The contribution of second primary cancers to the mortality of patients with a first primary breast cancer.

PURPOSE: Second primary cancers (SPCs) are estimated to affect nearly 5% of patients with breast cancer within 10 years of their diagnosis. This study aimed to estimate the contribution of SPCs to the mortality of patients with a breast first primary cancer (FPC). METHODS: A population-based cohort of 17,210 patients with a breast FPC diagnosed between 2000 and 2010 was followed for SPCs (31/12/2015) and vital status (30/06/2021). Patients diagnosed with an SPC (265 synchronous and 897 metachronous, ≤ 1 and > 1 year after the FPC, respectively) were matched (1:3, by five-year age group and year of breast FPC diagnosis) to those without an SPC and alive when the corresponding SPC was diagnosed. RESULTS: Significantly higher hazards of death were found among patients with an SPC [hazard ratio of 1.56, 95% confidence interval (CI) 1.29-1.89 for synchronous SPCs; and 2.85, 95%CI 2.56-3.17 for metachronous SPCs] compared to patients with a breast FPC only. Estimates were higher for synchronous lung, stomach, non-Hodgkin lymphoma and breast SPCs, and metachronous liver, stomach, ovary, lung, rectum, corpus uteri, colon, breast, and non-Hodgkin lymphoma SPCs. The 15-year cumulative mortality was 59.5% for synchronous SPCs and 68.7% for metachronous SPCs, which was higher than in patients with a breast FPC only (43.6% and 44.8%, respectively). CONCLUSIONS: In Northern Portugal, patients with an SPC following a breast FPC have a higher mortality compared with patients with a breast FPC only.

Second primary cancers among females with a first primary breast cancer: a population-based study in Northern Portugal.

PURPOSE: To estimate the incidence rate of second primary cancers (SPCs) and the cumulative incidence of metachronous [diagnosed > 2 months after a first primary cancer (FPC)] SPCs in patients with a breast FPC, and to compare the incidence of SPC [overall, synchronous (≤ 2 months of the FPC) and metachronous] with that expected in the general female population. METHODS: A cohort of patients with a breast FPC from the North Region Cancer Registry of Portugal, diagnosed in 2000-2010 (n = 15,981), was followed to 31 December 2015 for synchronous and metachronous SPCs. Cumulative incidence of metachronous SPCs considering death as a competing event, and incidence rates and standardized incidence ratios of SPCs were estimated. RESULTS: The diagnosis of an SPC occurred in 1229 (7.7%) of patients with a breast FPC. SPCs occurred mainly in the breast, followed by digestive organs, lung, thyroid, and female genital organs. Globally, patients with a breast FPC had a higher incidence for all types of cancer compared to the general female population, and in particular for cancers of the breast, stomach, colon, lung, lymphoma, uterus, and ovary. The 10-year cumulative incidence of metachronous SPCs following a breast FPC was 6.6% and the corresponding 10-year cumulative mortality was 26.2%. CONCLUSION: In Portugal, patients with a breast FPC have a higher incidence of cancer compared to the general female population, highlighting important aspects of care, surveillance, and counselling among this growing number of patients.

Phenylseleninate-Connected Telluroxane Clusters.

Hydrolysis of PhTeI3 in the presence of sodium phenylseleninate and M3+ ions (M = Y, Nd, Ce) gives well-defined, bowl-shaped telluroxane clusters. Each of the two half-spheres of the compositions [(PhTe)18{ML}O24]7+/8+ ({ML} = {Y(NO3)(H2O)}2+ (1), {Nd(NO3)(H2O)2+} (2), or {Ce(NO3)2}+ (3)) are connected by two (compound 3) or four (compounds 1 and 2) PhSeO2- bridges. The resulting chalcogenoxane spheres have internal volumes of approximately 1500 Å3. Charge compensation is provided by nitrate ions and/or [Na2(NO3)8]6- clusters, which are located inside and surrounding these spheres.

Low-Value Practices for Pelvic Floor Dysfunction-Choosing Wisely Recommendations from the Brazilian Association of Physiotherapy in Women's Health: Observational Study.

INTRODUCTION AND HYPOTHESIS: The Choosing Wisely campaign is an international initiative that is aimed at promoting a dialog between professionals, helping the population to choose an evidence-based, truly necessary and risk-free care. The aim of the study was to develop the Choosing Wisely Brazil list on Women's Health Physiotherapy in the area of the pelvic floor. METHODS: A observational study was carried out between January 2022 and July 2023, proposed by the Brazilian Association of Physiotherapy in Women's Health, and developed by researchers working in the area of the pelvic floor. The development of the list consisted of six stages: a panel of experts, consensus building, national research, a review by the Choosing Wisely Brazil team, preparation of the list, and publication of the recommendations. Descriptive and content analyses were carried out in order to include evidence-based recommendations with over 80% agreement by physiotherapists in Brazil. RESULTS: The expert panel was made up of 25 physiotherapists who submitted 63 recommendations. Seven physiotherapists/researchers carried out a critical analysis of the literature and refined the recommendations, resulting in 11 recommendations that were put to a national vote, in which 222 physiotherapists took part. After a review by the Choosing Wisely Brazil team, five recommendations with an average agreement of 88.2% agreement were chosen for publication. CONCLUSIONS: The Choosing Wisely Brazil team in Physiotherapy in Women's Health/Pelvic Floor proposed a list of five recommendations that showed a high agreement among Brazilian physiotherapists working in the area.

Effects of health education on women with urinary incontinence: systematic review and meta-analysis.

INTRODUCTION AND HYPOTHESIS: The objective was to investigate the effects of health education (HE) on urinary symptoms and quality of life in women with urinary incontinence (UI). METHODS: A systematic review and meta-analysis of trials evaluating HE for women with UI. The risk of bias was assessed using the revised Cochrane risk-of-bias tool for randomized trials. RESULTS: The search identified 5,118 articles. Eighteen papers were considered eligible. The interventions investigated included health education (HE), combined intervention, self-management (SM), and structured training (ST). Outcomes included quality of life (QoL), UI frequency, UI severity, impression of improvement, incontinence symptoms, urine leakage, fear of leakage, urgency, and incontinence impact. Compared with the control group there was a significant improvement in the frequency, severity, and impact on the QoL for women with UI (assessed by the total score of the International Consultation on Incontinence Questionnaire Short Form (ICIQ SF); RR = -1.47, 95% CI [-2.07, -0.88]; two trials; low certainty of the evidence). CONCLUSIONS: This review shows that HE seems to be beneficial in the treatment of women with UI when compared with control women (no treatment or general health care), improving the frequency, severity, and impact on QoL assessed by the ICIQ SF total score. However, the certainty of this evidence is low.

Prevalence, pain intensity and symptoms associated with primary dysmenorrhea: a cross-sectional study.

BACKGROUND: Primary dysmenorrhea (PD) is an etiological cyclic pelvic pain related to the menstrual period; it can negatively impact women's quality of life and productivity. The aim of the present study was to estimate the prevalence of PD and analyze associated symptoms in Brazilian women. METHODS: An online cross-sectional study was carried out in Brazil, with a structured questionnaire regarding dysmenorrhea and associated symptoms. PD intensity was measured with the Numerical Rating Scale for Pain and classified as mild (1-3), moderate (4-7) and severe (> 8). The association between qualitative variables was performed using Pearson's Chi-Square Test. The quantification of this association was measured using multinomial logistic regression models, with calculation of Odds Ratio and confidence interval. A significance level of 5% was considered. RESULTS: A total of 10,070 women were included. Most participants classified PD intensity as moderate (40.4%, 41.9% and 49.7%) and severe (21.2%, 24.8% and 28.4%) in the previous month, 3 months and 5 years, respectively. The most common symptoms associated with PD were irritability, abdominal distension sensation, anxiety and feeling more emotional. The increased of the risk (OR > 1.0) for moderate and severe PD-related pain intensity is related to age, nulliparity and presence PD since adolescence. CONCLUSION: There is a high prevalence of PD among Brazilian women, and the most common symptoms reported were irritability, abdominal distension sensation, anxiety and feeling more emotional.

A bird's-eye view of research practices in mathematical cognition, learning, and instruction: Reimagining the status quo.

Research on mathematical cognition, learning, and instruction (MCLI) often takes cognition as its point of departure and considers instruction at a later point in the research cycle. In this article, we call for psychologists who study MCLI to reflect on the "status quo" of their research practices and to consider making instruction an earlier and more central aspect of their work. We encourage scholars of MCLI (a) to consider the needs of educators and schools when selecting research questions and developing interventions; (b) to compose research teams that are diverse in the personal, disciplinary, and occupational backgrounds of team members; (c) to make efforts to broaden participation in research and to conduct research in authentic settings; and (d) to communicate research in ways that are accessible to practitioners and to the general public. We argue that a more central consideration of instruction will lead to shifts that make research on MCLI more theoretically valuable, more actionable for educators, and more relevant to pressing societal challenges.

Divergence among rice cultivars reveals roles for transposition and epimutation in ongoing evolution of genomic imprinting.

Parent-of-origin-dependent gene expression in mammals and flowering plants results from differing chromatin imprints (genomic imprinting) between maternally and paternally inherited alleles. Imprinted gene expression in the endosperm of seeds is associated with localized hypomethylation of maternally but not paternally inherited DNA, with certain small RNAs also displaying parent-of-origin-specific expression. To understand the evolution of imprinting mechanisms in Oryza sativa (rice), we analyzed imprinting divergence among four cultivars that span both japonica and indica subspecies: Nipponbare, Kitaake, 93-11, and IR64. Most imprinted genes are imprinted across cultivars and enriched for functions in chromatin and transcriptional regulation, development, and signaling. However, 4 to 11% of imprinted genes display divergent imprinting. Analyses of DNA methylation and small RNAs revealed that endosperm-specific 24-nt small RNA-producing loci show weak RNA-directed DNA methylation, frequently overlap genes, and are imprinted four times more often than genes. However, imprinting divergence most often correlated with local DNA methylation epimutations (9 of 17 assessable loci), which were largely stable within subspecies. Small insertion/deletion events and transposable element insertions accompanied 4 of the 9 locally epimutated loci and associated with imprinting divergence at another 4 of the remaining 8 loci. Correlating epigenetic and genetic variation occurred at key regulatory regions-the promoter and transcription start site of maternally biased genes, and the promoter and gene body of paternally biased genes. Our results reinforce models for the role of maternal-specific DNA hypomethylation in imprinting of both maternally and paternally biased genes, and highlight the role of transposition and epimutation in rice imprinting evolution.

Development of collagenous scaffolds for wound healing: characterization and in vivo analysis.

The development of wound dressings from biomaterials has been the subject of research due to their unique structural and functional characteristics. Proteins from animal origin, such as collagen and chitosan, act as promising materials for applications in injuries and chronic wounds, functioning as a repairing agent. This study aims to evaluate in vitro effects of scaffolds with different formulations containing bioactive compounds such as collagen, chitosan, N-acetylcysteine (NAC) and ε-poly-lysine (ε-PL). We manufactured a scaffold made of a collagen hydrogel bioconjugated with chitosan by crosslinking and addition of NAC and ε-PL. Cell viability was verified by resazurin and live/dead assays and the ultrastructure of biomaterials was evaluated by SEM. Antimicrobial sensitivity was assessed by antibiogram. The healing potential of the biomaterial was evaluated in vivo, in a model of healing of excisional wounds in mice. On the 7th day after the injury, the wounds and surrounding skin were processed for evaluation of biochemical and histological parameters associated with the inflammatory process. The results showed great cell viability and increase in porosity after crosslinking while antimicrobial action was observed in scaffolds containing NAC and ε-PL. Chitosan scaffolds bioconjugated with NAC/ε-PL showed improvement in tissue healing, with reduced lesion size and reduced inflammation. It is concluded that scaffolds crosslinked with chitosan-NAC-ε-PL have the desirable characteristics for tissue repair at low cost and could be considered promising biomaterials in the practice of regenerative medicine.

Presenteeism and associated factors among women with menstrual symptoms.

PURPOSE: Menstrual characteristics can affect a woman's productivity at work and college, but studies in a general population of adult women are scarce. In addition, it is important to know which menstrual symptoms are most associated with presenteeism in women to promote specific health actions. The present study aimed to assess menstrual symptoms associated with presenteeism in adult women. METHODS: Online cross-sectional study in which menstrual characteristics, including menstrual flow, age of menarche, menstrual pain and cycle duration were assessed by a self-report questionnaire. The menstrual pain intensity was assessed by Numerical Rating Scale, and the presenteeism, by the Stanford Presenteeism Scale-6 (SPS-6). Women were divided in two groups, with and without presenteeism, based on the SPS-6 cutoff point. Data were analyzed by binary logistic regression and presented as odds ratios (OR). RESULTS: Among the 430 women who participated in the study, 44.2% were classified as with presenteeism. Women with severe menstrual flow were more likely to have presenteeism (OR = 2.12) compared with women with mild and moderate menstrual flow. The higher menstrual pain intensity the higher the chances of a woman presenting with presenteeism (OR = 1.29). CONCLUSIONS: These menstrual characteristics (intensity of menstrual flow and menstrual pain) seem to affect women's productivity at work and/or college, and should be assessed in research and clinical practice. Thus, public policies on women's health can be carried out based on these results.

Esthesioneuroblastoma: 38 years of experience in an oncological center.

Background: Esthesioneuroblastoma (ENB) is an uncommon malignant sinonasal tumor. There are few data regarding ENB management, namely its treatment. We review our institute's experience in the treatment of ENB and evaluate survival outcomes. Materials and methods: Retrospective study of patients with ENB treated between 1984-2022. A total of 20 patients were identified, 13 men and 7 women, aged between 20 and 76 years. Results: Eleven patients were stage C of the modified Kadish staging system at initial presentation, 7 stage B, 1 stage A and 1 stage D. Seventeen patients underwent surgery alone or combined with adjuvant treatment (radiotherapy or chemoradiotherapy). The majority of the patients (71.4%) treated with surgery alone were stage B, whereas most of the patients (63.6%) that underwent surgery combined with adjuvant treatment were stage C. Five of the 7 patients treated with surgery alone had a locoregional recurrence. Two of the 10 patients treated with surgery followed by adjuvant treatment had relapsed, locoregionally and at a distance, respectively. One patient was treated with chemotherapy and 2 patients were treated with chemoradiotherapy and neoadjuvant chemotherapy followed by chemoradiotherapy, respectively. The recurrence and persistence rates were 35% and 15%, respectively. The median time from the end of the first treatment to recurrence was 20.9 months. Two- and 5-year overall survival rates were 83.9% and 77.9%; while progression-free survival rates were 76.7% and 61.0%, respectively. Conclusions: Sixty percent of patients were treated with a multimodal approach, which appeared to be a favorable strategy for the majority of patients.

Evolution and function of genomic imprinting in plants.

Genomic imprinting, an inherently epigenetic phenomenon defined by parent of origin-dependent gene expression, is observed in mammals and flowering plants. Genome-scale surveys of imprinted expression and the underlying differential epigenetic marks have led to the discovery of hundreds of imprinted plant genes and confirmed DNA and histone methylation as key regulators of plant imprinting. However, the biological roles of the vast majority of imprinted plant genes are unknown, and the evolutionary forces shaping plant imprinting remain rather opaque. Here, we review the mechanisms of plant genomic imprinting and discuss theories of imprinting evolution and biological significance in light of recent findings.

Extruded urea levels in lamb supplementation in rainy tropical savanna conditions: the triad host-gastrointestinal nematodes-environment.

The objective of this study was to evaluate the influence of increasing levels of extruded urea (EU, Amireia®) in the diet of lambs naturally infected by gastrointestinal nematodes on the interactions in the host-pasture-soil components in edaphoclimatic conditions of the tropical rainy savanna. A total of 60 Texel lambs with a mean initial weight of 20.7 ± 0.87 and mean age of 2.5 ± 0.70 months were distributed in a completely randomized design, in five treatments consisting of different levels of EU supplementation viz., 0, 6, 12, 18, and 24 g 100 kg-1 live weight (LW). The performance of lambs, parasitological variables, gastrointestinal nematodes (NGIs), and larvae recovery in pasture and soil were evaluated. The highest animal performance was observed in animals that received 0 to 18 g kg-1 LW (146.0 g day-1) and the lowest in animals supplemented with 24 g kg-1 LW (81.0 g day-1) of EU. The body condition score (BCS) was similar in the animals (P > 0.05). Parasitic infection did not differ as a function of EU level (P > 0.05). Eggs of Haemonchus spp., Trichostrongylus spp., Cooperia spp., and Oesophagostomum spp. were found. The largest amount of larvae in the L1/L2 and L3 stages was recovered in the pastures occupied by the animals that received supplementation 0 g kg-1 LW of EU (750 larvae), the smallest in those that the animals received 6 g 100 kg-1 LW of EU (54 larvae). The presence of larvae in the L1/L2 stages changed significantly (P < 0.05) in the soil; in the other stages, it did not differ in the soil. Increasing levels of extruded urea do not influence the eggs per gram of feces (EPG) count. The 0 to 18 g 100 kg-1 LW level maintains animal performance, BCS and FAMACHA©. There is less dispersal of NGI larvae in pasture and soil when EU levels increase in the edaphoclimatic conditions of the rainy tropical savannah, which suggests that this supplement can be implemented in the diet of beef lambs, in addition to to be a lower cost nitrogen source.

Gastric cancer incidence and mortality trends 2007-2016 in three European countries.

BACKGROUND : Increased awareness of gastric cancer risk, easy access to upper endoscopy, and high definition endoscopes with virtual chromoendoscopy may have led to the increase in early diagnosis of gastric cancer observed in recent years in Europe, which may be associated with improved survival. Currently, no data exist on the impact of early diagnosis on survival at a populational level in Europe. Our aim was to assess gastric cancer incidence, early diagnosis, and survival in northwestern and southern European countries with a low-to-moderate incidence of gastric cancer. METHODS : Data on 41 138 gastric cancers diagnosed in 2007-2016 were retrieved from national cancer registries of Belgium, the Netherlands, and northern Portugal. Age-standardized incidence and mortality rates were assessed and expressed per 100 000 person-years. Early diagnosis was defined as T1 tumors. Net survival estimates for 2007-2011 vs. 2012-2016 were compared. RESULTS : Age-standardized incidence and mortality decreased over time in Belgium, northern Portugal, and the Netherlands (relative incidence decrease 8.6 %, 4.5 %, and 46.8 %, respectively; relative mortality decrease 22.0 %, 30.9 %, and 50.0 %, respectively). Early gastric cancer diagnosis increased over time for all countries. Net 1-year survival improved significantly between the two time periods in all countries, and at 5 years in Belgium and Portugal. CONCLUSIONS : This is the first study comparing trends (2007-2016) in gastric cancer incidence and mortality in some European countries. We found an increasing proportion of T1 gastric cancers and a decrease in age-standardized mortality over time, supporting the use of secondary prevention strategies.

'Painting my pain': the use of pain drawings to assess multisite pain in women with primary dysmenorrhea.

BACKGROUND: To verify the use of pain drawing to assess multisite pain in with primary dysmenorrhea (PD) and to assess its divergent validity, test-retest reliability, intra- and inter-rater reliability and measurement errors. METHODS: Cross-sectional study. Adult women with self-reported PD three months prior to the study. Women answered the Numerical Rating Scale (NRS) and the pain drawing during two consecutive menstruations. The pain drawings were digitalized and assessed for the calculation of total pain area (%). Intra- and inter-rater reliability and the test-retest reliability between the first and the second menstruations were assessed with the intraclass correlation coefficient (ICC). Measurement errors were calculated with the standard error of measurement (SEM), smallest detectable change (SDC) and the Bland-Altman plot. Spearman correlation (rho) was used to check the correlation between the total pain area and pain intensity of the two menstruations. RESULTS: Fifty-six women (24.1 ± 3.1 years old) participated of the study. Their average pain was 6.2 points and they presented pain in the abdomen (100%), low back (78.6%), head (55.4%) and lower limbs (50%). All reliability measures were considered excellent (ICC > 0.75) for the total pain area; test-retest SEM and SDC were 5.7% and 15.7%, respectively. Inter-rater SEM and SDC were 8% and 22.1%, respectively. Correlation between total pain area and pain intensity was moderate in the first (rho = 0.30; p = 0.021) and in the second menstruations (rho = 0.40; p = 0.002). CONCLUSION: Women with PD presented multisite pain, which could be assessed with the pain drawing, considered a reliable measurement.

Effect of fungal indoor air pollutant 1-octen-3-ol on levels of reactive oxygen species and nitric oxide as well as dehydrogenases activities in drosophila melanogaster males.

Fungal pollution of indoor environments contributes to several allergic symptoms and represents a public health problem. It is well-established that 1-octen-3-ol, also known as mushroom alcohol, is a fungal volatile organic compound (VOC) commonly found in damp indoor spaces and responsible for the typical musty odor. Previously it was reported that exposure to 1-octen-3-ol induced inflammations and disrupted mitochondrial morphology and bioenergetic rate in Drosophila melanogaster. The aim of this study was to examine the influence of 1-octen-3-ol on dehydrogenase activity, apoptotic biomarkers, levels of nitric oxide (NO) and reactive oxygen species (ROS), as well as antioxidant enzymes activities. D. melanogaster flies were exposed to an atmosphere containing 1-octen-3-ol (2.5 or ∞l/L) for 24 hr. Data demonstrated that 1-octen-3-ol decreased dehydrogenases activity and NO levels but increased ROS levels accompanied by stimulation of glutathione-S-transferase (GST) and superoxide dismutase (SOD) activities without altering caspase 3/7 activation. These findings indicate that adverse mitochondrial activity effects following exposure of D. melanogaster to 1-octen-3-ol, a fungal VOC, may be attributed to oxidant stress. The underlying mechanisms involved in adverse consequences of indoor fungal exposure appear to be related to necrotic but not apoptotic mechanisms. The adverse consequences were sex-dependent with males displaying higher sensitivity to 1-octen-3-ol. Based upon on the fact that the fly genome shares nearly 75% of disease-related genes to human exposure to this fungus may explain the adverse human responses to mold especially for males.

Numerical rating scale for dysmenorrhea-related pain: a clinimetric study.

Objective: To evaluate the numerical rating scale (NRS) measurement properties in women with dysmenorrhea. Methods: This was an online clinimetric study. Brazilian women aged over 18 years old with internet access to respond to online instruments were included in the study. We evaluated criterion validity (comparing women with and without dysmenorrhea), construct validity between the NRS and the bodily pain domain of the SF-36, test-retest reliability, and measurement errors (in women with dysmenorrhea). Results: Two hundred thirty-eight women with and 192 without dysmenorrhea participated in the study. For criterion validity, the area under the receiver operating characteristic curve was 0.902 (95%CI, 0.873-0.931), and a cutoff point of 3 was considered to have the best sensitivity (83%) and specificity (86%). For construct validity, the NRS showed a moderate negative correlation with the SF-36 bodily pain domain (r=-0.46; p < 0.001). For test-retest reliability and measurement errors, 105 women whose symptoms did not change between 7 and 10 days of retest, with intraclass correlation coefficient = 0.90, standard error of measurement = 0.97, and smallest detectable change = 2.76 points. Conclusions: The NRS can be considered a valid and reliable patient-reported outcome measure for assessing dysmenorrhea-related pain intensity.

Colorectal cancer incidence, mortality, and stage distribution in European countries in the colorectal cancer screening era: an international population-based study.

BACKGROUND: Colorectal cancer screening programmes and uptake vary substantially across Europe. We aimed to compare changes over time in colorectal cancer incidence, mortality, and stage distribution in relation to colorectal cancer screening implementation in European countries. METHODS: Data from nearly 3·1 million patients with colorectal cancer diagnosed from 2000 onwards (up to 2016 for most countries) were obtained from 21 European countries, and were used to analyse changes over time in age-standardised colorectal cancer incidence and stage distribution. The WHO mortality database was used to analyse changes over time in age-standardised colorectal cancer mortality over the same period for the 16 countries with nationwide data. Incidence rates were calculated for all sites of the colon and rectum combined, as well as the subsites proximal colon, distal colon, and rectum. Average annual percentage changes (AAPCs) in incidence and mortality were estimated and relevant patterns were descriptively analysed. FINDINGS: In countries with long-standing programmes of screening colonoscopy and faecal tests (ie, Austria, the Czech Republic, and Germany), colorectal cancer incidence decreased substantially over time, with AAPCs ranging from -2·5% (95% CI -2·8 to -2·2) to -1·6% (-2·0 to -1·2) in men and from -2·4% (-2·7 to -2·1) to -1·3% (-1·7 to -0·9) in women. In countries where screening programmes were implemented during the study period, age-standardised colorectal cancer incidence either remained stable or increased up to the year screening was implemented. AAPCs for these countries ranged from -0·2% (95% CI -1·4 to 1·0) to 1·5% (1·1 to 1·8) in men and from -0·5% (-1·7 to 0·6) to 1·2% (0·8 to 1·5) in women. Where high screening coverage and uptake were rapidly achieved (ie, Denmark, the Netherlands, and Slovenia), age-standardised incidence rates initially increased but then subsequently decreased. Conversely, colorectal cancer incidence increased in most countries where no large-scale screening programmes were available (eg, Bulgaria, Estonia, Norway, and Ukraine), with AAPCs ranging from 0·3% (95% CI 0·1 to 0·5) to 1·9% (1·2 to 2·6) in men and from 0·6% (0·4 to 0·8) to 1·1% (0·8 to 1·4) in women. The largest decreases in colorectal cancer mortality were seen in countries with long-standing screening programmes. INTERPRETATION: We observed divergent trends in colorectal cancer incidence, mortality, and stage distribution across European countries, which appear to be largely explained by different levels of colorectal cancer screening implementation. FUNDING: German Cancer Aid (Deutsche Krebshilfe) and the German Federal Ministry of Education and Research.

The impact of the COVID-19 pandemic on the short-term survival of patients with cancer in Northern Portugal.

The COVID-19 pandemic led to potential delays in diagnosis and treatment of cancer patients, which may negatively affect the prognosis of these patients. Our study aimed to quantify the impact of COVID-19 on the short-term survival of cancer patients by comparing a period of 4 months after the outbreak began (2 March 2020) with an equal period from 2019. All cancer cases of the esophagus, stomach, colon and rectum, pancreas, lung, skin-melanoma, breast, cervix, and prostate, from the Portuguese Oncology Institute of Porto (IPO-Porto) and diagnosed between 2 March and 1 July of 2019 (before COVID-19) and 2020 (after COVID-19) were identified. Information regarding sociodemographic, clinical and treatment characteristics were collected from the cancer registry database and clinical files. Vital status was assessed to 31 October of the respective years. Cox proportional hazards regression was used to estimate crude and propensity score-adjusted hazards ratio (HR) and 95% confidence intervals (95% CIs) of death. During follow-up to 31 October, there were 154 (11.8%) deaths observed before COVID-19 and 131 (17.2%) after COVID-19, corresponding to crude and adjusted HRs (95% CI) of 1.51 (1.20-1.91) and 1.10 (0.86-1.40), respectively. Significantly higher adjusted hazards of death were observed for patients with Stage III cancer (HR = 2.37; 95% CI: 1.14-4.94) and those undergoing surgical treatment (HR = 3.97; 95% CI: 1.14-13.77) or receiving radiotherapy (HR = 1.96; 95% CI: 1.96-3.74), while patients who did not receive any treatment had a lower mortality hazards (HR = 0.62; 95% CI: 0.46-0.83). The higher overall short-term mortality observed during the COVID-19 pandemic largely reflects the effects of the epidemic on the case-mix of patients being diagnosed with cancer.

Performance of DNA methylation-based biomarkers in the cervical cancer screening program of northern Portugal: A feasibility study.

Cervical cancer remains a health concern. Effective screening programs are critical to reduce the incidence and mortality. High-risk HPV (hr-HPV) testing as primary screening tool discloses high sensitivity but suboptimal specificity. Adequate triage tests to reduce unnecessary colposcopy referrals and overdiagnosis/overtreatment are crucial. Hence, we aimed to validate a panel of DNA methylation-based markers as triage test for women hr-HPV+ in the population-based Regional Cervical Cancer Screening Program of Northern Portugal. Firstly, CADM1, MAL, FAM19A4 and hsa-miR124-2 promoter methylation levels were assessed by multiplex QMSP in a testing set of 402 FFPE tissue samples (159 normal samples and 243 cervical lesions, including 39 low-grade intraepithelial squamous lesions [LSIL], 59 high-grade intraepithelial squamous lesions [HSIL] and 145 cancerous lesions). Then, preliminary validation was performed in 125 hr-HPV+ cervical scrapes (including 59 normal samples, 30 LSIL, 34 HSIL and 2 cancerous lesions). Higher MALme , FAM19A4me and hsa-miR124-2me methylation levels were disclosed in histological HSIL or worse (HSIL+) in testing set. Individually, markers depicted over 86% specificity for HSIL+ detection. In validation set, all these genes significantly differed between histological HSIL+ and low-grade squamous intraepithelial lesions or less. In combination, these markers reached 74% specificity and 61% sensitivity for identification of histological HSIL+. We concluded that host gene methylation might constitute a useful referral triage tool of hr-HPV+ women enrolled in the Cervical Cancer Screening Program of Northern Portugal.