Magnetic Sphincter Augmentation Outcomes in Severe Gastroesophageal Reflux Disease.

Introduction: Outcomes of laparoscopic procedures for gastroesophageal reflux disease (GERD) are variable depending on surgical expertise and/or patient-related factors. Some procedures may be inadequate in patients with severe disease. Effectiveness of laparoscopic magnetic sphincter augmentation (MSA) has not been extensively tested in patients with severe disease. Methods: A prospectively collected database was analyzed to identify patients who underwent MSA at a single institution. Individuals who had previous esophago-gastric surgery were excluded. Severe GERD was defined as lower esophageal sphincter pressure <5 mmHg, distal esophageal amplitude <30 mmHg, Barrett's metaplasia, stricture or grade C-D esophagitis, and/or DeMeester score >50. Clinical characteristics and outcomes of patients with severe GERD were compared with those of patients with mild to moderate GERD who served as control group. Results: Over the study period, a total of 336 patients met the inclusion criteria, and 102 (30.4%) had severe GERD. The median follow-up was 24 months (IQR = 75) in severe GERD patients and 32 months (IQR = 84) in those with non-severe GERD. Patients with severe GERD had a higher rate of dysphagia and higher GERD-HRQL scores. After the MSA procedure, symptoms, health-related quality of life scores, and proton-pump inhibitors consumption significantly decreased in both groups (p < 0.05). No difference between groups was found in the prevalence of severe post-operative dysphagia, the need for endoscopic dilation or device removal, and the DeMeester score. Conclusion: Laparoscopic MSA is safe and effective in reducing symptoms, PPI use, and esophageal acid exposure also in patients with severe GERD.

The semirecumbent position for high-resolution esophageal manometry. Results of a feasibility study.

OBJECTIVE: Normative values for high-resolution manometry (HRM) have been obtained with the patient lying supine. The aim of the study was to compare supine, semirecumbent and sitting positions during HRM in terms of variation in normative metrics, diagnostic yield, and patient's comfort. METHODS: A prospective, single-center feasibility study was planned in consecutive patients referred to the esophageal function laboratory. In each of the three positions, 10 consecutive 5 ml water swallows and three 10 ml multiple rapid swallows were administered. Validated reflux questionnaires were administered prior to the test, and a visual analogue scale (VAS) assessing the patient's comfort after the test. RESULTS: Twenty patients presenting with gastroesophageal reflux symptoms completed the study protocol. The intra-abdominal segment of the lower esophageal sphincter was significantly longer in the sitting position (P = 0.013), and the multiple rapid swallow distal contractile integral was lowest in the supine position (P = 0.012). The VAS comfort score did not significantly differ in the three body positions (P = 0.295). The concordance in the final diagnosis was 80% for semirecumbent vs. sitting (kappa = 0.15; P = 0.001), 70% for supine vs. sitting and 65.0% for semirecumbent vs. supine. CONCLUSION: Compared to the supine position, both the semirecumbent and sitting position seems to provide similar advantages. HRM metrics and the final manometric diagnosis may be affected by body position, but complementary maneuvers, such are the rapid drink challenge, can resolve diagnostic discrepancies and improve the overall accuracy of the test.

Reference high-resolution manometry values after magnetic sphincter augmentation.

BACKGROUND: Magnetic sphincter augmentation (MSA) is an innovative antireflux procedure that can improve lower esophageal sphincter (LES) competency and reduce symptoms of gastroesophageal reflux disease (GERD). Some patients report postoperative dysphagia. To date, no studies have described reference high-resolution manometry (HRM) values after MSA implantation. METHODS: High-resolution manometry was performed in patients free of dysphagia after MSA with or without concurrent crura repair. Reference values for all parameters of the Chicago Classification were defined as those between the 5th and 95th percentiles. The contribution of concurrent crura repair to LES competency and to reference values was also analyzed. KEY RESULTS: Eighty-four patients met the study inclusion criteria. The upper limit of normality for integrated relaxation pressure (IRP) and intrabolus pressure (IBP) was 20.2 mmHg and 30.3 mmHg, respectively. Both variables were higher after MSA compared to normative Chicago Classification v3.0 values. The Distal Contractile Integral upper limit was in the range of normality. Patients undergoing crura repair had a significantly higher IRP (p = 0.0378) and lower GERDQ-A scores (p = 0.0374) and Reflux Symptom Index (p = 0.0030) compared to those who underwent MSA device implantation alone. CONCLUSION & INFERENCES: This study provides HRM reference values for patients undergoing successful MSA implantation. Crural repair appears to be a key component of LES augmentation and is associated with improved clinical outcomes.

Sitagliptin Treatment at the Time of Hospitalization Was Associated With Reduced Mortality in Patients With Type 2 Diabetes and COVID-19: A Multicenter, Case-Control, Retrospective, Observational Study.

OBJECTIVE: Poor outcomes have been reported in patients with type 2 diabetes and coronavirus disease 2019 (COVID-19); thus, it is mandatory to explore novel therapeutic approaches for this population. RESEARCH DESIGN AND METHODS: In a multicenter, case-control, retrospective, observational study, sitagliptin, an oral and highly selective dipeptidyl peptidase 4 inhibitor, was added to standard of care (e.g., insulin administration) at the time of hospitalization in patients with type 2 diabetes who were hospitalized with COVID-19. Every center also recruited at a 1:1 ratio untreated control subjects matched for age and sex. All patients had pneumonia and exhibited oxygen saturation <95% when breathing ambient air or when receiving oxygen support. The primary end points were discharge from the hospital/death and improvement of clinical outcomes, defined as an increase in at least two points on a seven-category modified ordinal scale. Data were collected retrospectively from patients receiving sitagliptin from 1 March through 30 April 2020. RESULTS: Of the 338 consecutive patients with type 2 diabetes and COVID-19 admitted in Northern Italy hospitals included in this study, 169 were on sitagliptin, while 169 were on standard of care. Treatment with sitagliptin at the time of hospitalization was associated with reduced mortality (18% vs. 37% of deceased patients; hazard ratio 0.44 [95% CI 0.29-0.66]; P = 0.0001), with an improvement in clinical outcomes (60% vs. 38% of improved patients; P = 0.0001) and with a greater number of hospital discharges (120 vs. 89 of discharged patients; P = 0.0008) compared with patients receiving standard of care, respectively. CONCLUSIONS: In this multicenter, case-control, retrospective, observational study of patients with type 2 diabetes admitted to the hospital for COVID-19, sitagliptin treatment at the time of hospitalization was associated with reduced mortality and improved clinical outcomes as compared with standard-of-care treatment. The effects of sitagliptin in patients with type 2 diabetes and COVID-19 should be confirmed in an ongoing randomized, placebo-controlled trial.

Effect of Body Position on High-resolution Esophageal Manometry Variables and Final Manometric Diagnosis.

Background/Aims: According to the Chicago classification version 3.0, high-resolution manometry (HRM) should be performed in the supine position. However, with the patient in the upright/sitting position, the test could more closely simulate real-life behavior and may be better tolerated. We performed a systematic review of the literature to search whether the manometric variables and the final diagnosis are affected by positional changes. Methods: A literature search was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Studies published in English that compared HRM results in different body positions were included. Moreover, the change in diagnosis of esophageal motility disorders according to the shift of body position was investigated. Results: Seventeen studies including 1714 patients and healthy volunteers met the inclusion criteria. Six studies showed a significant increase in lower esophageal sphincter basal pressure in the supine position. Integrated relaxation pressure was significantly higher in the supine position in 10 of 13 studies. Distal contractile index was higher in the supine position in 9 out of 10 studies. One hundred and fifty-one patients (16.4%) out of 922 with normal HRM in the supine position were diagnosed with ineffective esophageal motility (IEM) when the test was performed in the upright position (P < 0.001). Conclusions: Performing HRM in the upright position affects some variables and may change the final manometric diagnosis. Further studies to determine the normal values in the sitting position are needed.

Esophageal foreign bodies: observational cohort study and factors associated with recurrent impaction.

BACKGROUND AND AIM: Esophageal foreign bodies, including food bolus impaction, represent a common clinical problem. The prevalence of underlying esophageal disease depends on study design and degree of suspicion of a structural or functional esophageal abnormality. Aim of this study was to analyze factors associated with recurrent impaction. METHODS: The prospectively collected database at a University Hospital and Swallowing Center was reviewed from January 2012 to June 2019 to identify all patients admitted for esophageal foreign bodies. Patients who underwent an emergency endoscopic procedure represented the final study sample. Patient characteristics, including history of previous esophageal foreign bodies, and type of endoscopic procedure were collected. RESULTS: Sixty-five patients, 41 males and 24 females with a median age of 59 years, underwent emergency endoscopy for esophageal foreign bodies during the study period. Food bolus was the most common foreign body (n = 43, 66%). Flexible endoscopy was successful in retrieving or pushing the foreign bodies in the stomach in 91% of patients. In 54% of patients, impaction was secondary to an underlying esophageal disorder, which was previously unrecognized in half of them. Recurrent impaction was more common in patients with esophageal disease (P < 0.011). Surgical therapy was required in 4 patients (6.1%). CONCLUSIONS: Food bolus impaction is a common sentinel event in patients with underlying esophageal disease and is associated with recurrent impaction. Diagnostic endoscopy with biopsies should possibly be performed at the first episode of impaction. Patients with negative biopsies should undergo barium swallow study and high-resolution esophageal manometry.

Systematic Review and Bayesian Network Meta-Analysis Comparing Laparoscopic Heller Myotomy, Pneumatic Dilatation, and Peroral Endoscopic Myotomy for Esophageal Achalasia.

Background: Laparoscopic Heller myotomy (LHM), pneumatic dilatation (PD), and peroral endoscopic myotomy (POEM) are common treatments for esophageal achalasia. Literature evidence is restricted to pairwise analysis and PD versus POEM comparison is missing. The aim of this network meta-analysis (NMA) was to comprehensively compare outcomes within these three surgical approaches with those of esophageal achalasia. Materials and Methods: PubMed, EMBASE, and Web of Science databases were consulted. A systematic review and a fully Bayesian study level arm-based random effect NMA were performed. Results: Nineteen studies (14 observational and 5 randomized controlled trial) and 4407 patients were included. Overall, 50.4% underwent LHM, 42.8% PD, and 6.8% POEM. The postoperative dysphagia remission was statistically significantly improved in POEM compared with LHM and PD (risk ratio [RR] = 1.21; 95% credible intervals [CIs] = 1.04-1.47 and RR = 1.40; 95% CIs = 1.14-1.79, respectively). Postoperative gastroesophageal reflux disease (GERD) rate was higher in POEM than in LHM and PD (RR = 1.75; 95% CIs = 1.35-2.03 and RR = 1.36; 95% CIs = 1.18-1.68, respectively). Postoperative Eckardt score was significantly lower in POEM than in LHM and PD (standardized mean difference (smd) = -0.6; 95% CIs = -1.4 to -0.2 and smd = -1.2; 95% CIs = -2.3 to -0.2, respectively). No statistically significant differences were found comparing LHM and PD in any of the analyzed outcomes. Conclusions: In the short-term follow-up, POEM seems to be associated with better dysphagia improvement and higher postoperative GERD than LHM and PD. The choice of the ideal initial management should be left to multidisciplinary team discussion and personalized on each patient basis.

High-resolution manometry findings after Linx procedure for gastro-esophageal reflux disease.

BACKGROUND: Magnetic sphincter augmentation with the Linx® system is a novel laparoscopic procedure for the treatment of gastro-esophageal reflux disease (GERD). Only few data are available regarding the impact of Linx on high-resolution manometry (HRM) variables. METHODS: The prospectively collected database of patients who underwent Linx procedure at a single institution was queried. All patients who completed pre- and postoperative HRM, GERD health-related quality of life (GERD-HRQL) questionnaire, and functional outcome swallowing scale (FOSS) questionnaire were included in the study. KEY RESULTS: Forty-five out of 304 patients were included. At a median follow-up of 12 months (IQR 10) after surgery, a statistically significant increase of lower esophageal sphincter (LES) total length (P = .002), intra-abdominal length (P = .001), integrated relaxation pressure (IRP), intrabolus pressure (IBP), and esophagogastric contractile integral (EGJ-CI) was noted (P < .001). Distal esophageal amplitude (P = .004), mean distal contractile integral (DCI) (P < .001), post multiple repeated swallows DCI (P = .001), and the percent of normal peristalsis increased (P = .040). All patients were relieved of reflux symptoms. Ineffective esophageal motility reversed to normal in 36% of patients after surgery. The only factor significantly associated with postoperative dysphagia was preoperative dysphagia (P = .006). Postoperatively, a significant correlation between IRP and DCI (r = 0.361 and P = .019) and between IBP and DCI (r = 0.443 and P = .003) was found. CONCLUSIONS AND INFERENCES: The Linx procedure had a remarkable effect on esophageal motility in the short-term follow-up. It appears that the overall postoperative increase of IRP and IBP may justify the higher DCI values. Preoperative dysphagia was the only factor associated with postoperative dysphagia.

Magnetic Sphincter Augmentation After Gastric Surgery.

BACKGROUND: Persistent or de novo gastroesophageal reflux disease (GERD) may be a significant clinical issue after gastric/bariatric surgical procedures. We investigated the effect of magnetic sphincter augmentation (MSA) in the treatment of GERD after previous gastric/bariatric surgery. DATABASE: We conducted a systematic review according to the Preferred Reporting Items For Systematic Reviews and Meta-analyses statement. We searched multiple databases (PubMed, Cochrane, Embase, Scopus) up to May 2019. We also queried the prospectively collected database of patients who underwent MSA at our tertiary-care hospital and compared postsurgical to naïve patients operated during the same time period. RESULTS: Seven studies (3 case series and 4 case reports), for a total of 35 patients, met the inclusion criteria in the systematic review. The most common index operation was a bariatric procedure, either sleeve gastrectomy or Roux-en-Y gastric bypass. After MSA implant, the Gastroesophageal Reflux Disease-Health-Related Quality of Life (GERD-HRQL) score significantly improved compared to baseline (P = .005). Two patients (5.7%) required laparoscopic device removal. In the local institutional cohort series of 67 patients treated by MSA, the prevalence of preoperative grade B esophagitis, operative time, size of MSA, and length of stay were greater in patients with prior gastric surgery compared to naïve patients. CONCLUSIONS: MSA is a safe, simple, and standardized antireflux procedure. It is also feasible in patients with refractory GERD following gastric/bariatric surgery. Further prospective and comparative studies are needed to validate the preliminary clinical experience in this subset of patients.

Esophageal emergencies: WSES guidelines.

The esophagus traverses three body compartments (neck, thorax, and abdomen) and is surrounded at each level by vital organs. Injuries to the esophagus may be classified as foreign body ingestion, caustic ingestion, esophageal perforation, and esophageal trauma. These lesions can be life-threatening either by digestive contamination of surrounding structures in case of esophageal wall breach or concomitant damage of surrounding organs. Early diagnosis and timely therapeutic intervention are the keys of successful management.

Evaluation of Amides, Carbamates, Sulfonamides, and Ureas of 4-Prop-2-ynylidenecycloalkylamine as Potent, Selective, and Bioavailable Negative Allosteric Modulators of Metabotropic Glutamate Receptor 5.

Negative allosteric modulators (NAMs) of the metabotropic glutamate receptor 5 (mGlu5) hold great promise for the treatment of a variety of central nervous system disorders. We have recently reported that prop-2-ynylidenecycloalkylamine derivatives are potent and selective NAMs of the mGlu5 receptor. In this work, we explored the amide, carbamate, sulfonamide, and urea derivatives of prop-2-ynylidenecycloalkylamine compounds with the aim of improving solubility and metabolic stability. In silico and experimental analyses were performed on the synthesized series of compounds to investigate structure-activity relationships. Compounds 12, 32, and 49 of the carbamate, urea, and amide classes, respectively, showed the most suitable cytochrome inhibition and metabolic stability profiles. Among them, compound 12 showed excellent selectivity, solubility, and stability profiles as well as suitable in vitro and in vivo pharmacokinetic properties. It was highly absorbed in rats and dogs and was active in anxiety, neuropathic pain, and lower urinary tract models.

Esophageal foreign bodies in adults: systematic review of the literature.

OBJECTIVE: Esophageal Foreign Body (FB) impaction represents a major challenge for healthcare providers. Aim of this systematic review was to analyse the current literature evidence on prevalence, presentation, treatment, and outcomes of impacted esophageal FB. MATERIALS AND METHODS: Literature search was conducted between 2000 and 30th June 2018 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. RESULTS: Sixty-one studies matched the inclusion criteria. The total number of included patients was 13,092. The cervical esophagus was the most frequent impaction site (67%) and sharp-pointed objects were the most common FB (38.1%). Retrosternal pain (78%), dysphagia (48%), and odynophagia (43.4%) were the most common symptoms. A flexible or rigid endoscopic approach was adopted in 65.1% and 16.8% of patients, respectively. Overall, 17.8% of patients had a complication related to the impacted esophageal FB or to the endoscopic manoeuvers. A surgical approach was required in 3.4% of patients. The overall mortality was 0.85%. CONCLUSIONS: Surgery is the upfront treatment in patients with esophageal perforation or endoscopically irretrievable esophageal FB. A minimally invasive approach can be adopted in selected patients. Effective prevention of FB impaction should focus on accurate diagnostic work-up to search for an underlying motility disorder after a first episode of esophageal impaction, even if transient and self-resolving.

Flexible versus rigid endoscopy in the management of esophageal foreign body impaction: systematic review and meta-analysis.

Background: Foreign body (FB) impaction accounts for 4% of emergency endoscopies in clinical practice. Flexible endoscopy (FE) is recommended as the first-line therapeutic option because it can be performed under sedation, is cost-effective, and is well tolerated. Rigid endoscopy (RE) under general anesthesia is less used but may be advantageous in some circumstances. The aim of the study was to compare the efficacy and safety of FE and RE in esophageal FB removal. Methods: PubMed, MEDLINE, Embase, and Cochrane databases were consulted matching the terms "Rigid endoscopy AND Flexible endoscopy AND foreign bod*". Pooled effect measures were calculated using an inverse-variance weighted or Mantel-Haenszel in random effects meta-analysis. Heterogeneity was evaluated using I2 index and Cochrane Q test. Results: Five observational cohort studies, published between 1993 and 2015, matched the inclusion criteria. One thousand four hundred and two patients were included; FE was performed in 736 patients and RE in 666. Overall, 101 (7.2%) complications occurred. The most frequent complications were mucosal erosion (26.7%), mucosal edema (18.8%), and iatrogenic esophageal perforations (10.9%). Compared to FE, the estimated RE pooled success OR was 1.00 (95% CI 0.48-2.06; p = 1.00). The pooled OR of iatrogenic perforation, other complications, and overall complications were 2.87 (95% CI 0.96-8.61; p = 0.06), 1.09 (95% CI 0.38-3.18; p = 0.87), and 1.50 (95% CI 0.53-4.25; p = 0.44), respectively. There was no mortality. Conclusions: FE and RE are equally safe and effective for the removal of esophageal FB. To provide a tailored or crossover approach, patients should be managed in multidisciplinary centers where expertise in RE is also available. Formal training and certification in RE should probably be re-evaluated.

Unusual foreign body impacted in the upper oesophagus: original technique for transoral extraction.

Foreign body ingestion is a common event; in the adult population, most ingestions occur in patients with mental disability, psychiatric disorders, alcohol intoxication or in prisoners seeking secondary gain. Removal through flexible endoscopy is generally the first-line approach but rescue oesophagotomy may be necessary for foreign bodies impacted in the upper oesophagus. A 27-year-old man was admitted in the emergency room after intentional ingestion of a wooden spherical object with a central hole. A total body CT scan showed that the object was completely obstructing the upper oesophageal lumen but there were no signs of perforation. In the operating room, a Weerda diverticuloscope and a 5 mm 0° telescope were used to visualise the foreign body under general anaesthesia. A standard endoscopic biopsy forceps was passed through the hole of the sphere and was retracted with the jaws open allowing transoral extraction without complications.

Giant cane (Arundo donax L.) can substitute traditional energy crops in producing energy by anaerobic digestion, reducing surface area and costs: A full-scale approach.

Arundo donax L. (Giant cane) was used in a full-scale anaerobic digester (AD) plant (power of 380kWhEE) in partial substitution for corn to produce biogas and electricity. Corn substitution was made on a biomethane potential (BMP) basis so that A. donax L. after substitution accounted for 15.6% of the total mix-BMP (BMPmix) and corn for 66.6% BMPmix. Results obtained indicated that Giant cane was able to substitute for corn, reducing both biomass and electricity production costs, because of both higher biomass productivity (Mg total solid Ha(-1)) and lower biomass cost (€Ha(-1)). Total electricity biogas costs were reduced by 5.5%. The total biomass cost, the total surface area needed to produce the energy crop and the total cost of producing electricity can be reduced by 75.5%, 36.6% and 22%, by substituting corn completely with Giant cane in the mix fed to the full-scale plant.

The role of biological processes in reducing both odor impact and pathogen content during mesophilic anaerobic digestion.

Mesophilic anaerobic digestion (MAD) produces renewable energy, but it also plays a role in reducing the impact of digestates, both by reducing odor and pathogen content. Ten full-scale biogas plants characterized by different plant designs (e.g. single digesters, parallel or serial digesters), plant powers (ranging from 180 to 999 kWe), hydraulic retention time (HRT) (ranging between 20 to 70 days) and feed mixes were monitored and odors and pathogens were observed in both ingestates and digestates. Results obtained indicated that MAD reduced odors (OU) from, on average, OUingestate=99,106±149,173 OU m(-2) h(-1) (n=15) to OU digestate=1106±771 OU m(-2) h(-1) (n=15). Pathogens were also reduced during MAD both because of ammonia production during the process and competition for substrate between pathogens and indigenous microflora, i.e. Enterobacteriaceae from 6.85∗10(3)±1.8∗10(1) to 1.82∗10(1)±3.82∗10(1); fecal Coliform from 1.82∗10(4)±9.09 to 2.45∗10(1)±3.8∗10(1); Escherichia coli from 8.72∗10(3)±2.4∗10(1) to 1.8∗10(1)±2.94∗10(1); Clostridium perfringens from 6.4∗10(4)±7.7 to 5.2∗10(3)±8.1 (all data are expressed as CFU g(-1) ww). Plants showed different abilities to reduce pathogen indicators, depending on the pH value and toxic ammonia content.

Insights into the interaction of negative allosteric modulators with the metabotropic glutamate receptor 5: discovery and computational modeling of a new series of ligands with nanomolar affinity.

Metabotropic glutamate receptor 5 (mGlu5) is a biological target implicated in major neurological and psychiatric disorders. In the present study, we have investigated structural determinants of the interaction of negative allosteric modulators (NAMs) with the seven-transmembrane (7TM) domain of mGlu5. A homology model of the 7TM receptor domain built on the crystal structure of the mGlu1 template was obtained, and the binding modes of known NAMs, namely MPEP and fenobam, were investigated by docking and molecular dynamics simulations. The results were validated by comparison with mutagenesis data available in the literature for these two ligands, and subsequently corroborated by the recently described mGlu5 crystal structure. Moreover, a new series of NAMs was synthesized and tested, providing compounds with nanomolar affinity. Several structural modifications were sequentially introduced with the aim of identifying structural features important for receptor binding. The synthesized NAMs were docked in the validated homology model and binding modes were used to interpret and discuss structure-activity relationships within this new series of compounds. Finally, the models of the interaction of NAMs with mGlu5 were extended to include important non-aryl alkyne mGlu5 NAMs taken from the literature. Overall, the results provide useful insights into the molecular interaction of negative allosteric modulators with mGlu5 and may facilitate the design of new modulators for this class of receptors.