Toxicants with the potential to bioaccumulate in humans and animals have long been a cause for concern, particularly due to their association with multiple diseases and organ injuries. Per- and polyfluoro alkyl substances (PFAS) and polycyclic aromatic hydrocarbons (PAH) are two such classes of chemicals that bioaccumulate and have been associated with steatosis in the liver. Although PFAS and PAH are classified as chemicals of concern, their molecular mechanisms of toxicity remain to be explored in detail. In this study, we aimed to identify potential mechanisms by which an acute exposure to PFAS and PAH chemicals can induce lipid accumulation and whether the responses depend on chemical class, dose, and sex. To this end, we analyzed mechanisms beginning with the binding of the chemical to a molecular initiating event (MIE) and the consequent transcriptomic alterations. We collated potential MIEs using predictions from our previously developed ToxProfiler tool and from published steatosis adverse outcome pathways. Most of the MIEs are transcription factors, and we collected their target genes by mining the TRRUST database. To analyze the effects of PFAS and PAH on the steatosis mechanisms, we performed a computational MIE-target gene analysis on high-throughput transcriptomic measurements of liver tissue from male and female rats exposed to either a PFAS or PAH. The results showed peroxisome proliferator-activated receptor (PPAR)-α targets to be the most dysregulated, with most of the genes being upregulated. Furthermore, PFAS exposure disrupted several lipid metabolism genes, including upregulation of fatty acid oxidation genes (Acadm, Acox1, Cpt2, Cyp4a1-3) and downregulation of lipid transport genes (Apoa1, Apoa5, Pltp). We also identified multiple genes with sex-specific behavior. Notably, the rate-limiting genes of gluconeogenesis (Pck1) and bile acid synthesis (Cyp7a1) were specifically downregulated in male rats compared to female rats, while the rate-limiting gene of lipid synthesis (Scd) showed a PFAS-specific upregulation. The results suggest that the PPAR signaling pathway plays a major role in PFAS-induced lipid accumulation in rats. Together, these results show that PFAS exposure induces a sex-specific multi-factorial mechanism involving rate-limiting genes of gluconeogenesis and bile acid synthesis that could lead to activation of an adverse outcome pathway for steatosis.

The re-emission and subsurface migration of legacy mercury (Hg) are not well understood due to limited knowledge of the driving processes. To investigate these processes at a decommissioned chlor-alkali plant, we used mercury stable isotopes and chemical speciation analysis. The isotopic composition of volatilized Hg(0) was lighter compared to the bulk total Hg (THg) pool in salt-sludge and adjacent surface soil with mean ε202HgHg(0)-THg values of -3.29 and -2.35‰, respectively. Hg(0) exhibited dichotomous directions (E199HgHg(0)-THg = 0.17 and -0.16‰) of mass-independent fractionation (MIF) depending on the substrate from which it was emitted. We suggest that the positive MIF enrichment during Hg(0) re-emission from salt-sludge was overall controlled by the photoreduction of Hg(II) primarily ligated by Cl- and/or the evaporation of liquid Hg(0). In contrast, O-bonded Hg(II) species were more important in the adjacent surface soils. The migration of Hg from salt-sludge to subsurface soil associated with selective Hg(II) partitioning and speciation transformation resulted in deep soils depleted in heavy isotopes (δ202Hg = -2.5‰) and slightly enriched in odd isotopes (Δ199Hg = 0.1‰). When tracing sources using Hg isotopes, it is important to exercise caution, particularly when dealing with mobilized Hg, as this fraction represents only a small portion of the sources.

BACKGROUND: In minimally invasive esophagectomy, a circular stapled anastomosis is common, but no evidence exists investigating the role of the specific localization of the anastomosis. The aim of this study is to evaluate the impact of an esophagogastrostomy on the anterior or posterior wall of the gastric conduit on the postoperative outcomes.
METHODS: All oncologic minimally invasive Ivor Lewis procedures, performed between 2017 and 2022, were included in this study. The cohort was divided in two groups: a) intrathoracic esophagogastrostomy on the anterior gastric wall of the conduit (ANT, n = 285, 65%) and b) on the posterior gastric wall (POST, n = 154, 35%). Clinicopathological parameters and short-term outcomes were compared between both groups by retrieving data from the prospective database.
RESULTS: Overall, 439 patients were included, baseline characteristics were similar in both groups, there was a higher proportion of squamous cell carcinoma in ANT (22.8% vs. 16.2%, P = 0.043). A higher rate of robotic-assisted procedures was observed in ANT (71.2% vs. 49.4%). Anastomotic leakage rate was similar in both groups (ANT 10.4% vs. POST 9.8%, P = 0.851). Overall complication rate and Clavien-Dindo > 3 complication rates were higher in POST compared to ANT: 53.2% vs. 40% (P = 0.008) and 36.9% vs. 25.7% (P = 0.014), respectively. The rate of delayed gastric emptying (20.1% vs. 7.4%, P < 0.001) and nosocomial pneumonia (22.1% vs. 14.8%, P = 0.05) was significantly higher in POST.
CONCLUSIONS: Patients undergoing minimally invasive Ivor Lewis esophagectomy with an intrathoracic circular stapled anastomosis may benefit from esophagogastrostomy on the anterior wall of the gastric conduit, in terms of lower rate of delayed gastric emptying.

Minimally invasive esophagectomy is associated with lower postoperative morbidity and better quality of life compared to open esophagectomy in patients with comparable oncological outcomes. Robotic-assisted surgery represents the next step in the development of mini- mally invasive surgery. We aim to present the results of a pilot cohort of patients undergoing robotic-assisted minimally invasive esophagectomy (RAMIE).
An initial cohort of patients with RAMIE was retrospectively analyzed. Operative characteristics, histopathological results, postoperative course, incidence of complications, and postoperative mortality were evaluated.
From 3/2022 to 6/2023, a total of 31 patients underwent RAMIE at our institution, including hybrid RAMIE (robotic abdomen, open chest) in 11 and total RAMIE in 20 patients. Most patients were male, had locally advanced tumors, predominantly adenocarcinoma and neoadjuvant treat- ment. Thirty patients had Ivor-Lewis and one patient had McKeown esophagectomy. The median total operative time was 495 minutes and median blood loss was 200 mL. R0 resection was achieved in 87% of patients. A median of 26 lymph nodes were removed. Postoperative Clavien-Dindo ≥3 complications occurred in 9 (29%) patients. Four (13%) patients required reoperation. Anastomotic leak was found in 5 (16%) and pneumonia in 9 (29%) patients. The median hospital stay was 9 days. One patient died in the postoperative period. Thirty-day and 90-day mortality rates were 0% and 3.2%, respectively.
Our initial experience shows that RAMIE is a safe surgical procedure and we consider its implementation at our institution to be success- ful. After overcoming the learning curve, we hope to reduce the operative time and increase the medical benefit for the patient.

Infectious complications following oesophagectomy are associated with significant morbidity. Early prediction of these complications may mitigate significant morbidity and mortality. Patients undergoing minimally invasive oesophagectomy for carcinoma oesophagus between January 2019 and June 2020 were included in the study. All patients underwent standard preoperative investigations and preparation. Post-operative complications including infectious complications were recorded. Association of post-operative serum interleukin-6 (IL-6) levels with post-operative complications were analysed. A total of twenty-two participants were included in the study (median age; 51 years, 13 (%) male). The tumour site was middle 1/3rd of oesophagus in 13 (59.1%), lower 1/3rd of oesophagus in 9 (40.9%). The tumour histology was squamous cell carcinoma in all patients. Eight (36.4 %) patients developed major complications and five of them developed anastomotic leak. IL-6 levels were significantly higher on POD 3 in patients who developed major complications (p = 0.009) and anastomotic leak (p = 0.031). At receiver operating characteristic curve (ROC curve) analysis, an IL-6 cut-off level of 36.4 pg/ml on POD 3 yielded a sensitivity of 87% and a specificity of 79% for the prediction of major complication and cut-off level of 44.3 pg/ml on POD 3 yielded a sensitivity of 80% and a specificity of 82% for the prediction of anastomotic leak. A high post-operative IL-6 level helps in the prediction of major complications and cervical oesophagogastric anastomotic leak.

Minimally invasive esophagectomy (MIE) for esophageal cancer is a complex procedure that reduces postoperative morbidity in comparison to open approach. In this study, thoracic cage width as a factor to predict surgical difficulty in MIE was evaluated.
All patients of our institution receiving either total MIE or robotic-assisted MIE (RAMIE) with intrathoracic anastomosis between February 2016 and April 2021 for esophageal cancer were included in this study. Right unilateral thoracic cage width on the level of vena azygos crossing the esophagus was measured by the horizontal distance between the esophagus and parietal pleura on preoperative computer tomography. Patients\' data as well as operative and postoperative details were collected in a prospective database. Correlation between thoracic cage width with duration of the thoracic procedure and postoperative complication rates was analyzed.
Overall, 313 patients were eligible for this study. Thoracic width on vena azygos level ranged from 85 to 149 mm with a mean of 116.5 mm. In univariate analysis, a small thoracic width significantly correlated with longer duration of the thoracic procedure (p = 0.014). In multivariate analysis, small thoracic width and neoadjuvant therapy were identified as independent factors for long duration of the thoracic procedure (p = 0.006). Regarding postoperative complications, thoracic cage width was a significant risk factor for occurrence of postoperative pneumonia in the multivariate analysis (p = 0.045). Dividing the cohort into two groups of patients with narrow (≤ 107 mm, 19.5%) and wide thoraces (≥ 108 mm, 80.5%), the thoracic procedure was significantly prolonged by 17 min (204 min vs. 221 min, p = 0.014).
A small thoracic cage width is significantly correlated with longer operation time during thoracic phase of a MIE in Europe, which suggests increased surgical difficulty. Patients with small thoracic cage width may preferably be operated by MIE-experienced surgeons.

A visible-extended shortwave infrared indium gallium arsenide (InGaAs) focal plane array (FPA) detector is the ideal choice for reducing the size, weight and power (SWaP) of infrared imaging systems, especially in low-light night vision and other fields that require simultaneous visible and near-infrared light detection. However, the lower quantum efficiency in the visible band has limited the extensive application of the visible-extended InGaAs FPA. Recently, a novel optical metasurface has been considered a solution for a high-performance semiconductor photoelectric device due to its highly controllable property of electromagnetic wave manipulation. Broadband Mie resonator arrays, such as nanocones and nanopillars designed with FDTD methods, were integrated on a back-illuminated InGaAs FPA as an AR metasurface. The visible-extended InGaAs detector was fabricated using substrate removal technology. The nanostructures integrated into the Vis-SWIR InGaAs detectors could realize a 10-20% enhanced quantum efficiency and an 18.8% higher FPA response throughout the wavelength range of 500-1700 nm. Compared with the traditional AR coating, nanostructure integration has advantages, such as broadband high responsivity and omnidirection antireflection, as a promising route for future Vis-SWIR InGaAs detectors with higher image quality.

BACKGROUND: The previously published ROBOT trial demonstrated that robot assisted minimally invasive esophagectomy (RAMIE) is associated with a lower percentage of postoperative complications compared to open esophagectomy (OTE) for patients with esophageal cancer. The implications of these results on healthcare costs are important given the increased attention for cost-reduction in healthcare. Therefore the aim of this study was to report the hospital costs of RAMIE compared to OTE as treatment for esophageal cancer.
METHODS: The ROBOT trial randomized 112 patients with esophageal cancer between RAMIE and OTE through January 2012 and August 2016 in a single tertiary care academic centre in the Netherlands. The primary outcome of the current study was hospital costs from the day of esophagectomy until 90 days after discharge based on Time-Driven Activity-Based Costing methodology. Secondary outcomes included the incremental cost-effectiveness ratio per complication prevented and risk factors for increased hospital costs.
RESULTS: Of the 112 included patients, 109 patients underwent an esophagectomy, of whom 54 RAMIE and 55 OTE. The mean total hospital costs were comparable between RAMIE €40211 and OTE €39495 (mean difference €-715; bias-corrected and accelerated confidence interval € -14831 to 14783, p = 0.932). At a willingness-to-pay threshold of €20.000 to €25.000 (i.e. estimated additional costs to the hospital to treat patients with a complication) RAMIE had a probability 62%-70% of being cost effective to prevent postoperative complications. In multivariable regression analysis, major postoperative complications were the main driver of hospital costs after esophagectomy (€31839, p = 0.009).
CONCLUSIONS: In this randomized trial RAMIE resulted in fewer postoperative complications compared to OTE without increasing total hospital costs.

Surgery remains the mainstay for curative treatment of carcinoma of midthoracic and lower thoracic oesophagus. In the twentieth century, open esophagectomy was the standard of care. In the twenty-first century, treatment for carcinoma oesophagus has revolutionized with incorporation of neoadjuvant treatment and application of various minimally invasive techniques for esophagectomy. At present, there is no consensus about the optimum position to perform minimally invasive esophagectomy (MIE). We share our experience of MIE with modification in the port position in this article.

UNASSIGNED: Several studies reported the advantages of minimally invasive esophagectomy over the conventional open approach, particularly in terms of postoperative morbidity and mortality. The literature regarding the elderly population is however scarce and it is still not clear whether elderly patients may benefit from a minimally invasive approach as the general population. We sought to evaluate whether thoracoscopic/ laparoscopic (MIE) or fully robotic (RAMIE) Ivor-Lewis esophagectomy significantly reduces postoperative morbidity in the elderly population.
UNASSIGNED: We analyzed data of patients who underwent open esophagectomy or MIE/RAMIE at Mainz University Hospital and at Padova University Hospital between 2016 and 2021. Elderly patients were defined as those ≥ 75 years old. Clinical characteristics and the postoperative outcomes were compared between elderly patients who underwent open esophagectomy or MIE/RAMIE. A 1-to-1 matched comparison was also performed. Patients < 75 years old were evaluated as a control group.
UNASSIGNED: Among elderly patients MIE/RAMIE were associated with a lower overall morbidity (39.7% vs. 62.7%, p=0.005), less pulmonary complications (32.8 vs. 56.9%, p=0.003) and a shorter hospital stay (13 vs. 18 days, p=0.03). Comparable findings were obtained after matching. Similarly, among < 75 years-old patients, a reduced morbidity (31.2% vs. 43.5%, p=0.01) and less pulmonary complications (22% vs. 36%, p=0.001) were detected in the minimally invasive group.
UNASSIGNED: Minimally invasive esophagectomy improves the postoperative course of elderly patients reducing the overall incidence of postoperative complications, particularly of pulmonary complications.