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1.
World J Oncol ; 16(1): 51-58, 2025 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-39850531

RESUMO

Background: The prognosis for urothelial carcinoma remains poor, with limited therapeutic options, emphasizing the need for further research into targeted therapies. The prognostic and predictive significance of human epidermal growth factor receptor 2 (HER2) expression in urothelial carcinoma remains unclear, with previous studies reporting conflicting results. Methods: We conducted a retrospective analysis of advanced urothelial carcinoma cases diagnosed between January 2017 and December 2022. HER2 status was prospectively determined using the Leica CB11 antibody on available biopsy specimens. Patient data, tumor characteristics, and survival outcomes were retrieved from hospital records for analysis. Results: Of the 84 patients initially identified with muscle-invasive disease, HER2 immunohistochemistry (IHC) was performed on 50 samples. Among these, 54% exhibited HER2 scores ≥ 1+, with 22% classified as HER2-positive (3+ score by IHC), 10% as equivocal (2+ score by IHC), and 22% as HER2-low (1+ score by IHC). The distribution of HER2 score ≥ 1+ tumors included 25.7% in the bladder, 20.0% in the renal pelvis, and none in the ureter. HER2-positive (3+ score by IHC) tumors were all histological grade 3. Among these patients, 13.4% presented with localized disease, 20% with locally advanced disease, and 50% with metastatic disease at the time of diagnosis. Notably, 42.8% of recurrent tumors originating from the renal pelvis and 62.5% of those from the bladder exhibited HER2 scores ≥ 1+. Among patients diagnosed with non-metastatic disease, 100% with renal pelvis tumors and 75% with bladder tumors experienced metastatic recurrence if they were HER2-positive (3+ score by IHC). The overall survival for HER2-negative patients was 31.0 months (95% confidence interval (CI): 15.29 - 66.70) compared to 13.0 months (95% CI: 7.32 - 18.68) in the HER2 score ≥ 1+ population (P = 0.0029). Conclusions: In this cohort of Mexican patients with urothelial carcinoma, HER2 expression was observed in 54.4% of cases. HER2-positive (+3 by IHC) tumors were associated with higher histological grade and worse prognostic outcomes, including increased recurrence, progression, and mortality.

2.
Healthcare (Basel) ; 13(2)2025 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-39857130

RESUMO

BACKGROUND/OBJECTIVES: Obesity is associated with chronic low-grade inflammation. Polyunsaturated fatty acids (PUFAs) such as omega-3 (n-3), are essential in anti-inflammatory processes. Therefore, the aim of this study was to evaluate the effect of a dietary intervention along with supplementation of 1.8 g of marine n-3 PUFAs on anthropometric, biochemical, and inflammatory markers in adults. METHODS: An 8-week double-blind randomized clinical trial was conducted with a diet (200 kcal/day reduction each 4 weeks based on the estimated basal caloric expenditure) containing a n-6/n-3 PUFA ratio ≤ 5:1, along with daily 1.8 g of marine n-3 supplementation (EPA and DHA) vs. active placebo 1.6 g (ALA). A total of 40 subjects were included in the study, 21 in the marine omega-3 group and 19 in the active placebo group. Inclusion criteria included subjects aged 25 to 50 years with obesity as determined by body mass index (BMI) and/or abdominal obesity according to ATP III criteria. RESULTS: The marine omega-3 supplemented group had a better effect compared to the active placebo group, increasing Resolvin D1 [129.3 (-90.1-193.5) vs. -16.8 (-237.8-92.5) pg/mL, p = 0.041], IL-10 [1.4 (-0.7-4.6) vs. -2.0 (-5-0.05) pg/mL, p = 0.001], and decreasing IL-6 [-0.67 (2.72--0.59) vs. 0.03 (-0.59-1.84) pg/mL, p = 0.015], and MCP-1 [-29.6 (-94.9-5.50) vs. 18.3 (-97.3-66.35) pg/mL, p = 0.040]. CONCLUSIONS: A diet supplemented with marine n-3 improves inflammatory markers by increasing systemic levels of Resolvin D1 and IL-10 and decreasing IL-6 and MCP-1.

3.
Cancers (Basel) ; 16(23)2024 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-39682103

RESUMO

Background: Clinical staging (CS) and tumor burden (TB) play a significant role in FL prognosis and direct its up-front therapy. The aim of this study is to report prognostic factors and clinical outcomes in newly-diagnosed FL patients stratified according to CS and TB in early-stage (ES) disease, advanced-stage with low tumor burden (AS-LTB) and advanced-stage with high tumor burden (AS-HTB). Methods: Two hundred fourteen patients with FL grades 1-3A had baseline clinical characteristics and outcomes assessed. Survival according to up-front immunochemotherapeutic (ICT) regimens was assessed in the AS-HTB subgroup. Independent predictors for OS, PFS, POD-24, and Histological Transformation (HT) were identified. Results: Seventy-five percent of cases were categorized as AS-HTB, 13.5% as AS-LTB and 11.5% as ES. With a median follow-up of 8.15 years, the estimated 5-year OS and PFS were 75.4% and 57.2%, respectively. OS, but not PFS was markedly decreased in AS-HTB FL patients compared to ES and AS-LTB cases. POD-24 rate was 21.7% and overall mortality rate was 38.7% during the entire follow-up. The annual cumulative rate of HT to high-grade B-cell lymphoma (HGBCL) was 0.5%, and higher in AS-HTB cases, in comparison to ES and AS-LTB. Considering patients with AS-HTB there were no differences in clinical outcomes among cases submitted to ICT based on R-CHOP, R-CVP and regimens containing purine analogs. Additionally, ECOG ≥ 2, hypoalbuminemia, B-symptoms and HT were independently associated with poor survival. High content of centro-blasts (grade 3A), involvement of ≥3 nodal sites by FL and rituximab omission in up-front therapy predicted POD-24. Conclusions: FL has marked clinical-prognostic heterogeneity, translated into diverse CS and TB subcategories. Here, we demonstrated that FL patients classified as AS-HTB demonstrated decreased survival and higher rates of HT to HGBCL compared to ES and AS-LTB cases. Prognostic factors identified in our analysis may help to identify FL patients with higher-risk of HT and early-progression (POD-24).

4.
J Surg Oncol ; 2024 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-39539035

RESUMO

INTRODUCTION: The incidence of anal squamous cell carcinoma (SCC) has been increasing over the last decades. Human papillomavirus (HPV) infection accounts for more than 90% of anal cancers, and HIV co-infection increases the risk of invasive cancer. Men who have sex with men (MSM) with HIV are the highest risk group for developing anal high-grade squamous intraepithelial lesions (aHSILs), which can be found in 45%-50% of these patients and are precursor lesions for invasive cancer. Anal cytology is an effective screening tool, but it lacks sensitivity. High-resolution anoscopy (HRA) is the gold standard procedure for diagnosis and treatment of aHSILs. Recent data suggest that early detection and treatment of aHSILs could prevent the development of invasive cancer in this population. OBJECTIVE: The objective of the study was to describe the implementation of an office-based screening program for anal cancer prevention in a Comprehensive Cancer Center in Brazil. METHODS: Training included participation in the International Anal Neoplasia Society (IANS) HRA course at UCSF Medical Center Mount Zion in San Francisco, CA, USA, by three colorectal cancer surgeons. In-person and hands-on training was provided by a specialist through the AIDS Malignancy Consortium (AMC) of the US NIH. Equipment purchased and provided by the AMC included a colposcope with a digital camera, a hands-free mouse pedal, and a photo documentation imaging software program that allows images to be recorded for documentation and training purposes. RESULTS: The program was implemented in 2022 after a delay of more than two years due to the COVID-19 pandemic. An average of 24 exams are performed monthly. Patients with HIV aged 35 years or older who are undergoing antiretroviral therapy were recruited from the metropolitan area of Rio de Janeiro and referred by primary care providers for screening. Patients diagnosed with aHSILs are scheduled for in-office ablative treatment in the clinic. From March 2022 to June 2024, 324 exams were performed, and aHSIL was found in 38.2% of 220 high-risk patients, including 45 of 129 MSMs (34.9%), 6 of 19 transgender women (31.6%), and 33 of 72 women living with HIV (45.8%). A total of 69 treatments for aHSIL were performed in 62 patients. Patients are followed on a regular basis and long-term results are awaited, including the effectiveness of local therapy for aHSIL. CONCLUSIONS: The screening and treatment program was successfully implemented in a tertiary comprehensive Cancer Center. Team training and external proctorship were decisive for the achievement of benchmark standards. The program aims to permanently provide screening for the prevention of anal cancer through the detection and treatment of aHSIL within the National Cancer Institute of Brazil for populations considered at-risk for anal cancer.

5.
Acta Ortop Mex ; 38(5): 340-344, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39586324

RESUMO

INTRODUCTION: surface sarcomas are a rare entity that need correct diagnosis to differentiate parosteal (cPOS), periosteal and the high grade surface osteosarcomas (HGSO). HGSO has malignant behavior similarities with osteosarcomas and wide resection is the key to a successful treatment.1 The Capanna and Hemi-Capanna reconstruction techniques have being developed in order to avoid amputation after an oncological resection, allowing structural support from an allograft and biological advantages from a vascularised autograft. CASE PRESENTATION: 46 years old male presenting with knee pain and 4 × 3 cm soft tissue tumor on the right tibial surface diagnosed of High Grade Surface Osteosarcoma (HGSO). Was treated by oncological resection followed by reconstruction with allograft and ipsilateral fibula autograft following the "Hemi-Capanna" technique and pedicled medial gastrocnemius flap. CONCLUSION: sufficient evidence supports the use of the Capanna technique in major musculoskeletal reconstructions. The new "Hemi-Capanna" technique has less evidence but proves to be an easier surgical technique with good functional results and little complications.


INTRODUCCIÓN: los sarcomas de superficie son una entidad rara que necesita un diagnóstico correcto para diferenciar el parostio (cPOS), el perióstico y el osteosarcoma de superficie de alto grado (HGSO). HGSO tiene similitudes de comportamiento maligno con los osteosarcomas y la resección amplia es la clave para un tratamiento exitoso. Las técnicas de reconsrucción Capanna y Hemi-Capanna han sido desarrolladas para evitar la amputación después de una resección por cáncer, permitiendo el soporte estructural de un aloinjerto y las ventajas biológicas de un autoinjerto vascularizado. PRESENTACIÓN DEL CASO: varón de 46 años que presenta dolor en rodilla y tumor de tejido blando de 4 × 3 cm en superficie tibial derecha diagnosticado con osteosarcoma de superficie de alto grado (OSAG). Se trató mediante resección oncológica seguida de reconstrucción con aloinjerto y autoinjerto de peroné ipsilateral siguiendo la técnica de "Hemi-Capanna" y colgajo pediculado de gastrocnemio medial. CONCLUSIÓN: existe evidencia suficiente que respalda el uso de la técnica de Capanna en reconstrucciones musculoesqueléticas mayores. La nueva técnica "Hemi-Capanna" tiene menos evidencia, pero demuestra ser una técnica quirúrgica más sencilla, con buenos resultados funcionales y pocas complicaciones.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Humanos , Osteossarcoma/cirurgia , Masculino , Pessoa de Meia-Idade , Neoplasias Ósseas/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Tíbia/cirurgia , Retalhos Cirúrgicos , Fíbula/transplante , Fíbula/cirurgia , Transplante Ósseo/métodos , Neoplasias de Tecidos Moles/cirurgia
6.
Clin Transl Oncol ; 2024 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-39579332

RESUMO

OBJECTIVE: Recurrent high-grade gliomas are complicated cancers that require additional treatment options. Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) is a safe method for treating recurrent high-grade glioma; however, its use in China has not been reported. In this study, we aimed to investigate the safety and efficacy of an MRgLITT system (SinoVision™) developed in China for treating recurrent high-grade glioma. METHODS: We included a prospective cohort of patients with recurrent high-grade glioma treated with the Chinese MRgLITT system between March 2021 and December 2022. Clinical data, including basic information, complication rates, outcomes, and survival analyses, were collected for patients who had at least 12 months of follow-up. RESULTS: 32 patients who completed a rountine follow-up period were enrolled. The estimated 1-year overall survival rate was 65.63%, including 56.52% and 88.89% patients with World Health Organization Grades IV and III gliomas, respectively. Baseline Karnofsky Performance Scale score, tumor grade and volume, and post-LITT chemo- and or radiotherapy were positive factors associated with MRgLITT for recurrent high-grade glioma outcomes. The overall complication rate was 9.38%. CONCLUSION: The Chinese MRgLITT system is a safe and effective treatment option for recurrent high-grade glioma. As it is a minimally invasive treatment approach that can be tailored to the individual's anatomy and physiology, MRg LITT may offer a viable alternative for patients who are not suitable candidates for conventional surgical resection.

7.
Front Oncol ; 14: 1483882, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39610929

RESUMO

Cervical cancer is a significant public health issue in Mexico and many developing countries. Early detection is crucial for combating this disease. The official screening test for cervical cancer is cytology, but this technique faces several barriers, including methodological, educational, and sociocultural challenges. Liquid-based cytology is an improved version of this test, however it does not address the aforementioned complications. Biomarkers for cervical precursor lesions and cervical cancer can improve timely detection of the disease. A previous study from our group identified four circulating human proteins as potential biomarkers for these conditions. For molecular screening, we selected GAPDH as the biomarker for cervical precursor lesions and HNRNPA1 as the biomarker for cervical cancer -chosen from the three previously identified options based on antibody availability- to be detected in sera. Participants underwent a comprehensive panel of tests, including liquid-based cytology, PCR detection of Human papillomavirus (HPV), colposcopy, and histopathology -when applicable-. The last two tests were used as references for determining sensitivity and specificity, with histopathology being the gold standard for cervical cancer diagnosis. All the participants successfully received colposcopies (n = 99) and only those women with visible or suspected cervical lesions/malignancies were biopsied (n = 62). A subset of randomly selected biopsies underwent p16INK4a immunohistochemistry (n = 36). This study compares the performance of liquid-based cytology with the molecular screening. With colposcopy as reference, liquid-based cytology showed 30% sensitivity and 96% specificity, while the molecular screening showed 90% sensitivity and 43% specificity. With histopathology as reference, liquid-based cytology showed 21% sensitivity and 93% specificity, while the molecular screening showed 85% sensitivity and 61% specificity. The molecular screening outperformed the liquid-based cytology in several areas, including detecting true-positive cases, reducing false-negative cases by 34.62%, application time, simplicity of result´s categories, and acceptance among participants. An ideal screening test requires high sensitivity, maintains moderate specificity, and minimizes false negatives. Our proposed screening test meets these criteria, making it an ideal complement -or alternative- for cervical cancer screening.

8.
Clin Transl Oncol ; 2024 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-39482457

RESUMO

OBJECTIVE: The purpose of this retrospective analysis was to evaluate the clinical presentations, radiological characteristics, patient outcomes, and therapeutic approaches among individuals diagnosed with primary central nervous system lymphoma (PCNSL), high-grade glioma (HGG), and metastatic brain tumors (METS). METHODS: We assembled a cohort of brain tumor patients from two medical centers, with two oncologists independently reviewing their clinical profiles. A retrospective examination of 87 PCNSL, 87 HGG, and 71 METS cases was performed to assess the aforementioned parameters. RESULTS: Notable variations were identified in the incidence of epileptic seizures and cognitive impairments between PCNSL and METS patients. Cerebral hemisphere involvement was predominantly observed in HGG and METS cases. PCNSL cases exhibited a higher likelihood of multiple lesions, whereas HGG showed a greater tendency for recurrence. The median survival times were established at 24.3 months for PCNSL, 44.5 months for HGG, and 27.1 months for METS patients. In PCNSL cases, the number of lesions was identified as a significant predictor of mortality (P = 0.008). CONCLUSIONS: Our findings highlight the importance of clinical and imaging features in diagnosing PCNSL, which may present distinct features compared to HGG and METS.

9.
Medwave ; 24(9): e3029, 2024 Oct 29.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-39471304

RESUMO

Introduction: Orthognathic surgery is widely accepted for correcting dentofacial deformities. Due to the rich blood supply in the head and neck region, considerable bleeding can occur from the incised soft tissues and bone during orthognathic surgery. Hypotensive anesthesia is a method used in surgical practice by which blood pressure is decreased predictably and deliberately to reduce blood loss and improve surgical field. However, there is still uncertainty regarding its effectiveness and safety in orthognathic surgery. Methods: We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis, and generated a summary of findings table using the GRADE approach. Results and Conclusions: We identified three systematic reviews, including 11 studies overall, which are randomized trials. We concluded that hypotensive anesthesia may reduce intraoperative blood loss and may improve the quality of surgical field, however, the certainty of the evidence has been assessed as low. On the other hand, orthognathic surgery with HA may make little or no difference in surgical time (low certainty evidence). Finally, no studies were found that reported adverse effects or mortality.


Introducción: La cirugía ortognática se encuentra ampliamente aceptada para la corrección de anomalías dentofaciales. Debido al importante suministro de sangre en la región de cabeza y cuello, puede ocurrir una considerable pérdida de sangre proveniente de los tejidos duros y blandos intervenidos durante una cirugía ortognática. La anestesia hipotensiva es un método utilizado en la práctica quirúrgica mediante el cual se disminuye de manera predecible y deliberada la presión sanguínea con el fin de reducir la pérdida hemática y mejorar el campo quirúrgico. Sin embargo, aún existe incertidumbre respecto a su efectividad y seguridad en cirugía ortognática. Métodos: Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. Resultados y Conclusiones: Identificamos tres revisiones sistemáticas, que en conjunto incluyeron 11 estudios primarios, todos ensayos aleatorizados. Concluimos que la anestesia hipotensiva podría reducir la pérdida de sangre intraoperatoria y mejorar la calidad del campo quirúrgico, pero la certeza de la evidencia es baja. Por otro lado, el uso de anestesia hipotensiva podria podría resultar en poca o nula diferencia en el tiempo quirúrgico (certeza de la evidencia baja). Finalmente, no se encontraron estudios que reportaran efectos adversos o mortalidad.


Assuntos
Anestesia , Hipotensão Controlada , Procedimentos Cirúrgicos Ortognáticos , Humanos , Anestesia/métodos , Perda Sanguínea Cirúrgica/prevenção & controle , Pressão Sanguínea/efeitos dos fármacos , Bases de Dados Factuais , Hipotensão Controlada/métodos , Duração da Cirurgia , Procedimentos Cirúrgicos Ortognáticos/efeitos adversos , Procedimentos Cirúrgicos Ortognáticos/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
Head Neck Pathol ; 18(1): 117, 2024 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-39466448

RESUMO

OBJECTIVE: This study aimed to implement and evaluate a Deep Convolutional Neural Network for classifying myofibroblastic lesions into benign and malignant categories based on patch-based images. METHODS: A Residual Neural Network (ResNet50) model, pre-trained with weights from ImageNet, was fine-tuned to classify a cohort of 20 patients (11 benign and 9 malignant cases). Following annotation of tumor regions, the whole-slide images (WSIs) were fragmented into smaller patches (224 × 224 pixels). These patches were non-randomly divided into training (308,843 patches), validation (43,268 patches), and test (42,061 patches) subsets, maintaining a 78:11:11 ratio. The CNN training was caried out for 75 epochs utilizing a batch size of 4, the Adam optimizer, and a learning rate of 0.00001. RESULTS: ResNet50 achieved an accuracy of 98.97%, precision of 99.91%, sensitivity of 97.98%, specificity of 99.91%, F1 score of 98.94%, and AUC of 0.99. CONCLUSIONS: The ResNet50 model developed exhibited high accuracy during training and robust generalization capabilities in unseen data, indicating nearly flawless performance in distinguishing between benign and malignant myofibroblastic tumors, despite the small sample size. The excellent performance of the AI model in separating such histologically similar classes could be attributed to its ability to identify hidden discriminative features, as well as to use a wide range of features and benefit from proper data preprocessing.


Assuntos
Redes Neurais de Computação , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Aprendizado Profundo , Sensibilidade e Especificidade , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/classificação
12.
Medwave ; 24(9): e2803, 30-10-2024.
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1585398

RESUMO

Introduction Orthognathic surgery is widely accepted for correcting dentofacial deformities. Due to the rich blood supply in the head and neck region, considerable bleeding can occur from the incised soft tissues and bone during orthognathic surgery. Hypotensive anesthesia is a method used in surgical practice by which blood pressure is decreased predictably and deliberately to reduce blood loss and improve surgical field. However, there is still uncertainty regarding its effectiveness and safety in orthognathic surgery. Methods We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis, and generated a summary of findings table using the GRADE approach. Results and Conclusions We identified three systematic reviews, including 11 studies overall, which are randomized trials. We concluded that hypotensive anesthesia may reduce intraoperative blood loss and may improve the quality of surgical field, however, the certainty of the evidence has been assessed as low. On the other hand, orthognathic surgery with HA may make little or no difference in surgical time (low certainty evidence). Finally, no studies were found that reported adverse effects or mortality.


Introducción La cirugía ortognática se encuentra ampliamente aceptada para la corrección de anomalías dentofaciales. Debido al importante suministro de sangre en la región de cabeza y cuello, puede ocurrir una considerable pérdida de sangre proveniente de los tejidos duros y blandos intervenidos durante una cirugía ortognática. La anestesia hipotensiva es un método utilizado en la práctica quirúrgica mediante el cual se disminuye de manera predecible y deliberada la presión sanguínea con el fin de reducir la pérdida hemática y mejorar el campo quirúrgico. Sin embargo, aún existe incertidumbre respecto a su efectividad y seguridad en cirugía ortognática. Métodos Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. Resultados y Conclusiones Identificamos tres revisiones sistemáticas, que en conjunto incluyeron 11 estudios primarios, todos ensayos aleatorizados. Concluimos que la anestesia hipotensiva podría reducir la pérdida de sangre intraoperatoria y mejorar la calidad del campo quirúrgico, pero la certeza de la evidencia es baja. Por otro lado, el uso de anestesia hipotensiva podria podría resultar en poca o nula diferencia en el tiempo quirúrgico (certeza de la evidencia baja). Finalmente, no se encontraron estudios que reportaran efectos adversos o mortalidad.

13.
Arch Physiol Biochem ; : 1-18, 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39324220

RESUMO

AIM: This study examined the effects of hyperthermic therapy (HT) on mice fed normal chow or a high-fat diet (HFD) for 18 or 22 weeks, undergoing four or eight weekly HT sessions. METHODS: Mice were housed within their thermoneutral zone (TNZ) to simulate a physiological response. HFD-induced obesity-related changes, including weight gain, visceral fat accumulation, muscle loss (indicative of obesity sarcopenia), glucose intolerance, and hepatic triglyceride buildup. MAIN RESULTS: HT upregulated HSP70 expression in muscles, mitigated weight gain, normalised QUICK index, and reduced plasma HSP70 concentrations. It also lowered the H-index of HSP70 balance, indicating improved immunoinflammatory status, and decreased activated caspase-1 and proliferative senescence in adipose tissue, both linked to insulin resistance. CONCLUSION: The findings suggest that even animals on a "control" diet but with insufficient physical activity and within their TNZ may experience impaired glycaemic homeostasis.

14.
J Neurooncol ; 170(3): 483-493, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39230804

RESUMO

BACKGROUND: High-grade gliomas (HGG) are the most aggressive primary brain tumors with poor prognoses despite conventional treatments. Immunotherapy has emerged as a promising avenue due to its potential to elicit a targeted immune response against tumor cells. OBJECTIVE: This meta-analysis aimed to evaluate the efficacy and safety of various immunotherapeutic strategies, including immune checkpoint inhibitors (ICI), virotherapy, and dendritic cell vaccines (DCV) in treating HGG. METHODS: Following the PRISMA framework, we searched PubMed, Cochrane, and Embase for studies reporting outcomes of HGG patients treated with immunotherapy. Key metrics included overall survival, progression-free survival, and treatment-related adverse events. RESULTS: We reviewed 47 studies, analyzing data from 3674 HGG patients treated with immunotherapy. The mean overall survival for patients treated with ICI was 11.05 months, with virotherapy at 11.79 months and notably longer for DCV at 24.11 months. The mean progression-free survival (PFS) for ICIs was 3.65 months. Virotherapy demonstrated a PFS favoring the control group, indicating minimal impact, while DCV showed substantial PFS improvement with a median of 0.43 times lower hazard compared to controls (95% CI: 29-64%). Adverse events were primarily Grade 1 or 2 for ICI, included a Grade 5 event for virotherapy, and were predominantly Grade 1 or 2 for DCV, indicating a favorable safety profile. CONCLUSION: Immunotherapy holds potential as an effective treatment for HGG, especially DCV. However, results vary significantly with the type of therapy and individual patient profiles. Further randomized controlled trials are necessary to establish robust clinical guidelines and optimize treatment protocols.


Assuntos
Neoplasias Encefálicas , Glioma , Imunoterapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Imunoterapia/métodos , Glioma/terapia , Glioma/imunologia , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/imunologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Vacinas Anticâncer/uso terapêutico , Terapia Viral Oncolítica/métodos
15.
Neurosurg Rev ; 47(1): 617, 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39276262

RESUMO

Stereotactic Brachytherapy Iodine-125 (SBT I-125) has been investigated by some studies for the treatment of lowgrade gliomas. We performed a meta-analysis to assess the efficacy and safety of SBT I-125 Brachytherapy for treatment of patients with Low-Grade Gliomas. PubMed, Cochrane, Web of Science, and EMBASE databases were searched for randomized and observational studies. This systematic review and meta-analysis was conducted according to the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement guidelines. We used relative risk (RR) with 95% confidence intervals and random effects model to compare the effects of I-125 SBT treatment on the interest outcomes. We evaluated heterogeneity using I2 statistics; we considered heterogeneity to be significant if the p-value was less than 0.05 and I2 was higher than 35%. We performed statistical analysis using the software R (version 4.2.3). A total of 20 studies with a cohort of 988 patients with low grade gliomas who received SBT I-125 as a treatment option. The pooled analysis evidenced: (1) Complication rate of 10% (95% CI: 7-12%; I² = 60%); (2) 5-year PFS of 66% (99% CI: 45-86%; I²= 98%); (3) 10-year PFS was 66% (99% CI: 45-86%; I²= 98%); (4) Malignant transformation rate of 26% (95% CI: 8-45%; I²=0); (5) Mortality of 33% (95% CI: 15-51%; I² = 0%). Our systematic review and meta-analysis of SBT I-125 for low-grade gliomas have revealed significant concerns regarding its safety and efficacy. Despite a proportion of patients remaining progression-free, elevated rates of complications and mortality cast doubt on the intervention's reliability. Future research should prioritize long-term follow-up studies, standardized protocols, and comparative effectiveness research.


Assuntos
Braquiterapia , Neoplasias Encefálicas , Glioma , Radioisótopos do Iodo , Humanos , Braquiterapia/efeitos adversos , Braquiterapia/métodos , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/radioterapia , Glioma/mortalidade , Glioma/patologia , Glioma/radioterapia , Radioisótopos do Iodo/efeitos adversos , Radioisótopos do Iodo/uso terapêutico , Resultado do Tratamento
16.
Clin Transl Oncol ; 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39141278

RESUMO

OBJECTIVE: High-grade gliomas are aggressive brain tumors with poor prognoses. Understanding the factors that influence their progression is crucial for improving treatment outcomes. This study investigates the prognostic significance of panimmune inflammation in patients diagnosed with high-grade gliomas. MATERIALS-METHODS: Data from 89 high-grade glioma patients were analysed retrospectively. The Panimmune inflammation Value (PIV) of each patient meeting the eligibility criteria was calculated on the basis of platelet, monocyte, neutrophil, and lymphocyte counts obtained from peripheral blood samples taken on the first day of treatment. PIV is calculated using the following formula: PIV = T × M × N ÷ L. A receiver operating characteristic (ROC) analysis was employed to identify the optimal cut-off value for PIV about progression-free survival (PFS) and overall survival (OS) outcomes. The primary and secondary endpoints were the differences in OS and PFS between the PIV groups. The Kaplan‒Meier method was used for survival analyses. RESULTS: The ROC analysis indicated that the optimal PIV threshold was 545.5, which exhibited a significant interaction with PFS and OS outcomes. Patients were subsequently divided into two groups based on their PIV levels: a low PIV (L-PIV) group comprising 45 patients and a high PIV (H-PIV) group comprising 44 patients. A comparative analysis of survival rates indicated that patients with elevated PIV had a shorter median PFS of 4.0 months compared to 8.0 months in the low PIV group (P = 0.797), as well as a reduced median OS of 19.0 months versus not available (NA) in the low PIV group (P = 0.215). CONCLUSION: Our study results did not reveal a statistically significant association between H-PIV measurements and reduced PFS or OS. However, PIV effectively stratified newly diagnosed high-grade glioma patients into two distinct groups with significantly different PFS and OS outcomes.

17.
Food Chem Toxicol ; 192: 114912, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39121895

RESUMO

Food grade titanium dioxide E171 has been used in products such as confectionery, doughs and flours to enhance organoleptic properties. The European Union has warned about adverse effects on humans due to oral consumption. After oral exposure, E171 reaches the bloodstream which raises the concern about effects on blood cells such as monocytes. One of the main functions of these cells is the differentiation of macrophages leading to the phagocytosis of foreign particles. The aim of this study was to evaluate the effect of E171 exposure on the phagocytic capacity and differentiation process of monocytes (THP-1) into macrophages. Physicochemical E171 properties were evaluated, and THP-1 monocytes were exposed to 4, 40 and 200 µg/ml. Cell viability, uptake capacity, cytokine release, the differentiation process, cytoskeletal arrangement and E171 internalization were assayed. Results showed that E171 particles had an amorphous shape with a mean of hydrodynamic size of ∼46 nm in cell culture media. Cell viability decreased until the 9th day of exposure, while the uptake capacity decreased up to 62% in a concentration dependent manner in monocytes. Additionally, the E171 exposure increased the proinflammatory cytokines release and decreased the cell differentiation by a 61% in macrophages. E171 induced changes in cytoskeletal arrangement and some of the E171 particles were located inside the nuclei. We conclude that E171 exposure in THP-1 monocytes induced an inflammatory response, impaired the phagocytic capacity, and interfered with cell differentiation from monocytes to macrophages.


Assuntos
Diferenciação Celular , Sobrevivência Celular , Macrófagos , Monócitos , Fagocitose , Titânio , Titânio/toxicidade , Titânio/química , Humanos , Diferenciação Celular/efeitos dos fármacos , Fagocitose/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Monócitos/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Células THP-1
18.
Medicina (B Aires) ; 84(4): 689-707, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39172569

RESUMO

In Argentina, the dengue virus has experienced an increase in recent years. This study aims to conduct a systematic review to evaluate the effectiveness and safety of the TAK-003 tetravalent dengue vaccine in this context. A systematic review of randomized controlled trials comparing the effectiveness and safety of the vaccine with placebo in the general population was conducted. The search was carried out in Epistemonikos, and two researchers independently assessed the studies. Risk of bias was evaluated using the Cochrane Rob 2 tool. A meta-analysis of the results was performed, and the certainty of evidence was assessed using the GRADE methodology. We concluded, with high certainty of evidence, that the tetravalent dengue vaccine reduces severe infections (RR 0.17, 95% CI 0.12 to 0.24) and infections by the dengue virus (RR 0.40, 95% CI 0.36 to 0.45) in a population ≤17 years. The vaccine may not increase the risk of serious adverse events, although it is important to note the low certainty of evidence (RR 1.04, 95% CI: 0.69-1.55). The use of the tetravalent dengue vaccine decreases the risk of severe and non-severe dengue infections in this population. However, there is low certainty of evidence regarding the vaccine's safety. The decision to vaccinate should consider the magnitude of benefits relative to the risk of infection.


En Argentina, el virus del dengue ha experimentado un aumento en los últimos años. Este estudio se propone realizar una revisión sistemática para evaluar la efectividad y seguridad de la vacuna TAK-003 tetravalente contra el dengue en este contexto. Se llevó a cabo una revisión sistemática de ensayos clínicos controlados aleatorizados que comparaban la efectividad y seguridad de la vacuna con placebo en la población general. La búsqueda se efectuó en Epistemonikos y dos investigadores evaluaron los estudios de manera independiente. El riesgo de sesgo se evaluó con la herramienta Rob 2 de Cochrane. Se realizó un metaanálisis de los resultados y la certeza en la evidencia se evaluó mediante la metodología GRADE. Concluimos, con alta certeza de evidencia, que la vacuna tetravalente contra el dengue reduce las infecciones graves (RR 0.17, IC 95% 0.12 a 0.24) e infecciones por el virus del dengue (RR 0.40, IC 95% 0.36 a 0.45) en una población de ≤17 años. La vacuna podría no incrementar el riesgo de eventos adversos serios, aunque es importante destacar la baja certeza de evidencia (RR 1.04, IC 95%: 0.69-1.55). La aplicación de la vacuna tetravalente contra el dengue disminuye el riesgo de infecciones graves y no graves por el dengue en esta población. No obstante, existe baja certeza en la evidencia en relación a la seguridad de la vacuna. La decisión de la vacunación debe considerar la magnitud de los beneficios en función del riesgo de infección.


Assuntos
Vacinas contra Dengue , Dengue , Humanos , Vacinas contra Dengue/efeitos adversos , Vacinas contra Dengue/administração & dosagem , Vacinas contra Dengue/imunologia , Dengue/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Eficácia de Vacinas , Vírus da Dengue/imunologia
19.
Acta Neurochir (Wien) ; 166(1): 346, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39167255

RESUMO

BACKGROUND: The Simpson grading scale assumes dural resection (grade I) is more effective against recurrence than coagulation (grade II). However, the results of recent studies have raised doubts about this effectiveness in spinal meningiomas. Therefore, we aimed to perform a meta-analysis comparing outcomes between Simpson grades I and II in spinal meningiomas. METHODS: According to the PRISMA statement, we systematically searched PubMed, EMBASE, and Web of Science for studies involving patients with spinal meningiomas who underwent Simpson grades I, II, III, or IV. Outcomes were radiological tumor recurrence, postoperative neurological deficits, and procedure-related complications. RESULTS: We included 54 studies with a total of 3334 patients. Simpson grades I, II, III, and IV were performed in 674 (20%), 2205 (66%), 254 (8%), and 201 (6%) patients, respectively. The follow-up ranged from 9 to 192 months, and 95.4% of all tumors were WHO grade 1. There was no difference in radiological tumor recurrence (OR 0.80, 95% CI: 0.46-1.36, P = 0.41; I2 = 0%), postoperative neurological deficits (OR 0.74, 95% CI: 0.32-1.75, P = 0.50; I2 = 0%) or procedure-related complications (OR 2.22, 95% CI: 0.80-6.13, P = 0.12; I2 = 3%) between Simpson grades I and II. Furthermore, no significant difference in postoperative neurological deficits or procedure-related complications was detected when comparing all Simpson's to each other. However, radiological tumor recurrences in Simpson I and II were significantly lower than in III and IV, with Simpson III outperforming IV (OR 0.19, 95% CI: 0.09-0.40, P < 0.01; I2 = 0%). CONCLUSION: Simpson grade I is not more effective than grade II in any outcome, although both are superior to III and IV in tumor recurrence. Our results might suggest that dural coagulation is preferable over resection when the latter carries a higher risk of complications.


Assuntos
Dura-Máter , Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/cirurgia , Meningioma/patologia , Neoplasias Meníngeas/cirurgia , Neoplasias Meníngeas/patologia , Dura-Máter/cirurgia , Dura-Máter/patologia , Recidiva Local de Neoplasia/cirurgia , Procedimentos Neurocirúrgicos/métodos , Resultado do Tratamento , Complicações Pós-Operatórias/etiologia
20.
Childs Nerv Syst ; 40(12): 4259-4264, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39110187

RESUMO

PURPOSE: Unresectable pediatric low-grade gliomas (LGG) usually need adjuvant therapy, and carboplatin hypersensitivity reaction (HR) commonly leads to premature treatment cessation of a standard chemotherapy regimen. In the molecular era, advances in understanding tumor genetic characteristics allowed the development of targeted therapies for this group of tumors; however, cost-effectiveness assessment of treatments, especially in low-income countries, is crucial. The aim is to describe the results of carboplatin desensitization protocol in a single center in a middle-income country. METHOD: Prospective analysis of children with LGG submitted to carboplatin desensitization from December 2017 to June 2020 with follow-up until April 2024. RESULTS: Nine patients were included. The mean age was 11 years. Five patients were male. Seven had optic pathway and two cervicomedullary location. Six had histologic diagnosis and four molecular analyses. The incidence of carboplatin reactions during the study period was 39.1%. Six patients underwent skin prick test, three with positive results. The first HR occurred, on average, around the 9th cycle of treatment. All patients had cutaneous symptoms, and five out of nine had anaphylaxis as the first reaction. 77.7% of the patients completed the protocol, and the clinical benefit rate (stable disease and partial response) was 88.8%. Six patients further required other lines of therapy. Monthly, the total cost for carboplatin was $409.09, and for target therapies (dabrafenib plus trametinib), $4929.28 to $5548.57. CONCLUSION: Our study presented an interesting and cost-effective option where desensitization allowed children with HR to be treated with first-line therapy, avoiding the discontinuation of an effective treatment.


Assuntos
Antineoplásicos , Carboplatina , Dessensibilização Imunológica , Glioma , Humanos , Carboplatina/efeitos adversos , Masculino , Criança , Feminino , Antineoplásicos/efeitos adversos , Adolescente , Dessensibilização Imunológica/métodos , Estudos Prospectivos , Glioma/tratamento farmacológico , Hipersensibilidade a Drogas/terapia , Neoplasias Encefálicas/tratamento farmacológico , Pré-Escolar
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