Search

Background: Silicosis remains a critical public and occupational health issue, exacerbated by its expansion into non-traditional industries and resulting in significant global morbidity and mortality., Aims: This study aims to investigate the death rates associated with silicosis from jean sandblasting by comparing the results of diagnosed individuals to those of the general population., Methods: Conducted from 2008 to 2023 in Taşlıçay and Toklular villages, Bingöl City, Turkey, this retrospective cohort study analysed mortality among 220 diagnosed males versus 2851 undiagnosed residents. Data were derived from the Cohort database and validated with the Bingöl Provincial Health Directorate and the Turkish Statistical Institute. Statistical analysis involved univariate comparisons and survival analysis, utilizing the Mann-Whitney U-test, Kruskal-Wallis test and Cox proportional hazards model, with significance set at P < 0.05., Results: The analysis revealed a silicosis mortality rate of 10% in diagnosed individuals over 15 years, notably higher than the 4% in the general population. Higher radiological profusions and younger ages at diagnosis were significant mortality factors. A radiological profusion above five notably increased the mortality risk by 1.37 times, with age and radiological density proving critical in survival rates., Conclusions: This research highlights the increased mortality risk in silicosis patients, particularly among former jean sandblasters, underscoring the significant effects of radiological density and early age exposure on mortality, thereby addressing a crucial gap in understanding the impact of silicosis on life expectancy and community health., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Failure to rescue (FTR) is defined as the inability to prevent death after the development of a complication. FTR is a parameter in evaluating multidisciplinary postoperative complication management. The aim of this study was to evaluate FTR rates after major liver resection for perihilar cholangiocarcinoma (pCCA) and analyze factors associated with FTR., Patients and Method: Patients who underwent major liver resection for pCCA at 27 centers were included. FTR was defined as the presence of a Dindo grade III or higher complication followed by death within 90 days after surgery. Liver failure ISGLS grade B/C were scored. Multivariable logistic analysis was performed to identify predictors of FTR and reported using odds ratio and 95% confidence intervals., Results: In the 2186 included patients, major morbidity rate was 49%, 90-day mortality rate 13%, and FTR occurred in 24% of patients with a grade III or higher complication. Across centers, major complication rate varied from 19 to 87%, 90-day mortality rate from 5 to 33%, and FTR ranged from 11 to 50% across hospitals. Age [1.04 (1.02-1.05) years], ASA 3 or 4 [1.40 (1.01-1.95)], jaundice at presentation [1.79 (1.16-2.76)], right-sided resection [1.45 (1.06-1.98)], and annual hospital volume < 6 [1.44 (1.07-1.94)] were positively associated with FTR. When liver failure is included, the odds ratio for FTR is 9.58 (6.76-13.68)., Conclusion: FTR occurred in 24% of patients after resection for pCCA. Liver failure was associated with a nine-fold increase of FTR and hospital volume below six was also associated with an increased risk of FTR., (© 2024. The Author(s).)

Flap surgery is an integral part of plastic surgery, and ischemia-reperfusion (I/R) injury significantly affects the viability of the flap. Carvedilol (CRV), a nonselective beta-blocker with alpha-1 blocking and antioxidant properties, and known for its potential in reducing I/R damage, was chosen as the active substance for our study. The aim of this study was to investigate the vasodilator and antioxidant effects of CRV on rat inferior epigastric artery skin flap using orally disintegrating tablets (ODTs). The optimized ODT formulation was subjected to in vivo experiments using Sprague-Dawley female rats (n = 24) divided into three groups: Group I (control, I/R), Group II (treatment, I/R + CRV), and Group III (treatment, I/R), I/R + CRV ODT). Reperfusion was then observed following the release of the microclamp from the pedicle, and the flap was then re-adapted to its original position. Control rats were given oral isotonic solution via gavage and were subjected to 8 h of ischemia and 12 h of reperfusion. Group II was given 2 mg/kg CRV oral tablets for 7 days before and after surgery. Group III was given 2 mg/kg/day CRV ODT for the same period. Biopsies were taken from the flap and histopathological and biochemical analyses including superoxide dismutase, glutathionenitric oxide, malondialdehyde, paraoxonase 1, total oxidant, and total antioxidant capacities were performed. This study demonstrates that CRV ODTs significantly increased flap viability by approximately 25% compared to the control group, highlighting their promising therapeutic potential., (© 2024 Deutsche Pharmazeutische Gesellschaft.)

A spontaneously occurring temperature increase in solid tumors has been reported sporadically, but is largely overlooked in terms of cancer biology. Here we show that temperature is increased in tumors of patients with pancreatic ductal adenocarcinoma (PDAC) and explore how this could affect therapy response. By mimicking this observation in PDAC cell lines, we demonstrate that through adaptive changes in lipid metabolism, the temperature increase found in human PDAC confers protection to lipid peroxidation and contributes to gemcitabine resistance. Consistent with the recently uncovered role of p38 MAPK in ferroptotic cell death, we find that the reduction in lipid peroxidation potential following adaptation to tumoral temperature allows for p38 MAPK inhibition, conferring chemoresistance. As an increase in tumoral temperature is observed in several other tumor types, our findings warrant taking tumoral temperature into account in subsequent studies related to ferroptosis and therapy resistance. More broadly, our findings indicate that tumoral temperature affects cancer biology., (© 2024. The Author(s).)

Case series describing excellent outcomes for patients with dMMR GI cancer after resection of a single progressive lesion under immunotherapy.

In recent years, important efforts have been made to elucidate the mechanisms of epigenetic regulation, and one of the most studied epigenetic modifications was DNA methylation/demethylation. In this study, the voltammetric behaviour of 5-hydroxymethylcytosine was studied in the pH range of 2.00-11.00 using pencil graphite electrodes by differential pulse and square wave voltammetry. The effect of buffer solutions, scan rate, square wave voltammetry parameters, and stripping conditions on the voltammetric responses of 5-hydroxymethylcytosine were performed. The electrochemical oxidation process of 5-hydroxymethylcytosine on the pencil graphite electrode was realized under adsorption control. In human urine, by square wave stripping voltammetry, 5-hydroxymethylcytosine was quantified in a concentration range of 1.00 × 10 -5 M-2.00 × 10 -4  M. The proposed method was tested in the presence of cytosine in human urine. The recovery value of 5-hydroxymethylcytosine was found to be 99.57 %., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Many individuals with cancer are resistant to immunotherapies. Here, we identify the gene encoding the pyrimidine salvage pathway enzyme cytidine deaminase (CDA) among the top upregulated metabolic genes in several immunotherapy-resistant tumors. We show that CDA in cancer cells contributes to the uridine diphosphate (UDP) pool. Extracellular UDP hijacks immunosuppressive tumor-associated macrophages (TAMs) through its receptor P2Y 6 . Pharmacologic or genetic inhibition of CDA in cancer cells (or P2Y 6 in TAMs) disrupts TAM-mediated immunosuppression, promoting cytotoxic T cell entry and susceptibility to anti-programmed cell death protein 1 (anti-PD-1) treatment in resistant pancreatic ductal adenocarcinoma (PDAC) and melanoma models. Conversely, CDA overexpression in CDA-depleted PDACs or anti-PD-1-responsive colorectal tumors or systemic UDP administration (re)establishes resistance. In individuals with PDAC, high CDA levels in cancer cells correlate with increased TAMs, lower cytotoxic T cells and possibly anti-PD-1 resistance. In a pan-cancer single-cell atlas, CDA high cancer cells match with T cell cytotoxicity dysfunction and P2RY6 high TAMs. Overall, we suggest CDA and P2Y 6 as potential targets for cancer immunotherapy., (© 2024. The Author(s).)

Background: A right- or left-sided liver resection can be considered in about half of patients with perihilar cholangiocarcinoma (pCCA), depending on tumor location and vascular involvement. This study compared postoperative mortality and long-term survival of right- versus left-sided liver resections for pCCA., Methods: Patients who underwent major liver resection for pCCA at 25 Western centers were stratified according to the type of hepatectomy-left, extended left, right, and extended right. The primary outcomes were 90-day mortality and overall survival (OS)., Results: Between 2000 and 2022, 1701 patients underwent major liver resection for pCCA. The 90-day mortality was 9% after left-sided and 18% after right-sided liver resection (p < 0.001). The 90-day mortality rates were 8% (44/540) after left, 11% (29/276) after extended left, 17% (51/309) after right, and 19% (108/576) after extended right hepatectomy (p < 0.001). Median OS was 30 months (95% confidence interval [CI] 27-34) after left and 23 months (95% CI 20-25) after right liver resection (p < 0.001), and 33 months (95% CI 28-38), 27 months (95% CI 23-32), 25 months (95% CI 21-30), and 21 months (95% CI 18-24) after left, extended left, right, and extended right hepatectomy, respectively (p < 0.001). A left-sided resection was an independent favorable prognostic factor for both 90-day mortality and OS compared with right-sided resection, with similar results after excluding 90-day fatalities., Conclusions: A left or extended left hepatectomy is associated with a lower 90-day mortality and superior OS compared with an (extended) right hepatectomy for pCCA. When both a left and right liver resection are feasible, a left-sided liver resection is preferred., (© 2024. The Author(s).)

Objective: A novel posteriolateral surgical approach is described that will provide safe access to intradural and extradural lesions located in the anterior part of the spinal cord (SC) at the C1-2 level and to the odontoid in single session., Methods: A total of five cadavers and two dry C1 vertebrae were used in this study. The study involved obtaining computed tomography magnetic resonance imaging scans and magnetic resonance imaging of all cadaver groups before and after the procedures. Group 1: Control; Group 2: Unilateral C1 posterior arch was removed, the inferomedial part of C1 lateral mass was removed, and access the anterior and lateral aspects of the SC. Group 3: In addition, odontoid was removed, Group 4: In addition, unilateral C1- C2 screw was placed. Group 5: In addition, bilateral C1-C2 screw was placed., Results: The median distance from the midpoint of C1 posterior tubercle to vertebral groove which was removed in groups is 21.4 ± 2.88 mm. The average width of C1 lateral mass was 13.4±2.4 mm. After the lateral mass was drilled, its width decreased to 10,2 mm.This area was sufficient to open a surgical corridor and reach the anterior of SC and odontoid. After the procedure, no instability was found in group 2 without instrumentation on computed tomography and magnetic resonance imaging scans., Conclusions: It is possible to access the anterior C1-C2 via a posterolateral paramass approach by drilling 20%-30% of the lateral mass, providing an open pathway for easy intervention in C1-C2 intradural lesions. It is also possible to perform odontoid resection using this approach., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Improving novel and efficient biosensors for determining organic/inorganic compounds is a challenge in analytical chemistry for clinical diagnosis and research in biomedical sciences. Electrochemical enzyme-based biosensors are one of the commercially successful groups of biosensors that make them highly appealing because of their low cost, high selectivity, and sensitivity. Core/shell nanoparticles have emerged as versatile platforms for developing enzyme-based electrochemical biosensors due to their unique physicochemical properties and tunable surface characteristics. This study provides a comprehensive review of recent trends and advancements in the utilization of core/shell nanoparticles for the development of enzyme-based electrochemical biosensors. Moreover, a statistical evaluation of the studies carried out in this field between 2007 and 2023 is made according to the preferred electrochemical techniques. The recent applications of core/shell nanoparticles in enzyme-based electrochemical biosensors were summarized to quantify environmental pollutants, food contaminants, and clinical biomarkers. Additionally, the review highlights recent innovations and strategies to improve the performance of enzyme-based electrochemical biosensors using core/shell nanoparticles. These include the integration of nanomaterials with specific functions such as hydrophilic character, chemical and thermal stability, conductivity, biocompatibility, and catalytic activity, as well as the development of new hybrid nanostructures and multifunctional nanocomposites., (© 2024. The Author(s).)

Metastatic breast cancer (mBC) remains incurable and liver metastases (LM) are observed in approximately 50% of all patients with mBC. In some cases, surgical resection of breast cancer liver metastases (BCLM) is associated with prolonged survival. However, there are currently no validated marker to identify these patients. The interactions between the metastatic cancer cells and the liver microenvironment result in two main histopathological growth patterns (HGP): replacement (r-HGP), characterized by a direct contact between the cancer cells and the hepatocytes, and desmoplastic (d-HGP), in which a fibrous rim surrounds the tumor cells. In patients who underwent resection of BCLM, the r-HGP is associated with a worse postoperative prognosis than the d-HGP. Here, we aim at unraveling the biological differences between these HGP within ten patients presenting both HGP within the same metastasis. The transcriptomic analyses reveal overexpression of genes involved in cell cycle, DNA repair, vessel co-option and cell motility in r-HGP while angiogenesis, wound healing, and several immune processes were found overexpressed in d-HGP LM. Understanding the biology of the LM could open avenues to refine treatment of BC patients with LM., (© 2024. The Author(s).)

Background & Aims: In non-alcoholic fatty liver disease (NAFLD), monocytes infiltrate visceral adipose tissue promoting local and hepatic inflammation. However, it remains unclear what drives inflammation and how the immune landscape in adipose tissue differs across the NAFLD severity spectrum. We aimed to assess adipose tissue macrophage (ATM) heterogeneity in a NAFLD cohort., Methods: Visceral adipose tissue macrophages from lean and obese patients, stratified by NAFLD phenotypes, underwent single-cell RNA sequencing. Adipose tissue vascular integrity and breaching was assessed on a protein level via immunohistochemistry and immunofluorescence to determine targets of interest., Results: We discovered multiple ATM populations, including resident vasculature-associated macrophages (ResVAMs) and distinct metabolically active macrophages (MMacs). Using trajectory analysis, we show that ResVAMs and MMacs are replenished by a common transitional macrophage (TransMac) subtype and that, during NASH, MMacs are not effectively replenished by TransMac precursors. We postulate an accessory role for MMacs and ResVAMs in protecting the adipose tissue vascular barrier, since they both interact with endothelial cells and localize around the vasculature. However, across the NAFLD severity spectrum, alterations occur in these subsets that parallel an adipose tissue vasculature breach characterized by albumin extravasation into the perivascular tissue., Conclusions: NAFLD-related macrophage dysfunction coincides with a loss of adipose tissue vascular integrity, providing a plausible mechanism by which tissue inflammation is perpetuated in adipose tissue and downstream in the liver., Impact and Implications: Our study describes for the first time the myeloid cell landscape in human visceral adipose tissue at single-cell level within a cohort of well-characterized patients with non-alcoholic fatty liver disease. We report unique non-alcoholic steatohepatitis-specific transcriptional changes within metabolically active macrophages (MMacs) and resident vasculature-associated macrophages (ResVAMs) and we demonstrate their spatial location surrounding the vasculature. These dysfunctional transcriptional macrophage states coincided with the loss of adipose tissue vascular integrity, providing a plausible mechanism by which tissue inflammation is perpetuated in adipose tissue and downstream in the liver. Our study provides a theoretical basis for new therapeutic strategies to be directed towards reinstating the endogenous metabolic, homeostatic and cytoprotective functions of ResVAMs and MMacs, including their role in protecting vascular integrity., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: While resection remains the only curative option for perihilar cholangiocarcinoma, it is well known that such surgery is associated with a high risk of morbidity and mortality. Nevertheless, beyond facing life-threatening complications, patients may also develop early disease recurrence, defining a "futile" outcome in perihilar cholangiocarcinoma surgery. The aim of this study is to predict the high-risk category (futile group) where surgical benefits are reversed and alternative treatments may be considered., Methods: The study cohort included prospectively maintained data from 27 Western tertiary referral centers: the population was divided into a development and a validation cohort. The Framingham Heart Study methodology was used to develop a preoperative scoring system predicting the "futile" outcome., Results: A total of 2271 cases were analyzed: among them, 309 were classified within the "futile group" (13.6%). American Society of Anesthesiology (ASA) score ≥ 3 (OR 1.60; p = 0.005), bilirubin at diagnosis ≥50 mmol/L (OR 1.50; p = 0.025), Ca 19-9 ≥ 100 U/mL (OR 1.73; p = 0.013), preoperative cholangitis (OR 1.75; p = 0.002), portal vein involvement (OR 1.61; p = 0.020), tumor diameter ≥3 cm (OR 1.76; p < 0.001), and left-sided resection (OR 2.00; p < 0.001) were identified as independent predictors of futility. The point system developed, defined three (ie, low, intermediate, and high) risk classes, which showed good accuracy (AUC 0.755) when tested on the validation cohort., Conclusions: The possibility to accurately estimate, through a point system, the risk of severe postoperative morbidity and early recurrence, could be helpful in defining the best management strategy (surgery vs. nonsurgical treatments) according to preoperative features., (Copyright © 2023 American Association for the Study of Liver Diseases.)