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The Lancet. Public Health Jul 2024Even though alcohol consumption is an established risk factor for cancer, evidence regarding the effect of a reduction or cessation of alcohol consumption on cancer...
BACKGROUND
Even though alcohol consumption is an established risk factor for cancer, evidence regarding the effect of a reduction or cessation of alcohol consumption on cancer incidence is scarce. Our main study aim was to assess the effect of alcohol rehabilitation and abstinence on cancer incidence in people with alcohol dependence.
METHODS
We conducted a nationwide hospital retrospective cohort study which included all adults residing in mainland France and discharged in 2018-21. Multivariable Cox proportional hazards models were used to estimate the effect of rehabilitation treatment at hospital or a history of abstinence versus alcohol dependence without rehabilitation or abstinence on the risk for incident alcohol-associated cancers by sex, controlled for potential confounding risk factors.
FINDINGS
10 260 056 men and 13 739 369 women were discharged from French hospitals in 2018-21. Alcohol dependence was identified in 645 720 (6·3%) men and 219 323 (1·6%) women. Alcohol dependence was strongly related to alcohol-associated cancer sites in both sexes (hepatocellular carcinoma and oral, pharyngeal, laryngeal, oesophageal, and colorectal cancers), except for breast cancer. Rehabilitation treatment or abstinence was associated with significantly lower risks compared with alcohol dependence without rehabilitation or abstinence (adjusted hazard ratios: 0·58, 99·89% CI 0·56-0·60 in men and 0·62, 0·57-0·66 in women). Relative risk reductions were significant for each alcohol-associated cancer site in both sexes and supported by all subgroup and sensitivity analyses.
INTERPRETATION
Our study results support the clear benefits of alcohol rehabilitation and abstinence in reducing the risk for alcohol-associated cancers. As only two in five patients with alcohol dependence were recorded with a history of rehabilitation treatment or abstinence, a large untapped potential exists for reducing cancer incidence.
FUNDING
European Union's EU4Health programme.
Topics: Humans; Male; Female; France; Neoplasms; Middle Aged; Retrospective Studies; Alcoholism; Adult; Aged; Risk Factors; Incidence
PubMed: 38942557
DOI: 10.1016/S2468-2667(24)00107-5 -
Progress in Molecular Biology and... 2024Female cancers, which include breast and gynaecological cancers, represent a significant global health burden for women. Despite advancements in research pertinent to... (Review)
Review
Female cancers, which include breast and gynaecological cancers, represent a significant global health burden for women. Despite advancements in research pertinent to unearthing crucial pathological characteristics of these cancers, challenges persist in discovering potential therapeutic strategies. This is further exacerbated by economic burdens associated with de novo drug discovery and clinical intricacies such as development of drug resistance and metastasis. Drug repurposing, an innovative approach leveraging existing FDA-approved drugs for new indications, presents a promising avenue to expedite therapeutic development. Computational techniques, including virtual screening and analysis of drug-target-disease relationships, enable the identification of potential candidate drugs. Integration of diverse data types, such as omics and clinical information, enhances the precision and efficacy of drug repurposing strategies. Experimental approaches, including high-throughput screening assays, in vitro, and in vivo models, complement computational methods, facilitating the validation of repurposed drugs. This review highlights various target mining strategies based on analysis of differential gene expression, weighted gene co-expression, protein-protein interaction network, and host-pathogen interaction, among others. To unearth drug candidates, the technicalities of leveraging information from databases such as DrugBank, STITCH, LINCS, and ChEMBL, among others are discussed. Further in silico validation techniques encompassing molecular docking, pharmacophore modelling, molecular dynamic simulations, and ADMET analysis are elaborated. Overall, this review delves into the exploration of individual case studies to offer a wide perspective of the ever-evolving field of drug repurposing, emphasizing the multifaceted approaches and methodologies employed for the same to confront female cancers.
Topics: Drug Repositioning; Humans; Female; Antineoplastic Agents; Neoplasms
PubMed: 38942544
DOI: 10.1016/bs.pmbts.2024.05.002 -
Progress in Molecular Biology and... 2024In the dynamic landscape of cancer therapeutics, the innovative strategy of drug repurposing emerges as a transformative paradigm, heralding a new era in the fight... (Review)
Review
In the dynamic landscape of cancer therapeutics, the innovative strategy of drug repurposing emerges as a transformative paradigm, heralding a new era in the fight against malignancies. This book chapter aims to embark on the comprehension of the strategic deployment of approved drugs for repurposing and the meticulous journey of drug repurposing from earlier times to the current era. Moreover, the chapter underscores the multifaceted and complex nature of cancer biology, and the evolving field of cancer drug therapeutics while emphasizing the mandate of drug repurposing to advance cancer therapeutics. Importantly, the narrative explores the latest tools, technologies, and cutting-edge methodologies including high-throughput screening, omics technologies, and artificial intelligence-driven approaches, for shaping and accelerating the pace of drug repurposing to uncover novel cancer therapeutic avenues. The chapter critically assesses the breakthroughs, expanding the repertoire of repurposing drug candidates in cancer, and their major categories. Another focal point of this book chapter is that it addresses the emergence of combination therapies involving repurposed drugs, reflecting a shift towards personalized and synergistic treatment approaches. The expert analysis delves into the intricacies of combinatorial regimens, elucidating their potential to target heterogeneous cancer populations and overcome resistance mechanisms, thereby enhancing treatment efficacy. Therefore, this chapter provides in-depth insights into the potential of repurposing towards bringing the much-needed big leap in the field of cancer therapeutics.
Topics: Drug Repositioning; Humans; Neoplasms; Antineoplastic Agents; Animals
PubMed: 38942535
DOI: 10.1016/bs.pmbts.2024.03.032 -
Progress in Molecular Biology and... 2024Personalized medicine has emerged as a revolutionary approach to healthcare in the 21st century. By understanding a patient's unique genetic and biological... (Review)
Review
Personalized medicine has emerged as a revolutionary approach to healthcare in the 21st century. By understanding a patient's unique genetic and biological characteristics, it aims to tailor treatments specifically to the individual. This approach takes into account factors such as an individual's lifestyle, genetic makeup, and environmental factors to provide targeted therapies that have the potential to be more effective and lower the risk of side reactions or ineffective treatments. It is a paradigm shift from the traditional "one size fits all" approach in medicine, where patients with similar symptoms or diagnoses receive the same standard treatments regardless of their differences. It leads to improved clinical outcomes and more efficient use of healthcare resources. Drug repurposing is a strategy that uses existing drugs for new indications and aims to take advantage of the known safety profiles, pharmacokinetics, and mechanisms of action of these drugs to accelerate the development process. Precision medicine may undergo a revolutionary change as a result, enabling the rapid development of novel treatment plans utilizing drugs that traditional methods would not otherwise link to. In this chapter, we have focused on a few strategies wherein drug repurposing has shown great success for precision medicine. The approach is particularly useful in oncology as there are many variations induced in the genetic material of cancer patients, so tailored treatment approaches go a long way. We have discussed the cases of breast cancer, glioblastoma and hepatocellular carcinoma. Other than that, we have also looked at drug repurposing approaches in anxiety disorders and COVID-19.
Topics: Drug Repositioning; Humans; Precision Medicine; COVID-19; Neoplasms
PubMed: 38942534
DOI: 10.1016/bs.pmbts.2024.02.007 -
Neuroimaging Clinics of North America Aug 2024Atypical demyelinating lesions (ADLs) can be idiopathic, occurring as isolated and self-limited events, or can appear in different stages of relapsing demyelinating... (Review)
Review
Atypical demyelinating lesions (ADLs) can be idiopathic, occurring as isolated and self-limited events, or can appear in different stages of relapsing demyelinating diseases. Not infrequently, ADLs occur in inflammatory syndromes associated with exogenous or endogenous toxic factors, metabolic imbalance, or infectious agents. It is important to recognize imaging patterns that indicate an inflammatory/demyelinating substrate in central nervous system lesions and to investigate potential triggers or complicating factors that might be associated. The prognostic and treatment strategies of ADLs are influenced by the underlying etiopathogenesis.
Topics: Humans; Demyelinating Diseases; Magnetic Resonance Imaging; Brain
PubMed: 38942525
DOI: 10.1016/j.nic.2024.03.006 -
Korean Journal of Radiology Jul 2024Evaluating the performance of a binary diagnostic test, including artificial intelligence classification algorithms, involves measuring sensitivity, specificity,... (Review)
Review
Evaluating the performance of a binary diagnostic test, including artificial intelligence classification algorithms, involves measuring sensitivity, specificity, positive predictive value, and negative predictive value. Particularly when comparing the performance of two diagnostic tests applied on the same set of patients, these metrics are crucial for identifying the more accurate test. However, comparing predictive values presents statistical challenges because their denominators depend on the test outcomes, unlike the comparison of sensitivities and specificities. This paper reviews existing methods for comparing predictive values and proposes using the permutation test. The permutation test is an intuitive, non-parametric method suitable for datasets with small sample sizes. We demonstrate each method using a dataset from MRI and combined modality of mammography and ultrasound in diagnosing breast cancer.
Topics: Humans; Breast Neoplasms; Female; Predictive Value of Tests; Magnetic Resonance Imaging; Mammography; Sensitivity and Specificity; Algorithms; Ultrasonography, Mammary
PubMed: 38942459
DOI: 10.3348/kjr.2024.0049 -
Korean Journal of Radiology Jul 2024To develop and validate a preoperative risk score incorporating carbohydrate antigen (CA) 19-9, CT, and fluorine-18-fluorodeoxyglucose (F-FDG) PET/CT variables to...
Predicting Recurrence-Free Survival After Upfront Surgery in Resectable Pancreatic Ductal Adenocarcinoma: A Preoperative Risk Score Based on CA 19-9, CT, and F-FDG PET/CT.
OBJECTIVE
To develop and validate a preoperative risk score incorporating carbohydrate antigen (CA) 19-9, CT, and fluorine-18-fluorodeoxyglucose (F-FDG) PET/CT variables to predict recurrence-free survival (RFS) after upfront surgery in patients with resectable pancreatic ductal adenocarcinoma (PDAC).
MATERIALS AND METHODS
Patients with resectable PDAC who underwent upfront surgery between 2014 and 2017 (development set) or between 2018 and 2019 (test set) were retrospectively evaluated. In the development set, a risk-scoring system was developed using the multivariable Cox proportional hazards model, including variables associated with RFS. In the test set, the performance of the risk score was evaluated using the Harrell C-index and compared with that of the postoperative pathological tumor stage.
RESULTS
A total of 529 patients, including 335 (198 male; mean age ± standard deviation, 64 ± 9 years) and 194 (103 male; mean age, 66 ± 9 years) patients in the development and test sets, respectively, were evaluated. The risk score included five variables predicting RFS: tumor size (hazard ratio [HR], 1.29 per 1 cm increment; < 0.001), maximal standardized uptake values of tumor ≥ 5.2 (HR, 1.29; = 0.06), suspicious regional lymph nodes (HR, 1.43; = 0.02), possible distant metastasis on F-FDG PET/CT (HR, 2.32; = 0.03), and CA 19-9 (HR, 1.02 per 100 U/mL increment; = 0.002). In the test set, the risk score showed good performance in predicting RFS (C-index, 0.61), similar to that of the pathologic tumor stage (C-index, 0.64; = 0.17).
CONCLUSION
The proposed risk score based on preoperative CA 19-9, CT, and F-FDG PET/CT variables may have clinical utility in selecting high-risk patients with resectable PDAC.
Topics: Humans; Male; Fluorodeoxyglucose F18; Female; Positron Emission Tomography Computed Tomography; Middle Aged; Carcinoma, Pancreatic Ductal; Aged; Pancreatic Neoplasms; Retrospective Studies; Radiopharmaceuticals; CA-19-9 Antigen; Tomography, X-Ray Computed; Neoplasm Recurrence, Local; Risk Assessment; Disease-Free Survival; Predictive Value of Tests
PubMed: 38942458
DOI: 10.3348/kjr.2023.1235 -
Korean Journal of Radiology Jul 2024This study systematically reviewed the role of diffusion-weighted imaging (DWI) in the assessment of molecular prognostic biomarkers in breast cancer, focusing on the... (Meta-Analysis)
Meta-Analysis Review
This study systematically reviewed the role of diffusion-weighted imaging (DWI) in the assessment of molecular prognostic biomarkers in breast cancer, focusing on the correlation of apparent diffusion coefficient (ADC) with hormone receptor status and prognostic biomarkers. Our meta-analysis includes data from 52 studies examining ADC values in relation to estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), and Ki-67 status. The results indicated significant differences in ADC values among different receptor statuses, with ER-positive, PgR-positive, HER2-negative, and Ki-67-positive tumors having lower ADC values compared to their negative counterparts. This study also highlights the potential of advanced DWI techniques such as intravoxel incoherent motion and non-Gaussian DWI to provide additional insights beyond ADC. Despite these promising findings, the high heterogeneity among the studies underscores the need for standardized DWI protocols to improve their clinical utility in breast cancer management.
Topics: Humans; Breast Neoplasms; Diffusion Magnetic Resonance Imaging; Female; Biomarkers, Tumor; Prognosis; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Ki-67 Antigen
PubMed: 38942456
DOI: 10.3348/kjr.2023.1188 -
The European Respiratory Journal Jun 2024
Topics: Humans; Pleural Neoplasms; Mesothelioma; Treatment Outcome; Mesothelioma, Malignant
PubMed: 38942440
DOI: 10.1183/13993003.00896-2024 -
The Journal of Pain Jun 2024Chronic pain (CP) significantly impacts quality of life and increases non-communicable disease risk, with recent U.S. data showing a 6.3% incidence rate, surpassing...
Chronic pain (CP) significantly impacts quality of life and increases non-communicable disease risk, with recent U.S. data showing a 6.3% incidence rate, surpassing diabetes, depression, and hypertension. International studies suggest higher mortality in CP populations, yet prior U.S. data is inconclusive. To investigate CP's mortality risk, we analyzed National Health Interview Survey (NHIS) and National Death Index (NDI) data. We hypothesized individuals with CP and high-impact CP (HICP, (≥1 activity limitation) would exhibit higher mortality rates. NHIS provided demographics, pain reporting, lifestyle, and psychosocial data, matched with NDI mortality records. Chi-Square analyses explored relationships between CP/HICP and demographics, lifestyle factors, psychosocial variables, and mortality. Cox proportional hazards models assessed mortality risk between groups. The weighted sample was 245,899,776; 20% reported CP and 8% HICP, both groups exhibiting higher mortality rates than pain-free individuals (CP: 5.55%, HICP: 8.79%, total: 2.82%). Hazard ratios indicated nearly double the mortality risk for CP and two-and-a-half times higher risk for HICP compared to those without these conditions. Adjusting for lifestyle and psychosocial factors reduced mortality risk but remained elevated compared to non-CP individuals. Heart disease, malignant neoplasms, and chronic lower respiratory diseases accounted for a higher percentage of deaths in CP cases. CP individuals showed higher rates of smoking, alcohol consumption, obesity, inactivity, depression, anxiety, emotional problems, and sleep disturbances. CP and HICP significantly influence mortality outcomes, leading to excess deaths compared to pain-free individuals. Given the relationship between pain, lifestyle, psychosocial variables, and mortality, further investigations are needed into CP causation and prevention strategies. PERSPECTIVE: This article presents evidence regarding the relationship between chronic pain, high impact chronic pain, and mortality. Additional findings are discussed regarding the impact of demographics, lifestyle, and psychosocial variables on mortality in those with versus without chronic pain and high impact chronic pain. These findings are crucial for informing future research, prevention, and healthcare management strategies.
PubMed: 38942415
DOI: 10.1016/j.jpain.2024.104620