UNASSIGNED: Biliary tract cancer (BTC) consists of a group of hepatic and perihepatic tumors that are in close proximity but are anatomically different, including gallbladder cancer (GBC), cholangiocarcinoma (extrahepatic and intrahepatic [ICC]), and ampulla of Vater cancer (AVC). Most epidemiologic research has focused on 1 or more anatomic subtypes, or does not differentiate BTC from hepatocellular carcinoma or other primary liver cancers. Here, we provide a descriptive update on global incidence and mortality rates for BTC, overall and by anatomic subtypes.
UNASSIGNED: Age-standardized rates (per 100,000 person-years) were derived from the International Agency for Research on Cancer, Cancer Incidence in Five Continents, Volume XI (2008-2012; 22 countries), and the World Health Organization Mortality Database (2006-2016; 38 countries).
UNASSIGNED: BTC incidence varied by country, with the highest in Chile (14.35) and the lowest in Vietnam (1.25). Mortality rates for BTC were highest for the Republic of Korea (11.64) and lowest for the Republic of Moldova (1.65). BTC mortality rates increased over time in 24 of 34 countries. Patients aged ≥75 years had 5-10 times higher mortality rates than the overall BTC rate in all countries. In most countries, incidence rates were highest for GBC, and mortality rates highest for ICC, while both were lowest for AVC. Females had and died from GBC more frequently than males. For ICC, extrahepatic cholangiocarcinoma, and AVC, males trended toward higher incidence and mortality rates.
UNASSIGNED: The increasing incidence and mortality trends reported here indicate a need for improved prevention and treatment for all BTC subtypes.

BACKGROUND: Over the past 25 years, global opioid consumption has increased. Denmark ranks fifth in opioid use globally, exceeding other Scandinavian countries. Postsurgical pain is a common reason for opioid prescriptions, but opioid use patterns after patient discharge from the hospital are unclear. This study examines trends in opioid prescription among Danish surgical patients over a year.
METHODS: This register-based cohort study will use data from Danish governmental databases related to patients undergoing the 10 most frequent surgical procedures in 2018, excluding cancer-related and minor procedures. The primary outcome will be the dispensed postoperative opioid prescriptions at retail pharmacies over four quarters. Secondary analyses will include associations with sex, age, education attainment, and oral morphine equivalent quotient. Surgical treatments and diagnoses will be identified using NOMESCO procedure codes and ICD-10 codes. Opioids will be identified by ATC codes N02A and R05DA04. Subjects will be classified as preoperative opioid consumers or non-opioid consumers based on opioid prescriptions redeemed in the 6 months before surgery.
CONCLUSIONS: The study will use extensive national register-based data, ensuring consistent data collection and enhancing the generalizability of the findings to similar healthcare systems. The study may identify high-risk populations for long-term opioids and provide information to support opioid prescribing guidelines and public health policies.

PURPOSE OF REVIEW: Evidence suggests neurotoxicity of endocrine disrupting chemicals (EDCs) during sensitive periods of development. We present an overview of pediatric population neuroimaging studies that examined brain influences of EDC exposure during prenatal period and childhood. RECENT FINDINGS: We found 46 studies that used magnetic resonance imaging (MRI) to examine brain influences of EDCs. These studies showed associations of prenatal exposure to phthalates, organophosphate pesticides (OPs), polyaromatic hydrocarbons and persistent organic pollutants with global and regional brain structural alterations. Few studies suggested alteration in functional MRI associated with prenatal OP exposure. However, studies on other groups of EDCs, such as bisphenols, and those that examined childhood exposure were less conclusive. These findings underscore the potential profound and lasting effects of prenatal EDC exposure on brain development, emphasizing the need for better regulation and strategies to reduce exposure and mitigate impacts. More studies are needed to examine the influence of postnatal exposure to EDC on brain imaging.

BACKGROUND: Regular monitoring of the air pollutant nitrogen dioxide (NO2), an indicator for traffic-related emissions, is a priority in urban environments. The health impacts associated with NO2 exposure are the result of a combination of factors, including concentration, duration of exposure, and interactions with other pollutants. WHO has established air quality guidelines based on epidemiological studies.
OBJECTIVE: This study develops a new concept \"Health Impact Pathways (HIPs)\" using adversity as a probabilistic indicator of health effects. For this purpose, it integrates available toxicological and epidemiological information, using Adverse Outcome Pathways (AOPs), in order to understand chemical-biological interactions and their consequences on health.
METHODS: Literature review and meta-analysis of toxicological data supported by expert judgment were performed to establish: a) adversity pathways, b) quantitative criteria for scoring the observed toxicological effects (adversity indicators), c) NO2 exposure - adversity relationship for both long-term (1-36 months) and shortterm (1-7 days). The NO2 daily concentrations from January 2001 to December 2022, were obtained from Madrid city Air Quality network monitoring database. Adversity levels were compared with relative risk levels for all-cause and respiratory mortality estimated using linear equations from WHO 2021 guidelines.
RESULTS: Non-linear relations were obtained for all long- and short-term NO2 related adversity indicators; for long-term effects, the best fitting was obtained with a modified Haber\'s law model with an exponential coefficient for the exposure time of 0.25. Estimations are presented for a set of case studies for Madrid city, covering temporal and spatial variability. A clear improvement trend along the two decades was observed, as well as high inter- and intra-station variability; the adversity indicators provided integrated information on the temporal and spatial evolution of population level risk.
CONCLUSIONS: The proposed HIP conceptual approach offers promising advances for integrating experimental and epidemiological data. The next step is linking the concentration-adversity relationship with population health impacts through probability estimations, the preliminary estimations confirm the need for assessing independently different population groups.

EFSA requested its Scientific Committee to prepare a guidance document on appraising and integrating evidence from epidemiological studies for use in EFSA\'s scientific assessments. The guidance document provides an introduction to epidemiological studies and illustrates the typical biases, which may be present in different epidemiological study designs. It then describes key epidemiological concepts relevant for evidence appraisal. This includes brief explanations for measures of association, exposure assessment, statistical inference, systematic error and effect modification. The guidance then describes the concept of external validity and the principles of appraising epidemiological studies. The customisation of the study appraisal process is explained including tailoring of tools for assessing the risk of bias (RoB). Several examples of appraising experimental and observational studies using a RoB tool are annexed to the document to illustrate the application of the approach. The latter part of this guidance focuses on different steps of evidence integration, first within and then across different streams of evidence. With respect to risk characterisation, the guidance considers how evidence from human epidemiological studies can be used in dose-response modelling with several different options being presented. Finally, the guidance addresses the application of uncertainty factors in risk characterisation when using evidence from human epidemiological studies.

BACKGROUND: The scientific literature has reported an inverse association between broccoli consumption and the risk of suffering from several types of cancer; however, the results were not entirely consistent across studies. A systematic review and meta-analysis of observational studies were conducted to determine the association between broccoli consumption and cancer risk with the aim of clarifying the beneficial biological effects of broccoli consumption on cancer.
METHODS: PubMed/MEDLINE, Web of Science, Scopus, Cochrane Library (CENTRAL), and Epistemonikos databases were searched to identify all published papers that evaluate the impact of broccoli consumption on the risk of cancer. Citation chasing of included studies was conducted as a complementary search strategy. The risk of bias in individual studies was assessed using the Newcastle-Ottawa Scale. A random-effects model meta-analysis was employed to quantitatively synthesize results, with the I2 index used to assess heterogeneity.
RESULTS: Twenty-three case-control studies (n = 12,929 cases and 18,363 controls; n = 31,292 individuals) and 12 cohort studies (n = 699,482 individuals) were included in the meta-analysis. The results suggest an inverse association between broccoli consumption and the risk of cancer both in case-control studies (OR: 0.64, 95% CI from 0.58 to 0.70, p < 0.001; Q = 35.97, p = 0.072, I2 = 30.49%-moderate heterogeneity; τ2 = 0.016) and cohort studies (RR: 0.89, 95% CI from 0.82 to 0.96, p = 0.003; Q = 13.51, p = 0.333, I2 = 11.21%-low heterogeneity; τ2 = 0.002). Subgroup analysis suggested a potential benefit of broccoli consumption in site-specific cancers only in case-control studies.
CONCLUSIONS: In summary, the findings indicate that individuals suffering from some type of cancer consumed less broccoli, suggesting a protective biological effect of broccoli on cancer. More studies, especially cohort studies, are necessary to clarify the possible beneficial effect of broccoli on several types of cancer.

Engineered nanomaterials (ENMs) have been suggested as being capable of promoting inflammation, a key component in the pathways associated with carcinogenesis, cardiovascular disease, and other conditions. As a result, the risk assessment of biological markers as early-stage indicators has the potential to improve translation from experimental toxicologic findings to identifying evidence in human studies. The study aims to review the possible early biological changes in workers exposed to carbon black (CB), followed by an evidentiary quality evaluation to determine the predictive value of the biological markers.
We conducted a literature search to identify epidemiological studies that assessed biological markers that were involved in the inflammatory process at early stages among workers with exposure to CB. We reviewed the studies with specific reference to the study design, statistical analyses, findings, and limitations.
We identified five Chinese studies that investigated the potential impact of exposure to CB on inflammatory markers, bronchial wall thickening, genomic instability, and lung function impairment in CB production workers. Of the five Chinese studies, four were cross-sectional; another study reported results at two-time points over six years of follow-up. The authors of all five studies concluded positive relationships between exposure and the inflammatory cytokine profiles. The weak to very weak correlations between biomarkers and early-stage endpoints were reported.
Most inflammatory markers failed to satisfy the proposed evidentiary quality criteria. The significance of the results of the reviewed studies is limited by the cross-sectional study design, inconsistency in results, uncertain clinical relevance, and high occupational exposures. Based on this review, the risk assessment relying on inflammatory markers does not seem appropriate at this time. Nevertheless, the novel research warrants further exploration in assessing exposure to ENMs and corresponding potential health risks in occupational settings.

The toxicity and carcinogenicity of hexavalent chromium via the inhalation route is well established. However, a scientific debate has arisen about the potential effects of oral exposure to chromium on human health. Epidemiological studies evaluating the connection between ingested chromium and adverse health effects on the general population are limited. In recent years, a wealth of biomonitoring studies has emerged evaluating the associations between chromium levels in body fluids and tissues and health outcomes. This systematic review brings together epidemiological and biomonitoring evidence published over the past decade on the health effects of the general population related to oral exposure to chromium. In total, 65 studies were reviewed. There appears to be an inverse association between prenatal chromium exposure and normal fetal development. In adults, parameters of oxidative stress and biochemical alterations increase in response to chromium exposure, while effects on normal renal function are conflicting. Risks of urothelial carcinomas cannot be overlooked. However, findings regarding internal chromium concentrations and abnormalities in various tissues and systems are, in most cases, controversial. Environmental monitoring together with large cohort studies and biomonitoring with multiple biomarkers could fill the scientific gap.

Wildfire smoke (WFS) is a mixture of respirable particulate matter, environmental gases, and other hazardous pollutants that originate from the unplanned burning of arid vegetation during wildfires. The increasing size and frequency of recent wildfires has escalated public and occupational health concerns regarding WFS inhalation, by either individuals living nearby and downstream an active fire or wildland firefighters and other workers that face unavoidable exposure because of their profession. In this review, we first synthesize current evidence from environmental, controlled, and interventional human exposure studies, to highlight positive associations between WFS inhalation and cardiovascular morbidity and mortality. Motivated by these findings, we discuss preventative measures and suggest interventions to mitigate the cardiovascular impact of wildfires. We then review animal and cell exposure studies to call attention on the pathophysiological processes that support the deterioration of cardiovascular tissues and organs in response to WFS inhalation. Acknowledging the challenges of integrating evidence across independent sources, we contextualize laboratory-scale exposure approaches according to the biological processes that they model and offer suggestions for ensuring relevance to the human condition. Noting that wildfires are significant contributors to ambient air pollution, we compare the biological responses triggered by WFS to those of other harmful pollutants. We also review evidence for how WFS inhalation may trigger mechanisms that have been proposed as mediators of adverse cardiovascular effects upon exposure to air pollution. We finally conclude by highlighting research areas that demand further consideration. Overall, we aspire for this work to serve as a catalyst for regulatory initiatives to mitigate the adverse cardiovascular effects of WFS inhalation in the community and alleviate the occupational risk in wildland firefighters.

OBJECTIVE: This integrative search aimed to provide a scoping overview of the relationships between the benefits and harms of alcohol drinking with cardiovascular events as associated to body fat mass and fatty liver diseases, as well as offering critical insights for precision nutrition research and personalized medicine implementation concerning cardiovascular risk management associated to ethanol consumption.
RESULTS: Frequent alcohol intake could contribute to a sustained rise in adiposity over time. Body fat distribution patterns (abdominal/gluteus-femoral) and intrahepatic accumulation of lipids have been linked to adverse cardiovascular clinical outcomes depending on ethanol intake. Therefore, there is a need to understand the complex interplay between alcohol consumption, adipose store distribution, metabolic dysfunction-associated steatotic liver disease (MASLD), and cardiovascular events in adult individuals. The current narrative review deals with underconsidered and apparently conflicting benefits concerning the amount of alcohol intake, ranging from abstention to moderation, and highlights the requirements for additional robust methodological studies and trials to interpret undertrained and existing controversies. The conclusion of this review emphasizes the need of newer multifaceted clinical approaches for precision medicine implementation, considering epidemiological strategies and pathophysiological mechanistic. Newer investigations and trials should be derived and performed particularly focusing both on alcohol\'s objective consequences as putatively mediated by fat deposition, including associated roles in fatty liver disease as well as to differentiate the impact of different levels of alcohol consumption (absence or moderation) concerning cardiovascular risks and accompanying clinical manifestations. Indeed, the threshold for the safe consumption of alcoholic drinks remains to be fully elucidated.