Cause-Specific Excess Mortality During the COVID-19 Pandemic (2020-2021) in 12 Countries of the C-MOR Consortium.

BACKGROUND: This study investigated cause-specific mortality rates in 12 countries during the COVID-19 pandemic in 2020 and 2021. METHODS: We collected weekly cause-specific mortality data from respiratory disease, pneumonia, cardiovascular disease (CVD) and cancer from national vital statistic databases. We calculated excess mortality for respiratory disease (excluding COVID-19 codes), pneumonia, and CVD in 2020 and 2021 by comparing observed weekly against expected mortality based on historical data (2015-2019), accounting for seasonal trends. We used multilevel regression models to investigate the association between country-level pandemic-related variables and cause-specific mortality. RESULTS: Significant reductions in cumulative mortality from respiratory disease and pneumonia were observed in 2020 and/or 2021, except for Georgia, Northern Ireland, Kazakhstan, and Ukraine, which exhibited excess mortality for one or both causes. Australia, Austria, Cyprus, Georgia, and Northern Ireland experienced excess cumulative CVD mortality in 2020 and/or 2021. Australia, Austria, Brazil, Cyprus, Georgia, Northern Ireland, Scotland and Slovenia, experienced increased crude cumulative cancer mortality during 2020 and/or 2021 compared to previous years. Among pandemic-related variables, reported COVID-19 incidence was negatively associated with increased cancer mortality, excess respiratory, (2020) and pneumonia (2021) mortality, and positively associated with respiratory and CVD mortality (2021). Stringency of control measures were negatively associated with excess respiratory disease, CVD, and increased cancer mortality (2021). CONCLUSIONS: This study provides evidence of substantial excess mortality from CVD, and notable reductions in respiratory disease and pneumonia in both years across most countries investigated. Our study also highlights the beneficial impact of stringent control measures in mitigating excess mortality from most causes in 2021.

Impact of Electronic Cigarette use on Cardiovascular Health: Current Evidence, Causal Pathways, and Public Health Implications.

Electronic cigarette (e-cigarette) use is increasing in Europe and the USA. While mounting evidence exists regarding an array of associated adverse health effects, to date limited evidence exists regarding the health effects of e-cigarette use on cardiovascular (CV) disease (CVD). The present review summarizes the effects of e-cigarette use on CV health. A search strategy of in vivo experimental, observational studies (including population-based cohort studies), and interventional studies was conducted in PubMed, MEDLINE, and Web of Science (April 1, 2009-April 1, 2022). The main findings revealed that the influence of e-cigarette on health are attributed mainly to the individual and interactive effects of flavors and additives used in e-cigarette fluids, along with the extended heating. The above collectively stimulate prolonged sympathoexcitatory CV autonomic effects, such as increased heart rate and diastolic blood pressure (BP), as well as decreased oxygen saturation. Hence, e-cigarette users are at increased risk of developing atherosclerosis, hypertension, arrhythmia, myocardial infarction, and heart failure. Such risks are anticipated to increase, especially among the young who are increasingly adopting e-cigarette use particularly with flavored additives. Further investigations are urgently needed to evaluate the long-term effects of e-cigarette use, particularly among susceptible population groups such as youth.

Barriers and facilitators for adopting healthy lifestyles in breast cancer survivors: a scoping review protocol.

OBJECTIVE: This scoping review will identify barriers and facilitators for the adoption of 7 healthy lifestyle components by female breast cancer survivors. This will be achieved by mapping the World Cancer Research Fund/American Institute for Cancer Research recommendations and the Lifestyle Medicine pillars. INTRODUCTION: Adherence to healthy lifestyle components (including weight management, physical activity, healthy diet, restorative sleep, avoidance of risky substances, forming and maintaining healthy relationships, and stress management) may improve the quality of life of breast cancer survivors and reduce the risk of adverse patient outcomes. However, cancer survivors' adherence to recommendations of multiple healthy lifestyle components is low, and decreases over time. INCLUSION CRITERIA: The review will consider peer-reviewed studies investigating barriers and facilitators for adopting any of the 7 healthy lifestyle components by female adult (18+ years old) breast cancer survivors (ie, from the time of diagnosis) in community, hospital, and/or cancer care settings, without any geographical restrictions. All study designs and articles published in English will be included. METHODS: The review will follow the JBI methodology for scoping reviews. Databases to be searched will include MEDLINE (PubMed), Embase, CINAHL (EBSCOhost), PsycINFO (Ovid), and the Cochrane Library databases. Articles published from 2007 to the present will be considered since this was the year in which the World Cancer Research Fund/American Institute for Cancer Research recommendations were published. Two independent reviewers will screen the retrieved articles and extract the data. Barriers and facilitators for each lifestyle component will be grouped according to the Theoretical Domain Framework. A narrative summary will explicate the charted data. REVIEW REGISTRATION: Open Science Framework https://osf.io/cn3va.

Diet-wide association study of 92 foods and nutrients and lung cancer risk in the European Prospective Investigation into Cancer and Nutrition study and the Netherlands Cohort Study.

It is unclear whether diet, and in particular certain foods or nutrients, are associated with lung cancer risk. We assessed associations of 92 dietary factors with lung cancer risk in 327 790 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC). Cox regression yielded adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) per SD higher intake/day of each food/nutrient. Correction for multiple comparisons was performed using the false discovery rate and identified associations were evaluated in the Netherlands Cohort Study (NLCS). In EPIC, 2420 incident lung cancer cases were identified during a median of 15 years of follow-up. Higher intakes of fibre (HR per 1 SD higher intake/day = 0.91, 95% CI 0.87-0.96), fruit (HR = 0.91, 95% CI 0.86-0.96) and vitamin C (HR = 0.91, 95% CI 0.86-0.96) were associated with a lower risk of lung cancer, whereas offal (HR = 1.08, 95% CI 1.03-1.14), retinol (HR = 1.06, 95% CI 1.03-1.10) and beer/cider (HR = 1.04, 95% CI 1.02-1.07) intakes were positively associated with lung cancer risk. Associations did not differ by sex and there was less evidence for associations among never smokers. None of the six associations with overall lung cancer risk identified in EPIC were replicated in the NLCS (2861 cases), however in analyses of histological subtypes, inverse associations of fruit and vitamin C with squamous cell carcinoma were replicated in the NLCS. Overall, there is little evidence that intakes of specific foods and nutrients play a major role in primary lung cancer risk, but fruit and vitamin C intakes seem to be inversely associated with squamous cell lung cancer.

A Prospective Diet-Wide Association Study for Risk of Colorectal Cancer in EPIC.

BACKGROUND & AIMS: Evidence regarding the association of dietary exposures with colorectal cancer (CRC) risk is not consistent with a few exceptions. Therefore, we conducted a diet-wide association study (DWAS) in the European Prospective Investigation into Cancer and Nutrition (EPIC) to evaluate the associations between several dietary exposures with CRC risk. METHODS: The association of 92 food and nutrient intakes with CRC risk was assessed in 386,792 participants, 5069 of whom developed incident CRC. Correction for multiple comparisons was performed using the false discovery rate, and emerging associations were examined in the Netherlands Cohort Study (NLCS). Multiplicative gene-nutrient interactions were also tested in EPIC based on known CRC-associated loci. RESULTS: In EPIC, alcohol, liquor/spirits, wine, beer/cider, soft drinks, and pork were positively associated with CRC, whereas milk, cheese, calcium, phosphorus, magnesium, potassium, riboflavin, vitamin B6, beta carotene, fruit, fiber, nonwhite bread, banana, and total protein intakes were inversely associated. Of these 20 associations, 13 were replicated in the NLCS, for which a meta-analysis was performed, namely alcohol (summary hazard ratio [HR] per 1-SD increment in intake: 1.07; 95% confidence interval [CI], 1.04-1.09), liquor/spirits (HR per 1-SD increment in intake, 1.04; 95% CI, 1.02-1.06), wine (HR per 1-SD increment in intake, 1.04; 95% CI, 1.02-1.07), beer/cider (HR per 1-SD increment in intake, 1.06; 95% CI, 1.04-1.08), milk (HR per 1-SD increment in intake, 0.95; 95% CI, 0.93-0.98), cheese (HR per 1-SD increment in intake, 0.96; 95% CI, 0.94-0.99), calcium (HR per 1-SD increment in intake, 0.93; 95% CI, 0.90-0.95), phosphorus (HR per 1-SD increment in intake, 0.92; 95% CI, 0.90-0.95), magnesium (HR per 1-SD increment in intake, 0.95; 95% CI, 0.92-0.98), potassium (HR per 1-SD increment in intake, 0.96; 95% CI, 0.94-0.99), riboflavin (HR per 1-SD increment in intake, 0.94; 95% CI, 0.92-0.97), beta carotene (HR per 1-SD increment in intake, 0.96; 95% CI, 0.93-0.98), and total protein (HR per 1-SD increment in intake, 0.94; 95% CI, 0.92-0.97). None of the gene-nutrient interactions were significant after adjustment for multiple comparisons. CONCLUSIONS: Our findings confirm a positive association for alcohol and an inverse association for dairy products and calcium with CRC risk, and also suggest a lower risk at higher dietary intakes of phosphorus, magnesium, potassium, riboflavin, beta carotene, and total protein.

Association of adherence to the Mediterranean diet and physical activity habits with the presence of insomnia in patients with obstructive sleep apnea.

PURPOSE: Insomnia and obstructive sleep apnea (OSA) are among the most prevalent sleep disorders and frequently co-occur, defining the sleep apnea-insomnia syndrome. However, data exploring associations between insomnia and lifestyle habits in patients with OSA are lacking. Therefore, the aim of the present study was to investigate potential associations between insomnia presence and individual lifestyle parameters in patients with mild/moderate-to-severe OSA evaluated by attended polysomnography. METHODS: These are secondary analyses, using data from a cross-sectional study among 269 Greek patients with OSA. Clinical, anthropometric, socioeconomic, and lifestyle data were collected for all participants. Insomnia presence was evaluated through the validated psychometric instrument "Athens Insomnia Scale" (AIS). Adherence to the Mediterranean diet was estimated with the MedDietScale index and physical activity habits were assessed through a validated questionnaire. Backward stepwise multiple logistic regression analysis was used to estimate the association between lifestyle habits (i.e., adherence to the Mediterranean diet and physical activity) and the likelihood of having insomnia, while adjusting for potential confounders. RESULTS: Of 269 patients newly diagnosed with OSA (aged 21-70 years; 73% men), 146 (54%) were categorized as having insomnia. In multivariable models, higher adherence to the Mediterranean diet and engagement in physical activity for ≥ 30 min/day were both associated with a lower likelihood of having insomnia (odds ratio (95% confidence intervals): 0.40 (0.18-0.91) and 0.49 (0.28-0.86), respectively). CONCLUSIONS: Results add to the limited data on the role of lifestyle in insomnia and should be further explored both in epidemiological and clinical studies.

An umbrella review of the evidence associating diet and cancer risk at 11 anatomical sites.

There is evidence that diet and nutrition are modifiable risk factors for several cancers, but associations may be flawed due to inherent biases. Nutritional epidemiology studies have largely relied on a single assessment of diet using food frequency questionnaires. We conduct an umbrella review of meta-analyses of observational studies to evaluate the strength and validity of the evidence for the association between food/nutrient intake and risk of developing or dying from 11 primary cancers. It is estimated that only few single food/nutrient and cancer associations are supported by strong or highly suggestive meta-analytic evidence, and future similar research is unlikely to change this evidence. Alcohol consumption is positively associated with risk of postmenopausal breast, colorectal, esophageal, head & neck and liver cancer. Consumption of dairy products, milk, calcium and wholegrains are inversely associated with colorectal cancer risk. Coffee consumption is inversely associated with risk of liver cancer and skin basal cell carcinoma.

Primary Sjögren's Syndrome of Early and Late Onset: Distinct Clinical Phenotypes and Lymphoma Development.

Objectives: To study the clinical, serological and histologic features of primary Sjögren's syndrome (pSS) patients with early (young ≤35 years) or late (old ≥65 years) onset and to explore the differential effect on lymphoma development. Methods: From a multicentre study population of 1997 consecutive pSS patients, those with early or late disease onset, were matched and compared with pSS control patients of middle age onset. Data driven analysis was applied to identify the independent variables associated with lymphoma in both age groups. Results: Young pSS patients (19%, n = 379) had higher frequency of salivary gland enlargement (SGE, lymphadenopathy, Raynaud's phenomenon, autoantibodies, C4 hypocomplementemia, hypergammaglobulinemia, leukopenia, and lymphoma (10.3% vs. 5.7%, p = 0.030, OR = 1.91, 95% CI: 1.11-3.27), while old pSS patients (15%, n = 293) had more frequently dry mouth, interstitial lung disease, and lymphoma (6.8% vs. 2.1%, p = 0.011, OR = 3.40, 95% CI: 1.34-8.17) compared to their middle-aged pSS controls, respectively. In young pSS patients, cryoglobulinemia, C4 hypocomplementemia, lymphadenopathy, and SGE were identified as independent lymphoma associated factors, as opposed to old pSS patients in whom SGE, C4 hypocomplementemia and male gender were the independent lymphoma associated factors. Early onset pSS patients displayed two incidence peaks of lymphoma within 3 years of onset and after 10 years, while in late onset pSS patients, lymphoma occurred within the first 6 years. Conclusion: Patients with early and late disease onset constitute a significant proportion of pSS population with distinct clinical phenotypes. They possess a higher prevalence of lymphoma, with different predisposing factors and lymphoma distribution across time.

Nutrient-wide association study of 92 foods and nutrients and breast cancer risk.

BACKGROUND: Several dietary factors have been reported to be associated with risk of breast cancer, but to date, unequivocal evidence only exists for alcohol consumption. We sought to systematically assess the association between intake of 92 foods and nutrients and breast cancer risk using a nutrient-wide association study. METHODS: Using data from 272,098 women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we assessed dietary intake of 92 foods and nutrients estimated by dietary questionnaires. Cox regression was used to quantify the association between each food/nutrient and risk of breast cancer. A false discovery rate (FDR) of 0.05 was used to select the set of foods and nutrients to be replicated in the independent Netherlands Cohort Study (NLCS). RESULTS: Six foods and nutrients were identified as associated with risk of breast cancer in the EPIC study (10,979 cases). Higher intake of alcohol overall was associated with a higher risk of breast cancer (hazard ratio (HR) for a 1 SD increment in intake = 1.05, 95% CI 1.03-1.07), as was beer/cider intake and wine intake (HRs per 1 SD increment = 1.05, 95% CI 1.03-1.06 and 1.04, 95% CI 1.02-1.06, respectively), whereas higher intakes of fibre, apple/pear, and carbohydrates were associated with a lower risk of breast cancer (HRs per 1 SD increment = 0.96, 95% CI 0.94-0.98; 0.96, 95% CI 0.94-0.99; and 0.96, 95% CI 0.95-0.98, respectively). When evaluated in the NLCS (2368 cases), estimates for each of these foods and nutrients were similar in magnitude and direction, with the exception of beer/cider intake, which was not associated with risk in the NLCS. CONCLUSIONS: Our findings confirm a positive association of alcohol consumption and suggest an inverse association of dietary fibre and possibly fruit intake with breast cancer risk.

Exposure to second hand smoke and 10-year (2002-2012) incidence of cardiovascular disease in never smokers: The ATTICA cohort study.

BACKGROUND: Despite WHO Framework Convention of Tobacco Control (FCTC) adoption, effective implementation of national smoking bans remains pending in several countries. This study quantified the association of second hand smoke (SHS) exposure and 10-year cardiovascular disease (CVD) among never smokers in such settings. METHODS: In 2001-2002, a sample of 1514 males and 1528 females (range: 18-89 years old) were randomly selected in Greece. Frequency and duration of SHS exposure (i.e. exposure extending >30 min/day) within the home and/or workplace were assessed by interview. Following a 10-year follow-up period (2002-2012), incidence of non-fatal and fatal CVD (ICD-10) was evaluated among n = 2020 participants. The analytic study sample consisted of all never smokers (n = 910). RESULTS: Despite national smoking ban implementation (2009), 44.6% (n = 406) of never smokers reported SHS exposure. While SHS exposed never smokers exhibited a more favorable profile of CVD-related risk factors at baseline, they subsequently developed similar 10-year CVD incidence rates, at a younger mean age (p = 0.001), than their non-exposed counterparts. Following adjustment for several lifestyle and clinical factors, SHS exposed never smokers exhibited a two-fold elevated 10-year CVD risk (adj. HR: 2.04, 95% CI: 1.43-2.92), particularly among women (adj. HR: 2.45, 95% CI: 1.45-4.06). SHS exposure accounted for 32% excess Population Attributable Risk (PAR) for 10-year CVD events in never smokers, with highest rates (PAR: 52%) being among those exposed in the workplace. CONCLUSION: The prevention of SHS associated CVD and related healthcare costs mandates additional strategies for securing the effective implementation of comprehensive WHO FCTC based national smoking bans.

The Effect of Exclusive Olive Oil Consumption on Successful Aging: A Combined Analysis of the ATTICA and MEDIS Epidemiological Studies.

The consumption of dietary fats, which occur naturally in various foods, poses important impacts on health. The aim of this study was to elucidate the association of exclusive use of olive oil for culinary purposes with successful aging in adults aged >50 years old and residing in Greece. Use of olive oil in food preparation and bio-clinical characteristics of the Greek participants enrolled in the ATTICA (n = 1128 adults from Athens metropolitan area) and the MEDiterranean Islands Study (MEDIS) (n = 2221 adults from various Greek islands and Mani) studies, were investigated in relation to successful aging (SA). Participants were divided into the following three categories: (a) no olive oil consumption; (b) combined consumption of olive oil and other dietary fats; and (c) exclusive olive oil consumption. The SA was measured using the previously validated successful aging index (SAI). After adjusting for age, sex, and smoking habits, combined consumption of olive oil and other fats (vs. no olive oil use) was not significantly associated with SAI levels (p = 0.114). However, exclusive olive oil intake (vs. no use of olive oil) was significantly associated with SAI (p = 0.001), particularly among those aged older than 70 years. Therefore, the exclusive consumption of olive oil, as opposed to either combined or no olive oil consumption, beneficially impacts successful aging, particularly among individuals over 70 years of age. Primary public health prevention strategies should seek to encourage the enhanced adoption of such dietary practices in order to promote healthy aging and longevity.

Diagnostic and Prognostic Performance of Secreted Protein Acidic and Rich in Cysteine (SPARC) Assay for Detecting Primary and Recurrent Urinary Bladder Cancer.

PURPOSE: To evaluate the diagnostic and prognostic performance of Secreted Protein Acidic and Rich in Cysteine (SPARC) in detecting urinary bladder cancer (UBC). METHODS: The Integrated Study on Bladder Cancer (n = 571; mean age:69.4 ± 12.2 years) evaluates cross-sectionally SPARC diagnostic performance in primary (n = 264) and recurrent (n = 307) UBC. SPARC prognostic performance is evaluated in a nested cohort (n = 250) prospectively followed for 80 months to detect tumor relapse, recurrence and/or progression. Baseline urine samples are analyzed blindly using a commercially available SPARC ELISA assay, characterized for its analytical performance according to clinical test regulatory requirements (R&D Manufactures Inc.). RESULTS: While higher mean SPARC levels are detected in primary (p = 0.008) and recurrent (p < 0.0001) UBC, the assay has limited diagnostic performance (AUC:0.593; 95% CI:0.524-0.663). SPARC positive patients undergoing disease monitoring are more likely to develop tumor relapse (age and gender Adj. HR:1.52; 95% CI:1.04-2.22) and progression (Adj. HR:1.83; 95% CI:1.02-3.27). However, prognostic performance is affected by hematuria. CONCLUSIONS: SPARC diagnostic performance for detecting UBC appears insufficient for clinical implementation. In patients undergoing disease monitoring, SPARC is a promising prognostic marker for tumor relapse and/or progression, but is affected by hematuria.

Olive oil consumption and human health: A narrative review.

The potential health benefits of olive oil consumption, particularly within the context of the Mediterranean diet, have been extensively investigated. However, its specific health benefits remain to be confirmed. The aim of the present work is to review the scientific evidence regarding the specific impact of olive oil consumption on human health, including the prevention of cardiovascular disease, cancers, and diabetes mellitus. Ten related meta-analyses were reviewed to this effect. Olive oil consumption was found to be beneficial for several chronic non-communicable diseases (e.g. including cardiovascular disease, breast cancer and type 2 diabetes), whereas there were contradictory findings regarding its impact on several biomarkers. In conclusion, the aggregated evidence supports the assertion that olive oil consumption is beneficial for human health, and particularly for the prevention of cardiovascular diseases, breast cancer, and type 2 diabetes mellitus.

Cost-effectiveness of screening type 2 diabetes patients for chronic kidney disease progression with the CKD273 urinary peptide classifier as compared to urinary albumin excretion.

Background: In type 2 diabetes mellitus (T2DM) patients, chronic kidney disease (CKD) progression may occur without detectable changes in urinary albumin excretion (UAE) rate. A new urinary peptide classifier (CKD273) has exhibited greater ability to detect CKD progression, however, its cost-effectiveness remains unknown. This study evaluated the cost-effectiveness of screening for CKD progression with the CKD273 classifier, as compared to UAE, in diabetic patients. Methods: A decision-analytic Markov model was developed to estimate costs and health outcomes [including overall survival and quality-adjusted life years (QALYs)] from a health system perspective for adopting a new annual screening strategy based on the CKD273 classifier as compared to annual UAE-based screening in a hypothetical cohort of T2DM patients. High-risk patients were defined as T2DM patients with at least one concomitant risk factor (i.e. patients with background genetic risk for developing the disease, obesity, hypertension and/or smoking history) for developing diabetic nephropathy secondary to cardiovascular disease (CVD)-related complications. Low-risk T2DM patients, were defined as those not having any of the aforementioned concomitant risk factors. Results: Over the projected course of a patient's lifetime, in all T2DM patients annual screening with the CKD273 classifier was more costly, but also more effective, than annual screening with UAE. The incremental costs incurred with screening based on the CKD273 classifier were €3,053 per patient, while patients gained 0.13 QALYs. Hence, in all patients, annual screening with the CKD273 classifier was cost effective [incremental cost-effectiveness ratio (ICER) €23,903/QALY gained], notably below current government thresholds for funding such health care interventions. For patients at high risk of developing diabetic nephropathy secondary to CVD-related complications, screening based on the CKD273 classifier was cost-saving (i.e. dominant, being both more effective and less expensive than UAE-based screening). Finally, in low-risk patients, CKD273 classifier-based screening was not cost effective (ICER €73,140/QALY) given current government willingness-to-pay thresholds. Conclusions: In diabetic patients, annual CKD273 classifier-based screening is more costly but also more effective in QALYs gained as compared to UAE. From a health provider perspective, the observed benefits are greatest when such screening is implemented in patients at high risk for diabetes-associated renal or cardiovascular diseases (CVDs).

Development and Validation of Urine-based Peptide Biomarker Panels for Detecting Bladder Cancer in a Multi-center Study.

PURPOSE: Urothelial bladder cancer presents high recurrence rates, mandating continuous monitoring via invasive cystoscopy. The development of noninvasive tests for disease diagnosis and surveillance remains an unmet clinical need. In this study, validation of two urine-based biomarker panels for detecting primary and recurrent urothelial bladder cancer was conducted. EXPERIMENTAL DESIGN: Two studies (total n = 1,357) were performed for detecting primary (n = 721) and relapsed urothelial bladder cancer (n = 636). Cystoscopy was applied for detecting urothelial bladder cancer, while patients negative for recurrence had follow-up for at least one year to exclude presence of an undetected tumor at the time of sampling. Capillary electrophoresis coupled to mass spectrometry (CE-MS) was employed for the identification of urinary peptide biomarkers. The candidate urine-based peptide biomarker panels were derived from nested cross-sectional studies in primary (n = 451) and recurrent (n = 425) urothelial bladder cancer. RESULTS: Two biomarker panels were developed on the basis of 116 and 106 peptide biomarkers using support vector machine algorithms. Validation of the urine-based biomarker panels in independent validation sets, resulted in AUC values of 0.87 and 0.75 for detecting primary (n = 270) and recurrent urothelial bladder cancer (n = 211), respectively. At the optimal threshold, the classifier for detecting primary urothelial bladder cancer exhibited 91% sensitivity and 68% specificity, while the classifier for recurrence demonstrated 87% sensitivity and 51% specificity. Particularly for patients undergoing surveillance, improved performance was achieved when combining the urine-based panel with cytology (AUC = 0.87). CONCLUSIONS: The developed urine-based peptide biomarker panel for detecting primary urothelial bladder cancer exhibits good performance. Combination of the urine-based panel and cytology resulted in improved performance for detecting disease recurrence. Clin Cancer Res; 22(16); 4077-86. ©2016 AACR.

Utility of the CKD273 peptide classifier in predicting chronic kidney disease progression.

BACKGROUND: Chronic kidney disease (CKD) is a growing public health concern, afflicting approximately one-tenth of adults in developed countries. However, the clinical need for an accurate test, such as a biomarker and/or peptide classifier, for predicting CKD progression and related adverse outcomes remains unaddressed. Recently, a proteomics approach based on capillary electrophoresis-mass spectrometry was employed to develop a urinary peptide-based high-dimensional classifier, namely CKD273, for predicting CKD progression. OBJECTIVES: The study aims to critically appraise the evidence level of the CKD273 classifier's utility in predicting CKD progression, according to the Oxford Evidence-Based Medicine (EBM) and Strength of Recommendation Taxonomy (SORT) guidelines. METHODS: Eligible studies were identified by a literature search of MEDLINE and Web of Science Expanded Core Collection databases. Limitations were set to prospective cohort studies evaluating the classifier's accuracy in predicting CKD progression. Data extraction was undertaken according to a predefined protocol by two independent reviewers. The EBM and SORT guidelines were applied to appraise the CKD273 classifier's utility for predicting CKD progression. RESULTS: The query search results rendered four prospective cohort studies. The classifier performed independently of age, gender and the type of urine storage containers used. The classifier predicted the development of micro- or macroalbuminuria and rapid decline (i.e. >-5% annual decrease) in the estimated glomerular filtration rate. One study assessed the association of the classifier with end-stage renal disease and death but did not take confounding factors into account. The CKD273 classifier attained high evidence levels according to the EBM (score range 1b), supporting its utility for predicting CKD progression. However, lower scores were attained when the studies were scored according the SORT guidelines (score ranges 1-4). CONCLUSIONS: Initial promising evidence supports the CKD273 classifier's utility in predicting CKD progression. The classifier's applicability should be corroborated with additional evidence arising from inception cohort studies assessing patient-oriented outcomes, which demonstrate its added value beyond currently available clinical risk predictors, as well as its cost-effectiveness in clinical practice.

Drugs acting on homeostasis: challenging cancer cell adaptation.

Cancer treatment aims to exploit properties that define malignant cells. In recent years, it has become apparent that malignant cells often survive cancer treatment and ensuing cell stress by switching on auxiliary turnover pathways, changing cellular metabolism and, concomitantly, the gene expression profile. The changed profile impacts the material exchange of cancer cells with affected tissues. Herein, we show that pathways of proteostasis and energy generation regulate common transcription factors. Namely, when one pathway of intracellular turnover is blocked, it triggers alternative turnover mechanisms, which induce transcription factor proteins that control expression of cytokines and regulators of apoptosis, cell division, differentiation, metabolism, and response to hormones. We focus on several alternative turnover mechanisms that can be blocked by drugs already used in clinical practice for the treatment of other non-cancer related diseases. We also discuss paradigms on the challenges posed by cancer cell adaptation mechanisms.

Developing proteomic biomarkers for bladder cancer: towards clinical application.

Clinical use of proteomic biomarkers has the potential to substantially improve the outcomes of patients with bladder cancer. An unmet clinical need evidently exists for noninvasive biomarkers, which might enable improvements in both the diagnosis and prognosis of patients with bladder cancer, as well as improved monitoring of patients for the presence of recurrence. Urine is considered the optimal noninvasive source of proteomic biomarkers in patients with bladder cancer. Currently, a number of single-protein biomarkers have been detected in urine and tissue using a variety of proteomic techniques, each having specific conceptual considerations and technical implications. Promising preclinical data are available for several of these proteins; however, the combination of single urinary proteins into multimarker panels might better encompass the molecular heterogeneity of bladder cancer within this patient population, and prove more effective in clinical use.

Dynamic aberrant NF-κB spurs tumorigenesis: a new model encompassing the microenvironment.

Recently it was discovered that a transient activation of transcription factor NF-κB can give cells properties essential for invasiveness and cancer initiating potential. In contrast, most oncogenes to date were characterized on the basis of mutations or by their constitutive overexpression. Study of NF-κB actually leads to a far more dynamic perspective on cancer: tumors caused by diverse oncogenes apparently evolve into cancer after loss of feedback regulation for NF-κB. This event alters the cellular phenotype and the expression of hormonal mediators, modifying signals between diverse cell types in a tissue. The result is a disruption of stem cell hierarchy in the tissue, and pervasive changes in the microenvironment and immune response to the malignant cells.

New use for old drugs? Prospective targets of chloroquines in cancer therapy.

During the last decade research is gradually repositioning the antimalarial drug chloroquine, and certain related quinoline derivatives, as anticancer agents. Chloroquine and hydroxychloroquine, in particular, have relatively well-characterized toxicity profiles due to several decades of use for treatment of malaria. Previously published review articles provide an excellent overview of the diversity of chloroquine effects on cancer cells, both in the cell culture as well as on human tumors grafted into mice; and an account of the increasing pace of incorporation of hydroxychloroquine in combination treatment schemes for clinical studies. In this review we present some features that are common between cancers that are sensitive to quinoline derivatives, in particular features that are amenable to pharmaceutical intervention.