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Introduction: This case report presents the intentional periodontal maintenance of two periodontal hopeless lower central incisors with a multidisciplinary approach and 20-year follow-up. Case presentation: A 36-year-old male, in 2001, was diagnosed with aggressive periodontitis, gingival swelling, bleeding, and mandibular central incisors with mobility and poor prognosis. Following periodontal therapy (phase I), root canal treatment, and occlusal adjustment, #31 and #41 were gently extracted to remove the granulation tissues, calculus, and infected cementum from the root surface. Then, tetracycline-HCl was applied for 5 minutes on the root surfaces. The teeth were repositioned into the sockets and splinted with a lingual bar. At 3 months, the bar was removed, and a free gingival autogenous graft was done to improve the local keratinized tissue width. Mobility scores, pocket depths, and clinical attachment levels were recorded, and radiographs were taken at 1, 5, and 20 years. The 5-year follow-up showed that the teeth were clinically and radiographically in function. There was a reduction in probing depth and a gain in clinical attachment and radiographic alveolar bone levels. After 20 years, #41 was stable, but #31 had external root resorption, leading to a new treatment plan (dental implants) and extraction. Conclusion: The clinical result of this case was satisfactory for 20 years. Intentional periodontal maintenance of the teeth may be an alternative treatment, even considering the high level of complexity.
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Humanos , Masculino , Adulto , Planejamento de Assistência ao Paciente , Periodontia , Procedimentos Cirúrgicos Operatórios , Tempo , Perda da Inserção PeriodontalRESUMO
Acute pulmonary embolism (APE) is one of the leading causes of cardiovascular emergencies and the third leading cause of death. Although efforts focus on treating the acute event, patients who survive APE may develop long-term sequelae. Research reveals that approximately half of patients who have suffered an APE do not regain their previous level of function and experience a reduction in their quality of life for several years after the episode. Acute pulmonary embolism can be classified according to the risk of short-term mortality, with most mortality and morbidity concentrated in high-risk and intermediate-risk cases. The first-line treatment for APE is systemic anticoagulation. However, identifying and more aggressively treating people with intermediate to high risk, who have a more favorable risk profile for reperfusion treatments, could reduce short-term mortality and mitigate post-pulmonary embolism syndrome (PPES). Post-pulmonary embolism syndrome refers to a variety of persistent symptoms and functional limitations that occur after an APE. The presence of persistent dyspnea, functional limitations, and/or decreased quality of life after an APE has been recently termed "PPES," although this entity encompasses different manifestations. The most severe cause of persistent dyspnea is chronic thromboembolic pulmonary hypertension, where increased pulmonary artery pressure is due to the fibrotic organization of unresolved APE. Post-PE Syndrome is not always systematically addressed in management guidelines, and its prevalence may be underestimated. More research is needed to fully understand its causes and risk factors. Interventions such as cardiopulmonary rehabilitation have been suggested to improve the quality of life of patients with PPES. A comprehensive, evidence-based approach is essential to effectively prevent and manage PPES and improve the long-term outcomes and well-being of affected patients.
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Embolia Pulmonar , Qualidade de Vida , Humanos , Embolia Pulmonar/terapia , Embolia Pulmonar/fisiopatologia , Fatores de Risco , Síndrome , Resultado do Tratamento , Anticoagulantes/uso terapêutico , Anticoagulantes/efeitos adversos , Dispneia/etiologia , Dispneia/fisiopatologia , Medição de Risco , Fatores de Tempo , Hipertensão Pulmonar/fisiopatologia , Hipertensão Pulmonar/etiologia , Estado FuncionalRESUMO
Purpose: This work sought to describe the experience of managers and caregivers with feeding and nutrition for older adults with dementia, in Colombian gerontological services. Participants and Methods: This is a qualitative focus group study with fourteen gerontological care centers for people with dementia. Results: The study reveals that care related to food and nutrition for people with dementia is organized based on the comprehensive assessment of the resident. Although there are basic support strategies, each caregiver requires specific knowledge, attitudes, behaviors, and institutional support, to generate a context that favors the health and quality of life of those involved. Conclusion: The experience of caring for people with dementia in aspects related to their food and nutrition, seen from the perspective of managers and caregivers of gerontological services in a developing country, strengthens specific strategies and public policies. This, in turn, reduces the burden on caregivers.
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Patients recovering from COVID-19 commonly exhibit cognitive and brain alterations, yet the specific neuropathological mechanisms and risk factors underlying these alterations remain elusive. Given the significant global incidence of COVID-19, identifying factors that can distinguish individuals at risk of developing brain alterations is crucial for prioritizing follow-up care. Here, we report findings from a sample of patients consisting of 73 adults with a mild to moderate SARS-CoV-2 infection without signs of respiratory failure and 27 with infections attributed to other agents and no history of COVID-19. The participants underwent cognitive screening, a decision-making task, and MRI evaluations. We assessed for the presence of anosmia and the requirement for hospitalization. Groups did not differ in age or cognitive performance. Patients who presented with anosmia exhibited more impulsive alternative changes after a shift in probabilities (r = - 0.26, p = 0.001), while patients who required hospitalization showed more perseverative choices (r = 0.25, p = 0.003). Anosmia correlated with brain measures, including decreased functional activity during the decision-making task, thinning of cortical thickness in parietal regions, and loss of white matter integrity. Hence, anosmia could be a factor to be considered when identifying at-risk populations for follow-up.
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Anosmia , Encéfalo , COVID-19 , Imageamento por Ressonância Magnética , SARS-CoV-2 , Humanos , COVID-19/complicações , COVID-19/psicologia , COVID-19/fisiopatologia , COVID-19/diagnóstico por imagem , COVID-19/patologia , Anosmia/etiologia , Anosmia/fisiopatologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/fisiopatologia , SARS-CoV-2/isolamento & purificação , Idoso , Tomada de Decisões , Cognição/fisiologiaRESUMO
Testicular germ cell tumors are the most common tumors in adolescent and young men. They are curable malignancies that should be treated with curative intent, minimizing acute and long-term side effects. Inguinal orchiectomy is the main diagnostic procedure, and is also curative for most localized tumors, while patients with unfavorable risk factors for recurrence, or those who are unable or unwilling to undergo close follow-up, may require adjuvant treatment. Patients with persistent markers after orchiectomy or advanced disease at diagnosis should be staged and classified according to the IGCCCG prognostic classification. BEP is the most recommended chemotherapy, but other schedules such as EP or VIP may be used to avoid bleomycin in some patients. Efforts should be made to avoid unnecessary delays and dose reductions wherever possible. Insufficient marker decline after each cycle is associated with poor prognosis. Management of residual masses after chemotherapy differs between patients with seminoma and non-seminoma tumors. Patients at high risk of relapse, those with refractory tumors, or those who relapse after chemotherapy should be managed by multidisciplinary teams in experienced centers. Salvage treatment for these patients includes conventional-dose chemotherapy (TIP) and/or high-dose chemotherapy, although the best regimen and strategy for each subgroup of patients is not yet well established. In late recurrences, early complete surgical resection should be performed when feasible. Given the high cure rate of TGCT, oncologists should work with patients to prevent and identify potential long-term side effects of the treatment. The above recommendations also apply to extragonadal retroperitoneal and mediastinal tumors.
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Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Humanos , Neoplasias Testiculares/terapia , Neoplasias Testiculares/patologia , Masculino , Neoplasias Embrionárias de Células Germinativas/terapia , Neoplasias Embrionárias de Células Germinativas/patologia , Orquiectomia , Oncologia/normas , Oncologia/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia de Salvação , Prognóstico , Recidiva Local de Neoplasia/terapia , Guias de Prática Clínica como Assunto , Sociedades MédicasRESUMO
Understanding the strength behavior and leaching characteristics of mining tailings stabilized with alkali-activated cements in the short, medium, and long term is crucial for the feasibility of material applications. In this context, this study assessed the stabilization/solidification of iron ore tailings (IOT) using alkali-activated binder (AAB) composed of sugarcane bagasse ash and eggshell lime at curing times of 7, 28, 60, 90, 180, and 365 days. Additionally, leaching tests were conducted, along with the examination of possible changes in the chemical and mineralogical composition resulting from exposure to acidic environments. Tests included unconfined compression strength (UCS), leaching, X-ray diffraction, and Fourier-transform infrared spectroscopy for the IOT-AAB mixtures. The highest increase in UCS was observed between 7 and 60 days, reaching 6.47 MPa, with minimal variation thereafter. The AAB-bonded IOT exhibited no metal toxicity over time. Elements Ba, Mn, Pb, and Zn present in IOT and ash were encapsulated in the cemented matrix, with complete encapsulation of all metals observed from 90 days of curing time. The mineralogy of the stabilized/solidified tailings showed no changes resulting from leaching tests. Characteristic bands associated with the presence of N-A-S-H gel were identified in both pre-leaching and post-leaching samples for all curing times analyzed. Exposure to acidic environments altered bands related to carbonate bonds formed in the IOT-AAB mixture.
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Ferro , Mineração , Ferro/química , Álcalis/química , Metais/química , Difração de Raios X , Saccharum/químicaRESUMO
Levels of 237 pesticides were assessed in 1063 fruit and vegetable samples from 12 São Paulo markets spanning the period May 2015 to December 2022. The QuEChERS method was employed for extraction, followed by GC-MS/MS and LC-MS/MS analysis. Findings indicated that 30% of the samples contained residues below the Maximum Residue Limits (MRLs), while 6% exceeded these. Additionally, 23% exhibited excessive residues for their respective crops and 40% had no detectable residues. Health risk evaluation focused on tomatoes, cabbage and oranges, revealing exposure within 0.002-0.9% of the Acceptable Daily Intake (ADI), indicating no chronic risks. However, pyraclostrobin in orange presented a potential acute risk for adults (112%). These results underscore the necessity for continuous monitoring of pesticide residues in fruits and vegetables to safeguard consumer health, especially considering the significant levels of consumption.
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Contaminação de Alimentos , Frutas , Resíduos de Praguicidas , Espectrometria de Massas em Tandem , Verduras , Frutas/química , Verduras/química , Brasil , Medição de Risco , Resíduos de Praguicidas/análise , Contaminação de Alimentos/análise , Humanos , Praguicidas/análise , Adulto , Cromatografia Gasosa-Espectrometria de MassasRESUMO
OBJECTIVE: To establish the utility of long-term electroencephalogram (EEG) in forecasting epilepsy onset in children with autism spectrum disorder (ASD). STUDY DESIGN: A single-institution, retrospective analysis of children with ASD, examining long-term overnight EEG recordings collected over a period of 15 years, was conducted. Clinical EEG findings, patient demographics, medical histories, and additional Autism Diagnostic Observation Schedule data were examined. Predictors for the timing of epilepsy onset were evaluated using survival analysis and Cox regression. RESULTS: Among 151 patients, 17.2% (n = 26) developed unprovoked seizures (Sz group), while 82.8% (n = 125) did not (non-Sz group). The Sz group displayed a higher percentage of interictal epileptiform discharges (IEDs) in their initial EEGs compared with the non-Sz group (46.2% vs 20.0%, P = .01). The Sz group also exhibited a greater frequency of slowing (42.3% vs 13.6%, P < .01). The presence of IEDs or slowing predicted an earlier seizure onset, based on survival analysis. Multivariate Cox proportional hazards regression revealed that the presence of any IEDs (HR 3.83, 95% CI 1.38-10.65, P = .01) or any slowing (HR 2.78, 95% CI 1.02-7.58, P = .046 significantly increased the risk of developing unprovoked seizures. CONCLUSION: Long-term EEGs are valuable for predicting future epilepsy in children with ASD. These findings can guide clinicians in early education and potential interventions for epilepsy prevention.
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Background: Kawasaki disease (KD), an acute febrile illness and systemic vasculitis, is the leading cause of acquired heart disease in children in industrialized countries. KD leads to the development of coronary artery aneurysms (CAA) in affected children, which may persist for months and even years after the acute phase of the disease. There is an unmet need to characterize the immune and pathological mechanisms of the long-term complications of KD. Methods: We examined cardiovascular complications in the Lactobacillus casei cell wall extract (LCWE) mouse model of KD-like vasculitis over 4 months. The long-term immune, pathological, and functional changes occurring in cardiovascular lesions were characterized by histological examination, flow cytometric analysis, immunofluorescent staining of cardiovascular tissues, and transthoracic echocardiogram. Results: CAA and abdominal aorta dilations were detected up to 16 weeks following LCWE injection and initiation of acute vasculitis. We observed alterations in the composition of circulating immune cell profiles, such as increased monocyte frequencies in the acute phase of the disease and higher counts of neutrophils. We determined a positive correlation between circulating neutrophil and inflammatory monocyte counts and the severity of cardiovascular lesions early after LCWE injection. LCWE-induced KD-like vasculitis was associated with myocarditis and myocardial dysfunction, characterized by diminished ejection fraction and left ventricular remodeling, which worsened over time. We observed extensive fibrosis within the inflamed cardiac tissue early in the disease and myocardial fibrosis in later stages. Conclusion: Our findings indicate that increased circulating neutrophil counts in the acute phase are a reliable predictor of cardiovascular inflammation severity in LCWE-injected mice. Furthermore, long-term cardiac complications stemming from inflammatory cell infiltrations in the aortic root and coronary arteries, myocardial dysfunction, and myocardial fibrosis persist over long periods and are still detected up to 16 weeks after LCWE injection.
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Parede Celular , Modelos Animais de Doenças , Fibrose , Lacticaseibacillus casei , Síndrome de Linfonodos Mucocutâneos , Vasculite , Animais , Camundongos , Parede Celular/imunologia , Vasculite/imunologia , Vasculite/etiologia , Vasculite/patologia , Síndrome de Linfonodos Mucocutâneos/imunologia , Síndrome de Linfonodos Mucocutâneos/complicações , Masculino , Miocardite/etiologia , Miocardite/patologia , Miocardite/imunologia , Inflamação/imunologiaRESUMO
AIM: To compare the subgingival microbiota of patients receiving supportive periodontal care (SPC) with and without subgingival instrumentation, over 2 years. MATERIALS AND METHODS: This study was a randomized clinical trial that included 62 participants (50.97 ± 9.26 years old; 40 females) who completed non-surgical periodontal therapy. Participants were randomly assigned to receive oral prophylaxis with oral hygiene instructions alone (test) or in combination with subgingival instrumentation (control) during SPC. Pooled subgingival biofilm samples were obtained from four sites per patient at SPC baseline and at 3, 6, 12, 18, and 24 months. Real-time polymerase chain reaction was used for absolute quantification of Eubacteria and the target bacteria Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola. Data were analysed using generalized estimating equations, taking into consideration the clustering of observations within individuals. RESULTS: No significant differences were found between the experimental groups regarding the mean counts of Eubacteria and target bacteria, as well as the periodontal parameters at the sampled sites. Although significant variability in bacterial counts was present during SPC, all counts after 2 years were not statistically different from those at baseline. Bacterial counts were associated with the presence of plaque, bleeding on probing, mean probing depth ≥3 mm, and follow-up period. CONCLUSIONS: SPC with or without subgingival instrumentation can result in comparable subgingival microbiological outcomes. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov: NCT01598155 (https://clinicaltrials.gov/study/NCT01598155?intr=supragingival%20control&rank=4#study-record-dates).
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Porphyromonas gingivalis , Tannerella forsythia , Treponema denticola , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Treponema denticola/isolamento & purificação , Porphyromonas gingivalis/isolamento & purificação , Tannerella forsythia/isolamento & purificação , Biofilmes , Adulto , Higiene Bucal , Carga Bacteriana , Seguimentos , Índice Periodontal , Gengiva/microbiologia , Raspagem Dentária/instrumentação , Raspagem Dentária/métodos , Placa Dentária/microbiologia , Periodontite Crônica/microbiologia , Periodontite Crônica/terapiaRESUMO
SUMMARY: Both the academic and popular worlds have paid close attention to the link between exercise and cognitive performance. It is increasingly important to understand the numerous mechanisms by which exercise might influence cognitive abilities in view of the continuous societal issues caused by aging populations and the prevalence of disorders associated to cognitive decline. A rising amount of evidence showing a favorable association between physical activity and cognitive well-being serves as the foundation for the justification for studying the effects of exercise on cognitive function and learning ability. The study employed an 8-week treadmill based on exercise on male adults C57BL/6 mice. The exercise group were engaged in 5 sessions a week gradually increasing the intensity of the protocol by 5 % each week. The Mice cognitive assessments were done using Morris Water Maze and Novel Object Recognition tests. The long term-impact on learning ability were further assessed through immmohistochemistry and molecular analysis of the hippocampal and prefrontal cortex tissues of the animals' brain tissues. The findings showed improved spatial learning abilities, recognition memory, and heighted synaptic plasticity indicated by elevated synaptic makers. The study underscores the role of long-term aerobic exercise in augmenting cognitive performance. It not only contributes to the understanding of the interplay between neuroplasticity and cognitive benefits but also the growing body of research on the impact of exercise on cognitive function.
Tanto el mundo académico como el popular han prestado mucha atención al vínculo entre el ejercicio y el rendimiento cognitivo. Es cada vez más importante comprender los numerosos mecanismos por los cuales el ejercicio podría influir en las capacidades cognitivas en vista de los continuos problemas sociales causados por el envejecimiento de la población y la prevalencia de trastornos asociados al deterioro cognitivo. Una cantidad cada vez mayor de evidencia que muestra una asociación favorable entre la actividad física y el bienestar cognitivo sirve como base para justificar el estudio de los efectos del ejercicio sobre la función cognitiva y la capacidad de aprendizaje. El estudio se realizó en ratones machos adultos C57BL/6 utilizándose en los ejercicios una cinta rodante durante 8 semanas. El grupo de ejercicio realizó 5 sesiones por semana aumentando gradualmente la intensidad del protocolo en un 5 % cada semana. Las evaluaciones cognitivas de los ratones se realizaron utilizando las pruebas Morris Water Maze y Novel Object Recognition. El impacto a largo plazo en la capacidad de aprendizaje se evaluó mediante inmunohistoquímica y análisis molecular de los tejidos del hipocampo y la corteza prefrontal de los tejidos cerebrales de los animales. Los hallazgos mostraron mejoras en las habilidades de aprendizaje espacial, la memoria de reconocimiento y una mayor plasticidad sináptica indicada por unos creadores sinápticos elevados. El estudio subraya el papel del ejercicio aeróbico a largo plazo para aumentar el rendimiento cognitivo. No sólo contribuye a la comprensión de la interacción entre la neuroplasticidad y los beneficios cognitivos, sino también al creciente conjunto de investigaciones sobre el impacto del ejercicio en la función cognitiva.
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Animais , Masculino , Camundongos , Exercício Físico , Hipocampo/anatomia & histologia , Hipocampo/fisiologia , Córtex Pré-Frontal , Cognição , Aprendizagem Espacial , Teste de Campo Aberto , Teste do Labirinto Aquático de Morris , Camundongos Endogâmicos C57BL , Plasticidade Neuronal , Neurônios/fisiologiaRESUMO
Introdução: O polimetilmetacrilato é um produto de preenchimento permanente. A injeção deste material na face pode levar a complicações. O objetivo deste estudo é determinar em uma série de casos o tempo mediano de ocorrência de complicações, as áreas mais comprometidas, os tipos de complicações e tratamentos mais realizados. Método: Foram estudados 209 casos de pacientes portadores de complicações relacionadas ao uso de polimetilmetacrilato na face que buscaram tratamento entre o período de janeiro de 2000 a junho de 2021. Os dados analisados foram sexo, idade, número de injeções, momento da aplicação, intervalo de tempo até surgir a complicação, tipo de complicação, região comprometida e tratamento realizado. Resultados: A idade média dos pacientes foi de 45 anos (23 a 79 anos). Destes, 172 eram mulheres e 37 homens. O número de aplicações variou de 1 a 5. O tempo mediano de surgimento de complicações foi de 71 meses. As regiões mais comprometidas foram a malar, em 102 pacientes; mandibular, em 100; e zigomática, em 91. Granuloma foi observado em 135 pacientes; edema, em 120; e inflamação, em 78. O tratamento mais realizado foi a injeção de corticoide, em 111 pacientes, seguido de remoção cirúrgica, em 40. Conclusão: Os resultados podem servir como base de conhecimento para uma melhor compreensão das complicações com o uso de polimetilmetacrilato na face.
Introduction: Polymethylmethacrylate is a permanent filler product. Injecting this material into the face can lead to complications. The objective of this study is to determine in a series of cases the median time for complications to occur, the most affected areas, the types of complications, and the treatments most performed. Method: 209 cases of patients with complications related to the use of polymethyl methacrylate on the face who sought treatment between the period of January 2000 and June 2021 were studied. The data analyzed were gender, age, number of injections, moment of application, interval time until the complication arises, type of complication, affected region, and treatment performed. Results: The average age of patients was 45 years (23 to 79 years). Of these, 172 were women and 37 men. The number of applications ranged from 1 to 5. The median time for complications to appear was 71 months. The most affected regions were the malar, in 102 patients; mandibular, in 100; and zygomatic, in 91. Granuloma was observed in 135 patients; edema, in 120; and inflammation, in 78. The most common treatment was corticosteroid injection, in 111 patients, followed by surgical removal, in 40. Conclusion: The results can serve as a knowledge base for a better understanding of complications with the use of polymethylmethacrylate in the face.
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INTRODUCTION: The objective of our study was to evaluate the long-term association between mortality and frailty in institutionalized patients in Mexico. Worldwide, there are limited lines of research in this population of geriatric patients and this entity generates a significant impact on the quality of life and prognosis of our patients. MATERIAL AND METHODS: It is a prospective cohort study of 81 patients in long-term care who met the selection criteria. Frailty was determined using the FRAIL scale. Data on mortality were collected during the follow-up period, and diagnosis was monitored. The risk of presenting this event was determined by logistic regression, Kaplan-Meier, and Cox proportional hazards analysis, adjusted for age and sex. RESULTS: The mean follow-up time of the patients was 36 months (1094 days), during which 33 subjects died (40.7%). In our population, at the beginning of the study the vast majority of frail patients had pathologies that independently generate risk of adverse events, disability (Barthel=30.9; SD 28.8), sarcopenia (n=40; 71.4%), one to 3 falls in the last year (n=17; 63%), ≥4 falls (n=4; 57.1%). Frail participants had a higher adjusted risk of mortality (HR 2.93; 95% CI 1.33-6.43; p=0.007). CONCLUSIONS: The frailty entity is associated in the long term with mortality in institutionalized patients in Mexico. Timely treatment and approach may allow a good prognosis and quality of life.
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Fragilidade , Assistência de Longa Duração , Humanos , México/epidemiologia , Masculino , Feminino , Idoso , Estudos Prospectivos , Fragilidade/mortalidade , Idoso de 80 Anos ou mais , Fatores de Tempo , Idoso Fragilizado , Prognóstico , Estudos de Coortes , MortalidadeRESUMO
INTRODUCTION: RTXM83, a biosimilar of rituximab, was approved after physicochemical, functional, non-clinical, and clinical studies demonstrated their similarity; these studies included RTXM83-AC-01-11, a multicentric double-blind international prospective pivotal study. Long-term data on biosimilars can potentially elucidate their clinical robustness and facilitate their broader adoption. METHODS: In this retrospective observational study, we analyzed a dataset from a Brazilian cohort previously randomized in the RTXM83-AC-01-11 study followed by the assessment of long-term outcomes in an observational extension phase from randomization in the RTXM83-AC-01-11 study to the last recorded evaluation. Patients with diffuse large B cell lymphoma (DLBCL) received either reference rituximab (R) or RTXM83 plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) as adjuvant treatment. RESULTS: The median follow-up period was 77.0 months. Patients with initial DLBCL stages III and IV comprised 50% of the R-CHOP group and 40% of the biosimilar group. Five (18.5%) patients, including two RTXM83-CHOP-treated and three R-CHOP-treated individuals, experienced late adverse events (AEs) of interest. No new safety signs were established. At the final assessment, the progression-free survival (PFS) rates were 93.3% and 50.0% in the RTXM83-CHOP and R-CHOP groups, respectively. Median PFS was not achieved in the RTXM83-CHOP group, which was 40.5 months in the R-CHOP group. The overall survival (OS) rates were 100% and 66.7% in the RTXM83-CHOP and R-CHOP groups, respectively. The median OS was not reached in any group. CONCLUSION: This study demonstrated the long-term safety and effectiveness of RTXM83 in treating DLBCL; outcomes comparable to those of the reference product and potentially improved access to treatment have been indicated. However, further research with more diverse patient groups can validate these findings and advocate the broader adoption of biosimilars in cancer care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04928573. June 16, 2021, "retrospectively registered".
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Background: The short-term complications from chimeric antigen receptor T-cell therapy (CART) are well characterized, but the long-term complications still need to be further investigated. Therefore, herein, we will review the currently available literature published on the late adverse events following CART. Methods: We reviewed published data available from pivotal trials and real-world experiences with anti-CD19 CART (CART19) for adults with lymphoma. We defined late events as occurring or persisting beyond 1 month after CART infusion. We focused our literature review on the following late-event outcomes post-CART19: cytopenia, immune reconstitution, infections, and subsequent malignancies. Results: Grade 3-4 cytopenia beyond 30 days occurs in 30%-40% of patients and beyond 90 days in 3%-22% of patients and is usually managed with growth-factor and transfusion support, along with neutropenic prophylaxis. B-cell aplasia and hypogammaglobulinemia are expected on-target off-tumor effects of CART19, 44%-53% of patients have IgG < 400 mg/dL, and approximately 27%-38% of patients receive intravenous immunoglobulin (IVIG) replacement. Infections beyond the initial month from CART19 are not frequent and rarely severe, but they are more prevalent and severe when patients receive subsequent therapies post-CART19 for their underlying disease. Late neurotoxicity and neurocognitive impairment are uncommon, and other causes should be considered. T-cell lymphoma (TCL) after CART is an extremely rare event and not necessarily related to CAR transgene. Myeloid neoplasm is not rare post-CART, but unclear causality given heavily pretreated patient population is already at risk for therapy-related myeloid neoplasm. Conclusion: CART19 is associated with clinically significant long-term effects such as prolonged cytopenia, hypogammaglobulinemia, and infections that warrant clinical surveillance, but they are mostly manageable with a low risk of non-relapse mortality. The risk of subsequent malignancies post-CART19 seems low, and the relationship with CART19 and/or prior therapies is unclear; but regardless of the possible causality, this should not impact the current benefit-risk ratio of CART19 for relapsed/refractory B-cell non-Hodgkin lymphoma (NHL).
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Non-steroidal anti-inflammatory drugs (NSAIDs) represent one of the most commonly used classes of drugs in both human and veterinary medicine. However, many clinical side effects have been observed, especially when treatment has been prolonged. While the anti-inflammatory efficacy and safety of repeated administration of firocoxib (Previcox®), which is a selective NSAID COX-2 inhibitor, has been evaluated for short-term use (one to fourteen days), its clinical relevance for longer-term use is not known. As a preliminary study, healthy, adult male and female horses (n = 7) were treated with firocoxib for 40 days concomitant with the collection of blood samples encompassing treatment to assess hematological and biochemical endpoints. Daily oral administration of firocoxib was performed with one 57 mg tablet/animal (0.11-0.14 mg/kg), which was crushed and mixed with feed. Blood samples were collected one day before treatment (D0 or basal sample), during (D10, D20, D30, and D40), and after treatment (D55 and D70). Results indicated some hematological and biochemical effects were significantly reduced (p < 0.05) towards the end of treatment on D40 relative to pre-treatment or baseline values on D0. Post-treatment, all values returned to pre-treatment values within 30 days without any apparent clinical adversities. In conclusion, while these preliminary results are favorable for prolonged use of firocoxib in horses, future studies are required to evaluate the efficacy of prolonged use accompanied with other clinically relevant endpoints in healthy as well as injured or diseased animals.
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Neurological complications are frequent during the active course of infective endocarditis (IE), and they are associated with high in-hospital mortality rates. However, limited data exist on the prognostic value of these complications for late outcomes. This study aimed to assess the long-term impact of neurological complications in patients surviving an IE episode. A total of 263 consecutive IE patients admitted to a tertiary care center between 2007 and 2022 were prospectively included. Neurological complications at admission included transient ischemic attack (TIA), ischemic stroke, hemorrhagic stroke, intracerebral abscess, and meningitis. The primary outcome was a composite of overall mortality or heart valve surgery. Of the patients, 34.2% died in the hospital, leaving 173 survivors for long-term follow-up. Over a median of 3.5 years, 29 patients died, and 13 (9%) underwent cardiac surgery, resulting in an overall adverse event rate of 30%. Neurological complications independently predicted long-term adverse outcomes (hazard ratio (HR) 2.237; 95% CI 1.006-4.976), after adjusting for age, chronic kidney disease (CKD), and heart failure (HF) development. In an IE patient cohort, neurological complications at admission, which is a complication directly related to the IE process, were independent predictors of long-term outcomes.
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Bothrops atrox envenomations in the Brazilian Amazon are responsible for a number of local and systemic effects. Among these, stroke presents the worst prognosis for the patient since it may evolve into disabilities and/or premature death. This complication is caused by coagulation disorders and generates hemorrhagic and thrombotic conditions. This study presents a case report of a 54-year-old female patient who presented extensive cerebral ischemia after a B. atrox envenomation that occurred in the state of Amazonas, Brazil. The patient was hospitalized for 102 days, which included a stay in the intensive care unit. Clinical and laboratory findings indicated a thrombogenic coagulopathy. On discharge, the patient had no verbal response, partial motor response, and right hemiplegia. The assessment carried out four years after discharge evidenced incapacitation, global aphasia and bilateral lower and upper limbs showed hypotrophy with a global decrease in strength. Ischemic stroke is a possible complication of B. atrox snakebites even after antivenom treatment, with the potential to cause debilitating long-term consequences.
Assuntos
Antivenenos , Bothrops , Mordeduras de Serpentes , Mordeduras de Serpentes/complicações , Feminino , Pessoa de Meia-Idade , Animais , Humanos , Brasil , Antivenenos/uso terapêutico , AVC Isquêmico/etiologia , Venenos de Crotalídeos/toxicidade , Venenos de Crotalídeos/intoxicação , Isquemia Encefálica/etiologia , Bothrops atroxRESUMO
Aging compromises brain function leading to cognitive decline. A cyclic ketogenic diet (KD) improves memory in aged mice after long-term administration; however, short-term effects later in life and the molecular mechanisms that govern such changes remain unclear. Here, we explore the impact of a short-term KD treatment starting at elderly stage on brain function of aged mice. Behavioral testing and long-term potentiation (LTP) recordings reveal that KD improves working memory and hippocampal LTP. Furthermore, the synaptosome proteome of aged mice fed a KD long-term evidence changes predominantly at the presynaptic compartment associated to the protein kinase A (PKA) signaling pathway. These findings were corroborated in vivo by western blot analysis, with high BDNF abundance and PKA substrate phosphorylation. Overall, we show that a KD modifies brain function even when it is administered later in life and recapitulates molecular features of long-term administration, including the PKA signaling pathway, thus promoting synaptic plasticity at advanced age.
Assuntos
Envelhecimento , Proteínas Quinases Dependentes de AMP Cíclico , Dieta Cetogênica , Potenciação de Longa Duração , Memória , Proteoma , Transdução de Sinais , Animais , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Envelhecimento/fisiologia , Envelhecimento/metabolismo , Dieta Cetogênica/métodos , Proteoma/metabolismo , Camundongos , Masculino , Memória/fisiologia , Potenciação de Longa Duração/fisiologia , Camundongos Endogâmicos C57BL , Hipocampo/metabolismo , Sinapses/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Plasticidade Neuronal/fisiologia , FosforilaçãoRESUMO
BACKGROUND: Despite 18 years since health surveillance regulations were promulgated in Brazil to govern Long-Term Care Institutions for Older Adults (LTCIs), many institutions fail to comply with the Differentiated Regime for Public Procurement (Resolution No. 502/2021) due to structural and operational conditions. This study aimed to investigate Brazilian LTCI managers' understanding of challenges that significantly impact institutional operation and gather suggestions for enhancing RDC No. 502/21. METHODS: A cross-sectional, exploratory, and qualitative study was conducted, involving 90 managers or technical supervisors from Brazilian LTCIs. Data were collected using a self-administered Google Forms instrument and analyzed through Thematic Analysis based on the Organizing for Quality (OQ) framework. RESULTS: The most impactful challenges for LTCIs were healthcare, financing, human resources, relationship with oversight bodies, and family members. DISCUSSION: Proposed improvements for RDC No. 502/21 included enhanced professional training, infrastructure revision, increased financial support from the state, realistic oversight/regulations, and tailored monitoring approaches. CONCLUSION: LTCIs in Brazil face numerous challenges, and the suggested improvements aim to adapt regulations to institutional realities. However, considering the regulations' variability and purposes, further investigation is warranted.