintained under 12h-light:12h-dark throughout the entire experimental period. Prefrontal cortex samples were isolated every 4 h during a 24h period. Our results demonstrated that an intracerebroventricular injection of Aß aggregates impaired learning and memory in rats at ZT 2 and ZT 14 and modified daily patterns of Aß, TNFα, and clock-related factors in the rat prefrontal cortex. Our findings showed that the increase of Aß altered temporal patterns of TNFα, and, consequently, induced alterations in daily rhythms of clock-related factors, affecting the cognitive performance of animals with Alzheimer's.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Cognição , Modelos Animais de Doenças , Hipocampo/metabolismo , Humanos , Masculino , Fragmentos de Peptídeos/farmacologia , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo
14.
Mult Scler ; 28(6): 910-924, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34605319

RESUMO

BACKGROUND: Ofatumumab, the first fully human anti-CD20 monoclonal antibody, is approved in several countries for relapsing multiple sclerosis (RMS). OBJECTIVE: To demonstrate the bioequivalence of ofatumumab administered by an autoinjector versus a pre-filled syringe (PFS) and to explore the effect of ofatumumab on B-cell depletion. METHODS: APLIOS (NCT03560739) is a 12-week, open-label, parallel-group, phase-2 study in patients with RMS receiving subcutaneous ofatumumab 20 mg every 4 weeks (q4w) (from Week 4, after initial doses on Days 1, 7, and 14). Patients were randomized 10:10:1:1 to autoinjector or PFS in the abdomen, or autoinjector or PFS in the thigh, respectively. Bioequivalence was determined by area under the curve (AUCτ) and maximum plasma concentration (Cmax) for Weeks 8-12. B-cell depletion and safety/tolerability were assessed. RESULTS: A total of 256 patients contributed to the bioequivalence analyses (autoinjector-abdomen, n = 128; PFS-abdomen, n = 128). Abdominal ofatumumab pharmacokinetic exposure was bioequivalent for autoinjector and PFS (geometric mean AUCτ, 487.7 vs 474.1 h × µg/mL (ratio 1.03); Cmax, 1.409 vs 1.409 µg/mL (ratio 1.00)). B-cell counts (median cells/µL) depleted rapidly in all groups from 214.0 (baseline) to 2.0 (Day 14). Ofatumumab was well tolerated. CONCLUSION: Ofatumumab 20 mg q4w self-administered subcutaneously via autoinjector is bioequivalent to PFS administration and provides rapid B-cell depletion.


Assuntos
Esclerose Múltipla , Anticorpos Monoclonais , Anticorpos Monoclonais Humanizados/efeitos adversos , Humanos , Injeções Subcutâneas , Esclerose Múltipla/induzido quimicamente
15.
Mult Scler Relat Disord ; 56: 103314, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34634624

RESUMO

OBJECTIVE: To determine the longitudinal changes in retinal microstructure, microvasculature, microcirculation, and axonal and neuronal functions in patients with relapsing-remitting multiple sclerosis (RRMS) over the time course of about two years. METHODS: A total of 30 patients (60 eyes) with RRMS were followed for a period of 27 ± 6 months and evaluated with a battery of clinical tests including low contrast letter acuity (LCLA), intraretinal layer thicknesses by optical coherence tomography (OCT), ganglion cell function by steady-state pattern electroretinography (PERG), axonal function by polarization-sensitive OCT, volumetric vessel density (VVD) by OCT angiography, and retinal tissue perfusion (RTP) by retinal function imager. RESULTS: Axonal function measured as retinal nerve fiber layer birefringence in the temporal quadrant and vessel density in the deep vascular plexus were significantly decreased at 2-year follow-up (P < 0.05). Subgroup analyses showed that the increased retinal blood flow volume occurred in patients with no evidence of disease activity (NEDA), and with stable or improved visual function (P < 0.05). There was no significant difference in the expanded disability state scale, LCLA, RTP, VVD, or PERG measures between the two visits (P > 0.05). CONCLUSION: To our best knowledge, this is the first 2-year prospective comprehensive study with a detailed assessment of retinal microstructure and neuronal functions in patients with RRMS. The recovery of retinal microcirculation occurred in patients with NEDA, and stable or improved visual function, suggesting these measurements as potential imaging biomarkers for monitoring disease progression.


Assuntos
Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Seguimentos , Humanos , Esclerose Múltipla/diagnóstico por imagem , Estudos Prospectivos , Retina/diagnóstico por imagem , Tomografia de Coerência Óptica
16.
Biogerontology ; 22(6): 603-621, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34554336

RESUMO

Aging is one of the main risk factors for cardiovascular diseases, and oxidative stress is a key element responsible for the development of age-related pathologies. In addition, the alteration of circadian rhythms also contributes to cardiovascular pathology, but the underlying mechanisms are not well defined. We investigated the aging consequences on the temporal patterns of antioxidant defenses, the molecular clock machinery, and the blood pressure, in the heart of male rats maintained under constant darkness (free running) conditions. Male Holtzman rats from young adult (3-month-old) and older (22-month-old) groups were maintained under constant darkness (12-h dark:12-h dark, DD) condition during fifteen days before the experiment. After the DD period, heart ventricle samples were isolated every 4-h throughout a 24-h period. We observed circadian rhythms of catalase (CAT) and glutathione peroxidase (GPx) mRNA expression, as well as ultradian rhythms of Nrf2 mRNA levels, in the heart of young adult rats. We also found circadian oscillations of CAT and GPx enzymatic activities, reduced glutathione (GSH) and BMAL1 protein in the same group. Interestingly, aging abolished the rhythms of CAT and GPx enzymatic activities, phase-shifted the rhythm's acrophases of GSH and BMAL1 protein levels and turned circadian the ultradian oscillation of Nrf2 expression. Moreover, aging phase-shifted the circadian pattern of systolic blood pressure. In conclusion, aging modifies the temporal organization of antioxidant defenses and blood pressure, probably, as a consequence of a disruption in the circadian rhythm of the clock's transcriptional regulator, BMAL1, in heart.


Assuntos
Antioxidantes , Ritmo Circadiano , Envelhecimento , Animais , Pressão Sanguínea , Masculino , Ratos , Ratos Sprague-Dawley
17.
World Neurosurg ; 155: e761-e769, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34500097

RESUMO

BACKGROUND: Surgical resection remains the standard treatment for most giant pituitary adenomas (GPAs). The selected surgical approach for these complex lesions depends mainly on their extension. Single approaches may be limited in some cases presenting with invasion into multiple compartments, thereby limiting extent of resection. METHODS: We report a series of patients with GPA operated on through a combined approach involving an endoscopic endonasal transsphenoidal approach and a tubular retractor-assisted transventricular approach, describing the technique, its indications, limitations, and outcomes. Baseline and postoperative clinical, functional, and morphologic variables were documented up until each patient's last follow-up visit. RESULTS: Five patients harboring tumors extending into the third and lateral ventricles were included. Mean extent of resection was 94.6%. Mean follow-up was 39.4 months. One patient presented with a growth hormone-secreting GPA, who achieved remission after repeat resection during follow-up. There were no intraoperative complications, and 1 patient required reoperation for cerebrospinal fluid leak repair. One patient received adjuvant radiotherapy, and 3 patients remained stable requiring no additional treatment. All patients maintained an adequate postoperative functional status. CONCLUSIONS: The combined approach herein described may be a safe and effective option for some patients with GPAs extending into the third and lateral ventricles. An adequate patient selection is mandatory to exploit the benefits of each individual approach.


Assuntos
Adenoma/cirurgia , Ventrículos Cerebrais/cirurgia , Endoscopia/métodos , Microcirurgia/métodos , Neoplasias Hipofisárias/cirurgia , Osso Esfenoide/cirurgia , Adenoma/diagnóstico por imagem , Adulto , Ventrículos Cerebrais/diagnóstico por imagem , Terapia Combinada/métodos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Cavidade Nasal/diagnóstico por imagem , Cavidade Nasal/cirurgia , Neoplasias Hipofisárias/diagnóstico por imagem , Osso Esfenoide/diagnóstico por imagem
18.
Ecancermedicalscience ; 15: 1224, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34158828

RESUMO

The availability of effective, accessible, safe and high-quality anticancer drugs for the medical treatment of cancer is fundamental in ensuring optimal healthcare in the public health system in Peru. The main objective is to assess the current situation regarding anticancer drugs (termed 'high-cost') for breast cancer, as well as an analysis of the possible factors which negatively impact access to the Peruvian public health systems.There are similarities in the availability of anticancer drugs, since most treatments are covered by the Peruvian Ministry of Health. EsSalud offers an extra monoclonal antibody (pertuzumab) in the metastatic treatment stage. Meanwhile, the National Institute of Neoplastic Diseases (INEN), mainly for metastatic disease, has relied on more tested treatments over the last year. An agreement has been reached with the armed forces, which will enable patients to receive oncology care at the INEN and, thereby, benefit from the use of high-cost drugs.

19.
Transl Vis Sci Technol ; 10(6): 6, 2021 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-34111252

RESUMO

Objective: The purpose of this study was to quantify retinal structural, vascular, and functional changes in patients with relapsing-remitting multiple sclerosis (RRMS) over 1 year. Methods: Eighty-eight eyes of 44 patients with RRMS underwent assessments of low contrast letter acuity (LCLA), retinal ganglion cell function detected by the steady-state pattern electroretinogram (PERG), axonal microstructural integrity measured as birefringence, intraretinal layer thicknesses by ultra-high-resolution optical coherence tomography (OCT), volumetric vessel density (VVD) by OCT angiography, and retinal tissue perfusion (RTP) by the Retinal Function Imager (RFI). All measurements were performed at baseline and 1-year follow-up. The impacts of disease activities and a history of optic neuritis (ON) were analyzed. Results: Compared to baseline, there were no significant differences in all variables (P > 0.05), except for the axonal birefringence and RTP. The birefringence's of the retinal fiber layer at the temporal and superior quadrants was significantly decreased (P < 0.05), whereas RTP was significantly increased (P < 0.05). In the subgroup with ON, significantly longer PERG latency and decreased VVD were observed at follow-up (P < 0.05). In patients with improved LCLA, significantly increased RTP and decreased VVD (P < 0.05) were also observed. Conclusions: This is the first longitudinal study that assessed the RTP and VVD, along with other retinal structural and functional parameters in MS. The recovery of retinal vascular function occurred with the improved LCLA, suggesting that these measurements may be associated with disease progression. Translational Relevance: The retinal microvascular changes could be potential biomarkers for monitoring therapeutic efficacy in MS.


Assuntos
Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Seguimentos , Humanos , Estudos Longitudinais , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Retina/diagnóstico por imagem
20.
Mult Scler J Exp Transl Clin ; 7(1): 2055217321995947, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33717502

RESUMO

BACKGROUND: Health communication tools like film are capable of reducing health disparities and could be effective in addressing negative illness perceptions of MS in Hispanics/Latinx. OBJECTIVE: To test the feasibility of using a culturally appropriate short narrative film to examine illness perceptions overtime and attitudes in Hispanics/Latinx affected with MS. METHODS: Participants were assigned to view a short narrative film (n = 130) or not (n = 106). The Brief Illness Perception Questionnaire (BIPQ) was used to examine illness perceptions at baseline, one and three months. Focus groups were conducted at 6 months. Measures of sociocultural integration were obtained. Individual group BIPQ domains were evaluated over time using paired sample t-test. Multivariate linear regression was used to examine predictors of BIPQ change. RESULTS: A more positive perception of treatment (p < 0.0001) and understanding (p = 0.0003) were seen at 3 months for those exposed to film. Focus groups were effective in highlighting that the perceived disease prognosis, family support and awareness of MS contributes to attitudes. Exposure to film was found to be the strongest predictor (Beta:6.31, p = 0.01) of BIPQ change at three months. CONCLUSION: Our results provide support that a short narrative film of MS in Hispanics/Latinx is a feasible intervention to change perceptions of MS to a more positive view.

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