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Background: Perfluoroalkyl substances (PFAS) are widely used, ubiquitous, and highly persistent man-made chemicals. Groundwater of a vast area of the Veneto Region (northeastern Italy) was found to be contaminated by PFAS from a manufacturing plant active since the late 1960s. As a result, residents were overexposed to PFAS through drinking water until 2013, mainly to perfluorooctanoic acid (PFOA). OBJECTIVES: The aim of the present study was to estimate the rates of decline in serum PFOA and their corresponding serum half-lives, while characterizing their determinants. Methods: We investigated 5,860 subjects more than 14 years of age who enrolled in the second surveillance round of the regional health surveillance program. Two blood samples were collected between 2017 and 2022 (average time between measurements: 4 years). Serum PFOA excretion rates and half-lives were estimated based on linear mixed effect models, modeling subject-specific serum PFOA concentrations over time and correcting for background concentrations. For modeling determinants of half-life [age, sex, body mass index (BMI), smoking- habit, alcohol consumption, and estimated glomerular filtration rate (eGFR)], we added interaction terms between each covariate and the elapsed time between measurements. Perfluorooctanesulfonate (PFOS) and perfluorohexanesulfonic acid (PFHxS) apparent half-lives were also estimated. A separate analysis was conducted in children (n = 480). All analyses were stratified by sex. Results: Median initial serum concentrations of PFOA was 49 ng/mL (range: 0.5- 1,090), with a median reduction of 62.45%. The mean estimated PFOA half-life was 2.36 years [95% confidence interval (CI): 2.33, 2.40], shorter in women (2.04; 95% CI: 2.00, 2.08) compared to men (2.83; 95% CI: 2.78, 2.89). Half-lives varied when stratified by some contributing factors, with faster excretion rates in nonsmokers and nonalcohol drinkers (especially in males). Conclusions: This study, to our knowledge the largest on PFOA half-life, provides precise estimates in young adults whose exposure via drinking water has largely ceased. For other PFAS, longer half-lives than reported in other studies can be explained by some ongoing exposure to PFAS via other routes. https://doi.org/10.1289/EHP13152, Introduction Perfluoroalkyl substances (PFAS) are a group of widely used, ubiquitous, and highly persistent man-made chemicals. (1) Despite the progressive phasing out of several long-chain PFAS from industrial processes, significant [...]

BACKGROUND: Ramucirumab-an IgG1 vascular endothelial growth factor receptor 2 antagonist-plus docetaxel was previously reported to improve progression-free survival in platinum-refractory, advanced urothelial carcinoma. Here, we report the secondary endpoint of overall survival results for the RANGE trial. METHODS: We did a randomised, double-blind, phase 3 trial in patients with advanced or metastatic urothelial carcinoma who progressed during or after platinum-based chemotherapy. Patients were enrolled from 124 investigative sites (hospitals, clinics, and academic centres) in 23 countries. Previous treatment with one immune checkpoint inhibitor was permitted. Patients were randomly assigned (1:1) using an interactive web response system to receive intravenous ramucirumab 10 mg/kg or placebo 10 mg/kg volume equivalent followed by intravenous docetaxel 75 mg/m2 (60 mg/m2 in Korea, Taiwan, and Japan) on day 1 of a 21-day cycle. Treatment continued until disease progression, unacceptable toxicity, or other discontinuation criteria were met. Randomisation was stratified by geographical region, Eastern Cooperative Oncology Group performance status at baseline, and visceral metastasis. Progression-free survival (the primary endpoint) and overall survival (a key secondary endpoint) were assessed in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT02426125; patient enrolment is complete and the last patient on treatment is being followed up for safety issues. FINDINGS: Between July 20, 2015, and April 4, 2017, 530 patients were randomly allocated to ramucirumab plus docetaxel (n=263) or placebo plus docetaxel (n=267) and comprised the intention-to-treat population. At database lock (March 21, 2018) for the final overall survival analysis, median follow-up was 7·4 months (IQR 3·5-13·9). In our sensitivity analysis of investigator-assessed progression-free survival at the overall survival database lock, median progression-free survival remained significantly improved with ramucirumab compared with placebo (4·1 months [95% CI 3·3-4·8] vs 2·8 months [2·6-2·9]; HR 0·696 [95% CI 0·573-0·845]; p=0·0002). Median overall survival was 9·4 months (95% CI 7·9-11·4) in the ramucirumab group versus 7·9 months (7·0-9·3) in the placebo group (stratified HR 0·887 [95% CI 0·724-1·086]; p=0·25). Grade 3 or worse treatment-related treatment-emergent adverse events in 5% or more of patients and with an incidence more than 2% higher with ramucirumab than with placebo were febrile neutropenia (24 [9%] of 258 patients in the ramucirumab group vs 16 [6%] of 265 patients in the placebo group) and neutropenia (17 [7%] of 258 vs six [2%] of 265). Serious adverse events were similar between groups (112 [43%] of 258 patients in the ramucirumab group vs 107 [40%] of 265 patients in the placebo group). Adverse events related to study treatment and leading to death occurred in eight (3%) patients in the ramucirumab group versus five (2%) patients in the placebo group. INTERPRETATION: Additional follow-up supports that ramucirumab plus docetaxel significantly improves progression-free survival, without a significant improvement in overall survival, for patients with platinum-refractory advanced urothelial carcinoma. Clinically meaningful benefit might be restricted in an unselected population. FUNDING: Eli Lilly and Company.

This study investigates the mechanical properties and fatigue performance of Ti6Al4V cellular lattice materials (CLMs) featuring five distinct unit cell types (BCC‐Z, BCC, Octet, Truncated cuboctahedron [TCO], and Trabecular) at a relative density of 25%. Compression tests were conducted to assess static properties, including Young's modulus and yield strength. Subsequently, compression–compression fatigue tests (R = 0.1) were performed to evaluate fatigue behavior. Acoustic emission analysis was employed during static and fatigue tests to explore the potential for failure prediction. Results reveal that BCC‐Z and TCO exhibit slightly higher Young's moduli, surpassing 20 GPa, while BCC, Octet, and Trabecular display moduli ranging from 6 to 12 GPa. Regarding normalized fatigue behavior, BCC‐Z demonstrates superior fatigue resistance, followed by TCO. Notably, the acoustic emission parameters significantly correlate with the unit cell type. Lastly, a strong relationship between the initiation of failure and changes in acoustic emission parameters is observed, establishing a meaningful link between the static and fatigue curves and acoustic emission results. Highlights: Five different lattice topologies have been investigated under static and fatigue loading.BCC‐Z and TCO cell topologies have shown better mechanical performance comparatively.Mechanical response correlates with AE signals in both loading conditions.AE changes near the yielding and crack initiation for static and fatigue loads. [ABSTRACT FROM AUTHOR]

Background: In both the elderly and children, pneumonia remains one of the leading causes of hospitalization. This study aimed to assess the impact of pneumonia-related hospitalizations in the population over 65 years of age in the Veneto Region. Methods: This retrospective study analyzed hospital discharge records for patients aged 65 and older who resided in the Veneto Region and had a diagnosis of pneumonia from 2007 to 2023. The hospitalizations were identified using specific ICD-9-CM codes for pneumonia as a discharge diagnosis. Hospitalization rates, mortality rates, the prevalence of complications and comorbidities, the length of stay, and associated costs were calculated by age and year. Results: From 2007 to 2023, there were 139,201 hospitalizations for pneumonia. Emergency admissions accounted for 92.1% of these cases, and only 2.0% had a specific diagnosis of pneumococcal pneumonia. The median length of stay was 10 days, and the median diagnosis-related group (DRG) tariff per hospitalization was EUR 3307. Excluding the pandemic years, the hospitalization rates remained stable at approximately 850 cases per 100,000 inhabitants before 2019. After 2022, the rates started to increase again. Overall, in the investigated period, the results showed a negative trend (average Annual Percentage Change (AAPC) of −1.931, p < 0.0001). However, when only considering the pre-pandemic years, the trend was stable, while a decline was observed starting in 2020 (AAPC of −19.697, p = 0.001). The overall discharge mortality rates ranged from 13% to 19.3% but were significantly higher in those over 85 years of age (20.6% compared with 6.5% and 12.0% in the 65–74 and 75–84 age groups, respectively). Conclusions: This study highlights the substantial burden of pneumonia in individuals over 65 years of age, showing the impacts on public health. [ABSTRACT FROM AUTHOR]

Objective: To evaluate medium‐term self‐reported respiratory and gastrointestinal (GI) outcomes in children with congenital diaphragmatic hernia (CDH). Design: Self‐reported respiratory and GI outcomes correlated with prenatal severity indicators. Setting: Prospective study at three fetal medicine units. Population: Families of children prenatally diagnosed with isolated, left‐sided CDH surviving for >1 year. Methods: Families received validated questionnaires for GI outcomes (Infant Gastroesophageal Reflux Questionnaire Revised, I‐GERQ‐R, for infants aged <2 years, or Paediatric Gastro‐oesophageal Symptom and Quality of Life Questionnaire, PGSQ, for children aged aged 2‐8 years or >9 years) and respiratory outcomes (preschool respiratory outcome questionnaire, for children aged ≤5 years, or the International Study of Asthma and Allergies in Childhood asthma questionnaire, for children aged 6–8 years or ≥9 years). Prenatal data collected from the medical records included lung size (percentage observed/expected lung‐to‐head ratio, O/E LHR %), liver position, fetal endoluminal tracheal occlusion (FETO) gestational age (GA) at delivery, and perinatal data included birthweight, location, patch repair and respiratory support. Main outcome measures: The GI and respiratory scores were correlated with O/E LHR using linear and logistic regression models. Univariate analysis was used to evaluate associations with perinatal variables. Results: We obtained 142 responses from 342 families (representing a response rate of 45%). The baseline characteristics of participants and non‐participants were comparable. No correlations between perinatal variables and respiratory or GI scores were identified. Children aged ≤5 years with lower O/E LHR values reported higher respiratory scores (P = 0.0175); this finding was not reported in older children. Overall, the children who underwent FETO (n = 51) had GI (P = 0.290) and respiratory (P = 0.052) scores that were comparable with those of children who were expectantly managed. Conclusions: Families and children with prenatally diagnosed CDH reported fewer respiratory symptoms with increasing age. There was no correlation between O/E LHR or the use of FETO and self‐reported outcomes. [ABSTRACT FROM AUTHOR]

We systematically reviewed experiments in the fetal lamb model of gastroschisis using PubMed, Embase, Web of Science, and Scopus, seeking for standardized surgical techniques to obtain complex gastroschisis. Eligible were studies where an abdominal wall defect was surgically induced and gross anatomical findings at birth were available. The primary outcome was complex gastroschisis, defined by the presence of bowel stenosis, atresia, volvulus, perforation, and/or necrosis. Secondary outcomes were fetal death and additional readouts reported. Of ten eligible studies, six included lambs that had no additional prenatal manipulations and were assessed at term (35 lambs). Gastroschisis was induced at day 70–80 (term = 140–145), typically (n = 4/6 studies) in the left lower abdomen with defect size ranging from 0.5 to 4.0 cm. Only one study, in which a 1.5 cm diameter silicone ring was utilized, resulted in complex gastroschisis in 100% of term survivors. Fetal loss was more frequent in studies where a silicone ring and/or a right‐sided defect were used. No changes unique to complex gastroschisis were identified in additional readouts, including bowel histology. When gastroschisis becomes "complex" following induction is uncertain. This knowledge is essential in studying potential prenatal interventions that may change the natural course. [ABSTRACT FROM AUTHOR]