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Anoop Shankar, Jie Xiao, Alan DucatmanDepartment of Community Medicine, West Virginia University School of Medicine, Morgantown, WV, USABackground: Perfluoroalkyl chemicals, including perfluorooctanoic acid and perfluorooctane sulfonate, are man-made chemicals that have been detected in the blood of over 98% of the US population. Serum uric acid is a novel biomarker, even mild elevations of which has been implicated in the development of hypertension, diabetes mellitus, cardiovascular disease, and chronic kidney disease. We examined the relationship of serum perfluoroalkyl chemicals, including perfluorooctanoic acid and perfluorooctane sulfonate, and elevated uric acid levels in a representative sample of US adults.Methods: We examined 3883 participants from the 1999–2000 and 2003–2006 National Health and Nutritional Examination Surveys,a representative, multiethnic population-based survey of noninstitutionalized US adults. Serum perfluorooctanoic acid and perfluorooctane sulfonate were analyzed as quartiles. The main outcome was hyperuricemia.Results: We found that serum levels of perfluoroalkyl chemicals, including perfluorooctanoic acid and perfluorooctane sulfonate, were positively associated with hyperuricemia. This association appeared to be independent of confounders such as age, gender, race-ethnicity, body mass index, diabetes, hypertension, and serum cholesterol. Compared with subjects in quartile 1 (referent), the multivariate odds ratio for hyperuricemia among subjects in quartile 4 was 1.97 (95% confidence interval 1.44–2.70, P < 0.0001) for perfluorooctanoic acid and 1.48% (95% confidence interval 0.99–2.22, P = 0.0433) for perfluorooctane sulfonate. This observed association persisted in subgroup analysis by gender and body mass index.Conclusion: Our results demonstrate that elevated levels of perfluoroalkyl chemicals are associated with hyperuricemia even at low perfluoroalkyl chemical exposure levels as seen in the US general population.Keywords: perfluoroalkyl chemicals, perfluorooctanoic acid, perfluorooctane sulfonate, uric acid

Background & aimsPer- and polyfluoroalkyl substances (PFAS) are widespread pollutants with demonstrated hepatotoxicity. Few studies have examined the association between PFAS and fatty liver disease (FLD) risk in an adult population.MethodsIn this cross-sectional study of participants from the 2017-2018 National Health and Nutrition Examination Survey, serum PFAS were measured, and FLD cases were ascertained by vibration-controlled transient elastography. Logistic regression models were used to examine the association between circulating PFAS levels and FLD risk. Analyses were stratified into non-alcoholic FLD and alcoholic FLD risk groups by alcohol intake status, as well as controlling for other risk factors, including personal demographics, lifestyle factors, and related health factors.ResultsAmong 1,135 eligible participants, 446 had FLD. For FLD risk, the multivariable-adjusted odds ratio per log-transformed SD increase (ORSD) in perfluorohexane sulfonate (PFHxS) was 1.13 (95% CI 1.01-1.26). The association between PFHxS and FLD appeared stronger among individuals with obesity or high-fat diets (both p interaction

Abstract The largest documented episode of human contamination by PFOA in the world (approximately 150,000 actual residents on 1 January 2020) has occurred in Italy’s Veneto Region. In this large, mostly flat plain area, a cluster of testicular cancers has also been observed. Preliminary data are reported, and the most relevant and recent recommendations regarding the health surveillance of exposed individuals are emphasized.

Abstract Background Two counter trends in injury mortality have been separately reported in the US in recent times - a declining suicide rate and a rapidly rising unintentional poisoning mortality rate. Poisoning suicides are especially difficult to detect, and injury of undetermined intent is the underlying cause-of-death category most likely to reflect this difficulty. We compare suicide and poisoning mortality trends over two decades in a preliminary assessment of their independence and implications for suicide misclassification. Methods Description of overall and gender- and age-specific trends using national mortality data from WISQARS, the Web-based Injury Statistics Query and Reporting System, maintained by the Centers for Disease Control and Prevention (CDC). Subjects were the 936,633 residents dying in the 50 states and the District of Columbia between 1987 and 2006 whose underlying cause of death was classified as suicide, unintentional poisoning, or injury mortality of undetermined intent. Results The official US suicide rate declined 18% between 1987 and 2000, from 12.71 to 10.43 deaths per 100,000 population. It then increased to 11.15 deaths per 100,000 by 2006, a 7% rise. By contrast to these much smaller rate changes for suicide, the unintentional poisoning mortality rate rose more than fourfold between 1987 and 2006, from 2.19 to 9.22 deaths per 100,000. Only the population aged 65 years and older showed a sustained decline in the suicide rate over the entire observation period. Consistently highest in gender-age comparisons, the elderly male rate declined by 35%. The elderly female rate declined by 43%. Unlike rate trends for the non-elderly, both declines appeared independent of corresponding mortality trends for unintentional poisoning and poisoning of undetermined intent. The elderly also deviated from younger counterparts by having a smaller proportion of their injury deaths of undetermined intent classified as poisoning. Poisoning manifested as a less common method of suicide for this group than other decedents, except for those aged 15-24 years. Although remaining low, the undetermined poisoning mortality rate increased over the observation period. Conclusions The official decline in the suicide rate between 1987 and 2000 may have been a partial artifact of misclassification of non-elderly suicides within unintentional poisoning mortality. We recommend in-depth national, regional, and local population-based research investigations of the poisoning-suicide nexus, and endorse calls for widening the scope of the definition of suicide and evaluation of its risk factors.

Abstract Background Suicide officially kills approximately 30,000 annually in the United States. Analysis of this leading public health problem is complicated by undercounting. Despite persisting socioeconomic and health disparities, non-Hispanic Blacks and Hispanics register suicide rates less than half that of non-Hispanic Whites. Methods This cross-sectional study uses multiple cause-of-death data from the US National Center for Health Statistics to assess whether race/ethnicity, psychiatric comorbidity documentation, and other decedent characteristics were associated with differential potential for suicide misclassification. Subjects were 105,946 White, Black, and Hispanic residents aged 15 years and older, dying in the US between 2003 and 2005, whose manner of death was recorded as suicide or injury of undetermined intent. The main outcome measure was the relative odds of potential suicide misclassification, a binary measure of manner of death: injury of undetermined intent (includes misclassified suicides) versus suicide. Results Blacks (adjusted odds ratio [AOR], 2.38; 95% confidence interval [CI], 2.22-2.57) and Hispanics (1.17, 1.07-1.28) manifested excess potential suicide misclassification relative to Whites. Decedents aged 35-54 (AOR, 0.88; 95% CI, 0.84-0.93), 55-74 (0.52, 0.49-0.57), and 75+ years (0.51, 0.46-0.57) showed diminished misclassification potential relative to decedents aged 15-34, while decedents with 0-8 years (1.82, 1.75-1.90) and 9-12 years of education (1.43, 1.40-1.46) showed excess potential relative to the most educated (13+ years). Excess potential suicide misclassification was also apparent for decedents without (AOR, 3.12; 95% CI, 2.78-3.51) versus those with psychiatric comorbidity documented on their death certificates, and for decedents whose mode of injury was "less active" (46.33; 43.32-49.55) versus "more active." Conclusions Data disparities might explain much of the Black-White suicide rate gap, if not the Hispanic-White gap. Ameliorative action would extend from training in death certification to routine use of psychological autopsies in equivocal-manner-of-death cases.

Abstract Background Clinician training deficits and a low and declining autopsy rate adversely impact the quality of death certificates in the United States. Self-report and records data for the general population indicate that proximate mental and physical health of minority suicides was at least as poor as that of white suicides. Methods This cross-sectional mortality study uses data from Multiple Cause-of-Death (MCOD) public use files for 1999–2003 to describe and evaluate comorbidity among black, Hispanic, and white suicides. Unintentional injury decedents are the referent for multivariate analyses. Results One or more mentions of comorbid psychopathology are documented on the death certificates of 8% of white male suicides compared to 4% and 3% of black and Hispanic counterparts, respectively. Corresponding female figures are 10%, 8%, and 6%. Racial-ethnic discrepancies in the prevalence of comorbid physical disease are more attenuated. Cross-validation with National Violent Death Reporting System data reveals high relative underenumeration of comorbid depression/mood disorders and high relative overenumeration of schizophrenia on the death certificates of both minorities. In all three racial-ethnic groups, suicide is positively associated with depression/mood disorders [whites: adjusted odds ratio (AOR) = 31.9, 95% CI = 29.80–34.13; blacks: AOR = 60.9, 95% CI = 42.80–86.63; Hispanics: AOR = 34.7, 95% CI = 23.36–51.62] and schizophrenia [whites: AOR = 2.4, 95% CI = 2.07–2.86; blacks: AOR = 4.2, 95% CI = 2.73–6.37; Hispanics: AOR = 4.1, 95% CI = 2.01–8.22]. Suicide is positively associated with cancer in whites [AOR = 1.8, 95% CI = 1.69–1.93] and blacks [AOR = 1.8, 95% CI = 1.36–2.48], but not with HIV or alcohol and other substance use disorders in any group under review. Conclusion The multivariate analyses indicate high consistency in predicting suicide-associated comorbidities across racial-ethnic groups using MCOD data. However, low prevalence of documented comorbid psychopathology in suicides, and concomitant racial-ethnic discrepancies underscore the need for training in death certification, and routinization and standardization of timely psychological autopsies in all cases of suicide, suspected suicide, and other traumatic deaths of equivocal cause.

Background & Aims: Per- and polyfluoroalkyl substances (PFAS) are widespread pollutants with demonstrated hepatotoxicity. Few studies have examined the association between PFAS and fatty liver disease (FLD) risk in an adult population. Methods: In this cross-sectional study of participants from the 2017–2018 National Health and Nutrition Examination Survey, serum PFAS were measured, and FLD cases were ascertained by vibration-controlled transient elastography. Logistic regression models were used to examine the association between circulating PFAS levels and FLD risk. Analyses were stratified into non-alcoholic FLD and alcoholic FLD risk groups by alcohol intake status, as well as controlling for other risk factors, including personal demographics, lifestyle factors, and related health factors. Results: Among 1,135 eligible participants, 446 had FLD. For FLD risk, the multivariable-adjusted odds ratio per log-transformed SD increase (ORSD) in perfluorohexane sulfonate (PFHxS) was 1.13 (95% CI 1.01–1.26). The association between PFHxS and FLD appeared stronger among individuals with obesity or high-fat diets (both p interaction

Background: Per- and polyfluoroalkyl substances (PFAS) are ubiquitous in the environment and have been shown to cause various adverse health impacts. In animals, sex- and species-specific differences in PFAS elimination half-lives have been linked to the activity of kidney transporters. However, PFAS molecular interactions with kidney transporters are still not fully understood. Moreover, the impact of kidney disease on PFAS elimination remains unclear. Objectives: This state-of-the-science review integrated current knowledge to assess how changes in kidney function and transporter expression from health to disease could affect PFAS toxicokinetics and identified priority research gaps that should be addressed to advance knowledge. Methods: We searched for studies that measured PFAS uptake by kidney transporters, quantified transporter-level changes associated with kidney disease status, and developed PFAS pharmacokinetic models. We then used two databases to identify untested kidney transporters that have the potential for PFAS transport based on their endogenous substrates. Finally, we used an existing pharmacokinetic model for perfluorooctanoic acid (PFOA) in male rats to explore the influence of transporter expression levels, glomerular filtration rate (GFR), and serum albumin on serum half-lives. Results: The literature search identified nine human and eight rat kidney transporters that were previously investigated for their ability to transport PFAS, as well as seven human and three rat transporters that were confirmed to transport specific PFAS. We proposed a candidate list of seven untested kidney transporters with the potential for PFAS transport. Model results indicated PFOA toxicokinetics were more influenced by changes in GFR than in transporter expression. Discussion: Studies on additional transporters, particularly efflux transporters, and on more PFAS, especially current- use PFAS, are needed to better cover the role of transporters across the PFAS class. Remaining research gaps in transporter expression changes in specific kidney disease states could limit the effectiveness of risk assessment and prevent identification of vulnerable populations. https://doi.org/ 10.1289/EHP11885, Introduction Per- and polyfluoroalkyl substances (PFAS), a class of thousands of manufactured chemicals with at least one perfluorinated carbon atom, have been ubiquitously detected in the environment, (1,2) humans, (3-5) [...]

We investigated the influence of pathology data to improve patient outcomes in the treatment of high-grade cervical neoplasia in a joint pathology and gynecology collaboration. Two of us (B.S.D. and M.D.) reviewed all cytology, colposcopy and surgical pathology results, patient history, and pregnancy outcomes from all patients with loop electrosurgical excision procedure specimens for a 33-month period (January 2011-September 2013). We used this to determine compliance to 2006 consensus guidelines for the performance of loop electrosurgical excision procedure and shared this information in 2 interprofessional and interdisciplinary educational interventions with Obstetrics/Gynecology and Pathology faculty at the end of September 2013. We simultaneously emphasized the new 2013 guidelines. During the postintervention period, we continued to provide follow-up using the parameters previously collected. Our postintervention data include 90 cases from a 27-month period (October 2013-December 2015). Our preintervention data include 331 cases in 33 months (average 10.0 per month) with 76% adherence to guidelines. Postintervention, there were 90 cases in 27 months (average 3.4 per month) and 96% adherence to the 2013 (more conservative) guidelines (P < .0001, χ2 test). Preintervention, the rate of high-grade squamous intraepithelial lesion in loop electrosurgical excision procedures was 44%, whereas postintervention, there was a 60% high-grade squamous intraepithelial lesion rate on loop electrosurgical excision procedure (P < .0087 by 2-tailed Fisher exact test). The duration between diagnosis of low-grade squamous intraepithelial lesion and loop electrosurgical excision procedure also increased significantly from a median 25.5 months preintervention to 54 months postintervention (P < .0073; Wilcoxon Kruskal-Wallis test). Postintervention, there was a marked decrease of loop electrosurgical excision procedure cases as well as better patient outcomes. We infer improved patient safety, and higher value can be achieved by providing performance-based pathologic data.

Background: Per- and polyfluoroalkyl substances (PFASs) including perfluorooctanoic acid (PFOA) are ubiquitous environmental contaminants. Prior analysis in the large “C8 Health Project” population defined abnormal alanine aminotransferase (ALT) with statistically derived cutoffs (>45 IU/L in men, >34 IU/L in women). Objective: To explore the degree to which PFOA was associated with modern, clinically predictive ALT biomarker cutoffs in obese and nonobese participants, excluding those with diagnosed liver disease. Methods: We reevaluated the relationship of serum PFOA to abnormal ALT using predictive cutoff recommendations including those of the American College of Gastroenterology (ACG). Evaluations modeled lifetime cumulative exposure and measured internal PFOA exposure. Results: ACG cutoff values (≥34 IU/L for males, ≥25 IU/L for females) classified 30% of males (3815/12,672) and 21% of females (3359/15,788) above ALT cutoff values. Odds ratios (OR) for above cutoff values were consistently associated with modeled cumulative and measured serum PFOA. Linear trends were highly significant. ORs by quintile showed near monotonic increases. Trends were stronger for the overweight and obese. However, all weight classes were affected. Conclusion: Predictive cutoffs increase the OR for abnormal ALT results. Obesity increases ORs, yet association with abnormal ALT pertains to all weight classes. The results are discussed in context of current knowledge about the health implications of PFOA hepatotoxicity.

Background: Per- and polyfluoroalkyl substances (PFAS) are human-made compounds with a widespread presence in human blood and other organs. PFAS have been associated with multiple health effects, including higher serum cholesterol and LDL cholesterol. Objective: Potential population differences in serum PFAS attributable to ezetimibe, a medication that inhibits cholesterol absorption, are of interest for several reasons. The “C8” Health Project survey data from six contaminated water districts in the mid-Ohio Valley of the United States provide a wide enough range of serum PFAS and a sufficient number of ezetimibe takers to explore this topic. Methods: A total of 44,126 adult participants of the C8 Health Survey were included in the community-based study. The status of taking (1075) or non-taking of ezetimibe, alone or in combination with another lipid-lowering agent, was acquired. The geometric mean serum concentrations of the four most commonly detected serum PFAS were compared based on the status of ezetimibe use. Results: There is no significant difference in serum concentrations of perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), and perfluorononanoic acid (PFNA) between ezetimibe users and non-users after adjustment for age, sex, body mass index, estimated glomerular filtration rate (eGFR), cigarette smoking, education, and average household income. Conclusion: The sterol absorption-inhibiting medication ezetimibe does not appear to affect serum PFAS concentrations. We sought but did not find direct evidence that ezetimibe could inhibit PFAS uptake nor inferential evidence that inter-individual differences in sterol absorption could provide a confounding factor explanation for the association of serum total- and LDL-cholesterol with serum PFAS.

Environ Health Perspect. 130(4):041303 (2022), https://doi.org/10.1289/EHP11149 The first sentence in the second paragraph of the article incorrectly defined PFOS as perfluorohexane sulfonic acid rather than perfluorooctane sulfonic acid. The sentence [...]

In this issue, Costello et al. (1) provide a meta-analysis for associations between per- and polyfluoroalkyl substances (PFAS) and human clinical biomarkers for liver injury. They simultaneously considered PFAS effects [...]

Background: The current coronavirus disease 2019 (COVID-19) is spreading globally at an accelerated rate. There is some previous evidence that weather may influence the incidence of COVID-19 infection. We assessed the role of meteorological factors including temperature (T) and relative humidity (RH) considering the concentrations of two air pollutants, inhalable coarse particles (PM10) and nitrogen dioxide (NO2) in the incidence of COVID-19 infections in Finland, located in arctic-subarctic climatic zone.Methods: We retrieved daily counts of COVID-19 in Finland from Jan 1 to May 31, 2020, nationwide and separately for all 21 hospital districts across the country. The meteorological and air quality data were from the monitoring stations nearest to the central district hospital. A quasi-Poisson generalized additional model (GAM) was fitted to estimate the associations between district-specific meteorological factors and the daily counts of COVID-19 during the study period. Sensitivity analyses were conducted to test the robustness of the results.Results: The incidence rate of COVID-19 gradually increased until a peak around April 6 and then decreased. There were no associations between daily temperature and incidence rate of COVID-19. Daily average RH was negatively associated with daily incidence rate of COVID-19 in two hospital districts located inland. No such association was found nationwide.Conclusions: Weather conditions, such as air temperature and relative humidity, were not related to the COVID-19 incidence during the first wave in the arctic and subarctic winter and spring. The inference is based on a relatively small number of cases and a restricted time period.

* Context.--Human papillomavirus (HPV) is implicated in the development of oropharyngeal squamous cell carcinomas (OPC), particularly those cancers developing in tonsillar tissue. Objectives.--To review the prevalence, subtypes, and methods of detecting HPV in OPC and to review the epidemiology, histology, staging, management, and prevention of these cancers. Data Sources.--The study comprised a review of the literature. Conclusions.--The incidence of HPV-OPC is rising globally and in the United States, but rates of HPV-positivity vary with the anatomic site(s) and the population studied, as well as the method of detecting HPV infection. These tumors are more common in men. In contrast to [HPV.sup.-] OPC, the rates of smoking and alcohol abuse are lower. The HPV 16 subtype is predominant, and immunohistochemistry staining for p16 and in situ hybridization are the most widely used methods clinically to detect transcriptionally active HPV. Moreover, HPV-OPC has a unique tumor phenotype with predominantly nonkeratinizing morphology and a variety of patterns. These cancers often present with cystic lymph node metastases. The prognosis for HPV-OPC is significantly better than HPV OPC and has led to differences in grading, staging, and management. Although there are similarities to cervical cancer, there are challenges in preventing such cancers. (Arch Pathol Lab Med. 2018;142:715-718; doi: 10.5858/arpa.2018-0083-RA), Although an infectious etiology for cervical cancer was postulated for decades, the association between human papillomavirus (HPV) and oropharyngeal carcinoma (OPC) spans only the past 2 decades. The anatomic sites [...]

This Viewpoint describes new maximum contaminant levels set by the Environmental Protection Agency for specific perfluoroalkyl and polyfluoroalkyl substances (PFASs) and discusses the role clinicians can play in addressing their patients' PFAS health concerns. [ABSTRACT FROM AUTHOR]

* Context.--Types 16 and 18 are the most widely studied high-risk types of human papillomavirus (HPV). However, other high-risk HPV types (HPV non-16/18) also play a significant role in cervical neoplasia. Currently, screening and management algorithms separate out HPV 16/18 from all other HPV non-16/18 types. In addition, most of the previously vaccinated population has only been vaccinated for these high-risk types, so many women are still vulnerable to HPV non-16/18 infections. Objective.--To review the prevalence and role of HPV non-16/18 neoplasia and to review current surveillance, management, and vaccination strategies in view of these findings. Data Sources.--The study comprised a review of the literature. Conclusions.--Although HPV non-16/18 types are less frequently associated with cervical intraepithelial neoplasia and cancer, they are nonetheless a significant cause of disease. Further stratification of higher-risk HPV non-16/18 may be necessary to improve prevention and management, however, regional prevalence differences may make a unified approach difficult. As HPV 16/18 infections decrease owing to vaccination of at-risk women, the relative frequency of HPV non-16/18 will increase, although the latest vaccine covers several more high-risk types. (Arch Pathol Lab Med. 2018;142:693-695; doi: 10.5858/arpa.2017-0563-RA), Most cervical cancers are associated with human papillomavirus (HPV) 16 (often squamous), with the second most common association being HPV type 18 (often adenocarcinomas). (1) Therefore, diagnosis and management of [...]