Scientific Reports / Phenotypes of Jackhammer esophagus in patients with typical symptoms of gastroesophageal reflux disease responsive to proton pump inhibitors

This trial was designed to assess the prevalence and characteristics of Jackhammer esophagus (JE), a novel hypercontractile disorder associated with progression to achalasia and limited outcomes following anti-reflux surgery in patients with typical symptoms of GERD and responsiveness to proton pump inhibitor (PPI) therapy. Consecutive patients, who were referred for surgical therapy because of PPI responsive typical symptoms of GERD, were prospectively assessed between January 2014 and May 2017. Patients diagnosed with JE subsequently underwent rigorous clinical screening including esophagogastroduodenoscopy (EGD), ambulatory pH impedance monitoring off PPI and a PPI trial. Out of 2443 evaluated patients, 37 (1.5%) subjects with a median age of 56.3 (51.6; 65) years were diagnosed with JE and left for final analysis. Extensive testing resulted in 16 (43.2%) GERD positive patients and 5 (13.9%) participants were observed to have an acid hypersensitive esophagus. There were no clinical parameters that differentiated phenotypes of JE. The prevalence of JE in patients with typical symptoms of GERD and response to PPI therapy is low. True GERD was diagnosed in less than half of this selected cohort, indicating the need for objective testing to stratify phenotypes of JE. (NCT03347903)(VLID)464183

Surgical Endoscopy / Persistent dysphagia is a rare problem after laparoscopic Nissen fundoplication

Background Although around 30% of patients with gastroesophageal reflux disease (GERD) are insufficiently treated with medical therapy, only 1% opt for surgical therapy. One of the reasons behind this multifactorial phenomenon is the described adverse effect of long-term dysphagia or gastric bloating syndrome after surgical treatment. Aim of this study was to evaluate the most common side effects associated with anti-reflux surgery, as well as long-term outcomes in a large cohort of highly surgically standardized patients after laparoscopic Nissen fundoplication (LNF). Methods Out of a prospective patients database including all patients that underwent anti-reflux surgery between 01/2003 and 01/2017 at our institution, 350 consecutive patients after highly standardized LNF were included in this study. A standardized interview was performed by one physician assessing postoperative gastrointestinal symptoms, proton pump inhibitor intake (PPI), GERD-Health-Related-Quality-of-Life (GERD-HRQL), Alimentary Satisfaction (AS), and patients overall satisfaction. Results After a median follow-up of 4 years, persistent dysphagia (PD) after LNF was observed in 8 (2%) patients, while postoperative gas-bloat syndrome in 45 (12.7%) cases. Endoscopic dilatation was needed in 7 (2%) patients due to dysphagia, and 19 (5%) patients underwent revision surgery due to recurrence of GERD. The postoperative GERD-HRQL total score was significantly reduced (2 (IQR 04.3) vs. 19 (IQR 1732); p < 0.000) and the median AS was 9/10. Heartburn relief was achieved in 83% of patients. Eighty-three percent of patients were free of PPI intake after follow-up, whereas 13% and 4% of the patients reported daily and irregular PPI use, respectively. Conclusion LNF is a safe and effective surgical procedure with low postoperative morbidity rates and efficient GERD-related symptom relief. PD does not represent a relevant clinical issue when LNF is performed in a surgical standardized way. These results should be the benchmark to which long-term outcomes of new surgical anti-reflux procedures are compared.(VLID)365680

Results of Magnetic Sphincter Augmentation for Gastroesophageal Reflux Disease

Background Magnetic sphincter augmentation (MSA) is a modern treatment option for gastroesophageal reflux disease (GERD); however, laparoscopic fundoplication remains the gold standard. The aim of the study was to evaluate outcomes of MSA patients at a reflux center. Methods A retrospective review was performed of all patients that underwent MSA between March 2012 and November 2017. Out of 110 patients, 68 with a follow-up >3 months were included. Postoperative gastrointestinal symptoms, proton pump inhibitor (PPI) intake, GERD-Health-related Quality of Life (GERD-HRQL) and alimentary satisfaction (AS) were assessed. Postoperative esophageal functioning tests were performed in 50% of patients. Results Sixty-eight patients underwent MSA; hiatal repair was performed in 31 cases. The median OR time was 27 min, and no intraoperative complications occurred. The median follow-up was 13 months (IQR 4.245). Endoscopic dilatation was performed in 2 patients (3%) and device removal in another 2 cases. The postoperative GERD-HRQL score was significantly reduced (3 vs. 24; p < 0.001) and the median AS was 8/10. Preoperative experienced heartburn, regurgitations and dysphagia were eliminated in 92, 96 and 100%. Postoperative new-onset difficulties swallowing with solids only were reported to occur occasionally by 16% and rarely by 21% of patients. Satisfaction with heartburn relief was 95%, and the overall outcome was rated excellent/good in 89%. PPI dependency was eliminated in 87%. The median total percentage pH < 4 and number of reflux episodes were significantly reduced. Postoperative pH results were negative or slightly above the norm in 79% and 12%, respectively. Conclusion Sphincter augmentation results in significantly reduced reflux symptoms, increased GERD-specific Quality of Life and excellent alimentary satisfaction with low perioperative morbidity. This procedure should be considered an excellent alternative to fundoplication in the treatment of GERD.(VLID)359210

Immunogenicity, safety, and tolerability of a recombinant measles-virus-based chikungunya vaccine: a randomised, double-blind, placebo-controlled, active-comparator, first-in-man trial

International audienceBackgroundChikungunya is an emerging arthropod-borne disease that has spread from tropical endemic areas to more temperate climates of the USA and Europe. However, no specific treatment or preventive measure is yet available. We aimed to investigate the immunogenicity and safety of a live recombinant measles-virus-based chikungunya vaccine.MethodsWe did a randomised, double-blind, placebo-controlled, active-comparator, phase 1, dose-escalation study at one centre in Vienna, Austria. Healthy men and women aged 18–45 years with no comorbidities were randomly assigned, by computer-generated block randomisation (block size of 14), to receive either one of three escalating doses of the measles-virus-based candidate vaccine (low dose [1·5 × 104 median tissue culture infection doses (TCID50) per 0·05 mL], medium dose [7·5 × 104 TCID50 per 0·25 mL], or high dose [3·0 × 105 TCID50 per 1·0 mL]), or the active comparator—Priorix. Participants were additionally block-randomised to receive a booster injection on either day 28 or day 90 after the first vaccination. Participants and study investigators were masked to group allocation. The primary endpoint was the presence of neutralising anti-chikungunya antibodies on day 28, as assessed by 50% plaque reduction neutralisation test. Analysis was by intention to treat and per protocol. This trial is registered with EudraCT, number 2013-001084-23.FindingsBetween Nov 22, 2013, and Feb 25, 2014, we randomly assigned 42 participants to receive the low dose (n=12), the medium dose (n=12), or the high dose (n=12) of the measles-virus-based candidate vaccine, or Priorix (n=6), of whom 36 participants (86%; n=9, n=12, n=10, n=5, respectively) were included in the per-protocol population. The candidate vaccine raised neutralising antibodies in all dose cohorts after one immunisation, with seroconversion rates of 44% (n=4) in the low-dose group, 92% (n=11) in the medium-dose group, and 90% (n=10) in the high-dose group. The immunogenicity of the candidate vaccine was not affected by pre-existing anti-measles immunity. The second vaccination resulted in a 100% seroconversion for all participants in the candidate vaccine groups. The candidate vaccine had an overall good safety profile, and the rate of adverse events increased with vaccine dose and volume. No vaccination-related serious adverse events were recorded.InterpretationThe live recombinant measles-virus-based chikungunya vaccine had good immunogenicity, even in the presence of anti-vector immunity, was safe, and had a generally acceptable tolerability profile. This vaccine is the first promising measles-virus-based candidate vaccine for use in human beings

Scientific Reports / Crural Closure improves Outcomes of Magnetic Sphincter Augmentation in GERD patients with Hiatal Hernia

Magnetic sphincter-augmentation (MSA) has been proven effective in the treatment of GERD. No consensus exists on whether crural closure should be performed. Our aim was to assess the impact of cruroplasty on reflux-control and quality of life. MSA-Patients treated between 03/2012-03/2017 were classified into those without hiatal hernia (“NHH”), those post-MSA (NHR) and those post-MSA/hiatal repair (HR). GERD-symptoms, PPI-intake, GERD-Health-related-Quality-of-Life (GERD-HRQL) and Alimentary Satisfaction were assessed. Sixty-eight patients underwent MSA, 26 patients had additional crural closure. PH-monitoring was negative in 80% of HR, 73% of NHR and 89% of NHH-patients. GERD-HRQL-total scores decreased significantly in all groups (p<0.001). Alimentary satisfaction was 8/10 in HR/NHH and 10/10 in NHR-patients. Satisfaction with heartburn relief was high (HR: 96%, NR: 95%, NHH: 94%) as was the elimination of PPI-intake (HR/NHH: 87%, NR: 86%). Heartburn and regurgitations were eliminated in 100% of HR, 88% and 94% of NHR and 87% and 91% of NHH-patients. Endoscopic dilatation or device explantation was performed in 3% each. MSA leads to significant symptom relief, increased quality of life and alimentary satisfaction with low perioperative morbidity. Cruroplasty tends to result in better reflux control and symptom relief than exclusive MSA without increasing dysphagia rates.(VLID)464140

Gamma-glutamyltransferase as novel biomarker in patients with uterine leiomyosarcoma

Gamma-glutamyltransferase (GGT) is an established marker for proliferative/apoptotic balance and has been associated with cancer risk and prognosis. The aim of this study was to evaluate the value of pre-treatment GGT serum levels as prognostic biomarker in patients with primary uterine leiomyosarcoma (ULMS). Data of women with ULMS were extracted from a multi-center database. Pre-treatment GGT serum levels were measured and patients assigned to predefined GGT risk groups. GGT values were correlated with clinico-pathological parameters and univariate and multivariable survival analyses were performed. A total of 44 patients with ULMS were analyzed. Mean (SD) pre-therapeutic GGT serum level was 33.8 (39.8) U/L. In Figo Stage I versus II-IV mean (SD) GGT values were 28.8 (34.0) U/l and 43.5 (49.2) U/l, respectively (p=0.25). Five-year overall survival (OS) rates in ULMS patients with normal low versus higher GGT levels were 70% and 37%, respectively (p=0.043). Univariate and multivariable analyses revealed that higher GGT serum levels (p=0.043, p=0.005) and high histological grade (p=0.029, p=0.012) were independently associated with impaired OS, respectively. Higher pre-treatment GGT serum levels were independently associated with unfavorable prognosis in women with ULMS. Thus, GGT seems to be a useful novel biomarker in ULMS.(VLID)468871