Botulinum toxin infusion into the mesenteric artery has selective action on peristalsis in a rat model: experimental research.

OBJECTIVE: Botulinum toxin type A (BoNT/A) reversibly blocks neurotransmission at voluntary and autonomic cholinergic nerve terminals, inducing paralysis. The aim of this study was to block panenteric peristalsis in rats through BoNT/A administration into the superior mesenteric artery (SMA) and to understand whether the toxin's action is selectively restricted to the perfused territory. MATERIALS AND METHODS: Rats were infused through a 0.25-mm surgically inserted SMA catheter with different doses of BoNT/A (10 U, 20 U, 40 U BOTOX®, Allergan Inc.) or with saline for 24 h. Animals were free to move on an unrestricted diet. As a sign of bowel peristalsis impairment, body weight and oral/water intake were collected for 15 days. Statistical analysis was conducted with nonlinear mixed effects models to study the variation over time of the response variables. In three 40 U-treated rats, the selectivity of the intra-arterial delivered toxin action was studied by examining bowel and voluntary muscle samples and checking the presence of BoNT/A-cleaved SNAP-25 (the smoking gun of the toxin action) using the Immunofluorescence (IF) method through a specific antibody recognition. RESULTS: While control rats exhibited an increasing body weight, treated rats showed an initial dose-dependent weight reduction (p<0.001 control vs. treated) with recovery after Day 11 for 10 and 20 U-treated rats. Food and water intake over time showed significantly different half-saturation constants with rats treated with higher doses who reached half of the maximum achievable in a greater number of days (p<0.0001 control vs. treated rats). BoNT/A-cleaved SNAP-25 was identified in bowel wall NMJs and not in voluntary muscles, demonstrating the remarkable selectivity of arterially infused BoNT/A. CONCLUSIONS: Blockade of intestinal peristalsis, can be induced in rats by slow infusion of BoNT/A into the SMA. The effect is long-lasting, dose-dependent and selective. BoNT/A delivery into the SMA through a percutaneous catheter could prove clinically useful in the treatment of entero-atmospheric fistula by temporarily reducing fistula output.

Distinguishable DNA methylation defines a cardiac-specific epigenetic clock.

BACKGROUND: The present study investigates whether epigenetic differences emerge in the heart of patients undergoing cardiac surgery for an aortic valvular replacement (AVR) or coronary artery bypass graft (CABG). An algorithm is also established to determine how the pathophysiological condition might influence the human biological cardiac age. RESULTS: Blood samples and cardiac auricles were collected from patients who underwent cardiac procedures: 94 AVR and 289 CABG. The CpGs from three independent blood-derived biological clocks were selected to design a new blood- and the first cardiac-specific clocks. Specifically, 31 CpGs from six age-related genes, ELOVL2, EDARADD, ITGA2B, ASPA, PDE4C, and FHL2, were used to construct the tissue-tailored clocks. The best-fitting variables were combined to define new cardiac- and blood-tailored clocks validated through neural network analysis and elastic regression. In addition, telomere length (TL) was measured by qPCR. These new methods revealed a similarity between chronological and biological age in the blood and heart; the average TL was significantly higher in the heart than in the blood. In addition, the cardiac clock discriminated well between AVR and CABG and was sensitive to cardiovascular risk factors such as obesity and smoking. Moreover, the cardiac-specific clock identified an AVR patient's subgroup whose accelerated bioage correlated with the altered ventricular parameters, including left ventricular diastolic and systolic volume. CONCLUSION: This study reports on applying a method to evaluate the cardiac biological age revealing epigenetic features that separate subgroups of AVR and CABG.

Risk factors and outcomes of restorative proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis. Retrospective study of 75 single center cases.

OBJECTIVE: Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the surgical gold standard in patients with ulcerative colitis (UC). Results are generally satisfactory but there is a significant rate of patients who experience postoperative complications. The aims of our study were to identify the pre- and intraoperative risk factors and their correlation with the reported outcomes. PATIENTS AND METHODS: A retrospective study was conducted on the medical records of all consecutive patients undergoing restorative proctocolectomy with IPAA for UC in our center from 2010 to 2021. Pre- and intraoperative factors were examined and correlated with pouchitis, endoscopic pouchitis, pouch failure, anastomotic leak, postoperative complications classified according to Clavien-Dindo score and stoma outlet obstruction. A univariate and multivariate statistical analysis was performed. RESULTS: Out of 75 patients undergoing 3- or 2-stage IPAA surgery, the coexistence of extraintestinal clinical manifestations and preoperative topical rectal stump therapy for active proctitis were significantly associated with the occurrence of pouchitis (OR=4.4, p=0.03 and OR=7.6, p=0.01). Endoscopic pouchitis was found to be related to preoperative topical rectal therapy (OR=10.2, p=0.007), but not to extraintestinal manifestations of disease. Anastomotic leak was found to be significantly related to pouch failure (OR=22.7, p=0.007). Surgical indication for malignancy increased the risk for early complications (Clavien-Dindo >2) (OR=16.0, p=0.04). Young age was associated with the occurrence of outlet stoma obstruction in patients with recent IPAA surgery (OR=0.97, p=0.05). CONCLUSIONS: Based on observed results, an appropriate preoperative patient assessment aimed at detecting specific risk factors is crucial to identify early or prevent worse outcomes in patients undergoing IPAA surgery.

Volcanic Vortex Rings: Axial Dynamics, Acoustic Features, and Their Link to Vent Diameter and Supersonic Jet Flow.

By injecting a mixture of gas and pyroclasts into the atmosphere, explosive volcanic eruptions frequently generate vortex rings, which are toroidal vortices formed by the jet's initial momentum. Here, we report high-speed imaging and acoustic measurements of vortex rings sourcing from gas-rich eruptive jets at Stromboli volcano (Italy). Volcanic vortex rings (VVRs) form at the vent together with an initial compression acoustic wave, VVRs maximum rise velocity being directly proportional to the amplitude and inversely proportional to the duration of the compression wave. The axial rise and acoustic signature of VVRs match well those predicted by recent fluid-dynamic experiments. This good match allows using the high-frequency (80-1,000 Hz) component of the jet sound and the time-dependent rise of VVRs to retrieve two key eruption parameters: the Mach number of the eruptive jets (<1.5) and vent diameter (∼0.7 m), respectively, the latter being confirmed independently by direct Uncrewed Aerial Vehicle observations.

Estimating COVID-19 recovery time in a cohort of Italian healthcare workers who underwent surveillance swab testing.

OBJECTIVES: The COVID-19 pandemic is putting a huge strain on the provision and continuity of care. The length of sickness absence of the healthcare workers as a result of SARS-CoV-2 infection plays a pivotal role in hospital staff management. Therefore, the aim of this study was to explore the timing of COVID-19 recovery and viral clearance, and its predictive factors, in a large sample of healthcare workers. STUDY DESIGN: This is a retrospective cohort study. METHODS: The analysis was conducted on data collected during the hospital health surveillance programme for healthcare staff at the University Hospital of Verona; healthcare workers were tested for SARS-CoV-2 through RT-PCR with oronasopharyngeal swab samples. The health surveillance programme targeted healthcare workers who either had close contact with SARS-CoV-2-infected patients or were tested as part of the screening-based strategy implemented according to national and regional requirements. Recovery time was estimated from the first positive swab to two consecutive negative swabs, collected 24 h apart, using survival analysis for both right-censored and interval-censored data. Cox proportional hazard was used for multivariate analysis. RESULTS: During the health surveillance programme, 6455 healthcare workers were tested for SARS-CoV-2 and 248 (3.8%, 95% confidence interval [CI]: 3.4-4.3) reported positive results; among those who tested positive, 49% were asymptomatic, with a median age of 39.8 years, which is significantly younger than symptomatic healthcare workers (48.2 years, P < 0.001). Screening tests as part of the health surveillance programme identified 31 (12.5%) of the positive cases. Median recovery time was 24 days (95% CI: 23-26) and 21.5 days (95% CI: 15.5-30.5) in right- and interval-censoring analysis, respectively, with no association with age, sex or presence of symptoms. Overall, 63% of participants required >20 days to test negative on two consecutive swabs. Hospitalised healthcare workers (4.8%) were older and had a significantly longer recovery time compared with non-hospitalised healthcare workers in both analyses (33.5 vs 24 days, P = 0.005). CONCLUSIONS: Recovery from COVID-19 and viral clearance may take a long time, especially in individuals who are hospitalised. To detect asymptomatic cases, screening programmes for healthcare workers is recommended.

Intensive lifestyle modifications with or without liraglutide 3mg vs. sleeve gastrectomy: A three-arm non-randomised, controlled, pilot study.

BACKGROUND/OBJECTIVES: As only 1% of clinically eligible subjects choose to undergo surgical treatment for obesity, other options should be investigated. This study aimed to assess the effects of intensive lifestyle modification (ILM) with or without 3-mg liraglutide daily vs. sleeve gastrectomy (SG) on BMI after 1 year. SUBJECTS/METHODS: In this study performed at an Italian university hospital, non-diabetic patients eligible for bariatric surgery were recruited from a weight-loss clinic and had the option to choose from three possible weight-loss programmes up to an allocation of 25 subjects in each arm matched by BMI and age. ILM consisted in 813kcal of a very low-calorie diet (VLCD) for 1 month, followed by a diet of 12kcal/kg body weight of high protein and high fat for 11 months plus 30min of brisk walking daily and at least 3h of aerobic exercise weekly. SG patients followed a VLCD for 1 month and a free diet thereafter. Patients were evaluated at baseline and at 1, 3, 6, 9 and 12 months. RESULTS: A total of 75 patients were enrolled; retention was 100% in the SG and 85% in the two medical arms. SG reduced BMI by 32% (P<0.001 vs. medical arm), while ILM+liraglutide and ILM led to BMI reductions of 24% and 14%, respectively (P<0.001). More women allocated themselves to the ILM+liraglutide group. Weight loss was 43kg with SG, 26kg with ILM+liraglutide and 15kg with ILM alone. Lean body mass reductions were -11.6kg with SG, -6.3kg with ILM and -8.3kg with ILM+liraglutide. Prevalence of prediabetes was significantly lower with ILM+liraglutide, and insulin resistance was reduced by about 70% by both ILM+liraglutide and SG vs. 39% by ILM alone. Cardiometabolic risk factors were greatly reduced in all three groups. DISCUSSION: At least in the short-term, liraglutide 3.0mg once daily associated with drastic calorie-intake restriction and intensive physical activity promoted a 24% weight loss, which was almost two times greater than ILM alone and only about 25% less than with SG, while preserving lean body mass. Although this study was non-randomised, it was designed to explore the efficacy of medical treatments for obesity in everyday clinical practice.

Validation of the French version of the Burn Specific Health Scale-Brief (BSHS-B) questionnaire.

INTRODUCTION: The Burn Specific Health Scale-Brief questionnaire is a widely validated tool for estimating the health related quality of life and for assessing the best multidisciplinary management of burn patients. The aim of this study was to translate the BSHS-B into French and to investigate its reliability and validity. METHODS: According to the procedure proposed by the Scientific Advisory Committee of the Medical Outcomes Trust, the Burn Specific Health Scale-Brief (BSHS-B) was translated from the English version into French. In order to test the reliability of the French version of the BSHS-B, 53 burn patients French speakers completed the BSHS-B and SF-36 questionnaires from two to four years after burn. Ten of them have been re-tested at 6 months after the first evaluation. To evaluate clinical utility of the BSHS-F, internal consistency, construct validity (using SF-36) and stability in time were assessed using Cronbach's alpha statistic, Spearman rank test, and intra-class correlation coefficient respectively. RESULTS: The French version of the BSHS-B Cronbach's alpha coefficient was 0.93 and was >0.80 for all the sub-domains. French version of the BSHS-B and the SF-36 were positively correlated, all the associations were statistically significant (p<0.01). Intra-class correlation coefficients for test-retest ranged between 0.95 and 0.99 for the sub-domains. The intra-class correlation coefficient (ICC) for the total score was 0.98. CONCLUSION: The French version of the BSHS-B shows a robust rate of internal consistency, construct validity and stability in time, supporting its application in routine clinical practice as well as in international studies.

Model-based control of plasma glycemia: Tests on populations of virtual patients.

Closed-loop devices delivering medical treatments in an automatic fashion clearly require a thorough preliminary phase according to which the proposed control law is tested and validated as realistically as possible, before arranging in vivo experiments in a clinical setting. The present note develops a virtual environment aiming to validate a recently proposed model-based glucose control law on a solid simulation framework. From a theoretical viewpoint, the artificial pancreas has been designed by suitably exploiting a minimal set of delay differential equations modeling the glucose-insulin regulatory system; on the other hand, the validation platform makes use of a different, multi-compartmental model to build up a population of virtual patients. Simulations are carried out by properly addressing the available technological limits and the unavoidable uncertainties in real-time continuous glucose sensors as well as possible malfunctioning on the insulin delivery devices. The results show the robustness of the proposed control law that turns out to be efficient and extremely safe on a heterogenous population of virtual patients.

Observational study on preoperative surgical field disinfection: povidone-iodine and chlorhexidine-alcohol.

BACKGROUND AND OBJECTIVES: Surgical site infection (SSI) rate is reported to range around 16%. Preoperative skin disinfection is keystone for SSI reduction. Chlorhexidine-alcohol has been reported to be more effective than Povidone-iodine (PVI). However, in many countries established habits and the inferior costs of PVI restrain the employment of chlorhexidine disinfection kits (ChloraPrep®) for the preparation of the surgical field. MATERIALS AND METHODS: The costs of surgical field preparation in clean-contaminated surgery utilizing PVI (Betadine) and chlorhexidine alcohol and the evaluation of surgeon compliance and satisfaction, were studied by a observational study on 50 surgical operations in which surgical field was prepared with PVI checking established guidelines, and on 50 surgical operations in which chlorhexidine-alcohol (ChloraPrep) was employed. The use of auxiliary material was tabulated as well as the timing of the phases of disinfection and the surgeon's opinions. RESULTS: The use of auxiliary material (gloves, gauzes, paper towels, surgical instruments, small swabs for umbilical cleaning) is associated with the type of disinfectant, with major use of auxiliary materials recorded in PVI disinfection. PVI disinfection does not follow stringent guidelines, in particular waiting for the disinfectant to dry. PVI guidelines are more demanding than those relative to ChloraPrep. The time necessary for the preparation of the field is significantly longer for PVI. Auxiliary material and guideline compliance must be taken into account when calculating costs; the former are direct costs (even though marginal) and the latter can determine major infective risk. CONCLUSIONS: Chlorhexidine in kits is easier and faster to use than PVI, requires less auxiliary material and has been shown previously to reduce SSI in clean contaminated surgery.

An economic evaluation of Clostridium difficile infection management in an Italian hospital environment.

BACKGROUND AND OBJECTIVES: Clostridium difficile infection (CDI) accounts for the majority of nosocomial cases of diarrhea, and with recent upsurge of multidrug-resistant strains, morbidity and mortality have increased. Data on clinical impact of CDI come mostly from Anglo-Saxon countries, while in Italy only two studies address the issue and no economic data exist on costs of CDI in the in hospital setting. A retrospective cross-sectional study with pharmacoeconomic analysis was performed on the CDI series of the Policlinico Gemelli of Rome, a major 1400 bed Hospital. PATIENTS AND METHODS: The clinical charts of 133 patients in a 26 month period were reviewed. All costs of the involved resources were calculated and statistical analysis was carried out with means and standard deviations, and categorical variables as number and percentages. RESULTS: The results show the significant sanitary costs of CDI in an Italian hospital setting. The cost analysis of the various elements (exams, imaging studies, therapies, etc.) shows that none independently influences the high cost burden of CDI, but that it is the simple length of hospital stay that represents the most important factor. CONCLUSIONS: Prevention of CDI is the most cost-effective approach. The major break-through in cost reduction of CDI would be a therapeutical intervention or procedure that shortens hospital length of stay.

Effect of botulinum toxin antral injection on gastric emptying and weight reduction in obese patients: a pilot study.

BACKGROUND: A potential approach to the treatment of morbid obesity is reduction of gastric emptying to achieve satiety. Botulinum toxin A (Btx-A) is a long-acting inhibitor of acetylcholine-mediated peristalsis, which is mainly responsible for gastric motility. AIM: To investigate whether botulinum toxin A, injected in the antrum of obese patients, delays gastric emptying. METHODS: In a double_blind study, 18 healthy obese subjects (body mass index >30) were randomized into three groups (BTX133, BTX200 and Saline); they received Btx-A133U, Btx-A200U, or saline under endoscopic control. Gastric emptying was tested by scintigraphy before and 10 days after treatment. Body weight variations and appetite sensation were recorded after 5 weeks. RESULTS: Fourteen patients completed the study. The botulinum toxin A-treated groups showed weight reduction, which was not statistically significant. The effects on gastric emptying were variable. Most of the botulinum toxin A treated patients reported a reduced appetite. CONCLUSION: This pilot clinical trial suggests potential activity of botulinum toxin A for the manipulation of appetite.

Interleukin 1B gene (IL-1B) and interleukin 1 receptor antagonist gene (IL-1RN) polymorphisms in Helicobacter pylori-negative gastric cancer of intestinal and diffuse histotype.

BACKGROUND: Polymorphisms in the interleukin 1beta gene (IL-1B-31T/C and IL-1B-511C/T single nucleotide changes) and in the interleukin 1 receptor anatagonist gene (IL-1RN2 variable number of tandem repeats) have been studied with respect to gastric cancer susceptibility. Available data support an aetiologic role of these genetic variants in the presence of concomitant Helicobacter pylori infection. Their contribution without H. pylori infection is still an open field of investigation. MATERIALS AND METHODS: IL-1B and IL-1RN polymorphisms were investigated in 138 H. pylori-negative Italian patients with sporadic gastric cancer and 100 H. pylori-negative controls. Unconditional regression with odd ratios (OR) and 95% confidence intervals (CI), haplotype and linkage disequilibrium analyses were used to investigate the association of the polymorphisms with disease. RESULTS: In all gastric cancer cases, carriers of the homozygous IL-1B-511T/T genotype showed a significant risk for the development of the disease (OR 3.2 with 95% CI 1.27-8.05). In cases with intestinal-type gastric cancer, however, both IL-1B-511T and IL-1RN2 alleles were associated with disease. In this subgroup, the odds ratio for carriers of both IL-1B-511T and IL-1RN2 was 6.49 (95% CI 2.07-20.4). Haplotype analysis supported the aetiologic contribution of these alleles in gastric cancer of the intestinal histotype. CONCLUSIONS: In conclusion, IL-1B-511T and IL-1RN2 may contribute to intestinal gastric cancer risk in the absence of concomitant H. pylori infection. In this setting, future epidemiologic studies should consider dietary habits and exposure to carcinogens interacting with pro-inflammatory host genotypes.