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1.
Rehabilitacion (Madr) ; 58(3): 100850, 2024.
Artigo em Espanhol | MEDLINE | ID: mdl-38705100

RESUMO

INTRODUCTION: The presence of different complications whilst follow-up amputee patients reaches 10-80%. The main objective of this research is to assess the impact of these in the return-to-work of lower-limb traumatic amputation cases. MATERIALS AND METHODS: A retrospective cohort research was carried out. Clinic-demographic variables information was recollected in order to assess its linkage to different medical-surgical complications and functional outcomes. Survival curves were created to evaluate the return-to-work of patients with and without complications. RESULTS: A total of 46 patients, on average aged 45.7 years old (91.3% men, 71.7% without comorbidities), were included on this research. The most frequent level of amputation was transtibial (65.2%). Residual limb pain, phantom pain, dermatological-infectious complications and painful neuroma were registered in 80.4%, 58.7%, 50% y 30.4% of the cases respectively. Half of the patients had returned to their workplace after 2years of post-surgical follow-up. The return-to-work rates were significantly lower in patients suffering from residual limb pain (p=0.0083) and from painful neuroma (p=0.0051). CONCLUSION: Complications are frequent during traumatic-amputee patients' follow-up and, some of them, may impact on the return-to-work rate.


Assuntos
Amputação Cirúrgica , Membro Fantasma , Complicações Pós-Operatórias , Retorno ao Trabalho , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Retorno ao Trabalho/estatística & dados numéricos , Estudos Retrospectivos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Adulto , Membro Fantasma/etiologia , Seguimentos , Espanha , Extremidade Inferior/cirurgia , Extremidade Inferior/lesões , Amputação Traumática/complicações , Neuroma/etiologia , Estudos de Coortes , Idoso
2.
Rev Clin Esp (Barc) ; 224(6): 393-397, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38701969

RESUMO

INTRODUCTION: The global increase in sexual transmitted infections (STI) makes it necessary to seek public health strategies that facilitate rapid and minimally invasive diagnosis. The objective was to evaluate the concordance between vaginal and endocervical samples for STI diagnosis. MATERIALS AND METHODS: A retrospective cross-sectional study was carried out on vaginal and endocervical samples from women attended in our reference area with symptoms suggestive of vulvovaginitis or for STI screening during the study period. RESULTS: A total of 130 paired samples were analyzed; fifty-seven and 59 samples were positive for vaginal and endocervical specimens (Kappa index of 0.969 (Standard error = 0.022). The sensitivity of the vaginal samples was 96.5% (IC95%: 87.2-99.4), with a specificity of 100% (IC95%: 93.0-100). DISCUSSION: The introduction of STI screening in vaginal samples in our environment can facilitate rapid and effective diagnosis and allow early treatment of STI. Additionally, it facilitates sample collection and diagnosis in the community setting, essential for optimal screening.


Assuntos
Infecções por Chlamydia , Gonorreia , Mycoplasma genitalium , Manejo de Espécimes , Humanos , Feminino , Estudos Transversais , Estudos Retrospectivos , Adulto , Espanha , Gonorreia/diagnóstico , Infecções por Chlamydia/diagnóstico , Mycoplasma genitalium/isolamento & purificação , Manejo de Espécimes/métodos , Adulto Jovem , Infecções por Mycoplasma/diagnóstico , Sensibilidade e Especificidade , Colo do Útero/microbiologia , Colo do Útero/patologia , Esfregaço Vaginal , Vagina/microbiologia , Pessoa de Meia-Idade , Tricomoníase/diagnóstico , Adolescente , Infecções Sexualmente Transmissíveis/diagnóstico , Infecções Sexualmente Transmissíveis/microbiologia
3.
Curr Urol Rep ; 25(6): 117-124, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38763948

RESUMO

PURPOSE OF REVIEW: Renal cell carcinoma presents a unique proclivity for vascular involvement giving rise to a peculiar form of locally advanced disease so-called tumor thrombus. To date, the only curative strategy for these cases remains surgery, which should aim to remove every vestige of macroscopic disease. Most of the preexisting literature advocates opening the vena cava to allow tumor thrombus removal and subsequent venous suture closure. However, inferior vena cava circumferential resection (cavectomy) without caval replacement is possible in the majority of cases since progressive occlusion facilitates the development of a collateral venous network aimed at maintaining cardiac preload. RECENT FINDINGS: Radical nephrectomy with tumor thrombectomy remains a surgical challenge not exempt of operative complications even in experienced hands. In opposition to what traditional cavotomy and thrombus withdrawal can offer, circumferential cavectomy without caval replacement would provide comparable or even better oncologic control, decrease the likelihood of operative bleeding, and prevent the development of perioperative pulmonary embolism. This review focuses on the rationale of circumferential IVC resection without caval replacement and the important technical aspects of this approach in cases of renal cell carcinoma with vascular involvement. We also include an initial report on the surgical outcomes of a contemporary series of patients managed under this approach at our center.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Células Neoplásicas Circulantes , Nefrectomia , Veia Cava Inferior , Humanos , Carcinoma de Células Renais/cirurgia , Neoplasias Renais/cirurgia , Veia Cava Inferior/cirurgia , Nefrectomia/métodos , Trombectomia/métodos
4.
Pharmaceuticals (Basel) ; 17(5)2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38794218

RESUMO

Astrocytes play a pivotal role in maintaining brain homeostasis. Recent research has highlighted the significance of palmitic acid (PA) in triggering pro-inflammatory pathways contributing to neurotoxicity. Furthermore, Genomic-scale metabolic models and control theory have revealed that metabolic switches (MSs) are metabolic pathway regulators by potentially exacerbating neurotoxicity, thereby offering promising therapeutic targets. Herein, we characterized these enzymatic MSs in silico as potential therapeutic targets, employing protein-protein and drug-protein interaction networks alongside structural characterization techniques. Our findings indicate that five MSs (P00558, P04406, Q08426, P09110, and O76062) were functionally linked to nervous system drug targets and may be indirectly regulated by specific neurological drugs, some of which exhibit polypharmacological potential (e.g., Trifluperidol, Trifluoperazine, Disulfiram, and Haloperidol). Furthermore, four MSs (P00558, P04406, Q08426, and P09110) feature ligand-binding or allosteric cavities with druggable potential. Our results advocate for a focused exploration of P00558 (phosphoglycerate kinase 1), P04406 (glyceraldehyde-3-phosphate dehydrogenase), Q08426 (peroxisomal bifunctional enzyme, enoyl-CoA hydratase, and 3-hydroxyacyl CoA dehydrogenase), P09110 (peroxisomal 3-ketoacyl-CoA thiolase), and O76062 (Delta(14)-sterol reductase) as promising targets for the development or repurposing of pharmacological compounds, which could have the potential to modulate lipotoxic-altered metabolic pathways, offering new avenues for the treatment of related human diseases such as neurological diseases.

5.
J Clin Oncol ; 42(20): 2446-2455, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38657187

RESUMO

PURPOSE: The anti-NECTIN4 antibody-drug conjugate enfortumab vedotin (EV) is approved for patients with metastatic urothelial cancer (mUC). However, durable benefit is only achieved in a small, yet uncharacterized patient subset. NECTIN4 is located on chromosome 1q23.3, and 1q23.3 gains represent frequent copy number variations (CNVs) in urothelial cancer. Here, we aimed to evaluate NECTIN4 amplifications as a genomic biomarker to predict EV response in patients with mUC. MATERIALS AND METHODS: We established a NECTIN4-specific fluorescence in situ hybridization (FISH) assay to assess the predictive value of NECTIN4 CNVs in a multicenter EV-treated mUC patient cohort (mUC-EV, n = 108). CNVs were correlated with membranous NECTIN4 protein expression, EV treatment responses, and outcomes. We also assessed the prognostic value of NECTIN4 CNVs measured in metastatic biopsies of non-EV-treated mUC (mUC-non-EV, n = 103). Furthermore, we queried The Cancer Genome Atlas (TCGA) data sets (10,712 patients across 32 cancer types) for NECTIN4 CNVs. RESULTS: NECTIN4 amplifications are frequent genomic events in muscle-invasive bladder cancer (TCGA bladder cancer data set: approximately 17%) and mUC (approximately 26% in our mUC cohorts). In mUC-EV, NECTIN4 amplification represents a stable genomic alteration during metastatic progression and associates with enhanced membranous NECTIN4 protein expression. Ninety-six percent (27 of 28) of patients with NECTIN4 amplifications demonstrated objective responses to EV compared with 32% (24 of 74) in the nonamplified subgroup (P < .001). In multivariable Cox analysis adjusted for age, sex, and Bellmunt risk factors, NECTIN4 amplifications led to a 92% risk reduction for death (hazard ratio, 0.08 [95% CI, 0.02 to 0.34]; P < .001). In the mUC-non-EV, NECTIN4 amplifications were not associated with outcomes. TCGA Pan-Cancer analysis demonstrated that NECTIN4 amplifications occur frequently in other cancers, for example, in 5%-10% of breast and lung cancers. CONCLUSION: NECTIN4 amplifications are genomic predictors of EV responses and long-term survival in patients with mUC.


Assuntos
Moléculas de Adesão Celular , Amplificação de Genes , Humanos , Moléculas de Adesão Celular/genética , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Anticorpos Monoclonais/uso terapêutico , Biomarcadores Tumorais/genética , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Hibridização in Situ Fluorescente , Variações do Número de Cópias de DNA , Idoso de 80 Anos ou mais , Neoplasias Urológicas/tratamento farmacológico , Neoplasias Urológicas/genética , Neoplasias Urológicas/patologia , Nectinas
6.
Cir Pediatr ; 37(2): 50-54, 2024 Apr 01.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-38623796

RESUMO

INTRODUCTION: The course in Primary Care in Pediatric Trauma (ATIP in Spanish) has been taught in Spain since 1997, and there are currently 9 accredited training centers. Care of polytraumatized pediatric patients often takes place in an environment conducive to errors resulting from forgetfulness, which is why checklists - mnemonic tools widely used in industry and medicine - are particularly useful to avoid such errors. Although several checklists exist for pediatric trauma care, none have been developed within the setting of our course. MATERIALS AND METHODS: The criteria for being selected as an expert in Primary Care in Pediatric Trauma were agreed upon with the scientific polytrauma committee of the Spanish Pediatric Surgery Society. The items that make up the checklist were obtained from a review of the literature and consultation with selected experts, using the Delphi Technique. RESULTS: 10 experts representing the 9 groups or training centers in Primary Care in Pediatric Trauma were selected, and a 28-item checklist was drawn up in accordance with their design recommendations. CONCLUSIONS: With the consensus of all the groups, a checklist for the treatment of polytraumatized pediatric patients was drawn up using the Delphi Technique, an essential requirement for the dissemination of this checklist, which should be adapted and validated for use in each healthcare center.


INTRODUCCION: El curso de Asistencia Inicial al Trauma Pediátrico se imparte en España desde 1997, existiendo en la actualidad 9 centros formadores acreditados. La asistencia al paciente pediátrico politraumatizado se produce muchas veces en un ambiente proclive al error por olvido, por lo que las listas de verificación, como herramientas mnemotécnicas de amplia difusión en la industria y en medicina, serían especialmente útiles para evitarlos. Aunque existen varias listas de verificación para la asistencia al traumatismo pediátrico, ninguna se ha desarrollado en el entorno de nuestro curso. MATERIAL Y METODOS: Se acordaron los criterios para ser seleccionado como experto en Asistencia Inicial al Trauma Pediátrico con la comisión científica de politrauma de la Sociedad Española de Cirugía Pediátrica. Los ítems para formar la lista de verificación se obtuvieron a partir de una revisión bibliográfica y de la consulta a los expertos seleccionados, empleando un método Delphi. RESULTADOS: Se seleccionaron 10 expertos que representan los 9 grupos o centros formadores en Asistencia Inicial al Trauma Pediátrico y se elaboró una lista de verificación con 28 ítems, siguiendo sus recomendaciones de diseño. CONCLUSIONES: Se diseñó una lista de verificación para el manejo del paciente pediátrico politraumatizado, con el consenso de todos los grupos empleando un método Delphi, requisito fundamental para facilitar la difusión de esta lista. Sería preciso adaptar y validar dicha lista para su uso en cada centro asistencial.


Assuntos
Lista de Checagem , Traumatismo Múltiplo , Humanos , Criança , Técnica Delphi , Consenso , Atenção Primária à Saúde
7.
Hernia ; 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38503978

RESUMO

INTRODUCTION: There has been a rapid proliferation of the robotic approach to inguinal hernia, mainly in the United States, as it has shown similar outcomes to the laparoscopic approach but with a significant increase in associated costs. Our objective is to conduct a cost analysis in our setting (Spanish National Health System). MATERIALS AND METHODS: A retrospective single-center comparative study on inguinal hernia repair using a robotic approach versus laparoscopic approach. RESULTS: A total of 98 patients who underwent either robotic or laparoscopic TAPP inguinal hernia repair between October 2021 and July 2023 were analyzed. Out of these 98 patients, 20 (20.4%) were treated with the robotic approach, while 78 (79.6%) underwent the laparoscopic approach. When comparing both approaches, no significant differences were found in terms of complications, recurrences, or readmissions. However, the robotic group exhibited a longer surgical time (86 ± 33.07 min vs. 40 ± 14.46 min, p < 0.001), an extended hospital stays (1.6 ± 0.503 days vs. 1.13 ± 0.727 days, p < 0.007), as well as higher procedural costs (2318.63 ± 205.15 € vs. 356.81 ± 110.14 €, p < 0.001) and total hospitalization costs (3272.48 ± 408.49 € vs. 1048.61 ± 460.06 €, p < 0.001). These results were consistent when performing subgroup analysis for unilateral and bilateral hernias. CONCLUSIONS: The benefits observed in terms of recurrence rates and post-surgical complications do not justify the additional costs incurred by the robotic approach to inguinal hernia within the national public healthcare system. Nevertheless, it represents a simpler way to initiate the robotic learning curve, justifying its use in a training context.

8.
Cell Genom ; 4(4): 100528, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38552621

RESUMO

Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) enzymes mutate specific DNA sequences and hairpin-loop structures, challenging the distinction between passenger and driver hotspot mutations. Here, we characterized 115 whole genomes of metastatic urothelial carcinoma (mUC) to identify APOBEC mutagenic hotspot drivers. APOBEC-associated mutations were detected in 92% of mUCs and were equally distributed across the genome, while APOBEC hotspot mutations (ApoHMs) were enriched in open chromatin. Hairpin loops were frequent targets of didymi (twins in Greek), two hotspot mutations characterized by the APOBEC SBS2 signature, in conjunction with an uncharacterized mutational context (Ap[C>T]). Next, we developed a statistical framework that identified ApoHMs as drivers in coding and non-coding genomic regions of mUCs. Our results and statistical framework were validated in independent cohorts of 23 non-metastatic UCs and 3,744 samples of 17 metastatic cancers, identifying cancer-type-specific drivers. Our study highlights the role of APOBEC in cancer development and may contribute to developing novel targeted therapy options for APOBEC-driven cancers.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Carcinoma de Células de Transição/genética , Neoplasias da Bexiga Urinária/genética , Mutagênese/genética , Mutação/genética , Mapeamento Cromossômico
10.
Artigo em Inglês | MEDLINE | ID: mdl-38423465

RESUMO

Spinal cord ischaemia leading to paraplegia or paraparesis is one of the most devastating complications of aortic surgery. The risk of ischaemia is particularly high in repairs involving both the thoracic and abdominal segments, because in these cases blood flow to the spinal arteries can be interrupted. Multimodal protocols have now been developed to reduce the incidence of this complication, and include measures such as cerebrospinal fluid (CSF) drainage, avoidance of hypotension and anaemia, systemic hypothermia, neuromonitoring, maintaining distal perfusion during proximal clamping of the aorta, and reimplantation of intercostal or lumbar arteries, whenever feasible. We describe a case in which, due to the special characteristics of the surgery, veno-arterial extracorporeal membrane oxygenation (VA ECMO) was used to maintain distal blood flow in the lumbar, inferior mesenteric, and hypogastric arteries during aortic clamping. This approach reduced the risk of spinal cord and visceral ischaemia, and also eliminated the need for thoracotomy because partial left bypass was not required.

11.
Actas Urol Esp (Engl Ed) ; 48(5): 398-403, 2024 Jun.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-38373482

RESUMO

INTRODUCTION AND OBJECTIVE: Generative artificial intelligence makes it possible to ask about medical pathologies in dialog boxes. Our objective was to analyze the quality of information about the most common urological pathologies provided by ChatGPT (OpenIA), BARD (Google), and Copilot (Microsoft). METHODS: We analyzed information on the following pathologies and their treatments as provided by AI: prostate cancer, kidney cancer, bladder cancer, urinary lithiasis, and benign prostatic hypertrophy (BPH). Questions in English and Spanish were posed in dialog boxes; the answers were collected and analyzed with DISCERN questionnaires and the overall appropriateness of the response. Surgical procedures were performed with an informed consent questionnaire. RESULTS: The responses from the three chatbots explained the pathology, detailed risk factors, and described treatments. The difference is that BARD and Copilot provide external information citations, which ChatGPT does not. The highest DISCERN scores, in absolute numbers, were obtained in Copilot; however, on the appropriacy scale it was noted that their responses were not the most appropriate. The best surgical treatment scores were obtained by BARD, followed by ChatGPT, and finally Copilot. CONCLUSIONS: The answers obtained from generative AI on urological diseases depended on the formulation of the question. The information provided had significant biases, depending on pathology, language, and above all, the dialog box consulted.


Assuntos
Idioma , Doenças Urológicas , Humanos , Inteligência Artificial , Inquéritos e Questionários , Internet
12.
Nat Commun ; 15(1): 1349, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38355607

RESUMO

Immune checkpoint inhibitors (ICI) improve overall survival in patients with metastatic urothelial cancer (mUC), but therapeutic success at the individual patient level varies significantly. Here we identify predictive markers of response, based on whole-genome DNA (n = 70) and RNA-sequencing (n = 41) of fresh metastatic biopsy samples, collected prior to treatment with pembrolizumab. We find that PD-L1 combined positivity score does not, whereas tumor mutational burden and APOBEC mutagenesis modestly predict response. In contrast, T cell-to-stroma enrichment (TSE) score, computed from gene expression signature data to capture the relative abundance of T cells and stromal cells, predicts response to immunotherapy with high accuracy. Patients with a positive and negative TSE score show progression free survival rates at 6 months of 67 and 0%, respectively. The abundance of T cells and stromal cells, as reflected by the TSE score is confirmed by immunofluorescence in tumor tissue, and its good performance in two independent ICI-treated cohorts of patients with mUC (IMvigor210) and muscle-invasive UC (ABACUS) validate the predictive power of the TSE score. In conclusion, the TSE score represents a clinically applicable metric that potentially supports the prospective selection of patients with mUC for ICI treatment.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Estudos Prospectivos , Linfócitos T , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/genética , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Antígeno B7-H1
15.
Foot Ankle Surg ; 30(2): 117-122, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37949704

RESUMO

BACKGROUND: Platelet-rich plasma (PRP) and botulinum toxin type A (BTX-A) injections have proven effective in clinical trials for plantar fasciitis treatment but have not been directly compared. We aimed to compare clinical outcomes in patients undergoing PRP or BTX-A injections. METHODS: We performed a randomised controlled trial (59 patients; 1-year follow-up) to assess efficacy, using pain and functional scales (VAS, AOFAS Hindfoot-scale and FAAM questionnaire) and fascia thickness reduction, in control and single ultrasound-guided BTX-A or PRP injection groups. RESULTS: The BTX-A group showed better results at 1-month after treatment. Conversely, the PRP injection was more effective in the long-term, with significant pain reduction and functional improvement. Plantar fascia thickness significantly reduced from months 1 and 3 in the PRP and BTX-A groups, respectively. CONCLUSION: PRP and BTX-A injections are effective in patients with plantar fasciitis with BTX-A achieving better short-term pain reduction and PRP better long-term results. LEVEL OF EVIDENCE: Level I; Randomised Controlled Trial.


Assuntos
Toxinas Botulínicas Tipo A , Fasciíte Plantar , Plasma Rico em Plaquetas , Humanos , Fasciíte Plantar/terapia , Fasciíte Plantar/tratamento farmacológico , Toxinas Botulínicas Tipo A/uso terapêutico , Dor , Ultrassonografia de Intervenção , Resultado do Tratamento
16.
Arch Soc Esp Oftalmol (Engl Ed) ; 99(1): 33-37, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38007000

RESUMO

We present the case of a 37-year-old male patient with symptoms compatible with adenoviral conjunctivitis of 5 days' evolution. Topical corticosteroids, lubricants and removal of pseudomembranes were prescribed. PCR analysis of conjunctival exudate was positive for Monkeypox virus. During follow-up, the patient developed corneal ulcers with a torpid course, requiring admission for treatment with Tecovirimat. Ocular involvement by Monkeypox virus is usually mild and self-limiting. Cases with severe visual involvement have been described when there is corneal damage, as exemplified in this case. After admission to hospital for systemic treatment, the patient progressed favourably.


Assuntos
Conjuntivite , Úlcera da Córnea , Mpox , Masculino , Humanos , Adulto , Monkeypox virus , Conjuntivite/diagnóstico , Glucocorticoides
17.
Braz. j. biol ; 842024.
Artigo em Inglês | LILACS-Express | LILACS, VETINDEX | ID: biblio-1469292

RESUMO

Abstract The present research was made to determine the micronuclei and cytotoxic capacity of the antidepressant venlafaxine in an in vivo acute and subchronic assays in mouse. In the first study, we administered once 5, 50, and 250 mg/kg of the drug, and included a negative and a daunorubicin treated group. Observations were daily made during four days. The subchronic assay lasted 5 weeks with daily administration of venlafaxine (1, 5, and 10 mg/kg) plus a negative and an imipramine administered groups. Observations were made each week. In the first assay results showed no micronucleated polychromatic erythrocytes (MNPE) increase, except with the high dose at 72 h. The strongest cytotoxic effect was found with 250 mg/kg at 72 h (a 51% cytotoxic effect in comparison with the mean control level). In the subchronic assay no MNPE increase was found; however, with the highest dose a significant increase of micronucleated normochromatic erythrocytes was observed in the last three weeks (a mean of 51% respect to the mean control value). A cytotoxic effect with the two high doses in the last two weeks was observed (a polychromatic erythrocyte mean decrease of 52% respect to the mean control value). Results suggest caution with venlafaxine.


Resumo A presente pesquisa foi feita para determinar a capacidade micronuclei e citotóxica do antidepressivo venlafaxina em ensaios agudos e subcrônicos in vivo em camundongos. No primeiro estudo, administramos uma vez 5, 50 e 250 mg/kg do medicamento e incluímos um grupo negativo e um grupo tratado com daunorubicina. As observações foram feitas diariamente durante quatro dias. O ensaio subcrônico durou cinco semanas com administração diária de venlafaxina (1, 5, e 10 mg/kg) mais um grupo negativo e um grupo administrado de imipramina. As observações foram feitas a cada semana. No primeiro ensaio, os resultados não mostraram aumento de eritrócitos policromáticos micronucleados (MNPE), exceto com a dose elevada a 72 h. O efeito citotóxico mais forte foi encontrado com 250 mg/kg a 72 h (um efeito citotóxico de 51% em comparação com o nível médio de controle). No ensaio subcrônico não foi encontrado aumento de MNPE; entretanto, com a dose mais alta, um aumento significativo de eritrócitos normocromáticos micronucleados foi observado nas últimas três semanas (média de 51% em relação ao valor médio de controle). Foi observado um efeito citotóxico com as duas altas doses nas últimas duas semanas (uma diminuição média de 52% em relação ao valor médio de controle dos eritrócitos policromáticos). Os resultados sugerem cautela com a venlafaxina.

18.
Braz. j. biol ; 84: e251289, 2024. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1355889

RESUMO

Abstract The present research was made to determine the micronuclei and cytotoxic capacity of the antidepressant venlafaxine in an in vivo acute and subchronic assays in mouse. In the first study, we administered once 5, 50, and 250 mg/kg of the drug, and included a negative and a daunorubicin treated group. Observations were daily made during four days. The subchronic assay lasted 5 weeks with daily administration of venlafaxine (1, 5, and 10 mg/kg) plus a negative and an imipramine administered groups. Observations were made each week. In the first assay results showed no micronucleated polychromatic erythrocytes (MNPE) increase, except with the high dose at 72 h. The strongest cytotoxic effect was found with 250 mg/kg at 72 h (a 51% cytotoxic effect in comparison with the mean control level). In the subchronic assay no MNPE increase was found; however, with the highest dose a significant increase of micronucleated normochromatic erythrocytes was observed in the last three weeks (a mean of 51% respect to the mean control value). A cytotoxic effect with the two high doses in the last two weeks was observed (a polychromatic erythrocyte mean decrease of 52% respect to the mean control value). Results suggest caution with venlafaxine.


Resumo A presente pesquisa foi feita para determinar a capacidade micronuclei e citotóxica do antidepressivo venlafaxina em ensaios agudos e subcrônicos in vivo em camundongos. No primeiro estudo, administramos uma vez 5, 50 e 250 mg/kg do medicamento e incluímos um grupo negativo e um grupo tratado com daunorubicina. As observações foram feitas diariamente durante quatro dias. O ensaio subcrônico durou cinco semanas com administração diária de venlafaxina (1, 5, e 10 mg/kg) mais um grupo negativo e um grupo administrado de imipramina. As observações foram feitas a cada semana. No primeiro ensaio, os resultados não mostraram aumento de eritrócitos policromáticos micronucleados (MNPE), exceto com a dose elevada a 72 h. O efeito citotóxico mais forte foi encontrado com 250 mg/kg a 72 h (um efeito citotóxico de 51% em comparação com o nível médio de controle). No ensaio subcrônico não foi encontrado aumento de MNPE; entretanto, com a dose mais alta, um aumento significativo de eritrócitos normocromáticos micronucleados foi observado nas últimas três semanas (média de 51% em relação ao valor médio de controle). Foi observado um efeito citotóxico com as duas altas doses nas últimas duas semanas (uma diminuição média de 52% em relação ao valor médio de controle dos eritrócitos policromáticos). Os resultados sugerem cautela com a venlafaxina.


Assuntos
Animais , Coelhos , Dano ao DNA , Antineoplásicos , Testes para Micronúcleos , Relação Dose-Resposta a Droga , Eritrócitos , Cloridrato de Venlafaxina/toxicidade
19.
BMC Gastroenterol ; 23(1): 375, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37915010

RESUMO

BACKGROUND: Natural orifice transluminal endoscopy surgery (NOTES) gastrojejunal anastomosis (GJA) with duodenal exclusion (DE) could be used as a less invasive alternative to surgical gastric bypass. The aim of this study was to compare the efficacy and safety of both methods for bariatric purpose. METHODS: This was a prospective, experimental and comparative study on 27 obese living pigs, comparing 4 groups: GJA alone (group 1, G1), GJA + DE (group 2, G2), surgical gastric bypass (group 3, G3), control group (group 4, G4). GJA was endoscopically performed, using NOTES technic and LAMS, while DE was performed surgically for limb length selection. Animals were followed for 3 months. Primary outcome included technical success and weight change, while secondary endpoints included the rate of perioperative mortality and morbidity, histological anastomosis analysis and biological analysis. RESULTS: Technical success was 100% in each intervention group. No death related to endoscopic procedures occurred in the endoscopic groups, while early mortality (< 1 month) was 57,1% in the surgical group, all due to anastomotic dehiscence. At 3 months, compared to baseline, mean weight change was + 3,1% in G1 (p = 0,46); -14,9% in G2 (p = 0,17); +5,6% in G3 (p = 0,38) and + 25% in G4 (p = 0,029). Histopathological analysis of endoscopic GJA showed complete fusion of different layers without leak or abscess. CONCLUSIONS: Endoscopic GJA with DE provides the efficacy of bypass on weight control in an animal model. Next steps consist of the development of devices to perform exclusively endoscopically limb length selection and DE.


Assuntos
Derivação Gástrica , Laparoscopia , Obesidade Mórbida , Suínos , Animais , Estudos Prospectivos , Endoscopia , Obesidade/cirurgia , Derivação Gástrica/métodos , Obesidade Mórbida/cirurgia , Resultado do Tratamento
20.
Front Immunol ; 14: 1221113, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38022574

RESUMO

The central nervous system (CNS) is one of the most frequent metastatic sites of various cancers, including lung cancer, breast cancer and melanoma. The development of brain metastases requires a specific therapeutic approach and is associated with high mortality and morbidity in cancer patients. Advances in precision medicine and the introduction in recent years of new drugs, such as immunotherapy, have made it possible to improve the prognosis of these patients by improving survival and quality of life. New diagnostic techniques such as liquid biopsy allow real-time monitoring of tumor evolution, providing molecular information on prognostic and predictive biomarkers of response to treatment in blood or other fluids. In this review, we perform an exhaustive update of the clinical trials that demonstrate the utility of immunotherapy in patients with brain metastases and the potential of circulating biomarkers to improving the results of efficacy and toxicity in this subgroup of patients.


Assuntos
Neoplasias Encefálicas , Melanoma , Humanos , Qualidade de Vida , Melanoma/patologia , Neoplasias Encefálicas/terapia , Imunoterapia/métodos , Biomarcadores Tumorais
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