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1.
Int J Mol Sci ; 25(16)2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39201728

RESUMO

Neoadjuvant therapy (NAT) for early-stage pancreatic ductal adenocarcinoma (PDA) has recently gained prominence. We investigated the clinical significance of mucin 5 AC (MUC5AC), which exists in two major glycoforms, a less-glycosylated immature isoform (IM) and a heavily glycosylated mature isoform (MM), as a biomarker in resected PDA. Immunohistochemistry was performed on 100 resected PDAs to evaluate the expression of the IM and MM of MUC5AC using their respective monoclonal antibodies, CLH2 (NBP2-44455) and 45M1 (ab3649). MUC5AC localization (cytoplasmic, apical, and extra-cellular (EC)) was determined, and the H-scores were calculated. Univariate and multivariate (MVA) Cox regression models were used to estimate progression-free survival (PFS) and overall survival (OS). Of 100 resected PDA patients, 43 received NAT, and 57 were treatment-naïve with upfront surgery (UpS). In the study population (n = 100), IM expression (H-scores for objective response vs. no response vs. UpS = 104 vs. 152 vs. 163, p = 0.01) and MM-MUC5AC detection rates (56% vs. 63% vs. 82%, p = 0.02) were significantly different. In the NAT group, MM-MUC5AC-negative patients had significantly better PFS according to the MVA (Hazard Ratio: 0.2, 95% CI: 0.059-0.766, p = 0.01). Similar results were noted in a FOLFIRINOX sub-group (n = 36). We established an association of MUC5AC expression with treatment response and outcomes.


Assuntos
Carcinoma Ductal Pancreático , Mucina-5AC , Neoplasias Pancreáticas , Humanos , Mucina-5AC/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/cirurgia , Carcinoma Ductal Pancreático/terapia , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/terapia , Biomarcadores Tumorais/metabolismo , Terapia Neoadjuvante , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resultado do Tratamento , Fluoruracila/uso terapêutico , Prognóstico , Leucovorina/uso terapêutico , Oxaliplatina/uso terapêutico , Irinotecano/uso terapêutico , Idoso de 80 Anos ou mais , Imuno-Histoquímica
2.
Int J Public Health ; 68: 1605991, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37711157

RESUMO

Objectives: The main objective of this research was to investigate the Work-life balance (WLB), mental health, and quality of life and their associated factors among Healthcare Professionals (HCPs) in Sudan during the peak of the COVID-19 pandemic during 2021. Methods: An observational cross-sectional web-based survey was conducted during August-December 2021 among a sample of 430 HCPs working in the hospitals of four Sudanese states. The study used the WHOQoLBREF scale, Work-Life Balance Scale, and General Anxiety Disorder (GAD-7). Results: HCPs reporting a poor quality of life made up 33.5% (95% CI 29.1-38.0), while those reporting worse WLB made up 52.6% (95% CI 47.8-57.2). HCPs reporting moderate to severe anxiety symptoms accounted for 35.8% (95% CI 31.4-40.5). The Multiple Regression model indicated that an increase in the anxiety scores is associated with a decrease in Health-related Quality of Life (HRQoL) (ß= 0.831, p < 0.05). Female HCPs exhibited 4.53-fold lower HRQoL scores than their male colleagues (p < 0.05). Conclusion: Approximately one-third of the HCPs in Sudan reported low HRQoL and suffered from moderate to severe anxiety, while a large portion of them had an unequal work-life balance during COVID-19. Health policies addressing these factors are needed to improve the quality of health of HCPs.


Assuntos
COVID-19 , Humanos , Feminino , Masculino , COVID-19/epidemiologia , Qualidade de Vida , Sudão/epidemiologia , Estudos Transversais , Saúde Mental , Pandemias , Equilíbrio Trabalho-Vida , Atenção à Saúde
3.
Pragmat Obs Res ; 14: 63-74, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37637511

RESUMO

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related mortality worldwide and accounts for 90% of all primary liver cancers. Chronic inflammation is the hallmark across most prevalent etiologies among which HBV is the leading cause worldwide (33%), followed by alcohol (30%), HCV (21%), other factors like non-alcoholic steatohepatitis linked to insulin resistance/metabolic syndrome, and obesity associated inflammation (16%). Deregulation of the tightly controlled immunological network leads to liver disease, including chronic infection, autoimmunity, and tumor development. While inflammation drives oncogenesis in the liver, HCC also recruits ICOS+ FOXP3+ Tregs and MDSCs and upregulates immune checkpoints to induce a state of immunosuppression in the tumor microenvironment. As such, research is focused on targeting and modulating the immune system to treat HCC. The Checkmate 040 and Keynote 224 studies established the role of immunotherapy in the treatment of patients with HCC. In Phase I and II trials, nivolumab and pembrolizumab demonstrated durable response rates of 15-20% and were subsequently approved as second-line agents after sorafenib. Due to the success of the IMbrave 150 and HIMALAYA trials, which examined the combination of atezolizumab/bevacizumab and tremelimumab/durvalumab, respectively, the FDA approved these regimens as first-time treatment options for patients with advanced HCC. The encouraging results of immunotherapy in the management of HCC has led researchers to evaluate if combination with locoregional therapies may result in a synergistic effect. Real-world studies represent an invaluable tool to assess and verify the applicability of clinical trials in the bedside setting with a more varied patient population. We herein review current real-life use of ICIs in the management of HCC and highlight some of the ongoing clinical trials that are expected to change current recommended first-line treatment in the near future.

4.
BMJ Case Rep ; 14(8)2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376418

RESUMO

Takotsubo cardiomyopathy (TCM) secondary to an infusion reaction is extremely rare in the literature. Here, we present an unusual case of TCM in a patient with cervical squamous cell carcinoma who presented with acute hypoxic respiratory failure following the initiation of the first-cycle paclitaxel infusion therapy.


Assuntos
Paclitaxel , Síndrome do Desconforto Respiratório , Cardiomiopatia de Takotsubo , Feminino , Humanos , Paclitaxel/efeitos adversos , Cardiomiopatia de Takotsubo/induzido quimicamente , Cardiomiopatia de Takotsubo/diagnóstico , Neoplasias do Colo do Útero/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico
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