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1.
Int J STD AIDS ; : 9564624241259512, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38905613

RESUMO

OBJECTIVE: Evaluate the clinical features in people with Hodgkin's lymphoma living with HIV (HIV-HL) during the combination ART (cART) era. DESIGN: Systematic review and meta-analysis. METHODS: The study was conducted in accordance with the recommendations of 2020 PRISMA and MOOSE statements. The protocol was prospectively registered through the PROSPERO (CRD42021289520). Manuscripts published until July 2023 were systematically searched in the PubMed, EMBASE, Cochrane Library, and Web of Science databases, with no language and year of publication restriction. Meta-analysis was performed to estimate a pooled proportion of each outcome using a random-effect analysis. Quality assessment was performed by using New-Castle Ottawa scale. Certainty of evidence was graded using the GRADE. RESULTS: Sixteen cohorts, representing 3.882 HIV-HL patients, were included in this review. Our findings indicate that HIV-HL patients showed a 2-year overall survival (OS) of 92% (95% CI 0.87, 0.95). However, the 5-year overall survival decreased to 79% (95% CI 0.74, 0.83), with a high certainty of evidence according to GRADE. Additionally, the 5-year progression-free survival declined to 79% and complete remission rate increased to 81%. Our meta-analysis indicates an increase for B symptoms (80%, 95% CI 0.75, 0.84) and extranodal involvement in bone marrow (43%, 95% CI 0.30, 0.47) among HIV-HL patients. CONCLUSION: The HIV-HL patients showed a 2-year OS of 92%. However, the 5-year OS decreased to 79%. The reported main cause of mortality among HIV-HL patients was progression of HL. Our systematic review and meta-analysis suggest that cART is associated with improved short-term survival of HIV-HL patients.

2.
Head Neck ; 46(6): 1340-1350, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38445804

RESUMO

INTRODUCTION: Cervical disease control might be challenging in advanced thyroid cancer (DTC). Indications for cervical external beam radiation therapy (EBRT) are controversial. PURPOSE: To identify clinical and molecular factors associated with control of cervical disease with EBRT. METHODS: Retrospective evaluation and molecular analysis of the primary tumor DTC patients who underwent cervical EBRT between 1995 and 2022 was performed. RESULTS: Eighty adults, median age of 61 years, were included. T4 disease was present in 43.7%, lymph node involvement in 42.5%, and distant metastasis in 47.5%. Those with cervical progression were older (62.5 vs. 57.3, p = 0.04) with more nodes affected (12.1 vs. 2.8, p = 0.04) and had EBRT performed later following surgery (76.6 vs. 64 months, p = 0.05). EBRT associated with multikinase inhibitors showed longer overall survival than EBRT alone (64.3 vs. 37.9, p = 0.018) and better local disease control. Performing EBRT before radioiodine (RAI) was associated with longer cervical progression-free survival (CPFS) than was RAI before (67.5 vs. 34.5, p < 0.01). EBRT ≥2 years after surgery was associated with worse CPFS (4.9 vs. 34, p = 0.04). The most common molecular alterations were ERBB2, BRAF, FAT1, RET and ROS1 and TERT mutation was predictive of worse disease control after EBRT (p = 0.04). CONCLUSION: Younger patients, with fewer affected nodes and treated earlier after surgery had better cervical disease control. Combination of EBRT with MKI improved OS. TERT mutation might indicate worse responders to EBRT; however, further studies are necessary to clarify the role of molecular testing in selecting candidates for cervical EBRT.


Assuntos
Recidiva Local de Neoplasia , Neoplasias da Glândula Tireoide , Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/patologia , Masculino , Estudos Retrospectivos , Idoso , Adulto , Neoplasia Residual , Radioisótopos do Iodo/uso terapêutico , Tireoidectomia , Fatores de Tempo
3.
Endocrine ; 84(3): 1081-1087, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38296913

RESUMO

INTRODUCTION: Differentiated thyroid carcinoma (DTC) is a rare oncological disease in the pediatric population, presenting with a more aggressive form. Stimulated thyroglobulin (sTg) and the 131-iodine whole-body scans (WBSs) are known adult markers related to the presence of distant metastasis. Little is known about their roles in the pediatric population. PURPOSE: To evaluate sTg levels and diagnostic WBS (DxWBS) as predictors of distant metastasis after thyroidectomy and to correlate with the response to treatment at the end of follow-up in pediatric DTC. MATERIALS AND METHODS: Patients under 19 years old diagnosed with DTC from 1980 to 2022 were retrospectively evaluated. sTg values and WBS were assessed after thyroidectomy and prior radioiodine treatment (RIT) and correlated with the possibility of finding distant metastasis and response to treatment at the end of follow-up. RESULTS: In a total of 142 patients with a median age of 14.6 (4-18) years who were followed for 9.5 ± 7.2 years and classified according to the ATA risk of recurrence as low (28%), intermediate (16%), and high risk (56%), 127 patients had their sTg evaluated. A sTg value of 21.7 ng/dl yielded a sensitivity of 88% compared to 30% for DxWBS in predicting distant metastasis. Specificity was 60% and 100% respectively. 42% of patients obtained discordant results between DxWBS and RxWBS. In high-risk patients, sTg levels were particularly able to differentiate those who would have distant metastasis with better diagnostic accuracy than the WBSs. CONCLUSIONS: The sTg level had better performance in detecting distant metastases in pediatric DTC than the DxWBS. DxWBS's low performance suggests that caution should be taken in interpreting their findings in terms of the underdiagnosis for metastatic disease, especially when the sTg level already suggests distant disease.


Assuntos
Radioisótopos do Iodo , Tireoglobulina , Neoplasias da Glândula Tireoide , Tireoidectomia , Imagem Corporal Total , Humanos , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Tireoglobulina/sangue , Criança , Adolescente , Masculino , Feminino , Radioisótopos do Iodo/uso terapêutico , Estudos Retrospectivos , Pré-Escolar , Metástase Neoplásica , Resultado do Tratamento
4.
Eur Thyroid J ; 13(2)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38290210

RESUMO

Introduction: Treatment of patients with pediatric differentiated thyroid cancer (DTC) often involves radioiodine (RAI), which is associated with increased risks of short- and long-term adverse outcomes. The impact of RAI treatment on the female reproductive system remains uncertain. Anti-Müllerian hormone (AMH) is a marker of ovarian reserve and is related to fertility. Objective: The aim was to analyze the association between RAI and serum AMH level in women treated with RAI. Methods: We evaluated women with pediatric DTC treated with RAI at the age of ≤19 years. Serum AMH was measured. Results: The study included 47 patients with a mean age of 25.1 years (12.4-50.8) at AMH measurement and follow-up of 11.8 ± 8.4 years. The mean RAI administered was 235 mCi (30-1150). Sixteen (34%) received multiple RAI doses (471 ± 215 mCi). Mean AMH level was 2.49 ng/mL (0.01-7.81); the level was 1.57 ng/mL (0.01-7.81) after multiple RAI doses and 2.99 ng/mL (0.01-6.63) after a single RAI dose (P = 0.01). Patients who received a cumulative RAI lower than 200 mCi had higher AMH levels (2.23 ng/mL, 0.39-7.81) than those who received more (1.0 ng/mL, 0.01-6.63; P = 0.02). In patients with similar cumulative RAI activities, administration of multiple RAI doses was significantly and independently associated with AMH level lower than the reference range for age (HR: 5.9, 1.55-52.2, P = 0.014) after age adjustments. Conclusion: Levels of AMH were lower after multiple RAI doses, especially after a cumulative RAI dose above 200 mCi. More studies are needed to clarify the impact of RAI on fertility considering its cumulative activity and treatment strategy.


Assuntos
Adenocarcinoma , Reserva Ovariana , Hormônios Peptídicos , Neoplasias da Glândula Tireoide , Humanos , Feminino , Criança , Adulto , Adulto Jovem , Radioisótopos do Iodo/uso terapêutico , Hormônio Antimülleriano , Neoplasias da Glândula Tireoide/radioterapia , Adenocarcinoma/induzido quimicamente
5.
Arq Bras Cardiol ; 120(10): e20230174, 2023 Nov.
Artigo em Português, Inglês | MEDLINE | ID: mdl-38055534

RESUMO

Genetic tests for dilated cardiomyopathy (DCM) have a diagnostic yield of up to 40%, but there is significant genetic heterogeneity and other challenges, such as variable expressivity and incomplete penetrance. Pedigree analysis is essential for distinguishing between sporadic and familial DCM cases by assessing family history. Familial DCM yields higher results in genetic testing, but sporadic DCM does not rule out the possibility of a genetic cause. Some genes have specific phenotypes, with the Lamin gene ( LMNA ) being associated with a phenotype of malignant arrhythmias and advanced heart failure (HF). The presence of a causal genetic variant can also aid in prognostic evaluation, identifying more severe cases with lower rates of reverse remodeling (RR) compared to individuals with a negative genotype. Current guidelines recommend genetic evaluation and counseling for individuals with DCM, along with cascade screening in first-degree relatives in cases where one or more variants are identified, offering an opportunity for early diagnosis and treatment. Relatives with a positive genotype and negative phenotype are candidates for serial evaluation, with frequency varying by age. Genotype also assists in individualized recommendations for implantable cardioverter-defibrillator (ICD) placement and advice regarding physical activity and family planning. Ongoing studies are progressively elucidating the details of genotype/phenotype relationships for a large number of variants, making molecular genetics increasingly integrated into clinical practice.


Os testes genéticos para cardiomiopatia dilatada (CMD) apresentam uma positividade de até 40%, mas há uma grande heterogeneidade genética e outros desafios decorrentes de expressividade variável e penetrância incompleta. O heredograma é fundamental para diferenciar os casos de CMD esporádica e familiar, por meio da avaliação do histórico familiar. A CMD familiar apresenta um rendimento maior nos testes genéticos, mas a CMD esporádica não exclui a possibilidade de causa genética. Alguns genes têm fenótipos específicos, sendo o gene da Lamina ( LMNA ) o mais fortemente associado a um fenótipo de arritmias malignas e quadros de insuficiência cardíaca (IC) avançada. A presença de uma variante genética causal também pode ajudar na avaliação prognóstica, identificando quadros mais graves e com menores taxas de remodelamento reverso em comparação com indivíduos com genótipo negativo. As diretrizes atuais recomendam a avaliação e aconselhamento genético em indivíduos com CMD, além do rastreamento em cascata nos familiares de primeiro grau nos casos em que há uma ou mais variantes identificadas, sendo uma oportunidade para o diagnóstico e tratamento precoces. Familiares com genótipo positivo e fenótipo negativo são candidatos à avaliação seriada, com periodicidade que varia conforme a idade. O genótipo também auxilia na indicação individualizada de cardiodesfibrilador implantável e em recomendações quanto à atividade física e planejamento familiar. Estudos em curso esclarecem progressivamente os detalhes das relações genótipo/fenótipo de um grande número de variantes e fazem com que a genética molecular esteja cada vez mais presente na prática clínica.


Assuntos
Cardiomiopatia Dilatada , Humanos , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/genética , Testes Genéticos , Fenótipo , Genótipo , Arritmias Cardíacas/etiologia , Mutação
6.
Rev Bras Ortop (Sao Paulo) ; 58(4): e611-e616, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37663194

RESUMO

Objective To evaluate the open surgical treatment for carpal tunnel syndrome as a risk factor for the development of stenosing tenosynovitis that results in trigger finger and De Quervain disease. Materials and Methods A retrospective study analyzing the medical records of patients submitted to open surgical release of carpal tunnel syndrome between 2010 and 2021 in a secondary- and tertiary-level hospital. The following data were collected: pathological history, duration of the follow-up after the surgical treatment for carpal tunnel syndrome, development of trigger finger or De Quervain tenosynovitis, affected fingers, and the interval between the end of surgery and symptom onset. Results We evaluated 802 patients of both genders and with a mean age of 50.1 (±12.6) years. The mean follow-up was of 13 (±16.4) months. The mean time until the development of trigger finger was of 61.4 months, and of 73.7 months for De Quervain disease. The incidence of development of De Quervain disease was of 4.12%, and for trigger finger it was of 10.2%. The most affected digits were the thumb (47.6%), the middle (24.4%), and the ring finger (8.54%). Age was the only factor that showed an association with the risk of developing trigger finger, with an increase of 2% for each increase in age of 1 year. Conclusion The incidence rates for the development of De Quervain disease (4.12%) and trigger finger (10.2%) after the surgical treatment for carpal tunnel syndrome were like those described in the literature. Only age was a factor that influenced the development of trigger finger.

7.
Rev. bras. ortop ; 58(4): 611-616, July-Aug. 2023. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1521794

RESUMO

Abstract Objective To evaluate the open surgical treatment for carpal tunnel syndrome as a risk factor for the development of stenosing tenosynovitis that results in trigger finger and De Quervain disease. Materials and Methods A retrospective study analyzing the medical records of patients submitted to open surgical release of carpal tunnel syndrome between 2010 and 2021 in a secondary- and tertiary-level hospital. The following data were collected: pathological history, duration of the follow-up after the surgical treatment for carpal tunnel syndrome, development of trigger finger or De Quervain tenosynovitis, affected fingers, and the interval between the end of surgery and symptom onset. Results We evaluated 802 patients of both genders and with a mean age of 50.1 (±12.6) years. The mean follow-up was of 13 (±16.4) months. The mean time until the development of trigger finger was of 61.4 months, and of 73.7 months for De Quervain disease. The incidence of development of De Quervain disease was of 4.12%, and for trigger finger it was of 10.2%. The most affected digits were the thumb (47.6%), the middle (24.4%), and the ring finger (8.54%). Age was the only factor that showed an association with the risk of developing trigger finger, with an increase of 2% for each increase in age of 1 year. Conclusion The incidence rates for the development of De Quervain disease (4.12%) and trigger finger (10.2%) after the surgical treatment for carpal tunnel syndrome were like those described in the literature. Only age was a factor that influenced the development of trigger finger.


Resumo Objetivo Avaliar o tratamento cirúrgico aberto da síndrome do túnel do carpo como fator de risco para o desenvolvimento das tenossinovites estenosantes formadoras do dedo em gatilho e da doença de De Quervain. Materiais e Métodos Estudo retrospectivo com análise dos prontuários de pacientes submetidos a liberação cirúrgica aberta da síndrome do túnel do carpo entre 2010 e 2021 em hospital de níveis secundário e terciário. Os seguintes dados foram coletados: histórico patológico, tempo de acompanhamento após o tratamento cirúrgico da síndrome do túnel do carpo, desenvolvimento de dedo em gatilho ou tenossinovite de De Quervain, dedos acometidos, e tempo decorrido entre o fim da cirurgia e o aparecimento dos sintomas. Resultados Foram avaliados 802 pacientes de ambos os sexos com média de idade de 50,1 (±12,6) anos. O tempo médio de seguimento foi de 13 (±16,4) meses. O tempo médio de desenvolvimento de dedo em gatilho foi de 61,4 meses, e o da doença de De Quervain, de 73,7 meses. A incidência de desenvolvimento da doença de De Quervain foi de 4,12% e a de dedo em gatilho, de 10,2%. Os dedos mais acometidos foram o polegar (47,6%), o médio (24,4%) e o anular (8,54%). A idade foi único fator que demonstrou associação com o risco de desenvolvimento de dedo em gatilho, com aumento de 2% a cada ano a mais de idade. Conclusão As taxas de incidência de desenvolvimento de doença de De Quervain (4,12%) e de dedo em gatilho (10,2%) após tratamento cirúrgico da síndrome do túnel do carpo foram semelhantes às descritas na literatura. Apenas a idade se apresentou como fator influenciador no desenvolvimento de dedo em gatilho.


Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Síndrome do Túnel Carpal , Doença de De Quervain , Dedo em Gatilho
8.
Pharmaceutics ; 15(6)2023 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-37376135

RESUMO

Kirsten rat sarcoma (KRAS) is a small GTPase which acts as a molecular switch to regulate several cell biological processes including cell survival, proliferation, and differentiation. Alterations in KRAS have been found in 25% of all human cancers, with pancreatic cancer (90%), colorectal cancer (45%), and lung cancer (35%) being the types of cancer with the highest mutation rates. KRAS oncogenic mutations are not only responsible for malignant cell transformation and tumor development but also related to poor prognosis, low survival rate, and resistance to chemotherapy. Although different strategies have been developed to specifically target this oncoprotein over the last few decades, almost all of them have failed, relying on the current therapeutic solutions to target proteins involved in the KRAS pathway using chemical or gene therapy. Nanomedicine can certainly bring a solution for the lack of specificity and effectiveness of anti-KRAS therapy. Therefore, nanoparticles of different natures are being developed to improve the therapeutic index of drugs, genetic material, and/or biomolecules and to allow their delivery specifically into the cells of interest. The present work aims to summarize the most recent advances related to the use of nanotechnology for the development of new therapeutic strategies against KRAS-mutated cancers.

9.
Rev. bras. ortop ; 58(3): 487-494, May-June 2023. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1449828

RESUMO

Abstract Objective To evaluate the functionality in patients with adhesive capsulitis undergoing suprascapular nerve block (SSNB). Methods A before-and-after clinical prospective study in a single center was conducted with patients with secondary adhesive capsulitis treated with four nerve blocks based on anatomical limits. The sample was non-probabilistic, and it was obtained after a routine appointment at a specialized outpatient clinic. The instruments used for evaluation were the International Classification of Functioning, Disability and Health (ICF) and the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire, which were applied at baseline (T0), one week after the fourth SSNB (T4), and three months after the first SSNB (T12). The paired t-test was used to compare the means of the ICF checklist items and DASH in the different: T0xT4;T4xT12;and T0xT12). The probability of rejecting the null hypothesis was 5%. Results The sample was composed of 25 individuals with a mean age of 58.16 years; 16 of them were female. The duration of the pain symptoms ranged from 2 to 16 months, with a mean of 5.92 months. The ICF checklist showed that all domains had already improved in T4 except for the environmental factors, which only improved at 03 months (p = 0.037). The patients reported improvements in shoulder function in T4, which increased more in T12, at the end of data collection (p = 0.019). Conclusion The SSNB technique is effective in patients with adhesive capsulitis after4 weeks of application, with improvements in individual's functionality lasting for 12 weeks.


Resumo Objetivo Avaliar a funcionalidade em pacientes com capsulite adesiva submetidos a bloqueio do nervo supraescapular (BNSE). Métodos Um estudo clínico prospectivo do tipo antes e depois foi realizado em um único centro com pacientes com capsulite adesiva secundária tratados com quatro bloqueios baseados em limites anatômicos. A amostra foi não probabilística, tendo sido obtida após consulta de rotina em ambulatório especializado. Os instrumentos utilizados para avaliação foram a Classificação Internacional de Funcionalidade, Incapacidade e Saúde (CIF) e o questionário de Disfunções do Braço, Ombro e Mão (DASH), que foram aplicados antes da intervenção (T0), uma semana após o quarto BNSE (T4),etrêsapósoprimeiroBNSE(T12).AsmédiasdositensdaCIFedoDASHnos diferentes tempos (T0 x T4; T4 x T12; e T0 x T12) foram comparadas por meio do teste t pareado. A probabilidade de rejeitar a hipótese nula foi de 5%. Resultados A amostra foi composta por 25 indivíduos com média de idade de 58,16 anos; 16 eram mulheres. A duração dos sintomas dolorosos variou de 2 a 16 meses, com média de 5,92 meses. A CIF mostrou que todos os domínios já haviam melhorado em T4 à exceção dos fatores ambientais, que só melhoraram aos 3 meses (p = 0,037). Os pacientes já relataram melhora na função do ombro em T4 emaisainda em T12,ao finaldacoletadedados (p = 0,019). Conclusão A técnica de BNSE é eficaz em pacientes com capsulite adesiva após 4 semanas de aplicação, com melhora da funcionalidade do indivíduo e sua manutenção até 12 semanas.


Assuntos
Humanos , Bursite , Classificação Internacional de Funcionalidade, Incapacidade e Saúde , Bloqueio Nervoso
10.
Pharmaceutics ; 15(3)2023 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-36986692

RESUMO

Despite all the advances seen in recent years, the severe adverse effects and low specificity of conventional chemotherapy are still challenging problems regarding cancer treatment. Nanotechnology has helped to address these questions, making important contributions in the oncological field. The use of nanoparticles has allowed the improvement of the therapeutic index of several conventional drugs and facilitates the tumoral accumulation and intracellular delivery of complex biomolecules, such as genetic material. Among the wide range of nanotechnology-based drug delivery systems (nanoDDS), solid lipid nanoparticles (SLNs) have emerged as promising systems for delivering different types of cargo. Their solid lipid core, at room and body temperature, provides SLNs with higher stability than other formulations. Moreover, SLNs offer other important features, namely the possibility to perform active targeting, sustained and controlled release, and multifunctional therapy. Furthermore, with the possibility to use biocompatible and physiologic materials and easy scale-up and low-cost production methods, SLNs meet the principal requirements of an ideal nanoDDS. The present work aims to summarize the main aspects related to SLNs, including composition, production methods, and administration routes, as well as to show the most recent studies about the use of SLNs for cancer treatment.

11.
Endocrine ; 81(1): 141-148, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36905576

RESUMO

PURPOSE: This study aimed to evaluate neutrophil to lymphocyte ratio (NLR) as a laboratory biomarker in radioactive iodine-refractory (RAIR) locally advanced and/or metastatic differentiated thyroid cancer (DTC) and determine its correlation with overall survival (OS). METHODS: We retrospectively included 172 patients with locally advanced and/or metastatic RAIR DTC admitted between 1993 and 2021 at INCA. Age at diagnosis, histology, presence of distant metastasis (DM), DM site, neutrophil-to- lymphocyte ratio (NLR), imaging studies such as PET/CT results, progression free survival (PFS) and overall survival (OS) data were analyzed. NLR was calculated at the time of locally advanced and/or metastatic disease diagnosis and the cutoff value was 3. Survival curves were established using the Kaplan-Meier method. The confidence interval is 95%, and a p-value of less than 0.05 was considered statistically significant RESULTS: Out of 172 patients, 106 were locally advanced, and 150 presented DM at some point during follow-up. Regarding NLR data, 35 had NLR over 3 and 137 had NLR under 3. Higher NLR at was associated with shorter OS (6 vs. 10; p = 0.05) and with highest SUV on FDG PET-CT (15.9 vs. 7.7, p = 0.013). We found no association between higher NLR and age at diagnosis, DM or final status. CONCLUSION: NLR higher than 3 at the time of locally advanced and/or metastatic disease diagnosis is an independent fator for shorter OS in RAIR DTC patients. Noteworthy higher NLR was also associated with highest SUV on FDG PET-CT in this population.


Assuntos
Adenocarcinoma , Neoplasias da Glândula Tireoide , Humanos , Neutrófilos , Radioisótopos do Iodo/uso terapêutico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Fluordesoxiglucose F18 , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/patologia , Linfócitos/patologia , Prognóstico , Adenocarcinoma/patologia
12.
ACS Appl Mater Interfaces ; 15(8): 10398-10413, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36795046

RESUMO

The Kirsten rat sarcoma viral oncogene (KRAS) is one of the most well-known proto-oncogenes, frequently mutated in pancreatic and colorectal cancers, among others. We hypothesized that the intracellular delivery of anti-KRAS antibodies (KRAS-Ab) with biodegradable polymeric micelles (PM) would block the overactivation of the KRAS-associated cascades and revert the effect of its mutation. To this end, PM-containing KRAS-Ab (PM-KRAS) were obtained using Pluronic F127. The feasibility of using PM for antibody encapsulation as well as the conformational change of the polymer and its intermolecular interactions with the antibodies was studied, for the first time, using in silico modeling. In vitro, encapsulation of KRAS-Ab allowed their intracellular delivery in different pancreatic and colorectal cancer cell lines. Interestingly, PM-KRAS promoted a high proliferation impairment in regular cultures of KRAS-mutated HCT116 and MIA PaCa-2 cells, whereas the effect was neglectable in non-mutated or KRAS-independent HCT-8 and PANC-1 cancer cells, respectively. Additionally, PM-KRAS induced a remarkable inhibition of the colony formation ability in low-attachment conditions in KRAS-mutated cells. In vivo, when compared with the vehicle, the intravenous administration of PM-KRAS significantly reduced tumor volume growth in HCT116 subcutaneous tumor-bearing mice. Analysis of the KRAS-mediated cascade in cell cultures and tumor samples showed that the effect of PM-KRAS was mediated by a significant reduction of the ERK phosphorylation and a decrease in expression in the stemness-related genes. Altogether, these results unprecedently demonstrate that the delivery of KRAS-Ab mediated by PM can safely and effectively reduce the tumorigenicity and the stemness properties of KRAS-dependent cells, thus bringing up new possibilities to reach undruggable intracellular targets.


Assuntos
Neoplasias Colorretais , Neoplasias , Animais , Camundongos , Carcinogênese , Proliferação de Células , Neoplasias Colorretais/patologia , Micelas , Mutação , Polímeros/farmacologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/farmacologia , Espaço Intracelular
13.
Hand (N Y) ; 18(7): 1208-1214, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-35321569

RESUMO

BACKGROUND: To evaluate the impact of coronavirus disease 2019 (COVID-19) on the clinical practice, health, and quality of life of Brazilian hand surgeons when only essential services and emergency procedures were being provided. METHOD: A questionnaire of 50 questions was sent to members of the Brazilian Society of Hand Surgery addressing work and life routines before the pandemic and during the initial quarantine period from April to August 2020. RESULTS: Two hundred ten hand surgeons answered the questionnaire; 55.2% lived in the southeast region and worked in the capital and metropolitan regions, in both the private and public systems. Thirty-eight percent of the sample had other sources of income besides medicine, and due to a drop of 50% or more in the volume of consultations and surgeries, one-third had to apply for financial loans or access personal savings, and 69% made financial cuts in their domestic and life routines. More than 40% gained weight and stopped doing physical activities, while 20% lost weight and started physical activities. Approximately 30% were diagnosed with COVID-19, 92% of whom had mild symptoms and quarantined at home, and 89% had psychological symptoms such as anxiety, fear, insecurity, and insomnia. CONCLUSIONS: Coronavirus disease 2019 had a significant impact on the lives of Brazilian hand surgeons by drastically reducing the number of consultations and surgical procedures, generating not only financial difficulties but also changes in the exercise routine, changes in body weight, associated psychological symptoms, and changes in the family/life routine.


Assuntos
COVID-19 , Cirurgiões , Humanos , COVID-19/epidemiologia , SARS-CoV-2 , Qualidade de Vida , Brasil/epidemiologia
14.
Thyroid ; 33(1): 82-90, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36222615

RESUMO

Background: Calcitonin measurement is widely used in the diagnosis, prognosis, and follow-up of patients with medullary thyroid carcinoma (MTC). The prognostic value of undetectable postoperative calcitonin (POCal) in long-term disease outcomes remains uncertain. Objective: The aim of this study is to evaluate POCal as a prognostic marker for long-term MTC disease status. Methods: A retrospective cohort study was carried out. We collected data from the medical records of patients with MTC attending two tertiary teaching hospitals. Patients were divided according to POCal into two groups: undetectable (below the detection limit) or detectable. The outcome was determined at the last medical visit and defined as disease free (undetectable calcitonin and no evidence of disease on imaging), persistent disease (detectable calcitonin with or without structural disease), or disease-related death. Results: Three hundred thirty-four MTC patients were included in the study. The mean age at diagnosis was 41.1 ± 18.6 years; 202 patients (60.5%) were women; and 167 patients (50.0%) had sporadic MTC. The median tumor size was 2.0 cm (1.1-3.5 cm); 164 patients (49.1%) had lymph node metastasis and 63 patients (18.9%) had distant metastasis. At the first postoperative evaluation (3-6 months after surgery), 141 patients had undetectable POCal (mean age = 37.9 years, 70.9% women, median tumor size 1.5 cm [0.7-2.5 cm]; 28 [19.9%] had lymph node metastasis and none had distant metastasis). After a median follow-up of 7.7 years (2.1-13.2 years), 127 (90.1%) of these patients were free of disease, whereas 14 (9.9%) had persistent biochemical disease with stable calcitonin levels. No patient with undetectable POCal died of the disease. In the detectable POCal group (mean age = 42.9 years, 52.8% women, median tumor size 3.0 cm [1.8-4.2 cm]; 136 [70.5%] had lymph node metastasis and 63 [32.6%] had distant metastasis), 18 (9.2%) patients achieved disease-free status, 51 (26.6%) had biochemical disease, and 61 (31.6%) had persistent structural disease. Sixty-three (32.6%) patients died of disease-related events. Further analysis using a multivariate model identified undetectable POCal as an independent prognostic variable for disease-free status (HR = 5.33, CI = 2.86-9.94; p < 0.001). Conclusions: POCal is a strong prognostic marker for long-term disease-free survival and might help define follow-up strategies for MTC patients.


Assuntos
Conservadores da Densidade Óssea , Carcinoma Medular , Carcinoma Neuroendócrino , Neoplasias da Glândula Tireoide , Humanos , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Masculino , Calcitonina , Intervalo Livre de Doença , Estudos Retrospectivos , Metástase Linfática , Carcinoma Medular/patologia , Carcinoma Neuroendócrino/cirurgia , Neoplasias da Glândula Tireoide/patologia , Prognóstico , Tireoidectomia
15.
Arq. bras. cardiol ; 120(10): e20230174, 2023. tab, graf
Artigo em Português | LILACS-Express | LILACS | ID: biblio-1520133

RESUMO

Resumo Os testes genéticos para cardiomiopatia dilatada (CMD) apresentam uma positividade de até 40%, mas há uma grande heterogeneidade genética e outros desafios decorrentes de expressividade variável e penetrância incompleta. O heredograma é fundamental para diferenciar os casos de CMD esporádica e familiar, por meio da avaliação do histórico familiar. A CMD familiar apresenta um rendimento maior nos testes genéticos, mas a CMD esporádica não exclui a possibilidade de causa genética. Alguns genes têm fenótipos específicos, sendo o gene da Lamina ( LMNA ) o mais fortemente associado a um fenótipo de arritmias malignas e quadros de insuficiência cardíaca (IC) avançada. A presença de uma variante genética causal também pode ajudar na avaliação prognóstica, identificando quadros mais graves e com menores taxas de remodelamento reverso em comparação com indivíduos com genótipo negativo. As diretrizes atuais recomendam a avaliação e aconselhamento genético em indivíduos com CMD, além do rastreamento em cascata nos familiares de primeiro grau nos casos em que há uma ou mais variantes identificadas, sendo uma oportunidade para o diagnóstico e tratamento precoces. Familiares com genótipo positivo e fenótipo negativo são candidatos à avaliação seriada, com periodicidade que varia conforme a idade. O genótipo também auxilia na indicação individualizada de cardiodesfibrilador implantável e em recomendações quanto à atividade física e planejamento familiar. Estudos em curso esclarecem progressivamente os detalhes das relações genótipo/fenótipo de um grande número de variantes e fazem com que a genética molecular esteja cada vez mais presente na prática clínica.


Abstract Genetic tests for dilated cardiomyopathy (DCM) have a diagnostic yield of up to 40%, but there is significant genetic heterogeneity and other challenges, such as variable expressivity and incomplete penetrance. Pedigree analysis is essential for distinguishing between sporadic and familial DCM cases by assessing family history. Familial DCM yields higher results in genetic testing, but sporadic DCM does not rule out the possibility of a genetic cause. Some genes have specific phenotypes, with the Lamin gene ( LMNA ) being associated with a phenotype of malignant arrhythmias and advanced heart failure (HF). The presence of a causal genetic variant can also aid in prognostic evaluation, identifying more severe cases with lower rates of reverse remodeling (RR) compared to individuals with a negative genotype. Current guidelines recommend genetic evaluation and counseling for individuals with DCM, along with cascade screening in first-degree relatives in cases where one or more variants are identified, offering an opportunity for early diagnosis and treatment. Relatives with a positive genotype and negative phenotype are candidates for serial evaluation, with frequency varying by age. Genotype also assists in individualized recommendations for implantable cardioverter-defibrillator (ICD) placement and advice regarding physical activity and family planning. Ongoing studies are progressively elucidating the details of genotype/phenotype relationships for a large number of variants, making molecular genetics increasingly integrated into clinical practice.

16.
Acta Paul. Enferm. (Online) ; 36: eAPE01862, 2023. tab, graf
Artigo em Português | LILACS-Express | LILACS, BDENF - Enfermagem | ID: biblio-1439057

RESUMO

Resumo Objetivo Comparar o uso de toalhas impregnadas com gluconato de clorexidina 2% e gluconato de clorexidina 2% líquida no preparo pré-operatório da pele para prevenir a ocorrência de infecção do sítio cirúrgico em pacientes submetidos a cirurgias eletivas potencialmente contaminadas. Métodos Ensaio clínico randomizado, piloto paralelo, simples-cego composto por 48 pacientes submetidos a cirurgias eletivas potencialmente contaminadas que foram aleatoriamente designados para o grupo intervenção (n=25, toalhas impregnadas com gluconato de clorexidina 2%) e grupo controle (n=23, banho pré-operatório com gluconato de clorexidina líquida 2%). O desfecho primário foi infecção do sítio cirúrgico dentro de 30 dias após a cirurgia. Os pacientes foram instruídos a usar os produtos na noite anterior e na manhã da cirurgia e receberam instruções verbais e escritas sobre o uso. Foram utilizados os testes Wilcoxon-Mann-Whitney, teste T para duas amostras, Pearson X2 e testes exatos de Fisher, risco relativo (RR) e intervalo de confiança de 95%. O nível de significância para todas as variáveis foi estabelecido em α = 5%. Resultados Oito (16,7%) dos 48 pacientes analisados desenvolveram infecção do sítio cirúrgico. Não houve diferenças estatisticamente significativas entre os grupos quanto à incidência de infecção do sítio cirúrgico (RR: 0,92; IC 95%: 0,25-3,25; p=0,898), contudo, não houve casos de infecção do sítio cirúrgico incisional superficial no grupo intervenção. Conclusão O uso de toalhas impregnadas com gluconato de clorexidina 2% para preparo pré-operatório da pele não apresentou diferença estatisticamente significativa na prevenção de infecção do sítio cirúrgico em comparação com o uso de banho pré-operatório com gluconato de clorexidina 2% líquida. Registro brasileiro de ensaios clínicos: RBR-8httxs Registrado em ClinicalTrials.gov: NCT03813693


Resumen Objetivo Comparar el uso de toallas impregnadas con gluconato de clorhexidina 2 % y gluconato de clorhexidina 2 % líquida en la preparación preoperatoria para prevenir casos de infección del sitio quirúrgico en pacientes sometidos a cirugías electivas potencialmente contaminadas. Métodos Ensayo clínico aleatorizado, piloto paralelo, simple ciego, compuesto por 48 pacientes sometidos a cirugías electivas potencialmente contaminadas que fueron designados aleatoriamente al grupo experimental (n=25, toallas impregnadas con gluconato de clorhexidina 2 %) y al grupo de control (n=23, baño preoperatorio con gluconato de clorhexidina líquida 2 %). El criterio principal de valoración fue la infección del sitio quirúrgico dentro de los 30 días posteriores a la cirugía. Se instruyó a los pacientes a usar los productos la noche anterior y a la mañana del día de la cirugía y recibieron instrucciones orales y escritas sobre su uso. Se utilizaron las pruebas de Wilcoxon-Mann-Whitney, test-T para dos muestras, χ2 de Pearson y pruebas exactas de Fisher, riesgo relativo (RR) e intervalo de confianza de 95 %. El nivel de significación para todas las variables fue establecido en α = 5 %. Resultados Ocho (16,7 %) de los 48 pacientes analizados presentaron infección del sitio quirúrgico. No hubo diferencias estadísticamente significativas entre los grupos respecto a la incidencia de infección del sitio quirúrgico (RR: 0,92; IC 95 %: 0,25-3,25; p=0,898). No obstante, no hubo casos de infección del sitio quirúrgico incisional superficial en el grupo experimental. Conclusión El uso de toallas impregnadas con gluconato de clorhexidina 2 % en la preparación preoperatoria de la piel no presentó diferencia estadísticamente significativa en la prevención de infecciones del sitio quirúrgico en comparación con el uso del baño preoperatorio con gluconato de clorhexidina 2 % líquida.


Abstract Objective To compare the use of 2% chlorhexidine gluconate-impregnated cloth and 2% liquid chlorhexidine gluconate in the preoperative skin preparation to prevent the occurrence of surgical site infections in patients undergoing clean-contaminated elective surgeries. Methods Parallel, single-blind, pilot study of the randomized clinical trial (RCT), composed by forty-eight patients underwent clean-contaminated elective surgeries were randomly assigned to the intervention group (n=25, 2% chlorhexidine gluconate-impregnated cloth) and the control group (n=23, pre-operative bathing with 2% liquid chlorhexidine gluconate). The primary outcome was surgical site infection within 30 days after surgery. The patients were instructed to use the products at the night before and at the morning of surgery and received verbal and written instruction on their use. The tests Wilcoxon-Mann-Whitney, Two Sample t-test, Pearson X2 and Fisher's exact tests, risk relative (RR) and 95% confidence interval (CI) were used. The level of significance for all variables was set at α = 5%. Results 48 patients analyzed, eight (16.7%) developed a surgical site infection. There were no statistically significant differences between the groups regarding the incidence of surgical site infection (RR: 0.92; 95% CI: 0.25-3.25; p=0.898), however there were not cases of superficial incisional surgical site infection in the intervention group. Conclusion The use of 2% chlorhexidine gluconate-impregnated cloth for preoperative skin preparation did not reveal a statistically significant difference in the prevention of surgical site infection compared to the use of pre-operative bathing with 2% liquid chlorhexidine gluconate. Brazilian clinical trial registry: RBR-8httxs Registered at ClinicalTrials.gov: NCT03813693

17.
Invest. educ. enferm ; 40(3): 119-132, 15 octubre de 2022. tab, ilus
Artigo em Inglês | LILACS, BDENF - Enfermagem, COLNAL | ID: biblio-1402179

RESUMO

Objective. To identify and map the types of analysis in nursing validation studies.Methods. This is a scoping review with collection carried out in July 2020. The following data extraction indicators were considered: year of publication, country of origin, type of study, level of evidence, scientific references for validation and types of analyses. Data were collected in the following bases: U.S. National Library of Medicine, Cumulative Index to Nursing and Allied Health Literature, SCOPUS, COCHRANE, Web of Science, PsycInfo, Latin American and Caribbean Literature in Health Sciences, CAPES Theses and Dissertation Portal, Education Resources Information Center, The National Library of Australia's Trobe, Academic Archive Online, DART-Europe E-Theses Portal, Electronic Theses Online Service, Open Access Scientific Repository of Portugal, National ETD Portal, Theses Canada, Theses and dissertations from Latin America. Results. The reviewsample consisted of 881 studies, with a predominance of articles (841; 95.5%), with a prevalence of publications in 2019 (152; 17.2%), of Brazilian origin (377; 42.8%), of the methodological study type (352; 39.9%). Polit and Beck stood out as the methodological reference (207; 23.5%) and Cronbach's Alpha (421; 47.8%) as the statistical test. Regarding the type of analysis, the exploratory factor analysis and the content validation index stood out. Conclusion. The use of at least one method of analysis was evident in more than half of the studies, which implied the need to carry out several statistical tests in order to evaluate the validation of the instrument used and show its reliability.


Objetivo. Identificar y mapear los tipos de análisis de los estudios de validación de enfermería. Métodos. Esta es una revisión de alcance, con recolección realizada en julio de 2020. Se consideraron los siguientes indicadores para la extracción de datos: año de publicación, país de origen, tipo de estudio, nivel de evidencia, referencias científicas para la validación y tipos de análisis. Los datos se recolectaron en las siguientes bases: U.S. National Library of Medicine, Cumulative Index to Nursing and Allied Health Literature, SCOPUS, COCHRANE, Web of Science, PsycInfo, Latin American and Caribbean Literature in Health Sciences, CAPES Theses and Dissertation Portal, Education Resources Information Center, The National Library of Australia's Trobe, Academic Archive Online, DART-Europe E-Theses Portal, Electronic Theses Online Service, Open Access Scientific Repository of Portugal, National ETD Portal, Theses Canada y Tesis y disertaciones de América Latina. Resultados. La muestra la constituyeron 881 estudios, con predominio de artículos (841; 95.5%), con una frecuencia mayor de publicaciones en 2019 (152; 17.2%), de origen brasileño (377; 42.8%), del tipo de estudio metodológico. (352; 39.9%). Polit y Beck se destacaron como referencia metodológica (207; 23.5%) y el Alpha de Cronbach (421; 47.8%) como prueba estadística. En cuanto al tipo de análisis, se destacó el análisis factorial exploratorio y el índice de validación de contenido. Conclusión. En más de la mitad de los estudios fue evidente la utilización de, al menos, un método de análisis, lo que implicó la necesidad de realizar varias pruebas estadísticas con el fin de evaluar la validación del instrumento empleado y mostrar su fiabilidad.


Objetivo. Identificar e mapear os tipos de análises dos estudos de validação em enfermagem. Métodos. Trata-se de uma scoping review, com coleta realizada em julho de 2020. Considerou-se como indicadores de extração de dados: ano de publicação, país de origem, tipo de estudo, nível de evidência, os referenciais científicos para validação e os tipos de análises. Os dados foram coletados nas bases: U.S. National Library of Medicine,Cumulative Index to Nursing and Allied Health Literature, SCOPUS, COCHRANE, Web of Science, PsycInfo,Literatura Latino-Americana e do Caribe em Ciências da Saúde, Portal de Teses e Dissertações da CAPES, Education Resources Information Center, The National Library of Australia's Trobe, Academic Archive Online, DART-Europe E-Theses Portal, Electronic Theses Online Service, Repositório Científico de Acesso Aberto de Portugal, National ETD Portal, Theses Canada, Teses e dissertações da América latina. Resultados. A amostra foi de 881 estudos, com predomínio de artigos (841; 95.5%), com prevalência de publicações em 2019 (152; 17.2%), de origem brasileira (377; 42.8%), do tipo estudo metodológico (352; 39.9%). Sobressaiu-se Polit e Beck como referencial metodológico (207; 23.5%) e Alfa de Cronbach (421; 47.8%) como teste estatístico. Em relação ao tipo de análise destacou-se a análise fatorial exploratória e o índice de validação de conteúdo. Conclusão. Em mais da metade dos estudos ficou evidente a utilização de pelo menos um método de análise, o que implicou a necessidade de realização de diversos testes estatísticos para avaliar a validade do instrumento utilizado e mostrar sua confiabilidade.


Assuntos
Pesquisa em Enfermagem , Enfermagem , Estudo de Validação , Análise de Dados
18.
Carbohydr Polym ; 295: 119859, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-35988981

RESUMO

Local cancer treatment by in situ injections of thermo-responsive hydrogels (HG) offers several advantages over conventional systemic anti-cancer treatments. In this work, a biodegradable and multicompartmental HG composed of N-isopropylacrylamide, cellulose, citric acid, and ceric ammonium nitrate was developed for the controlled release of hydrophilic (doxorubicin) and hydrophobic (niclosamide) drugs. The formulation presented ideal properties regarding thermo-responsiveness, rheological behavior, drug release profile, biocompatibility, and biological activity in colon and ovarian cancer cells. Cellulose was found to retard drugs release rate, being only 4 % of doxorubicin and 30 % of niclosamide released after 1 week. This low release was sufficient to cause cell death in both cell lines. Moreover, HG demonstrated a proper injectability, in situ prevalence, and safety profile in vivo. Overall, the HG properties, together with its natural and eco-friendly composition, create a safe and efficient platform for the local treatment of non-resectable tumors or tumors requiring pre-surgical adjuvant therapy.


Assuntos
Hidrogéis , Neoplasias , Acrilamidas , Celulose/farmacologia , Doxorrubicina/química , Doxorrubicina/farmacologia , Humanos , Hidrogéis/química , Niclosamida , Temperatura
20.
Rev Bras Ortop (Sao Paulo) ; 57(3): 455-461, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35785117

RESUMO

Objective The purpose of the present study was to evaluate the rate of patency in the postoperative period of arterial injuries of the forearm secondary to penetrating trauma. The injuries were subjected to primary repair and examined with the Allen test and a handheld Doppler device, and the results were later confirmed with Doppler ultrasonography. Methods Eighteen patients were included, with a total of 19 arterial lesions, 14 ulnar lesions, and 5 radial lesions; one patient had lesions on both forearms. All patients underwent surgery and three clinical evaluations: the Allen test and assessment of arterial blood flow by a handheld Doppler device at 4 and 16 weeks after surgery and Doppler ultrasonography performed at 12 weeks after surgery. Results At the first clinical evaluation, 77% of the patients had patency based on the Allen test, and 72% had a pulsatile sound identified by the handheld Doppler device. In the second evaluation, 61% of the patients had patency based on the Allen test, and the rate of pulsatile sound by the handheld Doppler device was 72%, similar to that observed 2 months earlier. Based on the Doppler ultrasonography evaluation (∼12 weeks after surgery), the success rate for arteriorrhaphy was 88%. Regarding the final patency (Doppler ultrasonography evaluation) and trauma mechanism, all patients with penetrating trauma had patent arteries. Conclusion We conclude that clinical evaluation using a handheld Doppler device and the Allen test is reliable when a patent artery can be palpated. However, if a patent artery cannot be located during a clinical examination, ultrasonography may be required.

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