Design and biopharmaceutical preclinical characterisation of a new thermosensitive hydrogel for the removal of gastric polyps.

BACKGROUND AND AIMS: Submucosal injection agents are widely used solutions in gastric polyp resection techniques. Currently, many different solutions are used in clinical practice, but most are not authorised for this use or are not biopharmaceutical characterised. The objective of this multidisciplinary work is to test the efficacy of a novel thermosensitive hydrogel designed specifically for this indication. METHODS: A mixture design of various components (Pluronic®, hyaluronic acid and sodium alginate) was carried out to select the combination with optimal properties for this use. Three final thermosensitive hydrogels were selected on which biopharmaceutical characterisation was performed and stability and biocompatibility were analysed. Efficacy in maintaining elevation was tested ex vivo on pig mucosa and in vivo in pigs RESULTS: The mixture design allowed selection of the ideal combinations of agents for the characteristics sought. The thermosensitive hydrogels studied showed high values of hardness and viscosity at 37 °C, maintaining good syringeability. One of them demonstrated superiority in maintaining polyp elevation in the ex vivo assay and non-inferiority in the in vivo assay. CONCLUSION: The thermosensitive hydrogel specifically designed for this use is promising both for its biopharmaceutical characteristics and for its demonstrated efficacy. This study lays the foundation for evaluating the hydrogel in humans.

Usefulness of peripheral blood monocyte count to predict relapse in patients with inflammatory bowel disease: a prospective longitudinal cohort study.

BACKGROUND: monocytes play an important role in the pathogenesis of inflammatory bowel disease but data are scarce regarding activity biomarkers, above all in patients under biologic therapies. OBJECTIVE: the aim of this study was to evaluate the value of monocyte measurements in predicting flares in inflammatory bowel disease patients under maintenance treatment with anti-TNF. METHODS: a prospective, observational cohort study was designed. Relapse was defined as a Harvey-Bradshaw score > 4 in Crohn's disease, and a partial Mayo score ≥ 2 in ulcerative colitis. Monocyte concentration was quantified at 4-month intervals for twelve months. A total of 95 consecutive patients were included. Median age was 42 years, 50.5 % were female, and 75 % had Crohn's disease. RESULTS: sixteen months after inclusion, 65 (68.4 %) patients remained in clinical remission. Mean monocyte count preceding a relapse was 563 (standard deviation: 144) compared to 405 (standard deviation: 177) in patients who remained in remission. Final monocyte count was significantly different between relapse and remission in Crohn's disease (0.82; 95 % CI: 0.71-0.90; p < 0.005). According to the multivariate analysis, only monocytes and fecal calprotectin were related to more relapses. CONCLUSION: in conclusion, in inflammatory bowel disease patients under anti-TNF therapy, repeat monocyte counts could help monitor patients, at least in Crohn's disease.

Endoscopic Pancreatic Drainage Improves Exocrine Pancreatic Function in Patients With Unresectable Pancreatic Cancer: A Double-Blind, Prospective, Randomized, Single-Center, Interventional Study.

OBJECTIVES: Exocrine pancreatic insufficiency is a frequent and clinically relevant complication of pancreatic cancer probably secondary to pancreatic duct obstruction. We aimed at evaluating the impact of endoscopic pancreatic drainage on pancreatic function in patients with unresectable pancreatic cancer. METHODS: A double-blind, prospective, randomized, single-center, interventional study was designed. Patients undergoing endoscopic retrograde cholangiopancreatography for jaundice secondary to unresectable pancreatic cancer were randomized to biliary drainage (group A) or biliopancreatic drainage (group B). Pancreatic function was evaluated by 13C-mixed triglyceride breath test before and 2 weeks after endoscopic retrograde cholangiopancreatography. Breath test result is expressed as 13C-cumulative recovery rate. Abdominal symptoms and nutritional markers were evaluated as secondary outcomes. RESULTS: Twenty patients were included. Sixteen patients had exocrine pancreatic insufficiency, and 13 completed the study (7 in group A and 6 in group B). The median absolute improvement of 13C-cumulative recovery rate was of 23.75% (interquartile range, 9.62-31.74) after biliopancreatic drainage compared with -1.92% (interquartile range, -4.17 to 13.92) after biliary drainage (P = 0.015). Nutritional markers improved after biliopancreatic drainage, but not after biliary drainage. CONCLUSIONS: Biliopancreatic and not biliary endoscopic drainage is associated with a significant improvement of exocrine pancreatic function in patients with unresectable pancreatic cancer.

Impact of the treatment of pancreatic exocrine insufficiency on survival of patients with unresectable pancreatic cancer: a retrospective analysis.

BACKGROUND: Malnutrition and weight loss are commonly observed in patients with pancreatic cancer and contribute to poor survival. Pancreatic exocrine insufficiency (PEI), which can be caused by ductal obstruction by a tumor, causes maldigestion and malabsorption of nutrients, thus contributing to malnutrition in these patients. In this study, we evaluated the effects of pancreatic enzyme replacement therapy (PERT) on survival in patients with unresectable pancreatic cancer. METHODS: A retrospective analysis was conducted on a database of patients with unresectable, pathologically confirmed pancreatic cancer. All patients were evaluated for palliative chemotherapy and received the optimal palliative care. Patients were divided into two groups: Group 1 received standard therapy; Group 2 underwent additional evaluation of the pancreatic function and therapy with PERT, if needed. Survival (median and 95% confidence interval [CI]) was analyzed using Kaplan-Meier and Cox regression; groups were compared using the log-rank test. RESULTS: Overall, 160 patients with unresectable pancreatic cancer were included in the analysis (mean age: 70.5 years [range 28-100]; gender: 57.5% male; tumor stage: 78.7% Stage IV). Eighty-six patients (53.75%) were in Group 1 and 74 (46.25%) were in Group 2. Age, gender, tumor size, location and stage, weight loss, and serum CA 19-9 were similar between groups. Ninety-three (58.1%) patients received palliative chemotherapy; 46.5% in Group 1 and 71.6% in Group 2 (P < 0.001). Forty-nine (66.2%) patients in Group 2 and none in Group 1 received PERT. Survival in Group 2 (189 days, 95% CI 167.0-211.0 days) was significantly longer than in Group 1 (95.0 days, 95% CI 75.4-114.6 days) (HR 2.117, 95% CI 1.493-3.002; P < 0.001). Chemotherapy and PERT were significantly and independently associated with longer survival in a model controlled by age and tumor stage. In patients with significant weight loss at diagnosis (> 10% bodyweight within 6 months), PERT was associated with longer survival (HR 2.52, 95% CI 1.55-4.11; P < 0.001). CONCLUSIONS: In patients with unresectable pancreatic cancer, PERT in patients with PEI was associated with longer survival compared with those not receiving PERT, especially in those experiencing significant weight loss. This finding should guide future prospective clinical trials of similar interventions.

Centenarians and their hearts: A prospective registry with comprehensive geriatric assessment, electrocardiogram, echocardiography, and follow-up.

BACKGROUND: Data on the cardiac characteristics of centenarians are scarce. Our aim was to describe electrocardiogram (ECG) and echocardiography in a cohort of centenarians and to correlate them with clinical data. METHODS: We used prospective multicenter registry of 118 centenarians (28 men) with a mean age of 101.5±1.7 years. Electrocardiogram was performed in 103 subjects (87.3%) and echocardiography in 100 (84.7%). All subjects underwent a follow-up for at least 6 months. RESULTS: Centenarians with abnormal ECG were less frequently females (72% vs 93%), had higher rates of previous consumption of tobacco (14% vs 0) and alcohol (24% vs 12%), and scored lower in the perception of health status (6.8±2.0 vs 8.3±6.8). Centenarians with significant abnormalities in echocardiography were less frequently able to walk 6 m (33% vs 54%). Atrial fibrillation/flutter was found in 27 subjects (26%). Mean left ventricular (LV) ejection fraction was 60.0±10.5%. Moderate or severe aortic valve stenosis was found in 16%, mitral valve regurgitation in 15%, and aortic valve regurgitation in 13%. Diastolic dysfunction was assessed in 79 subjects and was present in 55 (69.6%). Katz index and LV dilation were independently associated with the ability to walk 6 m. Age, Charlson and Katz indexes, and the presence of significant abnormalities in echocardiography were associated with mortality. CONCLUSIONS: Centenarians have frequent ECG alterations and abnormalities in echocardiography. More than one fifth has atrial fibrillation, and most have diastolic dysfunction. Left ventricular dilation was associated with the ability to walk 6 m. Significant abnormalities in echocardiography were associated with mortality.