Duration of the patient interval in breast cancer and factors associated with longer delays in low-and middle-income countries: A systematic review with meta-analysis.

OBJECTIVE: Breast cancer survival is lower in low- and middle-income countries (LMICs) partially due to many women being diagnosed with late-stage disease. The patient interval refers to the time elapsed between the detection of symptoms and the first consultation with a healthcare provider and is considered one of the core indicators for early diagnosis and treatment. The goal of the current research was to conduct a meta-analysis of the duration of the patient interval in LMICs and investigate the socio-demographic and socio-cultural factors related to longer delays in presentation. METHODS: We conducted a systematic review with meta-analysis (pre-registered protocol CRD42020200752). We searched seven information sources (2009-2022) and included 50 articles reporting the duration of patient intervals for 18,014 breast cancer patients residing in LMICs. RESULTS: The longest patient intervals were reported in studies from the Middle East (3-4 months), followed by South-East Asia (2 months), Africa (1-2 months), Latin America (1 month), and Eastern Europe (1 month). Older age, not being married, lower socio-economic status, illiteracy, low knowledge about cancer, disregarding symptoms or not attributing them to cancer, fear, negative beliefs about cancer, and low social support were related to longer delays across most regions. Longer delays were also related to use of alternative medicine in the Middle East, South-East Asia, and Africa and distrust in the healthcare system in Eastern Europe. CONCLUSIONS: There is large variation in the duration of patient intervals across LMICs in different geographical regions. Patient intervals should be reduced and, for this purpose, it is important to explore their determinants taking into account the social, cultural, and economic context.

Associations of circulating levels of phthalate metabolites with cytokines and acute phase reactants in a Spanish human cohort.

The associations between human phthalate exposure and the onset of chronic diseases with an immunological component (e.g., metabolic syndrome, cancer) remain unclear, partly due to the uncertainties in the underlying mechanisms. This study investigates cross-sectional associations of the concentrations of 10 phthalate metabolites with 19 cytokines and acute phase proteins in 213 serum samples of Spanish adults. The associations were explored by Spearman's correlation, multivariable linear regression, and weighted quantile sum regression analyses. In the multivariable analyses, levels of plasminogen activator inhibitor (PAI)-1 were positively associated with mono-n-butyl phthalate (fold-change per one IQR increase in phthalate levels, 95% Confidence Interval: 1.65, 1.45-1.88) and mono-iso-butyl phthalate (3.07, 2.39-3.95), mono-ethyl phthalate (2.05, 1.62-2.61), as well as categorized mono-iso-decyl and mono-benzyl phthalates. The same phthalates also were significantly associated with leptin, interleukin (IL)-18 and monocyte chemoattractant protein-1. Moreover, the proinflammatory markers IL-1ß, IL-17, IL-8, IL-6, IL-12, tumor necrosis factor, and lipopolysaccharide-binding protein showed positive and negative associations with, respectively, mono-(2-ethyl-hexyl) and mono-methyl phthalates. Finally, phthalate mixtures were positively associated with PAI-1, leptin, IL-18, IL-12, IL-8 and IL-1ß. Despite the cross-sectional design limitation, these associations point to relevant subclinical immuno-inflammatory actions of these pollutants, warranting confirmation in future studies.

Health-related quality of life in patients newly diagnosed with prostate cancer: CAPLIFE study.

PURPOSE: To analyse the Health-Related Quality of Life (HRQoL) at diagnosis of patients with prostate cancer (PCa) according to tumour extension and urinary symptomatology and to explore factors associated with HRQoL. METHODS: 408 Controls and 463 PCa cases were included. Eligibility criteria were a new diagnosis of PCa (cases), 40-80 years of age, and residence in the participating hospitals' coverage area for ≥ 6 months before recruitment. HRQoL was evaluated using the 12-Item Short-Form Health Survey, Mental (MCS) and Physical Component Summaries (PCS), and urinary symptoms with the International Prostate Symptom Score. HRQoL scores for all PCa cases, according to tumour extension and urinary symptoms, were compared with controls. In addition, information about lifestyles and comorbidities was collected and its association with low HRQoL (lower scores) were explored using logistic regression models. RESULTS: Overall cases had similar PCS score, but lower MCS score than controls. The lowest standardised scores for both PCS and MCS were reached by cases with severe urinary symptoms and a metastatic tumour [mean (SD); PCS: 41.9 (11.5), MCS: 42.3 (10.3)]. Having "below" PCS and MCS scores was associated with the presence of three or more comorbidities in the cases [aOR = 2.86 (1.19-6.84) for PCS and aOR = 3.58 (1.37-9.31) for MCS] and with severe urinary symptomatology [aOR = 4.71 (1.84-12.08) for PCS and aOR = 7.63 (2.70-21.58) for MCS]. CONCLUSION: The mental dimension of HRQoL at diagnosis of patients with PCa was lower than in controls, especially for cases with severe urinary symptoms and a metastatic tumour. Comorbidities and urinary symptoms were variables associated with the HRQoL of PCa cases.

Prevalence of frailty and its association with oral hypofunction in older adults: a gender perspective.

BACKGROUND: Previous studies have indicated an association between oral hypofunction and frailty in community-dwelling older adults. However, this issue has not been evaluated in institutionalized older patients. We aimed to determine the prevalence of physical frailty in this particularly vulnerable group and evaluate its association with oral hypofunction, analyzing possible differences by gender. METHODS: This cross-sectional study was conducted in private and public care homes in Guayaquil (Ecuador) from January 2018 until December 2019. Participants were classified as robust, pre-frail, and frail according to the Fried's frailty phenotype. Oral hypofunction was defined as the presence of at least three positive items in the following list: poor oral hygiene, oral dryness, reduced occlusal force, decreased masticatory function, and deterioration of swallowing function. The relationships between frailty and oral hypofunction were analyzed using logistic regression models for the whole sample and stratified by gender. Statistical analyses were performed using STATA 15.0 software (Stata Corp. LP, College Station, TX, USA). RESULTS: Among the 589 participants analyzed (65% women), the median age was 72 years (interquartile range: 66-82). Pre-frailty and frailty were presented in 66.7% and 28.9% of them respectively. Weakness was the most frequent item (84.6%). There was a significant relationship between frailty and oral hypofunction in women. In the overall sample, the frequency of frailty was 2.06 times higher (95% CI 1.30-3.29) in patients with oral hypofunction, and this association was maintained in women (ORa: 2.18; 95% CI 1.21-3.94). Reduced occlusal force and decreased swallowing function were items significantly associated with the presence of frailty (ORa: 1.95; 95% CI 1.18-3.22 and ORa: 2.11; 95% CI 1.39-3.19, respectively). CONCLUSION: The prevalence of frailty and pre-frailty was high among institutionalized older people and was associated with the presence of hypofunction, especially in women. Decreased swallowing function was the most strongly item associated with frailty.

Identification of novel prostate cancer genes in patients stratified by Gleason classification: Role of antitumoral genes.

Prostate cancer (PCa) is a tumor with a great heterogeneity, both at a molecular and clinical level. Despite its global good prognosis, cases can vary from indolent to lethal metastatic and scientific efforts are aimed to discern those with worse outcomes. Current prognostic markers, as Gleason score, fall short when it comes to distinguishing these cases. Identification of new early biomarkers to enable a better PCa distinction and classification remains a challenge. In order to identify new genes implicated in PCa progression we conducted several differential gene expression analyses over paired samples comparing primary PCa tissue against healthy prostatic tissue of PCa patients. The results obtained show that this approach is a serious alternative to overcome patient heterogeneity. We were able to identify 250 genes whose expression varies along with tissue differentiation-healthy to tumor tissue, 161 of these genes are described here for the first time to be related to PCa. The further manual curation of these genes allowed to annotate 39 genes with antitumoral activity, 22 of them described for the first time to be related to PCa proliferation and metastasis. These findings could be replicated in different cohorts for most genes. Results obtained considering paired differential expression, functional annotation and replication results point to: CGREF1, UNC5A, C16orf74, LGR6, IGSF1, QPRT and CA14 as possible new early markers in PCa. These genes may prevent the progression of the disease and their expression should be studied in patients with different outcomes.

Public healthcare costs associated with long-term exposure to mixtures of persistent organic pollutants in two areas of Southern Spain: A longitudinal analysis.

BACKGROUND: Polychlorinated biphenyls and organochlorine pesticides are persistent organic pollutants (POPs) that had been banned or restricted in many countries, including Spain. However, their ubiquity still poses environmental and human health threats. OBJECTIVE: To longitudinally explore public healthcare costs associated with long-term exposure to a mixture of 8 POPs in a cohort of residents of two areas of Granada Province, Southern Spain. METHODS: Longitudinal study in a subsample (n = 385) of GraMo adult cohort. Exposure assessment was performed by analyzing adipose tissue POP concentrations at recruitment. Average primary care (APC) and average hospital care (AHC) expenditures of each participant over 14 years were estimated using the data from their medical records. Data analyses were performed by robust MM regression, weighted quantile sum regression (WQS) and G-computation analysis. RESULTS: In the adjusted robust MM models for APC, most POPs showed positive beta coefficients, being Hexachlorobenzene (HCB) significantly associated (ß: 1.87; 95% Confidence interval (95%CI): 0.17, 3.57). The magnitude of this association increased (ß: 3.72; 95%CI: 0.80, 6.64) when the analyses were restricted to semi-rural residents, where ß-HCH was also marginally-significantly associated to APC (ß: 3.40; 95%CI: -0.10, 6.90). WQS revealed a positive but non-significant mixture association with APC (ß: 0.14; 95%CI: -0.06, 0.34), mainly accounted for by ß-HCH (54%) and HCB (43%), that was borderline-significant in the semi-rural residents (ß: 0.23; 95%CI: -0.01, 0.48). No significant results were observed in G-Computation analyses. CONCLUSION: Long-term exposure to POP mixtures might represent a modifiable factor increasing healthcare costs, thus affecting the efficiency of the healthcare systems. However, and owing the complexity of the potential causal pathways and the limitations of the present study, further research is warranted to fully elucidate ascertain whether interventions to reduce human exposure should be considered in healthcare policies.

Factors associated with the development of second primary tumours in head and neck cancer patients.

INTRODUCTION: The development of second primary tumours (SPTs) is one of the main causes of low survival in patients with head and neck cancer (HNC). The aim of this study was to review the evidence about factors associated with developing SPTs in patients with HNC. METHODS: An updated systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, and the search was performed in Pubmed and Scopus. Only original articles with a cohort or case-control design were included. Article quality was assessed with the Newcastle-Ottawa scale. RESULTS: Thirty-six and two case-control studies were included, with quality medium (n = 5) to high (n = 33). Tobacco showed a significant association with SPT development, with risks ranging from 1.41 (95%CI: 1.04-1.91) to 5.52 (95%CI: 2.91-10.49). Regarding alcohol, risks ranged from 1.46 (95%CI: 1.12-1.91) to 21.3 (95%CI: 2.9-156). Location of the index tumour in the hypopharynx/oropharynx, absence of human papillomavirus and presence of a premalignant lesion also increased the risk of SPTs. More controversy was found for sex, age and other clinical factors of the tumour. CONCLUSION: Toxic lifestyle habits and clinical factors were associated with the risk of SPTs in HNC patients. These findings may improve individualised prevention strategies in its follow-up.

Determinants of masticatory performance assessed by mixing ability tests.

STATEMENT OF PROBLEM: Studies determining the main predictors of masticatory performance by using mixing ability tests are sparse. PURPOSE: The purpose of this clinical study was to identify potential determinants of masticatory performance assessed by analyzing a patient's masticatory ability using bicolored chewing gum and visual, quantitative, and interactive methods. MATERIAL AND METHODS: Nondental participants attending healthcare centers were consecutively recruited in Granada, Spain. The inclusion criteria were older than18 years and resident in the coverage area of the reference healthcare centers for at least the previous 6 months. The participants were excluded if they had received dental treatment in the previous 6 months or they were unable to communicate. The masticatory performance was determined by using 2-colored chewing gum (Kiss 3 white and blue; Smint) that was masticated for a total of 20 strokes. The masticated gum was crushed between 2 transparent glass slides, creating a 1-mm-thick specimen that was subsequently scanned. The mixed-color area was calculated as a percentage by using Photoshop as described by Schimmel et al and designated as the standard method. In addition, all images made were analyzed by using the Web application the Chewing Performance Calculator. In addition, the masticated bolus was inspected visually, and mastication performance was classified as being poor, moderate, or good. Sociodemographic data, as well as data on behaviors, medical and nutritional status, health-related quality of life, saliva, and general oral health, were collected for all participants to identify the main determinants of masticatory performance. RESULTS: One hundred thirty-seven participants were enrolled. The masticatory performance values obtained using both methods (standard method and Chewing Performance Calculator) were significantly greater for well masticated gum (P<.001), which had been visually classified as being poorly masticated (69.1% for standard method and 43.5% for Chewing Performance Calculator), moderately masticated (89.7% for standard method and 67.3% for Chewing Performance Calculator), and well masticated (97.3% for standard method and 80.3% for Chewing Performance Calculator). The bivariate analyses revealed that masticatory performance was significantly higher in younger people (<65 years) (P=.008), who also had a higher basal salivary flow rate (P<.001), were nondenture users (P=.002), and had more standing teeth and occlusal units (P<.001). However, the multiple regression analyses showed that the number of occlusal units was the only significant predictor of masticatory performance. In addition, the mean masticatory performance (95% confidence interval: 47.7% to 56.8%) was found to be greatly improved (by 1.2% to 2.2%), with each occlusal unit, in accordance with the Chewing Performance Calculator and between 0.8% and 1.8% according to the standard method; the basal masticatory performance was calculated as 72.1% to 81.2% (95% confidence interval). CONCLUSIONS: The number of occlusal units is one of the main predictors of masticatory performance when a 2-color bolus is used to test mixing ability.

Adipose Tissue Redox Microenvironment as a Potential Link between Persistent Organic Pollutants and the 16-Year Incidence of Non-hormone-Dependent Cancer.

We aimed to assess the relationships among the adipose tissue's (AT) oxidative microenvironment, in situ accumulated persistent organic pollutant (POP) concentrations, and cancer development. POP and oxidative stress levels were quantified in AT samples from 382 adults recruited within the GraMo cohort (2003-2004) in Granada (Spain). The 16-year cancer incidence was ascertained by reviewing health/administrative databases. Cox-regression models and mediation analyses were performed. The enzymes superoxide dismutase (SOD) and glutathione reductase (GRd) were positively associated with the risk of non-hormone-dependent (NHD) cancer [adjusted hazard ratio (HR) 1.76; 95% confidence interval (CI): 1.17, 2.64 and HR 2.35; 95% CI: 1.41, 3.94, respectively]. After adjustment for covariates, polychlorinated biphenyl-138 (PCB-138) (HR 1.78; 95% CI: 1.03, 3.09), ß-hexachlorocyclohexane (ß-HCH) (HR 1.70; 95% CI: 1.09, 2.64), and hexachlorobenzene (HR 1.54; 95% CI: 1.02, 2.33) were also positively associated with the risk of NHD cancer. Although confidence intervals included the null value, probably because of the modest number of cancer cases, we observed a potential mediation effect of SOD and GRd on the associations between ß-HCH and the risk of NHD tumors (percent mediated = 33 and 47%, respectively). Our results highlight the relevance of human AT's oxidative microenvironment as a predictor of future cancer risk as well as its potential mediating role on POP-related carcinogenesis. Given their novelty, these findings should be interpreted with caution and confirmed in future studies.

Chewing Performance Calculator: An interactive clinical method for quantifying masticatory performance.

STATEMENT OF PROBLEM: There is a need to quantitatively differentiate between impaired and normal mastication by using straightforward and reliable methods because currently available methods are expensive, complex, and time-consuming. PURPOSE: The purpose of this clinical study was to assess the reliability, validity, and clinical utility of a new Web-based software program designed to calculate masticatory performance, the Chewing Performance Calculator (CPC) measuring masticatory performance (MP), by analyzing the area of mixed bicolored chewing gum. MATERIAL AND METHODS: One hundred and ten participants were consecutively recruited from the School of Dentistry of the University of Salamanca. MP was determined by using 2-colored chewing gum that was masticated for a total of 20 strokes. The masticated gum was then flattened between 2 transparent glass tiles, generating a 1-mm-thick specimen that was scanned to calculate the percentage of area where the 2 colors were mixed. The area was calculated by using a photo-editing software program as described by Schimmel et al (standard method). In addition, all the images were analyzed by using the CPC Web application, which took as input the image of the masticated bolus enclosed in a custom plastic platen that allowed 3 parts of the image to be selected interactively: the platen, the bolus background, and the mixed color fraction of the bolus. The application then computed MP as a percentage. Additionally, an oral examination was carried out to record the number of occlusal units. These data were used to assess the validity of CPC by using the Pearson correlation coefficient. Construct validity was assessed by using ANOVA by comparing the MP scores obtained for masticated gums, classified upon inspection as being poorly, moderately, or highly mixed. The time spent evaluating the specimens with GSM and CPC methods was also recorded and used to indicate the usefulness of the procedure. RESULTS: The MP was found to range between 5.2% and 100% (95% CI: 80.8-88.8) with the GSM and between 9.2% and 96.4% (95% CI: 60.0-67.6) with the CPC. The time needed to calculate MP by using the GSM was significantly higher (235.2 versus 260.5 seconds) than that with the CPC (42.3 to 48.6 seconds). Both methods were significantly intercorrelated (r=0.65; P<.001) and correlated with the number of occlusal units (r=0.54 for CPC and r=0.40 for GSM). The correlation coefficient of MP calculated by using CPC (r=0.54; P<.001) was greater than that calculated by using GSM (r=0.40; P<.001). Moreover, both methods showed adequate construct validity because the values calculated for MP significantly increased as the mixing of the masticated gums also increased, subjectively classified as poor, moderate, and high. CONCLUSIONS: The CPC software program allowed MP to be determined in a valid and easy-to-use manner by using 2-colored chewing gum.

Association study of dietary non-enzymatic antioxidant capacity (NEAC) and colorectal cancer risk in the Spanish Multicase-Control Cancer (MCC-Spain) study.

PURPOSE: Studies attempting to link dietary non-enzymatic antioxidant activity (NEAC) and colorectal cancer (CRC) risk have reported mixed results. We examined this association in the Spanish Multicase-Control Study considering the likely influence of coffee and other dietary factors. METHODS: 1718 CRC cases and 3312 matched-controls provided information about diet through a validated 140-item food frequency questionnaire. Dietary NEAC was estimated for three methods [total radical-trapping antioxidant parameters (TRAP), ferric reducing/antioxidant power (FRAP) and TEAC-ABTS] using published values of NEAC content in food, with and without coffee's NEAC. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated through unconditional logistic regression models adjusted for lifestyle and dietary factors. RESULTS: Overall dietary intake of NEAC was significantly lower in cases compared to controls and associated with a significantly reduced CRC risk, in both men (ORQ5vsQ1 = 0.67, 95% CI 0.47-0.96 for FRAP) and women (ORQ5vsQ1 = 0.53, 95% CI 0.32-085 for FRAP), in multivariate models with and without the antioxidant contribution from coffee. The effect was similar for all the NEAC methods evaluated and for both colon and rectum. The association between dietary NEAC and CRC risk became non-significant when adjusting for fiber intake. However, intakes of NEAC and fiber were correlated. CONCLUSION: This study indicates that intake of an antioxidant-rich plant-based diet, both with and without NEAC from coffee, is associated with decreased CRC risk.

Evaluation of inflammatory biomarkers and their association with anti-SARS-CoV-2 antibody titers in healthcare workers vaccinated with BNT162B2.

Introduction: Vaccine-induced immunity against COVID-19 generates antibody and lymphocyte responses. However, variability in antibody titers has been observed after vaccination, and the determinants of a better response should be studied. The main objective of this investigation was to analyze the inflammatory biomarker response induced in healthcare workers vaccinated with BNT162b2, and its association with anti-Spike (a SARS-CoV-2 antigen) antibodies measured throughout a 1-year follow-up. Methods: Anti-spike antibodies and 92 biomarkers were analyzed in serum, along with socio-demographic and clinical variables collected by interview or exploration. Results: In our study, four biomarkers (ADA, IL-17C, CCL25 and CD8α) increased their expression after the first vaccine dose; and 8 others (uPA, IL-18R1, EN-RAGE, CASP-8, MCP-2, TNFß, CD5 and CXCL10) decreased their expression. Age, body mass index (BMI), smoking, alcohol consumption, and prevalent diseases were associated with some of these biomarkers. Furthermore, higher baseline levels of T-cell surface glycoprotein CD6 and hepatocyte growth factor (HGF) were associated with lower mean antibody titers at follow-up, while levels of monocyte chemotactic protein 2 (MCP-2) had a positive association with antibody levels. Age and BMI were positively related to baseline levels of MCP-2 (ß=0.02, 95%CI 0.00-0.04, p=0.036) and HGF (ß=0.03, 95%CI 0.00-0.06, p=0.039), respectively. Conclusion: Our findings indicate that primary BNT162b2 vaccination had a positive effect on the levels of several biomarkers related to T cell function, and a negative one on some others related to cancer or inflammatory processes. In addition, a higher level of MCP-2 and lower levels of HGF and CD6 were found to be associated with higher anti-Spike antibody titer following vaccination.

Dietary and Smoking Acrylamide and Prostate Cancer Risk: CAPLIFE Study.

Acrylamide is a probable carcinogen. Its main sources are the diet and tobacco. The association between acrylamide intake from the diet and tobacco and prostate cancer (PCa) has not been previously evaluated. We aimed to evaluate the relationship between dietary acrylamide intake and exposure to acrylamide through cigarettes and PCa risk. A population-based case-control (CAPLIFE) study was conducted, including 428 incident PCa cases and 393 controls. Smoking and dietary information, with a validated food frequency questionnaire, was collected. We calculated the amount of acrylamide from both sources, and tertiles (Ts) were created. Multivariable logistic regression and restricted cubic spline models were applied to assess the association between exposure to acrylamide and PCa risk. The median was similar for acrylamide in both dietary and smoking acrylamide among PCa cases and controls. No association was observed between dietary acrylamide intake and overall PCa risk (adjusted ORT3vsT1 = 0.90 (95% CI 0.59, 1.37)). A risk trend was observed for acrylamide exposure from cigarette smoking (p-trend = 0.032), with the highest odds in those subjects with the high exposure to acrylamide through cigarettes (adjusted ORT3vsT1 = 1.67 (95% CI 0.92, 3.04)). The restricted cubic splines suggested a linear relationship. In conclusion, acrylamide from smoking could be positively associated with PCa risk, but no association was observed for dietary acrylamide.

Health-Related Quality of Life in Long-Term Colorectal Cancer Survivors.

The aim of our study is to evaluate the relationship between sociodemographic and clinical characteristics of individuals with Colorectal Cancer (CRC), tumour-intrinsic characteristics and treatment received with health-related quality of life (HRQoL). METHODS: Cross-sectional analysis of data from 805 survivors from the MCC study was conducted. HRQoL was assessed through a general and specific questionnaire, SF-12 and FCSI (Colorectal Symptom Index). Statistical analyses were performed with linear regression with adjustment for sociodemographic variables, stage at diagnosis and histological grade. RESULTS: Participants had survived a median of 7.9 years from diagnosis (IQR 7.1-8.5 years). Age at diagnosis, sex and area showed a clear association with HRQoL in both physical and mental dimensions of the SF-12 questionnaire. A direct association between CRC recurrence was also found in the PCS-12 and MCS-12 dimensions and radical surgery in the PCS-12. Regarding the scores in FCSI questionnaire, statistically significant differences were observed by sex, age and area, with older women being the most impaired (p < 0.001). CONCLUSIONS: Age, sex and area was associated with lower scores of HRQoL among CRC survivors. Knowing the determinants related to HRQoL would allow us to lay the groundwork to develop strategies that help reduce morbidity and mortality, relapses and increase HRQoL.

Mediterranean diet and risk of breast cancer: An umbrella review.

BACKGROUND: The Mediterranean Diet (MedDiet) is a healthy dietary pattern which has been related to a lower risk of certain chronic diseases, such as some cancers. However, its role in breast cancer development remains unclear. This umbrella review aims to summarize the highest available evidence on MedDiet and breast cancer risk. METHODS: Pubmed, Web of Science, and Scopus electronic platforms were searched for relevant systematic reviews and meta-analyses. The selection criteria included systematic reviews with or without meta-analysis including women aged 18 years or older which evaluated the adherence to a MedDiet as the exposure and incidence of breast cancer as the outcome variable. Overlapping and quality of the reviews using AMSTAR-2 tool were independently assessed by two authors. RESULTS: Five systematic reviews and six systematic reviews with meta-analysis were included. Overall, 4 systematic reviews - two with and two without meta-analysis - were rated as of high quality. An inverse association was found in 5 of the 9 reviews which evaluated the role of MedDiet on the risk of total breast cancer. The meta-analyses showed moderate-high heterogeneity. The risk reduction seemed to be more consistent among postmenopausal women. No association was found for MedDiet among premenopausal women. CONCLUSIONS: The results of this umbrella review suggest that adherence to a MedDiet pattern had a protective effect on the risk of breast cancer, especially for postmenopausal breast cancer. The stratification of breast cancer cases and conducting high-quality reviews are aspects needed to overcome the current results' heterogeneity and to improve knowledge in this field.

[Influence of diet in COVID-19 infection and severity risk: a systematic review]. / Influencia de la dieta en el riesgo de infección y de gravedad de la COVID-19: una revisión sistemática.

Introduction: Introduction: the risk and/or prognosis of COVID-19, caused by the SARS-CoV-2 virus, have been related to chronic diseases such as obesity, diabetes mellitus, and cardiovascular diseases, with poor-quality diet being a predisposing factor for these diseases. Objective: to synthesize the scientific evidence on the effect of diet on the risk of SARS-CoV-2 infection and severe COVID-19. Methods: a systematic review was carried out following the PRISMA guidelines. The bibliographic search was made in the databases Web of Science, Scopus and Medline (through the PubMed search engine). Risk of bias analysis was performed using the Newcastle-Ottawa and Joanna Briggs Institute Critical Appraisal Checklist for Analytical Cross-Sectional Studies scales. Results: 14 studies were included. Good adherence to the Mediterranean diet was associated with a decreased risk of SARS-CoV-2 infection (OR = 0.44; 95 % CI, 0.22-0.88, for high versus low adherence, and significant ORs of 0.88 and 0.95 in studies that analyzed adherence quantitatively) but not with the severity of COVID-19. A plant-based diet also had a protective association against both COVID-19 infection and severity. Specifically, a high consumption of vegetables, legumes and cereals, and a low intake of dairy products and red meat showed a protective effect against infection and/or COVID-19 severity, depending on the study. Vitamin and probiotic supplements also lowered the risk of infection. Conclusion: the available evidence suggests that a healthy diet, based on a Mediterranean or plant-based diet, with moderate consumption of dairy and red meat, exerts a protective effect against COVID-19.

Introducción: Introducción: el riesgo y/o el pronóstico de la COVID-19, causado por el virus SARS-CoV-2, se han relacionado con enfermedades crónicas como obesidad, diabetes mellitus y enfermedades cardiovasculares, siendo la dieta de mala calidad un factor predisponente para estas enfermedades. Objetivo: sintetizar la evidencia científica sobre el efecto de la dieta en el riesgo de infección por SARS-CoV-2 y de COVID-19 grave. Métodos: revisión sistemática realizada siguiendo las guías PRISMA. La búsqueda bibliográfica se hizo en las bases de datos Web of Science, Scopus y Medline (a través del buscador PubMed). El análisis del riesgo de sesgo se realizó mediante las escalas Newcastle-Ottawa y Joanna Briggs Institute Critical Appraisal Checklist for Analytical Cross-Sectional Studies. Resultados: se incluyeron 14 estudios. Una buena adherencia a la dieta mediterránea se asoció con una disminución del riesgo de infección por SARS-CoV-2 (razón de momios RM = 0,44; IC 95 %: 0,22-0,88, para adherencia alta versus baja, y RM significativas de 0,88 y 0,95 en los estudios que analizaron la adherencia de forma cuantitativa) pero no con la gravedad de la COVID-19. Una dieta basada en plantas presentó una asociación protectora frente a la infección y la enfermedad grave. Concretamente, un alto consumo de verdura, legumbres y cereales, y una baja ingesta de lácteos y carnes rojas mostraron un efecto protector frente a la infección y/o la COVID-19 grave, según el estudio. Los suplementos vitamínicos y probióticos también disminuyeron el riesgo de infección. Conclusión: la evidencia disponible sugiere que una dieta saludable, basada en un patrón de dieta mediterránea o en alimentos vegetales, con consumo de lácteos y carnes rojas moderado, ejerce un efecto protector frente a la COVID-19.

Serum copper levels and risk of major adverse cardiovascular events: a systematic review and meta-analysis.

Background: Despite the fact that several studies have investigated the association between serum copper levels (S-Cu) and the risk of cardiovascular diseases, this relationship remains unclear. The aims of this study were to investigate the association between S-Cu and risk of major adverse cardiovascular events (MACE), including total stroke, ischemic stroke, hemorrhagic stroke, myocardial infarction and cardiovascular mortality, and identify potential sources of results heterogeneity. Methods: We carried out a systematic review and meta-analysis. The selection criteria were: (1) Observational studies (cohort studies, case-control studies and hybrid studies); (2) Studies containing quantitative data about the relationship between S-Cu and risk of MACE; (3) Estimating association measures; and (4) Studies written in English, French or Spanish. Overall pooled Odds ratio (pOR) and 95% confidence intervals (95% CI) of MACE for the highest vs. lowest S-Cu category were calculated using random-effects models. Results: Sixteen studies with a total of 41,322 participants were included in the meta-analysis: 10 prospective cohort studies, 5 nested case-control studies and 1 case-control study. Comparing highest vs. lowest category, high S-Cu levels were associated with total stroke (pOR: 1.49, 95% CI 1.22-1.82; I2 = 0%, p = 0.54), myocardial infarction (pOR: 1.31, 95% CI 1.17-1.46; I2 = 0.0%, p = 0.92) and cardiovascular mortality (pOR: 1.60, 95% CI 1.39-1.86; I2 = 0.0%, p = 0.54). Subgroup analysis showed that studies with a hybrid design had higher risks for cardiovascular mortality (pOR: 3.42, 95% CI 1.98-5.92) and ischemic stroke (pOR: 1.54, 95% CI 1.30-1.83). Conclusion: High S-Cu levels were associated with an increased risk of total stroke, myocardial infarction and cardiovascular mortality. Hybrid studies seems to modify the strength of the association between S-Cu and the risk of cardiovascular mortality and ischemic stroke. Systematic review registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022370782], identifier [CRD42022370782].

The duration of intervals on the oral cancer care pathway and implications for survival: a systematic review and meta-analysis.

Introduction: Previous studies measuring intervals on the oral cancer care pathway have been heterogenous, showing mixed results with regard to patient outcomes. The aims of this research were (1) to calculate pooled meta-analytic estimates for the duration of the patient, diagnostic and treatment intervals in oral cancer, considering the income level of the country, and (2) to review the evidence on the relationship of these three intervals with tumor stage at diagnosis and survival. Materials and methods: We conducted a systematic review with meta-analysis following PRISMA 2020 guidelines (pre-registered protocol CRD42020200752). Following the Aarhus statement, studies were eligible if they reported data on the length of the patient (first symptom to first presentation to a healthcare professional), diagnostic (first presentation to diagnosis), or treatment (diagnosis to start of treatment) intervals in adult patients diagnosed with primary oral cancer. The risk of bias was assessed with the Aarhus checklist. Results: Twenty-eight studies reporting on 30,845 patients met the inclusion criteria. The pooled median duration of the patient interval was 47 days (95% CI = 31-73), k = 18, of the diagnosis interval 35 days (95% CI = 21-38), k = 11, and of the treatment interval 30 days (95% CI = 23-53), k = 19. In lower-income countries, the patient and treatment intervals were significantly longer, and longer patient intervals were related to later stage at diagnosis. In studies with a lower risk of bias from high-income countries, longer treatment intervals were associated with lower survival rates. Conclusion: Interval duration on the oral cancer care pathway is influenced by the socio-economic context and may have implications for patient outcomes.

Ejaculation Frequency and Prostate Cancer: CAPLIFE Study.

PURPOSE: To evaluate the association between ejaculation frequency (EF) during four stages of life and prostate cancer (PCa) according to tumor aggressiveness, PCa stage, and urinary symptomatology. MATERIALS AND METHODS: A total of 456 incident PCa cases histologically confirmed, and 427 controls aged 40-80 years from the CAPLIFE study were analyzed. This study is a population-based case-control study carried out in the south of Spain. Average EF was measured for: (1) 20s, (2) 30s, (3) 40s, and (4) one year before the interview. EF was categorized into: (1) 0-3, (2) 4, and (3) >4 ejaculations/month. Sociodemographic, lifestyle, and medical information were also collected. To estimate the association between EF and PCa, adjusted ORs (aORs) and 95% CIs were calculated by logistic regression models. RESULTS: A year before the interview, PCa cases ejaculated less frequently than the controls. An inverse association was observed between the EF a year before and PCa, aOR=1.64 (95% CI 1.03-2.61) for men with 4 ejaculations/month, and aOR=2.38 (95% CI 1.57-3.60) for men with 0-3 ejaculations/month, compared to men with >4. The association was higher for cases with ISUP 3-5 (aOR=2.76 [95% CI 1.34-5.67] for men with 0-3 ejaculations/month) or with a locally advanced-metastatic tumor (aOR=4.70 [95% CI 1.55-14.29]). Moreover, men with moderate urinary symptoms and 0-3 ejaculations/month had the highest risk, aOR=3.83 (95% CI 1.84-7.95). CONCLUSIONS: A low EF could be associated with a higher risk of PCa, especially for cases with ISUP 3-5 or with a locally advanced-metastatic tumor.

Psychological Impact of COVID-19 in the Setting of Dentistry: A Review Article.

The worldwide pandemic has exposed healthcare professionals to a high risk of infection, exacerbating the situation of uncertainty caused by COVID-19. The objective of this review was to evaluate the psychological impact of the COVID-19 pandemic on dental professionals and their patients. A literature review was conducted using Medline-Pubmed, Web of Science, and Scopus databases, excluding systematic reviews, narratives, meta-analyses, case reports, book chapters, short communications, and congress papers. A modified version of the Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the selected studies. The search retrieved 3879 articles, and 123 of these were selected for the review (7 longitudinal and 116 cross-sectional studies). Elevated anxiety levels were observed in dental professionals, especially in younger and female professionals. Except for orthodontic treatments, patients reported a high level of fear that reduced their demand for dentist treatment to emergency cases alone. The results suggest that the COVID-19 pandemic has had psychological and emotional consequences for dental professionals and their patients. Further research is necessary to evaluate the persistence of this problem over time.