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Arteriosclerosis, Thrombosis, and... Jun 2024Atherosclerosis is the major underlying pathology of cardiovascular disease and is driven by dyslipidemia and inflammation. Inhibition of the immunoproteasome, a...
BACKGROUND
Atherosclerosis is the major underlying pathology of cardiovascular disease and is driven by dyslipidemia and inflammation. Inhibition of the immunoproteasome, a proteasome variant that is predominantly expressed by immune cells and plays an important role in antigen presentation, has been shown to have immunosuppressive effects.
METHODS
We assessed the effect of ONX-0914, an inhibitor of the immunoproteasomal catalytic subunits LMP7 (proteasome subunit β5i/large multifunctional peptidase 7) and LMP2 (proteasome subunit β1i/large multifunctional peptidase 2), on atherosclerosis and metabolism in LDLr and APOE*3-Leiden.CETP mice.
RESULTS
ONX-0914 treatment significantly reduced atherosclerosis, reduced dendritic cell and macrophage levels and their activation, as well as the levels of antigen-experienced T cells during early plaque formation, and Th1 cells in advanced atherosclerosis in young and aged mice in various immune compartments. Additionally, ONX-0914 treatment led to a strong reduction in white adipose tissue mass and adipocyte progenitors, which coincided with neutrophil and macrophage accumulation in white adipose tissue. ONX-0914 reduced intestinal triglyceride uptake and gastric emptying, likely contributing to the reduction in white adipose tissue mass, as ONX-0914 did not increase energy expenditure or reduce total food intake. Concomitant with the reduction in white adipose tissue mass upon ONX-0914 treatment, we observed improvements in markers of metabolic syndrome, including lowered plasma triglyceride levels, insulin levels, and fasting blood glucose.
CONCLUSIONS
We propose that immunoproteasomal inhibition reduces 3 major causes underlying cardiovascular disease, dyslipidemia, metabolic syndrome, and inflammation and is a new target in drug development for atherosclerosis treatment.
Topics: Animals; Atherosclerosis; Metabolic Syndrome; Disease Models, Animal; Adipose Tissue, White; Receptors, LDL; Proteasome Endopeptidase Complex; Mice, Inbred C57BL; Male; Proteasome Inhibitors; Apolipoprotein E3; Aortic Diseases; Macrophages; Plaque, Atherosclerotic; Dendritic Cells; Mice, Knockout, ApoE; Mice; Energy Metabolism; Oligopeptides
PubMed: 38660806
DOI: 10.1161/ATVBAHA.123.319701 -
Endoscopy International Open Apr 2024Alterations to interstitial cells of Cajal (ICC) and collagen fibrosis have been implicated in the pathogenesis of gastroparesis. We aimed to evaluate the feasibility...
Alterations to interstitial cells of Cajal (ICC) and collagen fibrosis have been implicated in the pathogenesis of gastroparesis. We aimed to evaluate the feasibility and safety of pyloric muscle sampling during gastric peroral endoscopic myotomy (G-POEM) and the association between pyloric ICC density and degree of fibrosis with clinical outcomes. This was a single-center prospective study of gastroparetic patients who underwent G-POEM and intraprocedural pyloric muscle biopsies between January 2022 and April 2023. ICC count was estimated using CD117 stain and trichome for collagen fibrosis. Clinical response to G-POEM was defined as an improvement of ≥ 1 point on the Gastroparesis Cardinal Symptom Index. Fifty-six patients (median age 60 years, 71.4% women) underwent G-POEM (100% technical success; 71.4% clinical response). ICC depletion (< 10/high-power field) and fibrosis were encountered in 70.4% and 75% of the cases, respectively. There was no difference in mean ICC count between G-POEM responders vs. non-responders (7±3.6 vs. 7.7±3.3; = 0.9). There was no association between ICC density or degree of fibrosis with the etiology of gastroparesis, duration of symptoms, gastric emptying rate, or pyloric impedance planimetry. Patients who did not respond to G-POEM had a significantly higher degree of moderate/severe fibrosis when compared with those who responded (81.3% vs. 25%; = 0.0002). Pyloric muscle biopsies during G-POEM was feasible and safe. ICC depletion and pyloric muscle fibrosis are common in gastroparetic patients. The degree of fibrosis may be related to pyloric dysfunction and clinical response to G-POEM. Additional studies are needed to confirm these results.
PubMed: 38654965
DOI: 10.1055/a-2290-0502 -
Saudi Journal of Anaesthesia 2024We investigated factors affecting the low- and high-risk groups for aspiration by measuring gastric volume with ultrasound in diabetic patients who fasted for elective...
BACKGROUND
We investigated factors affecting the low- and high-risk groups for aspiration by measuring gastric volume with ultrasound in diabetic patients who fasted for elective surgery.
METHODS
The study was conducted as an observational study. Sixty-five patients scheduled for elective surgery, aged 18-86 years, with American Society of Anesthesiologists (ASA) scores II-III, and who have diabetes were included after local ethics committee approval. Written informed consent was obtained from all participants. Demographic data of cases were recorded. Patients whose gastric residual volume (GRV) was calculated using the pupils equal, round, reactive to light, and accommodation (PERLA) formula following gastric antrum measurement in the right lateral decubitus and supine position by ultrasound were categorized as low or high risk for aspiration.
RESULTS
Thirty-one patients were in the low-risk group, and 34 patients were in the high-risk group. Sex, weight, body mass index (BMI), hemoglobin A1c (HbA1c) values, and duration of diabetes were not statistically significant (p > 0.5). Age (p = 0.006) and fasting blood glucose (FBG) (p = 0.005) were statistically significant. The risk of aspiration decreases with age. Hyperglycemia is related to delayed gastric emptying and a high risk for aspiration. The duration of fasting, GRV, and cross-sectional area (CSA) were statistically significant (p = 0.017, p = 0.000, and p = 0.000, respectively).
CONCLUSION
Gastric emptying might be delayed in diabetic patients resulting in a high risk for aspiration pneumonia. The risk of aspiration increases in young diabetic patients, and preoperative FBG measurements can provide an idea about gastric emptying in diabetic patients. Gastric ultrasound (USG) may contribute to guidelines for determining more appropriate fasting times for other patient populations, such as obese, pregnant, or child patients.
PubMed: 38654864
DOI: 10.4103/sja.sja_339_23 -
Langenbeck's Archives of Surgery Apr 2024Pancreatoduodenectomies are complex surgical procedures with a considerable morbidity and mortality even in high-volume centers. However, postoperative morbidity and...
BACKGROUND
Pancreatoduodenectomies are complex surgical procedures with a considerable morbidity and mortality even in high-volume centers. However, postoperative morbidity and long-term oncological outcome are not only affected by the surgical procedure itself, but also by the underlying disease. The aim of our study is an analysis of pancreatoduodenectomies for patients with pancreatic ductal adenocarcinoma (PDAC) and ampullary carcinoma (CAMP) concerning postoperative complications and long-term outcome in a tertiary hospital in Germany.
METHODS
The perioperative and oncological outcome of 109 pancreatic head resections performed for carcinoma of the ampulla vateri was compared to the outcome of 518 pancreatic head resections for pancreatic ductal adenocarcinoma over a 20 year-period from January 2002 until December 2021. All operative procedures were performed at the University Hospital Freiburg, Germany. Patient data was analyzed retrospectively, using a prospectively maintained SPSS database. Propensity score matching was performed to adjust for differences in surgical and reconstruction technique. Primary outcome of our study was long-term overall survival, secondary outcomes were postoperative complications and 30-day postoperative mortality. Postoperative complications like pancreatic fistula (POPF), postpancreatectomy hemorrhage (PPH) and delayed gastric emptying (DGE) were graded following current international definitions. Survival was estimated using Kaplan Meier curves and log-rank tests. A p-value < 0.05 was considered statistically significant.
RESULTS
Operation time was significantly longer in PDAC patients (432 vs. 391 min, p < 0.001). The rate of portal vein resections was significantly higher in PDAC patients (p < 0.001). In CAMP patients, a pancreatogastrostomy as reconstruction technique was performed more frequently compared to PDAC patients (48.6% vs. 29.9%, p < 0.001) and there was a trend towards more laparoscopic surgeries in CAMP patients (p = 0.051). After propensity score matching, we found no difference in DGE B/C and PPH B/C (p = 0.389; p = 0.517), but a significantly higher rate of clinically relevant pancreatic fistula (CR-POPF) in patients with pancreatoduodenectomies due to ampullary carcinoma (30.7% vs. 16.8%, p < 0.001). Long-term survival was significantly better in CAMP patients (42 vs. 24 months, p = 0.003).
CONCLUSION
Patients with pancreatoduodenectomies due to ampullary carcinomas showed a better long-term oncological survival, by reason of the better prognosis of this tumor entity. However, these patients often needed a more elaborated postoperative treatment due to the higher rate of clinically relevant pancreatic fistula in this group.
Topics: Humans; Pancreatic Fistula; Retrospective Studies; Prognosis; Pancreatic Neoplasms; Pancreaticoduodenectomy; Carcinoma, Pancreatic Ductal; Postoperative Complications
PubMed: 38632147
DOI: 10.1007/s00423-024-03319-7 -
Cureus Mar 2024Gastroparesis is a syndrome characterised by delayed gastric emptying that is usually idiopathic, diabetic, or iatrogenic. This underdiagnosed disease has a substantial...
Gastroparesis is a syndrome characterised by delayed gastric emptying that is usually idiopathic, diabetic, or iatrogenic. This underdiagnosed disease has a substantial influence on the quality of life of its patients. We present the case of an 86-year-old man with dementia, benign prostatic hyperplasia, and gastroesophageal reflux disease who developed symptoms of gastroparesis during a lengthy hospital stay. Computed tomography (CT) and upper digestive endoscopy demonstrated gastric distention and pyloric stenosis. Despite cautious treatment and eventual pyloric dilation, the patient died from aspiration due to refractory respiratory failure. This example emphasises the need for early detection and thorough examination of gastroparesis to optimise patient outcomes and reduce morbidity and mortality.
PubMed: 38623117
DOI: 10.7759/cureus.56263 -
Clinical Nutrition (Edinburgh, Scotland) May 2024
PubMed: 38608403
DOI: 10.1016/j.clnu.2024.03.019 -
Cureus Apr 2024Background Gastroparesis, characterized by delayed gastric emptying without mechanical obstruction, is a significant complication, especially in diabetic individuals. It...
Background Gastroparesis, characterized by delayed gastric emptying without mechanical obstruction, is a significant complication, especially in diabetic individuals. It manifests through symptoms such as abdominal bloating, feelings of fullness, and pain. This study investigates the prevalence of gastroparesis among non-diabetic and diabetic patients, exploring associations with demographic data, hemoglobin A1C (HbA1C) levels, and symptoms. Methodology This retrospective, observational, cohort study included patients with gastroparesis symptoms who underwent a nuclear gastric emptying study from January 2021 to April 2023. The study analyzed demographic data, symptoms, and HbA1c levels to identify correlations with delayed gastric emptying. Results Of 157 patients, 34.4% exhibited delayed gastric emptying. Diabetic patients comprised 29.3% of the sample, with a notable disease duration of over 10 years in 77.3% of cases. Symptoms such as nausea, vomiting, epigastric pain, and early satiety were prevalent, with significant associations between delayed emptying and female gender, higher HbA1c, and vomiting. Conclusions Delayed gastric emptying is significantly associated with female gender, elevated HbA1c levels, and when vomiting is the presenting symptom. Highlighting the importance of awareness among healthcare providers and the community, the findings encourage collaborative efforts for further gastroparesis research to better understand the predictive factors and mechanisms.
PubMed: 38606023
DOI: 10.7759/cureus.58038 -
World Journal of Diabetes Mar 2024This editorial is stimulated by the article by Alqifari published in the (2024). Alqifari focus on practical advice for the clinical use of glucagon-like-peptide-1...
This editorial is stimulated by the article by Alqifari published in the (2024). Alqifari focus on practical advice for the clinical use of glucagon-like-peptide-1 (GLP-1) receptor agonists (GLP-1RAs) in the management of type 2 diabetes and this editorial provides complementary information. We initially give a brief historical perspective of the development of GLP-1RAs stimulated by recognition of the 'incretin effect', the substantially greater insulin increase to enteral when compared to euglycaemic intravenous glucose, and the identification of the incretin hormones, GIP and GLP-1. In addition to stimulating insulin, GLP-1 reduces postprandial glucose levels by slowing gastric emptying. GLP-1RAs were developed because native GLP-1 has a very short plasma half-life. The majority of current GLP-1RAs are administered by subcutaneous injection once a week. They are potent in glucose lowering without leading to hypoglycaemia, stimulate weight loss in obese individuals and lead to cardiovascular and renal protection. The landscape in relation to GLP-1RAs is broadening rapidly, with different formulations and their combination with other peptides to facilitate both glucose lowering and weight loss. There is a need for more information relating to the effects of GLP-1RAs to induce gastrointestinal symptoms and slow gastric emptying which is likely to allow their use to become more effective and personalised.
PubMed: 38591090
DOI: 10.4239/wjd.v15.i3.326 -
BMC Medical Education Apr 2024Pulmonary aspiration syndrome remains a significant complication of general anesthesia, particularly in unfasted patients. Gastric point-of-care ultrasound (POCUS)...
BACKGROUND
Pulmonary aspiration syndrome remains a significant complication of general anesthesia, particularly in unfasted patients. Gastric point-of-care ultrasound (POCUS) allows for both qualitative and quantitative assessment of gastric content, providing a safe and reliable method to assess gastric emptying and reduce the risk of aspiration during general anesthesia.
METHODS
The survey was distributed to Belgian certified anesthesiologists and trainees between April 2020 and June 2021. Participants received a simulated clinical case of a patient at risk of gastric aspiration, created and approved by two certified anesthesiologists trained to perform gastric POCUS. The objectives of this study were to assess recognition of high-risk clinical situations for gastric aspiration, awareness of the gastric POCUS and its indications, and knowledge of the technical and practical conditions of the procedure among respondents trained in the technique. Furthermore, the study assessed the state of training in gastric POCUS, the desire for education, and the practical availability of ultrasound equipment. The survey used conditional branching to ensure unbiased responses to POCUS-related questions. It included multiple-choice questions, quantitative variables, and 5-point Likert scales. The margin of error was calculated using Daniel's formula, corrected for a finite population.
RESULTS
The survey was conducted among 323 anesthesiologists. Only 20.8% (27) recognized the risk of a full stomach based on the patient's history. Anesthesiologists who recognized the indication for gastric POCUS and were trained in the procedure demonstrated good recall of the practical conditions for performing the procedure and interpreting the results. Only 13.08% (31) of all respondents had received training in gastric POCUS, while 72.57% (172) expressed interest in future training. Furthermore, 80.17% (190) of participants had access to adequate ultrasound equipment and 78.90% (187) supported teaching gastric POCUS to anesthesia trainees.
CONCLUSIONS
This survey offers insight into the epidemiology, clinical recognition, knowledge, and utilization of gastric POCUS among Belgian anesthesia professionals. The results emphasize the significance of proper equipment and training to ensure the safe and effective implementation of gastric POCUS in anesthesia practice. Additional efforts should focus on improving training and promoting the integration of gastric POCUS into daily clinical practice.
Topics: Humans; Anesthesiologists; Belgium; Point-of-Care Systems; Stomach; Surveys and Questionnaires; Ultrasonography
PubMed: 38589900
DOI: 10.1186/s12909-024-05359-5 -
Nutrition & Diabetes Apr 2024Gastric emptying (GE), with wide inter-individual but lesser intra-individual variations, is a major determinant of postprandial glycaemia in health and type 2 diabetes...
Gastric emptying of a glucose drink is predictive of the glycaemic response to oral glucose and mixed meals, but unrelated to antecedent glycaemic control, in type 2 diabetes.
BACKGROUND
Gastric emptying (GE), with wide inter-individual but lesser intra-individual variations, is a major determinant of postprandial glycaemia in health and type 2 diabetes (T2D). However, it is uncertain whether GE of a carbohydrate-containing liquid meal is predictive of the glycaemic response to physiological meals, and whether antecedent hyperglycaemia influences GE in T2D. We evaluated the relationships of (i) the glycaemic response to both a glucose drink and mixed meals with GE of a 75 g glucose drink, and (ii) GE of a glucose drink with antecedent glycaemic control, in T2D.
METHODS
Fifty-five treatment-naive Chinese adults with newly diagnosed T2D consumed standardised meals at breakfast, lunch and dinner with continuous interstitial glucose monitoring. On the subsequent day, a 75 g glucose drink containing 150 mg C-acetate was ingested to assess GE (breath test) and plasma glucose response. Serum fructosamine and HbA1c were also measured.
RESULTS
Plasma glucose incremental area under the curve (iAUC) within 2 hours after oral glucose was related inversely to the gastric half-emptying time (T50) (r = -0.34, P = 0.012). The iAUCs for interstitial glucose within 2 hours after breakfast (r = -0.34, P = 0.012) and dinner (r = -0.28, P = 0.040) were also related inversely to the T50 of oral glucose. The latter, however, was unrelated to antecedent fasting plasma glucose, 24-hour mean interstitial glucose, serum fructosamine, or HbA1c.
CONCLUSIONS
In newly diagnosed, treatment-naive, Chinese with T2D, GE of a 75 g glucose drink predicts the glycaemic response to both a glucose drink and mixed meals, but is not influenced by spontaneous short-, medium- or longer-term elevation in glycaemia.
Topics: Adult; Humans; Glucose; Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Gastric Emptying; Glycemic Control; Blood Glucose Self-Monitoring; Fructosamine; Meals; Postprandial Period; Insulin; Cross-Over Studies
PubMed: 38589353
DOI: 10.1038/s41387-024-00264-8