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Frontiers in Public Health 2024In recent years, the prevalence of obesity has continued to increase as a global health concern. Numerous epidemiological studies have confirmed the long-term effects of...
BACKGROUND
In recent years, the prevalence of obesity has continued to increase as a global health concern. Numerous epidemiological studies have confirmed the long-term effects of exposure to ambient air pollutant particulate matter 2.5 (PM) on obesity, but their relationship remains ambiguous.
METHODS
Utilizing large-scale publicly available genome-wide association studies (GWAS), we conducted univariate and multivariate Mendelian randomization (MR) analyses to assess the causal effect of PM exposure on obesity and its related indicators. The primary outcome given for both univariate MR (UVMR) and multivariate MR (MVMR) is the estimation utilizing the inverse variance weighted (IVW) method. The weighted median, MR-Egger, and maximum likelihood techniques were employed for UVMR, while the MVMR-Lasso method was applied for MVMR in the supplementary analyses. In addition, we conducted a series of thorough sensitivity studies to determine the accuracy of our MR findings.
RESULTS
The UVMR analysis demonstrated a significant association between PM exposure and an increased risk of obesity, as indicated by the IVW model (odds ratio [OR]: 6.427; 95% confidence interval [CI]: 1.881-21.968; = 0.005). Additionally, PM concentrations were positively associated with fat distribution metrics, including visceral adipose tissue (VAT) (OR: 1.861; 95% CI: 1.244-2.776; = 0.004), particularly pancreatic fat (OR: 3.499; 95% CI: 2.092-5.855; PFDR =1.28E-05), and abdominal subcutaneous adipose tissue (ASAT) volume (OR: 1.773; 95% CI: 1.106-2.841; = 0.019). Furthermore, PM exposure correlated positively with markers of glucose and lipid metabolism, specifically triglycerides (TG) (OR: 19.959; 95% CI: 1.269-3.022; = 0.004) and glycated hemoglobin (HbA1c) (OR: 2.462; 95% CI: 1.34-4.649; = 0.007). Finally, a significant negative association was observed between PM concentrations and levels of the novel obesity-related biomarker fibroblast growth factor 21 (FGF-21) (OR: 0.148; 95% CI: 0.025-0.89; = 0.037). After adjusting for confounding factors, including external smoke exposure, physical activity, educational attainment (EA), participation in sports clubs or gym leisure activities, and Townsend deprivation index at recruitment (TDI), the MVMR analysis revealed that PM levels maintained significant associations with pancreatic fat, HbA1c, and FGF-21.
CONCLUSION
Our MR study demonstrates conclusively that higher PM concentrations are associated with an increased risk of obesity-related indicators such as pancreatic fat content, HbA1c, and FGF-21. The potential mechanisms require additional investigation.
Topics: Humans; Particulate Matter; Obesity; Mendelian Randomization Analysis; Genome-Wide Association Study; White People; Air Pollutants; Environmental Exposure; Air Pollution
PubMed: 38947357
DOI: 10.3389/fpubh.2024.1366838 -
Frontiers in Immunology 2024Type I diabetes is an autoimmune disease mediated by T-cell destruction of β cells in pancreatic islets. Currently, there is no known cure, and treatment consists of...
Type I diabetes is an autoimmune disease mediated by T-cell destruction of β cells in pancreatic islets. Currently, there is no known cure, and treatment consists of daily insulin injections. Genome-wide association studies and twin studies have indicated a strong genetic heritability for type I diabetes and implicated several genes. As most strongly associated variants are noncoding, there is still a lack of identification of functional and, therefore, likely causal variants. Given that many of these genetic variants reside in enhancer elements, we have tested 121 CD4+ T-cell enhancer variants associated with T1D. We found four to be functional through massively parallel reporter assays. Three of the enhancer variants weaken activity, while the fourth strengthens activity. We link these to their cognate genes using 3D genome architecture or eQTL data and validate them using CRISPR editing. Validated target genes include and While these genes have been previously implicated in type 1 diabetes and other autoimmune diseases, we show that enhancers controlling their expression harbor functional variants. These variants, therefore, may act as causal type 1 diabetic variants.
Topics: Diabetes Mellitus, Type 1; Humans; CD4-Positive T-Lymphocytes; Enhancer Elements, Genetic; Genetic Predisposition to Disease; Suppressor of Cytokine Signaling 1 Protein; Genome-Wide Association Study; Lectins, C-Type; Genetic Variation; Polymorphism, Single Nucleotide; Quantitative Trait Loci
PubMed: 38947339
DOI: 10.3389/fimmu.2024.1387253 -
Endoscopic Ultrasound 2024EUS-guided fine-needle biopsy (FNB) is an established technique for the acquisition of tissue to diagnose lesions of the gastrointestinal tract and surrounding organs....
Comparing the diagnostic adequacy of 25-Gauge fork-tip franseen reverse-bevel-type needles in EUS-guided tissue acquisition: A prospective randomized study with a retrospective control.
BACKGROUND AND OBJECTIVES
EUS-guided fine-needle biopsy (FNB) is an established technique for the acquisition of tissue to diagnose lesions of the gastrointestinal tract and surrounding organs. Recently, newer-generation FNB needles have been introduced, including a second-generation reverse-bevel and the third-generation fork-tip and Franseen needles. We aimed to determine if there was any difference between these needles in terms of cytopathological diagnostic yield, sample cellularity, or sample bloodiness.
METHODS
One hundred twenty-seven consecutive patients undergoing EUS-guided FNB of any solid lesion were randomized to use either a Franseen or fork-tip needle in a 1:1 ratio and were compared with 60 consecutive historical cases performed with reverse-bevel needles. Patient and procedure characteristics were recorded. Cases were reviewed by a blinded cytopathologist and graded based on cellularity and bloodiness. Overall diagnostic yield was calculated for each study arm.
RESULTS
One hundred seventy-six cases were eligible for analysis, including 109 pancreatic masses, 24 lymphoid lesions, 17 subepithelial lesions, and 26 other lesions. The final diagnosis was malignancy in 127 cases (72%). EUS-guided FNB was diagnostic in 141 cases (80%) overall and in 89% of cases where malignancy was the final diagnosis. There was no difference in diagnostic yield, sample cellularity, or sample bloodiness between the different needle types. There was no difference in adverse events between groups.
CONCLUSIONS
EUS-guided FNB performed using 25-gauge Franseen, fork-tip, and reverse-bevel needles resulted in similar diagnostic yield, sample cellularity, and sample bloodiness. Our results may not be extrapolated to larger-caliber needles of the same design.
PubMed: 38947121
DOI: 10.1097/eus.0000000000000025 -
Endoscopic Ultrasound 2024Recent years have brought to light newly developed therapeutic modalities for the treatment of premalignant and malignant pancreatic lesions. The role of EUS-guided... (Review)
Review
Recent years have brought to light newly developed therapeutic modalities for the treatment of premalignant and malignant pancreatic lesions. The role of EUS-guided radiofrequency ablation (EUS-RFA) as a treatment modality for malignant pancreatic lesions is still under evaluation. Several animal studies and human studies have demonstrated the safety and efficacy of EUS-RFA in the management of premalignant and malignant pancreatic lesions. EUS-RFA therapy can potentially ablate these lesions safely and with minimally invasive techniques. In this article, we provide an updated review of the application of EUS-RFA of pancreatic lesions. We also review the clinical efficacy and safety of this technique and future directions.
PubMed: 38947120
DOI: 10.1097/eus.0000000000000036 -
Endoscopic Ultrasound 2024Previous studies showed that lumen-apposing metal stent (LAMS) provides a feasible route to perform direct endoscopic necrosectomy. However, the high risk of bleeding...
BACKGROUND AND OBJECTIVES
Previous studies showed that lumen-apposing metal stent (LAMS) provides a feasible route to perform direct endoscopic necrosectomy. However, the high risk of bleeding and migration induced by the placement of LAMS attracted attention. The aim of this study was to evaluate the safety and effectiveness of a novel LAMS.
METHODS
In this retrospective study, we enrolled patients with symptomatic pancreatic fluid collections (PFCs) to perform EUS-guided drainage with a LAMS in our hospital. Evaluation variables included technical success rate, clinical success rate, and adverse events.
RESULTS
Thirty-two patients with a mean age of 41.38 ± 10.72 years (53.1% males) were included in our study, and the mean size of PFC was 10.06 ± 3.03 cm. Technical success rate and clinical success rate reached 96.9% and 93.8%, respectively. Stent migration occurred in 1 patient (3.1%), and no stent-induced bleeding occurred. The outcomes of using LAMS in 10 patients with pancreatic pseudocyst and 22 patients with walled-off necrosis were comparable. Compared with pancreatic pseudocyst, walled-off necrosis needed more direct endoscopic necrosectomy times to achieve resolution ( = 0.024).
CONCLUSIONS
Our study showed that the novel LAMS is effective and safe for endoscopic drainage of PFCs with a relatively low rate of adverse events. Further large-scale multicenter studies are needed to confirm the present findings.
PubMed: 38947119
DOI: 10.1097/eus.0000000000000039 -
Endoscopic Ultrasound 2024Endoscopic treatment of obstructive jaundice and pancreatitis due to hepaticojejunostomy (H-J), pancreatojejunostomy (P-J) strictures, and tumor recurrence after...
BACKGROUND AND OBJECTIVES
Endoscopic treatment of obstructive jaundice and pancreatitis due to hepaticojejunostomy (H-J), pancreatojejunostomy (P-J) strictures, and tumor recurrence after pancreatoduodenectomy (PD) is technically challenging. Treatment of P-J strictures results in poor outcomes. Although conventional EUS that has an oblique view is not suitable for such patients, forward-viewing EUS (FV-EUS) may become a useful option. This study aimed to evaluate the feasibility and efficacy of FV-EUS in patients who have undergone PD.
METHODS
Patients with PD who were scheduled to undergo diagnosis and treatment using FV-EUS for H-J or P-J lesions were enrolled in this single-center prospective study. After observation of the P-J and H-J using FV-EUS according to a predetermined protocol, treatment using FV-EUS was performed as needed.
RESULTS
A total of 30 patients were enrolled, and FV-EUS was used to observe P-J and H-J in 24 and 28 patients, respectively. The detection rates of P-J and H-J by endoscopy were 50% (12/24) and 96.4% (27/28), respectively, and by EUS were 70.8% (17/24) and 100% (28/28), respectively. Of these, P-J and H-J were found by endoscopy only after EUS observation in 3 and 1 patient, respectively. The success rates of endoscopic treatment using FV-EUS were 66.7% (2/3), 95.2% (20/21), and 25% (1/4) for benign P-J strictures, benign H-J strictures, and tumor recurrence, respectively.
CONCLUSIONS
Endoscopic treatment using FV-EUS is feasible and effective for patients after PD. Moreover, FV-EUS increases the P-J lesion detection rate by adding EUS observation.
PubMed: 38947114
DOI: 10.1097/eus.0000000000000027 -
The Yale Journal of Biology and Medicine Jun 2024In the Netherlands, one out of two people will be confronted with the diagnosis of cancer sometime in their life. Against this increased number of patients, a large... (Review)
Review
In the Netherlands, one out of two people will be confronted with the diagnosis of cancer sometime in their life. Against this increased number of patients, a large proportion luckily can be cured. Today, a rather high proportion of people receive treatment to control cancer growth or stabilize the disease, sometimes, for the rest of their lives. If such long-standing treatment is administered for more than 10-20 years, the stage of cancer is presently often not referred to as "palliative" anymore, but much more often as "chronic." It could be argued that regardless of the cancer disease stage you are in and whether you are or can be cured, your cancer diagnosis nevertheless has become part of your life, including the experience of chronicity. Discussions surrounding the chronicity of cancer in the context of cancer are still ongoing. This is especially the case because "experiencing chronicity" is dependent on the type of cancer and is less applicable in cancers where the prognosis is often less than one year, such as is more frequently the case with lung or pancreatic cancer. In all situations, experiencing chronicity nevertheless brings along uncertainty, either with or without chronic stress. Combatting stress by choosing the right wording, maintaining an optimistic stance along with physical activity and/or psychosocial education seems important to optimize well-being and to stabilize tumor growth or remove the tumor. In conclusion, chronicity in the context of treating and caring for cancer seems a somewhat gray area. However, regardless in how we, as medical professionals, speak about cancer with long-standing disease trajectories (that sometimes even can be cured), it first of all seems important to approach, take care, and treat patients well. This can facilitate discussions with patients about their disease and disease experiences. Moreover, it can stimulate patients themselves to take responsibility for their own health, which can be of added value to the entire disease trajectory.
Topics: Humans; Neoplasms; Netherlands
PubMed: 38947106
DOI: 10.59249/FQVX3500 -
MedRxiv : the Preprint Server For... Jun 2024Circulating tumor cells (CTCs) captured from the bloodstream of patients with solid tumors have the potential to accelerate precision oncology by providing insight into...
UNLABELLED
Circulating tumor cells (CTCs) captured from the bloodstream of patients with solid tumors have the potential to accelerate precision oncology by providing insight into tumor biology, disease progression and response to treatment. However, their potential is hampered by the lack of standardized CTC enrichment platforms across tumor types. EpCAM-based CTC enrichment, the most commonly used platform, is limited by EpCAM downregulation during metastasis and the low EpCAM expression in certain tumor types, including the highly prevalent and lethal NSCLC. In this study we demonstrate that Transferrin Receptor (TfR) is a selective, efficient biomarker for CTC identification and capture in patients with prostate, pancreatic and NSCLC. TfR identifies significantly higher CTC counts than EpCAM, and TfR -CTC enumeration correlates with disease progression in metastatic prostate and pancreatic cancers, and overall survival and osimetrinib-resistance in non-small cell lung cancer (NSCLC). Profiling of TfR -CTCs provides a snapshot of the molecular landscape of each respective tumor type and identifies potential mechanisms underlying treatment response to EGFR TKi and immune checkpoint inhibitors in NSCLC.
ONE SENTENCE SUMMARY
Transferrin Receptor identifies circulating tumor cells in solid tumors.
PubMed: 38947080
DOI: 10.1101/2024.06.16.24309003 -
Research Square Jun 2024Stromal cells within the tumor tissue promote immune evasion as a critical strategy for cancer development and progression, but the underlying mechanisms remain poorly...
Stromal cells within the tumor tissue promote immune evasion as a critical strategy for cancer development and progression, but the underlying mechanisms remain poorly understood. In this study, we explore the role of endothelial cells (ECs) in the regulation of the immunosuppressive tumor microenvironment. Using mouse pancreatic ductal adenocarcinoma (PDAC) models, we found that canonical Notch signaling in endothelial cells suppresses the recruitment of antitumor T cells and promotes tumor progression by inhibiting the pro-inflammatory functions of cancer-associated fibroblasts (CAFs). Abrogation of endothelial Notch signaling modulates EC-derived angiocrine factors to enhance the pro-inflammatory activities of CAFs, which drive CXCL9/10-CXCR3-mediated T cell recruitment to inhibit tumor growth. Additionally, abrogation of endothelial Notch unleashed interferon gamma responses in the tumor microenvironment, upregulated PDL1 expression on tumor cells, and sensitized PDAC to PD1-based immunotherapy. Collectively, these data uncover a pivotal role of endothelial cells in shaping the immunosuppressive microenvironment, and suggest the potential of targeting EC-CAF interaction as a novel therapeutic modality to boost antitumor immunity.
PubMed: 38947054
DOI: 10.21203/rs.3.rs-4538031/v1 -
World Journal of Gastroenterology Jun 2024In this editorial, we focus specifically on the mechanisms by which pancreatic inflammation affects pancreatic cancer. Cancer of the pancreas remains one of the...
In this editorial, we focus specifically on the mechanisms by which pancreatic inflammation affects pancreatic cancer. Cancer of the pancreas remains one of the deadliest cancer types. The highest incidence and mortality rates of pancreatic cancer are found in developed countries. Trends of pancreatic cancer incidence and mortality vary considerably worldwide. A better understanding of the etiology and identification of the risk factors is essential for the primary prevention of this disease. Pancreatic tumors are characterized by a complex microenvironment that orchestrates metabolic alterations and supports a milieu of interactions among various cell types within this niche. In this editorial, we highlight the foundational studies that have driven our understanding of these processes. In our experimental center, we have carefully studied the mechanisms of that link pancreatic inflammation and pancreatic cancer. We focused on the role of mast cells (MCs). MCs contain pro-angiogenic factors, including tryptase, that are associated with increased angiogenesis in various tumors. In this editorial, we address the role of MCs in angiogenesis in both pancreatic ductal adenocarcinoma tissue and adjacent normal tissue. The assessment includes the density of c-Kit receptor-positive MCs, the density of tryptase-positive MCs, the area of tryptase-positive MCs, and angiogenesis in terms of microvascularization density.
Topics: Humans; Pancreatic Neoplasms; Mast Cells; Tumor Microenvironment; Neovascularization, Pathologic; Carcinoma, Pancreatic Ductal; Pancreas; Animals; Pancreatitis; Risk Factors; Inflammation Mediators; Tryptases; Inflammation
PubMed: 38946872
DOI: 10.3748/wjg.v30.i23.2927