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1.
Semin Immunol ; 65: 101703, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36481358

RESUMO

Whereas T cells in the tumor microenvironment have been the main focus as cancer controlling cells and targets of immunotherapies, B cells have recently gained strong attention. Being associated to Tertiary Lymphoid Structures (TLS) located at the vicinity of tumor nests, the fate of B cell depends on TLS maturity. In immature TLS they may evolve as regulatory B cells producing immunosuppressive cytokines and promote tumor growth. In mature TLS with a germinal center, B cells are selected, amplified, undergo affinity maturation and isotypic switching, resulting in plasma cell generation and production of anti-tumor antibodies. In that case, they are associated with longer patient's survival and therapeutic response to immunotherapy. Identification of tumor specific, or tumor overexpressed, antigens recognized by "in situ" produced antibodies and their discrimination from self-antigens induced by ICI treatments is a major challenge to develop novel antibody-based immunotherapies.


Assuntos
Neoplasias , Estruturas Linfoides Terciárias , Humanos , Prognóstico , Linfócitos B , Linfócitos T , Microambiente Tumoral
2.
J Lipid Res ; 65(7): 100576, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38866328

RESUMO

Hypercholesterolemia is frequently intertwined with hepatosteatosis, hypertriglyceridemia, and hyperglycemia. This study is designed to assess the therapeutic efficacy of miR-206 in contrast to statins in the context of managing hypercholesterolemia in mice. We previously showed that miR-206 is a potent inhibitor of de novo lipogenesis (DNL), cholesterol synthesis, and gluconeogenesis in mice. Given that these processes occur within hepatocytes, we employed a mini-circle (MC) system to deliver miR-206 specifically to hepatocytes (designated as MC-miR-206). A single intravenous injection of MC-miR-206 maintained high levels of miR-206 in the liver for at least two weeks, thereby maintaining suppression of hepatic DNL, cholesterol synthesis, and gluconeogenesis. MC-miR-206 significantly reduced DNA damage, endoplasmic reticulum and oxidative stress, and hepatic toxicity. Therapeutically, both MC-miR-206 and statins significantly reduced total serum cholesterol and triglycerides as well as LDL cholesterol and VLDL cholesterol in mice maintained on the normal chow and high-fat high-cholesterol diet. MC-miR-206 reduced liver weight, hepatic triglycerides and cholesterol, and blood glucose, while statins slightly increased hepatic cholesterol and blood glucose and failed to affect levels of liver weight and hepatic triglycerides. Mechanistically, miR-206 alleviated hypercholesterolemia by inhibiting hepatic cholesterol synthesis, while statins increased HMGCR activity, hepatic cholesterol synthesis, and fecal-neutral steroid excretion. MiR-206 facilitates the regression of hypercholesterolemia, hypertriglyceridemia, hyperglycemia, and hepatosteatosis. MiR-206 outperforms statins by reducing hyperglycemia, hepatic cholesterol levels, and hepatic toxicity.


Assuntos
Colesterol , Inibidores de Hidroximetilglutaril-CoA Redutases , MicroRNAs , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Camundongos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Colesterol/sangue , Colesterol/metabolismo , Masculino , Fígado/metabolismo , Fígado/efeitos dos fármacos , Anticolesterolemiantes/farmacologia , Anticolesterolemiantes/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Hipercolesterolemia/genética , Hipercolesterolemia/metabolismo , Camundongos Endogâmicos C57BL , Hepatócitos/metabolismo , Hepatócitos/efeitos dos fármacos , Lipogênese/efeitos dos fármacos , Lipogênese/genética
3.
Curr Issues Mol Biol ; 46(8): 7895-7943, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39194685

RESUMO

Capsaicin, the most prominent pungent compound of chilli peppers, has been used in traditional medicine systems for centuries; it already has a number of established clinical and industrial applications. Capsaicin is known to act through the TRPV1 receptor, which exists in various tissues; capsaicin is hepatically metabolised, having a half-life correlated with the method of application. Research on various applications of capsaicin in different formulations is still ongoing. Thus, local capsaicin applications have a pronounced anti-inflammatory effect, while systemic applications have a multitude of different effects because their increased lipophilic character ensures their augmented bioavailability. Furthermore, various teams have documented capsaicin's anti-cancer effects, proven both in vivo and in vitro designs. A notable constraint in the therapeutic effects of capsaicin is its increased toxicity, especially in sensitive tissues. Regarding the traditional applications of capsaicin, apart from all the effects recorded as medicinal effects, the application of capsaicin in acupuncture points has been demonstrated to be effective and the combination of acupuncture and capsaicin warrants further research. Finally, capsaicin has demonstrated antimicrobial effects, which can supplement its anti-inflammatory and anti-carcinogenic actions.

4.
Cancer ; 130(14): 2538-2551, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38520382

RESUMO

BACKGROUND: Androgen deprivation therapy (ADT) inhibits prostate cancer growth. However, ADT causes loss of bone mineral density (BMD) and an increase in fracture risk; effective interventions for ADT-induced bone loss are limited. METHODS: A phase 2 randomized controlled trial investigated the feasibility, safety, and preliminary efficacy of high-dose weekly vitamin D (HDVD, 50,000 IU/week) versus placebo for 24 weeks in patients with prostate cancer receiving ADT, with all subjects receiving 600 IU/day vitamin D and 1000 mg/day calcium. Participants were ≥60 years (mean years, 67.7), had a serum 25-hydroxyvitamin D level <32 ng/mL, and initiated ADT within the previous 6 months. At baseline and after intervention, dual-energy x-ray absorptiometry was used to assess BMD, and levels of bone cell, bone formation, and resorption were measured. RESULTS: The HDVD group (N = 29) lost 1.5% BMD at the total hip vs. 4.1% for the low-dose group (N = 30; p = .03) and 1.7% BMD at the femoral neck vs. 4.4% in the low-dose group (p = .06). Stratified analyses showed that, for those with baseline 25-hydroxyvitamin D level <27 ng/mL, the HDVD group lost 2.3% BMD at the total hip vs 7.1% for the low-dose group (p < .01). Those in the HDVD arm showed significant changes in parathyroid hormone (p < .01), osteoprotegerin (p < 0.01), N-terminal telopeptide of type 1 collagen (p < 0.01) and C-terminal telopeptide of type 1 collagen (p < 0.01). No difference in adverse events or toxicity was noted between the groups. CONCLUSIONS: HDVD supplementation significantly reduced hip and femoral neck BMD loss, especially for patients with low baseline serum 25-hydroxyvitamin D levels, although demonstrating safety and feasibility in prostate cancer patients on ADT.


Assuntos
Antagonistas de Androgênios , Densidade Óssea , Neoplasias da Próstata , Vitamina D , Humanos , Masculino , Neoplasias da Próstata/tratamento farmacológico , Vitamina D/sangue , Vitamina D/análogos & derivados , Vitamina D/administração & dosagem , Idoso , Antagonistas de Androgênios/efeitos adversos , Antagonistas de Androgênios/administração & dosagem , Antagonistas de Androgênios/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Pessoa de Meia-Idade , Osteoporose/induzido quimicamente , Osteoporose/prevenção & controle
5.
Cancer ; 130(9): 1577-1589, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38288941

RESUMO

Management of venous thromboembolism (VTE) in patients with primary and metastatic brain tumors (BT) is challenging because of the risk of intracranial hemorrhage (ICH). There are no prospective clinical trials evaluating safety and efficacy of direct oral anticoagulants (DOACs), specifically in patients with BT, but they are widely used for VTE in this population. A group of neuro-oncology experts convened to provide practical clinical guidance for the off-label use of DOACs in treating VTE in patients with BT. We searched PubMed for the following terms: BTs, glioma, glioblastoma (GBM), brain metastasis, VTE, heparin, low-molecular-weight heparin (LWMH), DOACs, and ICH. Although prospective clinical trials are needed, the recommendations presented aim to assist clinicians in making informed decisions regarding DOACs for VTE in patients with BT.


Assuntos
Neoplasias Encefálicas , Neoplasias , Tromboembolia Venosa , Humanos , Anticoagulantes/efeitos adversos , Tromboembolia Venosa/epidemiologia , Hemorragia , Estudos Prospectivos , Neoplasias/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/tratamento farmacológico , Administração Oral
6.
Br J Haematol ; 205(2): 624-633, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38934331

RESUMO

Studies on asparaginase enzyme activity (AEA) monitoring in Chinese patients receiving PEG-asparaginase remain limited. We monitored AEA in paediatric patients diagnosed with acute lymphoblastic leukaemia (ALL) and treated according to the Chinese Children's Cancer Group study protocols, CCCG-ALL-2015/CCCG-ALL-2020 protocols. We measured the AEA at days 7 ± 1 and 14 ± 1 and analysed their association with patient characteristics and PEG-asparaginase-related adverse effects (AEs). We measured 2147 samples from 329 patients. Mean AEA levels (interquartile range) were 931 iu/L (654-1174 iu/L) at day 7 ± 1 and 664 iu/L (463-860 iu/L) at day 14 ± 1. The AEA levels were higher in younger children and increased with the cumulative dose numbers. PEG-asparaginase inactivation rate was 19.1%, and the silent inactivation (SI) rate was 12.5%. Nine patients were identified with allergic-like reactions. Hypofibrinogenaemia, hypertriglyceridaemia, pancreatitis and thrombosis were associated with older age, whereas hypoglycaemia was associated with younger age. The risk of hypertriglyceridaemia and hypoglycaemia increased with cumulative dose numbers of PEG-asparaginase. Except for hypofibrinogenaemia, elevated AEA levels did not increase the risk of PEG-asparaginase-related AEs. Drug monitoring can be utilized as guidance for treatment decision-making. Individualizing asparaginase doses do not reduce toxicities. The treatment target of PEG-asparaginase remains to achieve sustained and adequate activity.


Assuntos
Asparaginase , Polietilenoglicóis , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Asparaginase/administração & dosagem , Asparaginase/efeitos adversos , China , População do Leste Asiático , Pancreatite/induzido quimicamente , Polietilenoglicóis/efeitos adversos , Polietilenoglicóis/administração & dosagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico
7.
Oncologist ; 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39167703

RESUMO

Platinum-based chemotherapy has been the standard first-line (1L) treatment for advanced urothelial carcinoma (UC) for decades, based on the proven efficacy and established safety profiles of cisplatin- and carboplatin-based regimens. With the emergence of novel regimens, it is important to reevaluate and contextualize the role of 1L platinum-based chemotherapy. Platinum-based chemotherapy followed by avelumab 1L maintenance in patients without disease progression following platinum-based chemotherapy was established as a standard 1L regimen based on the JAVELIN Bladder 100 phase III trial. More recently, the EV-302 phase III trial showed the superiority of 1L enfortumab vedotin (EV) + pembrolizumab versus platinum-based chemotherapy, and the Checkmate 901 phase III trial showed the superiority of 1L nivolumab + cisplatin/gemcitabine versus cisplatin/gemcitabine alone. These 2 regimens have now been included as standard 1L options in treatment guidelines for advanced UC. EV + pembrolizumab is now the preferred 1L treatment, and in locations where EV + pembrolizumab is not available or individual patients are not considered suitable, recommended options are platinum-based chemotherapy followed by avelumab maintenance or nivolumab + cisplatin-based chemotherapy. In this review, we discuss current treatment options for advanced UC recommended in guidelines, practical considerations with platinum-based chemotherapy, the role of avelumab 1L maintenance, recent phase III trials of EV + pembrolizumab and nivolumab + cisplatin/gemcitabine, safety profiles of recommended 1L treatments, and second-line treatment options.

8.
Breast Cancer Res Treat ; 203(1): 85-93, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37704834

RESUMO

PURPOSE: Phosphoinositide 3-kinase (PI3K) inhibition is used for the treatment of certain cancers, but can cause profound hyperglycemia and insulin resistance, for which sodium-glucose cotransporter-2 (SGLT2) inhibitors have been proposed as a preferred therapy. The objective of this research is to assess the effectiveness and safety of SGLT2 inhibitors for hyperglycemia in PI3K inhibition. METHODS: We conducted a single-center retrospective review of adults initiating the PI3K inhibitor alpelisib. Exposure to different antidiabetic drugs and adverse events including diabetic ketoacidosis (DKA) were assessed through chart review. Plasma and point-of-care blood glucoses were extracted from the electronic medical record. Change in serum glucose and the rate of DKA on SGLT2 inhibitor versus other antidiabetic drugs were examined as co-primary outcomes. RESULTS: We identified 103 patients meeting eligibility criteria with median follow-up of 92 days after starting alpelisib. When SGLT2 inhibitors were used to treat hyperglycemia, they were associated with a decrease in mean random glucose by -46 mg/dL (95% CI - 77 to - 15) in adjusted linear modeling. Five cases of DKA were identified, two occurring in patients on alpelisib plus SGLT2 inhibitor. Estimated incidence of DKA was: alpelisib plus SGLT2 inhibitor, 48 DKA cases per 100 patient-years (95% CI 6, 171); alpelisib with non-SGLT2 inhibitor antidiabetic drugs, 15 (95% CI 2, 53); alpelisib only, 4 (95% CI 0.1, 22). CONCLUSIONS: SGLT2 inhibitors are effective treatments for hyperglycemia in the setting of PI3K inhibition.


Assuntos
Neoplasias da Mama , Cetoacidose Diabética , Hiperglicemia , Inibidores do Transportador 2 de Sódio-Glicose , Adulto , Humanos , Feminino , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Fosfatidilinositol 3-Quinases , Fosfatidilinositol 3-Quinase , Neoplasias da Mama/tratamento farmacológico , Hipoglicemiantes , Cetoacidose Diabética/induzido quimicamente , Cetoacidose Diabética/tratamento farmacológico , Cetoacidose Diabética/epidemiologia , Glicemia , Hiperglicemia/induzido quimicamente , Hiperglicemia/tratamento farmacológico , Sódio
9.
BMC Med ; 22(1): 83, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38448992

RESUMO

BACKGROUND: Empirical evidence suggests that lack of blinding may be associated with biased estimates of treatment benefit in randomized controlled trials, but the influence on medication-related harms is not well-recognized. We aimed to investigate the association between blinding and clinical trial estimates of medication-related harms. METHODS: We searched PubMed from January 1, 2015, till January 1, 2020, for systematic reviews with meta-analyses of medication-related harms. Eligible meta-analyses must have contained trials both with and without blinding. Potential covariates that may confound effect estimates were addressed by restricting trials within the comparison or by hierarchical analysis of harmonized groups of meta-analyses (therefore harmonizing drug type, control, dosage, and registration status) across eligible meta-analyses. The weighted hierarchical linear regression was then used to estimate the differences in harm estimates (odds ratio, OR) between trials that lacked blinding and those that were blinded. The results were reported as the ratio of OR (ROR) with its 95% confidence interval (CI). RESULTS: We identified 629 meta-analyses of harms with 10,069 trials. We estimated a weighted average ROR of 0.68 (95% CI: 0.53 to 0.88, P < 0.01) among 82 trials in 20 meta-analyses where blinding of participants was lacking. With regard to lack of blinding of healthcare providers or outcomes assessors, the RORs were 0.68 (95% CI: 0.53 to 0.87, P < 0.01 from 81 trials in 22 meta-analyses) and 1.00 (95% CI: 0.94 to 1.07, P = 0.94 from 858 trials among 155 meta-analyses) respectively. Sensitivity analyses indicate that these findings are applicable to both objective and subjective outcomes. CONCLUSIONS: Lack of blinding of participants and health care providers in randomized controlled trials may underestimate medication-related harms. Adequate blinding in randomized trials, when feasible, may help safeguard against potential bias in estimating the effects of harms.


Assuntos
Pessoal de Saúde , Humanos , Estudos Retrospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Revisões Sistemáticas como Assunto , Modelos Lineares
10.
J Urol ; 211(1): 48-54, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38063168

RESUMO

PURPOSE: Harms are often overlooked, but important, outcomes of randomized controlled trial reporting. Our goal was to determine if harms reporting has improved in high-impact urology journals. MATERIALS AND METHODS: Randomized controlled trials published in The Journal of Urology®, Urology, European Urology, and BJU International in 2012 and 2020 were analyzed. Each randomized controlled trial was evaluated by 2 authors in a masked-duplicate fashion to evaluate for adherence to harms reporting guidelines recommended by the Consolidated Standards of Reporting Trials (CONSORT) group. RESULTS: One hundred and thirty-two published studies met inclusion criteria. Between 2012 and 2020, there was a statistically significant increase in the median number of harms criteria reported between 2012 and 2020 (5.3 vs 7.2; P = .01). Methods criteria demonstrating the greatest improvements included item #3 "which harms were assessed," item #4a "when harm information was collected," and item #4b "methods to attribute harm to intervention." Results sections with the most improvement in reporting include item #6 "reasons for patient withdrawal," item #8a "effect size for harms," and item #8b "stratified serious + minor harms." CONCLUSIONS: Reporting of adverse events in randomized trials published in several top urology journals has demonstrated marked improvement. Studies published in 2020 reported approximately 70% of CONSORT-Harms criteria-an increase of nearly 40% since 2004. While these improvements mark significant change, deficits remain present and should be addressed to provide clinicians with the most complete perspective possible.


Assuntos
Publicações Periódicas como Assunto , Urologia , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Padrões de Referência , Projetos de Pesquisa
11.
Heart Fail Rev ; 29(1): 207-217, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37917192

RESUMO

Sodium-glucose cotransoporter-2 inhibitors (SGLT-2Is) improve prognosis in heart failure (HF) patients both with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). However, these drugs can have some side effects. To estimate the relative risk of side effects in HF patients treated with SGLT-2Is irrespective from left ventricular EF and setting (chronic and non-chronic HF). Five randomized controlled trials (RCTs) enrolling patients with HFrEF, 4 RCTs enrolling non-chronic HF, and 3 RCTs enrolling HFpEF were included. Among side effects, urinary infection, genital infection, acute kidney injury, diabetic ketoacidosis, hypoglycemia, hyperkalemia, hypokalemia, bone fractures, and amputations were considered in the analysis. Overall, 24,055 patients were included in the analysis: 9020 (38%) patients with HFrEF, 12,562 (52%) with HFpEF, and 2473 (10%) with non-chronic HF. There were no differences between SGLT-2Is and placebo in the risk to develop diabetic ketoacidosis, hypoglycemia, hyperkalemia, hypokalemia, bone fractures, and amputations. HFrEF patients treated with SGLT-2Is had a significant reduction of acute kidney injury (RR = 0.54 (95% CI 0.33-0.87), p = 0.011), whereas no differences have been reported in the HFpEF group (RR = 0.94 (95% CI 0.83-1.07), p = 0.348) and non-chronic HF setting (RR = 0.79 (95% CI 0.55-1.15), p = 0.214). A higher risk to develop genital infection (overall 2.57 (95% CI 1.82-3.63), p < 0.001) was found among patients treated with SGLT-2Is irrespective from EF (HFrEF: RR = 1.96 (95% CI 1.17-3.29), p = 0.011; HFpEF: RR = 3.04 (95% CI 1.88-4.90), p < 0.001). The risk to develop urinary infections was increased among SGLT-2I users in the overall population (RR = 1.13 (95% CI 1.00-1.28), p = 0.046) and in the HFpEF setting (RR = 1.19 (95% CI 1.02-1.38), p = 0.029), whereas no differences have been reported in HFrEF (RR = 1.05 (95% CI 0.81-1.36), p = 0.725) and in non-chronic HF setting (RR = 1.04 (95% CI 0.75-1.46), p = 0.806). SGLT-2Is increase the risk of urinary and genital infections in HF patients. In HFpEF patients, the treatment increases the risk of urinary infections compared to placebo, whereas SGLT-2Is reduce the risk of acute kidney disease in patients with HFrEF.


Assuntos
Injúria Renal Aguda , Cetoacidose Diabética , Fraturas Ósseas , Insuficiência Cardíaca , Hiperpotassemia , Hipoglicemia , Hipopotassemia , Humanos , Volume Sistólico , Cetoacidose Diabética/induzido quimicamente , Hiperpotassemia/induzido quimicamente , Hiperpotassemia/epidemiologia , Glucose
12.
Osteoporos Int ; 35(3): 391-399, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38141142

RESUMO

The recreational use of cannabis products has risen considerably worldwide over the past decade. As the cannabis legal market grows, a critical challenge has been to make substantiated claims about the benefits and adverse health problems triggered by cannabis exposure. Despite accumulating evidence from animal studies demonstrating the role of cannabinoids on bone metabolism, there are conflicting results in clinical literature regarding their effects on bone health outcomes.We undertook a systematic review to assess the evidence for the safety of cannabis use on bone health. We searched the databases MEDLINE, EMBASE, Cochrane Library, and Web of Science up to March 2023 for studies evaluating the effect of the recreational use of cannabis on the bone mineral density (BMD) of adults.Among the 2620 studies reviewed, three cross-sectional studies and one randomized controlled trial comprised 4032 participants from 18 to 60 years who met the inclusion criteria. Two studies showed that cannabis exposure decreased BMD, while the other 2 indicated no alteration. Despite the different study designs, the included studies showed a low risk of bias according to the Joanna Briggs Institute tool.Eligible studies present differences in cannabis products, administration routes, and exposure determination. Further longitudinal research is needed to establish multiple clinical predictors associated with potentially negative consequences of cannabis exposure, especially in vulnerable populations such as elderly individuals.


Assuntos
Densidade Óssea , Cannabis , Adulto , Humanos , Osso e Ossos , Cannabis/efeitos adversos , Estudos Transversais , Projetos de Pesquisa , Adolescente , Adulto Jovem , Pessoa de Meia-Idade
13.
Strahlenther Onkol ; 200(3): 208-218, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37658924

RESUMO

PURPOSE: The purpose of the present prospective study was to evaluate the significance of geriatric conditions measured by a comprehensive geriatric assessment (GA) for the prediction of the risk of high-grade acute radiation-induced toxicity. METHODS: A total of 314 prostate cancer patients (age ≥ 65 years) undergoing definitive radiotherapy at a tertiary academic center were included. Prior to treatment, patients underwent a GA. High-grade toxicity was defined as acute toxicity grade ≥ 2 according to standard RTOG/EORTC criteria. To analyze the predictive value of the GA, univariable and multivariable logistic regression models were applied. RESULTS: A total of 40 patients (12.7%) developed acute toxicity grade ≥ 2; high grade genitourinary was found in 37 patients (11.8%) and rectal toxicity in 8 patients (2.5%), respectively. Multivariable analysis revealed a significant association of comorbidities with overall toxicity grade ≥ 2 (odds ratio [OR] 2.633, 95% confidence interval [CI] 1.260-5.502; p = 0.010) as well as with high-grade genitourinary and rectal toxicity (OR 2.169, 95%CI1.017-4.625; p = 0.045 and OR 7.220, 95%CI 1.227-42.473; p = 0.029, respectively). Furthermore, the Activities of Daily Living score (OR 0.054, 95%CI 0.004-0.651; p = 0.022), social status (OR 0.159, 95%CI 0.028-0.891; p = 0.036), and polypharmacy (OR 4.618, 95%CI 1.045-20.405; p = 0.044) were identified as independent predictors of rectal toxicity grade ≥ 2. CONCLUSION: Geriatric conditions seem to be predictive of the development of high-grade radiation-induced toxicity in prostate cancer patients treated with definitive radiotherapy.


Assuntos
Neoplasias da Próstata , Lesões por Radiação , Radioterapia Conformacional , Masculino , Idoso , Humanos , Dosagem Radioterapêutica , Estudos Prospectivos , Avaliação Geriátrica , Atividades Cotidianas , Neoplasias da Próstata/radioterapia , Lesões por Radiação/diagnóstico , Lesões por Radiação/epidemiologia , Lesões por Radiação/etiologia , Radioterapia Conformacional/efeitos adversos
14.
BMC Cancer ; 24(1): 17, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38166682

RESUMO

BACKGROUND: Although the side effects of chemotherapy are frequently described in research studies, there is little evidence on how common they are in everyday clinical care. This study's goal was to assess the most prevalent short-term side effects experienced by patients with localized breast cancer, undergoing chemotherapy based on anthracyclines and taxane-containing treatments, at the medical oncology department of the Mohammed VI University Hospital of Marrakech, Morocco. METHODS: This was a descriptive study. We conducted a listening session at the outpatient department of the hospital with the help of a structured questionnaire. The session engaged 122 women who had undergone cycles of chemotherapy. A chi-square test was used to compare the incidence and relative risk of short side effects with both anthracycline and taxane-containing regimens. RESULTS: The average age of participants was 49.1 years. In both regimens, the findings highlighted the frequency and relative risk of the following adverse effects: systemic symptoms (fever, asthenia and sleep disorder), gastrointestinal toxicity (Vomiting, nausea, diarrhoea, constipation, mucositis and loss of appetite), dermatological toxicity (Skin reactions on hands/feet, nail toxicity, allergies, alopecia and peripheral edema), neurological toxicity (neuropathy), arthromyalgia and ocular toxicity. CONCLUSIONS: In conclusion, it is crucial for healthcare professionals to be conscious of the significance of these adverse effects. They must also know how to manage them. Likewise, the listening approach highlights its importance in the daily follow-up and monitoring of patients.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/etiologia , Antraciclinas/efeitos adversos , Marrocos/epidemiologia , Taxoides/efeitos adversos , Quimioterapia Adjuvante , Oncologia , Hospitais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
15.
Int Arch Allergy Immunol ; : 1-11, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38934162

RESUMO

INTRODUCTION: Subcutaneous immunotherapy (SCIT) is the oldest and an efficient immunotherapy method that has been used for the treatment of allergic diseases. Systemic adverse effects (SAEs) may occur during the SCIT. For this reason, there may be problems in the continuing treatment. In this study, we primarily aimed to determine the frequency of SAEs, the risk factors that may be associated with SAEs, and clinical and laboratory parameters that can predict systemic reactions in the patients who underwent SCIT. Second, we aimed to evaluate the reasons for discontinuing SCIT and the conditions special to Turkey. METHODS: The files of 295 patients who had received SCIT were evaluated retrospectively. RESULTS: SCIT was administered against house dust mites (HDM) in almost all patients (n: 291, 98.6%). A total of 14,357 injections were administered to 295 patients included in the study, and 47.8% (n: 141) of the patients discontinued treatment. The most common reason for discontinuing treatment was the supply problem in Turkey for immunotherapy preparations (n: 70, 49.6%). The second reason was that the injection visits were not continued regularly, even though there were no adverse effects related to the treatment (n: 44, 31.2%). SAEs were observed in 16.6% of the patients and 0.66% of the injections. SAEs were more frequent in girls, in asthmatic patients, and in moderate asthmatic patients (p = 0.005, p = 0.016, p = 0.043, respectively). Treatment was terminated in 13 patients (4.4%) due to SAEs. The most common SAE was bronchoconstriction (n: 40, 85.1%). None of our patients developed hypotension or loss of consciousness. Median blood eosinophil count and basophil count and the skin prick test diameter for Dermatophagoides farinae were observed to be significantly higher in the group with SAE (p = 0.024, p = 0.034, p = 0.045, respectively). CONCLUSION: Although SAE may develop in pediatric patients undergoing HDM-specific SCIT, severe reactions are rare. Girls, asthmatic patients, especially moderate asthmatic patients, and patients with high blood eosinophil and basophil levels should be monitored more carefully for the development of SAE.

16.
Br J Psychiatry ; : 1-7, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39104017

RESUMO

BACKGROUND: Clozapine-induced inflammation, such as myocarditis and pneumonia, can occur during initial titration and can be fatal. Fever is often the first sign of severe inflammation, and early detection and prevention are essential. Few studies have investigated the effects of clozapine titration speed and concomitant medication use on the risk of clozapine-induced inflammation. AIMS: We evaluated the risk factors for clozapine-associated fever, including titration speed, concomitant medication use, gender and obesity, and their impact on the risk of fever and the fever onset date. METHOD: We conducted a case-control study. The medical records of 539 Japanese participants with treatment-resistant schizophrenia at 21 hospitals in Japan who received clozapine for the first time between 2010 and 2022 were retrospectively investigated. Of these, 512 individuals were included in the analysis. Individuals were divided into three groups according to the titration rate recommended by international guidelines for East Asians: the faster titration group, the slower titration group and the ultra-slower titration group. The use of concomitant medications (such as antipsychotics, mood stabilisers, hypnotics and anxiolytics) at clozapine initiation was comprehensively investigated. Logistic regression analysis was performed to identify the explanatory variables for the risk of a fever of 37.5°C or higher lasting at least 2 days. RESULTS: Fever risk significantly increased with faster titration, male gender and concomitant use of valproic acid or quetiapine. No increased fever risk was detected with the use of other concomitant drugs, such as olanzapine, lithium or orexin receptor antagonists. Fever onset occurred significantly earlier with faster titration. Multivariate analysis identified obesity as being a factor that accelerated fever onset. CONCLUSION: A faster titration speed and concomitant treatment with valproic acid and quetiapine at clozapine initiation increased the risk of clozapine-associated fever. Clinicians should titrate clozapine with caution and consider both the titration speed and concomitant medications.

17.
J Rheumatol ; 51(5): 523-528, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38428960

RESUMO

OBJECTIVE: Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is characterized by symmetrical synovitis with pitting edema and negative rheumatoid factor (RF). It has been described in a setting of malignancy, suggesting a paraneoplastic association. With the increasing use of immune checkpoint inhibitors (ICIs) for the treatment of cancers and emergence of immune-related adverse events (irAEs), our objective was to identify and describe cases of ICI-associated RS3PE (ICI-RS3PE) and compare them to non-ICI-RS3PE. METHODS: The Canadian Research Group of Rheumatology in Immuno-Oncology (CanRIO) network is a collaboration of Canadian rheumatologists with experience in the management of patients with rheumatic irAEs (Rh-irAEs). Standardized data on adult patients with Rh-irAE have been collected as part of retrospective and prospective cohorts. In this study, detailed information on all cases of ICI-RS3PE from both cohorts were extracted and analyzed. RESULTS: We identified 11 cases of ICI-RS3PE. The most frequently observed malignancy was nonsmall cell lung cancer (4 of 11), followed by malignant melanoma (2 of 11) and cutaneous squamous cell carcinoma (2 of 11). The median time to onset of ICI-RS3PE was 26 weeks from ICI start and 52 weeks from diagnosis of malignancy. Seven patients had stable cancer prior to onset of ICI-RS3PE, 3 had partial response, and 1 had complete response. All patients received glucocorticoids. Conventional synthetic disease-modifying antirheumatic drugs (csDMARD) were needed in 10 patients. CONCLUSION: ICI-RS3PE may be an independent Rh-irAE, separate from paraneoplastic RS3PE. The symptoms of ICI-RS3PE responded well to glucocorticoids, but concomitant treatment with csDMARDs may be necessary.


Assuntos
Edema , Inibidores de Checkpoint Imunológico , Sinovite , Humanos , Sinovite/tratamento farmacológico , Sinovite/induzido quimicamente , Inibidores de Checkpoint Imunológico/efeitos adversos , Edema/tratamento farmacológico , Edema/induzido quimicamente , Pessoa de Meia-Idade , Masculino , Feminino , Idoso , Estudos Retrospectivos , Canadá , Adulto , Melanoma/tratamento farmacológico , Estudos Prospectivos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Fator Reumatoide/sangue
18.
Mult Scler ; : 13524585241235539, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38459716

RESUMO

After 1.5 years of treatment with dimethyl fumarate (DMF) for multiple sclerosis, preceded 8 years earlier by intravenous (IV) cladribine and 1 year earlier by natalizumab, our patient developed myelodysplastic syndrome (MDS). The initial manifestation was a severe drop in absolute neutrophil and lymphocyte counts. Repeat bone marrow biopsy demonstrated a new unbalanced translocation (between the chromosome 1 long arm and chromosome 7 short arm). This case report, to our knowledge, is the first linking iatrogenic MDS to DMF and cladribine, while also suggesting caution with immunosuppressants in multiple sclerosis patients.

19.
Ann Hematol ; 103(9): 3605-3613, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38907072

RESUMO

Myelofibrosis is a rare and often fatal hematological neoplasm, and the treatment of myelofibrosis-associated anemia remains suboptimal, with no improved therapies. Luspatercept was shown to display some efficacy in a phase 2 clinical trial for Myelofibrosis with anemia, yet relevant research are limited. Threrfore, data from patients diagnosed with refractory anemic primary or post-essential thrombocythemia/polycythemia vera myelofibrosis, who were treated with luspatercept for at least 9 weeks, were retrospectively collected. Eighteen patients with myelofibrosis treated with luspatercept were enrolled. Median age was 68 years (range, 44-80 years), and 27.8% were males. Ten (55.6%) were transfusion-dependent. Ten (55.6%) were Dynamic International Prognostic Scoring System intermediate-1, and eight (44.4%) were intermediate-2. The median follow-up was 7 (4-16) months. Erythroid response occurred in eight patients (44.4%) at week 12, four patients (30.8%) at week 24, and nine (50%) at the end of follow-up. Patients who were transfusion-dependent and not transfusion-dependent had similar HI-E responses, at different time points (P > 0.05). Patients had a significantly higher hemoglobin level at 12 weeks, 24 weeks, and at the end of follow-up, than at baseline (P = 0.001, P = 0.021, and P = 0.005, respectively). Treatment-related adverse events occurred in five (16.7%) patients, with no serious adverse events. Two (11.1%) patients relapsed at weeks 15 and 31. One patient progressed to acute myeloid leukemia. No patients had died by the end of follow-up. Luspatercept induced a good response in patients with anemic myelofibrosis, with a low relapse rate and good tolerance.


Assuntos
Mielofibrose Primária , Proteínas Recombinantes de Fusão , Humanos , Masculino , Mielofibrose Primária/tratamento farmacológico , Mielofibrose Primária/complicações , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Proteínas Recombinantes de Fusão/uso terapêutico , Proteínas Recombinantes de Fusão/efeitos adversos , China , Anemia Refratária/tratamento farmacológico , Receptores de Activinas Tipo II/uso terapêutico , Fragmentos Fc das Imunoglobulinas/uso terapêutico , Resultado do Tratamento , Seguimentos , Anemia/tratamento farmacológico , Anemia/etiologia
20.
Epilepsia ; 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39190029

RESUMO

OBJECTIVE: Seizures have been reported as an adverse event of the COVID-19 vaccine. However, there is no solid evidence of increased seizure occurrence compared to the general population. This study was undertaken to investigate seizure occurrence among COVID-19 vaccine recipients compared to unvaccinated controls. METHODS: A systematic search was made of PubMed, Web of Science, Scopus, and Cochrane Library up to April 9, 2024. Studies reporting seizure occurrence following COVID-19 vaccination were included. This study is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework and was conducted using random- and common-effect models. The risk of bias in the studies was evaluated by the Newcastle-Ottawa Scale. The outcome of interest was new onset seizure incidence proportion compared among (1) COVID-19 vaccine recipients, (2) unvaccinated cohorts, and (3) various types of COVID-19 vaccines. RESULTS: Forty studies were included, of which seven entered the meta-analysis. Results of the pooled analysis of the new onset seizure incidence (21- or 28-day period after vaccination) in 13 016 024 vaccine recipients and 13 013 262 unvaccinated individuals by pooling the cohort studies did not show any statistically significant difference between the two groups (odds ratio [OR] = .48, 95% confidence interval [CI] = .19-1.20, p = .12, I2 = 95%, τ2 = .7145). Pooling four studies accounting for 19 769 004 mRNA versus 47 494 631 viral vector vaccine doses demonstrated no significant difference in terms of new onset seizure incidence between the groups (OR = 1.18, 95% CI = .78-1.78, p = .44, I2 = 0%, τ2 = .004). SIGNIFICANCE: This systematic review and meta-analysis shows no statistically significant difference in the risk of new onset seizure incidence between COVID-19 vaccinated individuals and unvaccinated individuals.

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