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Eosinophilic oesophagitis (EoE) may lead to severe complications if not promptly recognised.To assess the diagnostic delay in patients with EoE and to explore its risk factors.EoE patients followed-up at eight clinics were included via retrospective chart review. Diagnostic delay was estimated as the time lapse occurring between the appearance of the first likely symptoms indicative of EoE and the final diagnosis. Patient-dependent and physician-dependent diagnostic delays were assessed. Multivariable regression models were computed.261 patients with EoE (mean age 34±14 years; M:F ratio=3:1) were included. The median overall diagnostic delay was 36 months (IQR 12-88), while patient- and physician-dependent diagnostic delays were 18 months (IQR 5-49) and 6 months (IQR 1-24). Patient-dependent delay was greater compared to physician-dependent delay (95% CI 5.1-19.3, p0.001). A previous misdiagnosis was formulated in 109 cases (41.8%; gastro-oesophageal reflux disease in 67 patients, 25.7%). The variables significantly associated with greater overall diagnostic delay were being a non-smoker,1 episode of food impaction, previous endoscopy with no biopsies, regurgitation, and ≥2 assessing physicians. Being single was significantly associated with lower overall and patient-dependent diagnostic delay.EoE is burdened by substantial diagnostic delay, depending on both patient-related and physician-related factors.

The straight leg raise (SLR) maneuver during high-resolution manometry (HRM) can assess esophagogastric junction (EGJ) barrier function by measuring changes in intraesophageal pressure (IEP) when intra-abdominal pressure is increased. We aimed to determine whether increased esophageal pressure during SLR predicts pathologic esophageal acid exposure time (AET).Adult patients with persistent gastroesophageal reflux disease (GERD) symptoms undergoing HRM and pH-impedance or wireless pH study off proton pump inhibitor were prospectively studied between July 2021 and March 2022. After the HRM Chicago 4.0 protocol, patients were requested to elevate 1 leg at 45º for 5 seconds while supine. The SLR maneuver was considered effective when intra-abdominal pressure increased by 50%. IEPs were recorded 5 cm above the lower esophageal sphincter at baseline and during SLR. GERD was defined as AET greater than 6%.The SLR was effective in 295 patients (81%), 115 (39%) of whom had an AET greater than 6%. Hiatal hernia (EGJ type 2 or 3) was seen in 135 (46%) patients. Compared with patients with an AET less than 6%, peak IEP during SLR was significantly higher in the GERD group (29.7 vs 13.9 mm Hg; P.001). Using receiver operating characteristic analysis, an increase of 11 mm Hg of peak IEP from baseline during SLR was the optimal cut-off value to predict an AET greater than 6% (area under the receiver operating characteristic curve, 0.84; sensitivity, 79%; and specificity, 85%), regardless of the presence of hiatal hernia. On multivariable analysis, an IEP pressure increase during the SLR maneuver, EGJ contractile integral, EGJ subtype 2, and EGJ subtype 3, were found to be significant predictors of AET greater than 6% CONCLUSIONS: The SLR maneuver can predict abnormal an AET, thereby increasing the diagnostic value of HRM when GERD is suspected.gov ID: NCT04813029.

The most recent iteration of the classifications for functional esophageal disorders, Rome IV, proposed relevant modifications of the previous definitions for Rome III. They specifically considered increased esophageal acid exposure as the marker of gastroesophageal reflux disease (GERD), including the remaining part of non-erosive reflux disease patients with normal acid in the group with functional alterations, considering both reflux hypersensitivity and functional heartburn. However, recent pathophysiological and therapeutic data suggest the need for a return to including reflux hypersensitivity in the GERD spectrum. Indeed, physiologic alterations in esophageal mucosal integrity and chemical clearance, the presence of microscopic esophagitis, and strict symptom-reflux association support the concept that reflux hypersensitivity pertains to GERD. Surgical anti-reflux therapy has resulted in positive outcomes, even in the long term, in patients with reflux hypersensitivity and not in those with functional heartburn. Moreover, clinical trials using neuromodulators have been scarce and provided conflicting results. As a result, the real progress of the Rome IV classifications is in dispute. This article aims to summarize the most recent knowledge of non-erosive reflux disease and reflux hypersensitivity to discuss the utility of Rome IV criteria in the identification and management of functional esophageal disorders.

Highlights • Percutaneous dilatation tracheotomy enables non-surgeons to perform tracheotomies at patients bedside. • Bleeding is a common complication of percutaneous dilatation tracheotomies. • Performing a pre-operative neck ultrasound can help identifying aberrant vessels and reduce the risk of periprocedural bleeding., Introduction Percutaneous dilatation tracheotomy (PDT) is a relatively recent technique that enables non surgeons to perform tracheotomies at bedside reducing operation rooms schedules. It is burdened by a moderate risk of postoperative bleeding. Presentation of case The patient was a 57 years old with a temporal intraparenchymal hematoma, submitted to percutaneous dilatation tracheotomy. Despite the favorable anatomical features, a pre-procedural US was performed, identifying a pulsating vessel with an arterial pattern, 2 cm above the hollow. The procedure was then considered at high risk, an operation room was required for the technique and an on-call surgeon was alerted. The procedure was ended safely and any bleeding was avoided because the technique was practiced with the best precautions. Discussion PDT strength is the possibility for non surgeons to perform tracheotomies in selected patients at bedside, reducing operation rooms congestion. Such technique though is a “blind” technique, and postoperative bleedings can occur and represent a feared complication. Conversely, the surgical tracheotomy permits a better control of hemorrhages, but needs the involvement of a surgeon and availability of an operation room. Performing a PDT guided by a neck ultrasound is useful to identify eventual aberrant vessel whose course could complicate the tracheotomy, it is part of PDT guidelines of some States. Conclusion US-PDT could help reducing procedure related complications selecting those high risk patients still in need of operating room and surgical assistance. US-PDT feasibility combined to its easy availability and low costs encourage its introduction into everyday practice.

Chronic kidney disease (CKD) is a major clinical sign of patients with Bardet-Biedl syndrome (BBS), especially in those carrying BBS10 mutations. Twenty-nine patients with BBS and 30 controls underwent a serum-targeted metabolomic analysis. In vitro studies were conducted in two kidney-derived epithelial cell lines, where Bbs10 was stably deleted (IMCD3-Bbs10-/-cells) and over-expressed. The CKD status affected plasmatic metabolite fingerprinting in both patients with BBS and controls. Specific phosphatidylcholine and acylcarnitines discriminated eGFR decline only in patients with BBS. IMCD3-Bbs10-/ cells displayed intracellular lipidaccumulation, reduced mitochondrial potential membrane and citrate synthase staining. Mass-Spectrometry-based analysis revealed that human BBS10 interacted with six mitochondrial proteins, in vitro. In conclusion, renal dysfunction correlated with abnormal phosphatidylcholine and acylcarnitines plasma levels in patients with BBS; in vitro, Bbs10 depletion caused mitochondrial defects while human BBS10 interacted with several mitochondria-related proteins, suggesting an unexplored role of this protein.

Background: At present, no objective data are available on the effect of omega-loop gastric bypass (OGB) on gastroesophageal junction and reflux. Objectives: To evaluate the possible effects of OGB on esophageal motor function and a possible increase in gastroesophageal reflux. Setting: University Hospital, Italy; Public Hospital, Italy. Methods: Patients underwent clinical assessment for reflux symptoms, and endoscopy plus highresolution impedance manometry (HRiM) and 24-hour pH-impedance monitoring (MII-pH) before and 1 year after OGB. A group of obese patients who underwent sleeve gastrectomy (SG) were included as the control population. Results: Fifteen OGB patients were included in the study. After surgery, none of the patients reported de novo heartburn or regurgitation. At endoscopic follow-up 1 year after surgery, esophagitis was absent in all patients and no biliary gastritis or presence of bile was recorded. Manometric features and patterns did not vary significantly after surgery, whereas intragastric pressures (IGP) and gastro-esophageal pressure gradient (GEPG) statistically diminished (from a median of 15 to 9.5, P < .01, and from 10.3 to 6.4, P < .01, respectively) after OGB. In contrast, SG induced a significant elevation in both parameters (from a median of 14.8 to 18.8, P < .01, and from 10.1 to 13.1, P < .01, respectively). A dramatic decrease in the number of reflux events (from a median of 41 to 7; P < .01) was observed after OGB, whereas in patients who underwent SG a significant increase in esophageal acid exposure and number of reflux episodes (from a median of 33 to 53; P < .01) was noted. Conclusions: In contrast to SG, OGB did not compromise the gastroesophageal junction function and did not increase gastroesophageal reflux, which was explained by the lack of increased IGP and in GEPG as assessed by HRiM.

BACKGROUND Oesophageal clearance has been scarcely studied. AIMS Oesophageal clearance in endoscopy-negative heartburn was assessed to detect differences in bolus clearance time among patients sub-grouped according to impedance-pH findings. METHODS In 118 consecutive endoscopy-negative heartburn patients impedance-pH monitoring was performed off-therapy. Acid exposure time, number of refluxes, baseline impedance, post-reflux swallow-induced peristaltic wave index and both automated and manual bolus clearance time were calculated. Patients were sub-grouped into pH/impedance positive (abnormal acid exposure and/or number of refluxes) and pH/impedance negative (normal acid exposure and number of refluxes), the former further subdivided on the basis of abnormal/normal acid exposure time (pH+/-) and abnormal/normal number of refluxes (impedance+/-). RESULTS Poor correlation (r=0.35) between automated and manual bolus clearance time was found. Manual bolus clearance time progressively decreased from pH+/impedance+ (42.6s), pH+/impedance- (27.1s), pH-/impedance+ (17.8s) to pH-/impedance- (10.8s). There was an inverse correlation between manual bolus clearance time and both baseline impedance and post-reflux swallow-induced peristaltic wave index, and a direct correlation between manual bolus clearance and acid exposure time. A manual bolus clearance time value of 14.8s had an accuracy of 93% to differentiate pH/impedance positive from pH/impedance negative patients. CONCLUSIONS When manually measured, bolus clearance time reflects reflux severity, confirming the pathophysiological relevance of oesophageal clearance in reflux disease.

Introduction Aim of this study is to determine whether quality of life (QoL) assessment in association with instrumental evaluation can help to identify factors predictive of outcome both in surgically and medically treated GERD patients. Methods Between January 2005 and June 2010, 301 patients affected with GERD were included in the study. QoL was evaluated by means of GERD-HRQL and SF-36 questionnaires administered before treatment, at 6 months, at 1 year follow-up and at the end of the study. The multivariate analysis was used to detect if variables such as sex, age, heartburn, acid regurgitation, dysphagia, presence of esophagitis, percentage of total time at pH < 4, symptom index score (SI), the SF-36 and HRQL scores before treatment, at 6 months and 1 year could affect the QoL questionnaires scores at the end of the study. Results One hundred forty-seven patients were included in the surgical group and 154 in the medical group. No differences with regard to gender, age, mean SF-36 and HRQL scores before treatment were documented. At the end of the study, quality of life was significantly improved for SF-36 and HRQL scores, either for surgical or medical group. The multivariate analysis showed no factors individually affected the SF-36 and the HRQL scores, but symptom index score (SI) and QoL questionnaires scores at 6 months and 1 year follow-up. Conclusions The combined use of pHmetry with evaluation of SI and QoL questionnaires can predict the outcome of GERD patients managed either by medical or surgical therapy.