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IntroductionPre-existent pools of coronavirus-specific or cross-reactive T cells were shown to shape the development of cellular and humoral immune responses after primary mRNA vaccination against SARS-CoV-2. However, the cellular determinants of responses to booster vaccination remain incompletely understood. Therefore, we phenotypically and functionally characterized spike antigen-specific T helper (Th) cells in healthy, immunocompetent individuals and correlated the results with cellular and humoral immune responses to BNT162b2 booster vaccination over a six-month period. MethodsBlood of 30 healthy healthcare workers was collected before, 1, 3, and 6 months after their 3rd BNT162b2 vaccination. Whole blood was stimulated with spike peptides and analyzed using flow cytometry, a 13-plex cytokine assay, and nCounter-based transcriptomics. ResultsSpike-specific IgG levels at 1 month after booster vaccination correlated with pre-existing CD154+CD69+IFN-γ+CD4+ effector memory cells as well as spike-induced IL-2 and IL-17A secretion. Early post-booster (1-month) spike IgG levels (r=0.49), spike-induced IL‑2 (r=0.58), and spike-induced IFN‑γ release (r=0.43) correlated moderately with their respective long-term (6-month) responses. Sustained robust IgG responses were significantly associated with S-specific (CD69+±CD154+±IFN-γ+) Th-cell frequencies before booster vaccination (p=0.038), especially double/triple-positive type-1 Th cells. Furthermore, spike IgG levels, spike-induced IL‑2 release, and spike-induced IFN‑γ release after 6 months were significantly associated with increased IL‑2 & IL‑4, IP‑10 & MCP1, and IFN‑γ & IP‑10 levels at 1 month post-booster, respectively. On the transcriptional level, induction of pathways associated with both T-cell proliferation and antigen presentation was indicative of sustained spike-induced cytokine release and spike-specific IgG production 6 months post-booster. Using support vector machine models, pre-booster spike-specific T-cell frequencies and early post-booster cytokine responses predicted sustained (6-month) responses with F1 scores of 0.80-1.00.DiscussionIn summary, spike-specific Th cells and T-cellular cytokine signatures present before BNT162b2 booster vaccination shape sustained adaptive cellular and humoral responses post-booster. Functional T-cell assays might facilitate early identification of potential non-responders.

Background and aims Peroral endoscopic myotomy (POEM) is a standard treatment option for achalasia patients. Treatment response varies due to factors such as achalasia type, degree of dilatation, pressure and distensibility indices. We present an innovative approach for treatment response prediction based on an automatic three-dimensional (3-D) reconstruction of the tubular oesophagus (TE) and the lower oesophageal sphincter (LES) in patients undergoing POEM for achalasia.Methods A software was developed, integrating data from high-resolution manometry, timed barium oesophagogram and endoscopic images to automatically generate 3-D reconstructions of the TE and LES. Novel normative indices for TE (volume×pressure) and LES (volume/pressure) were automatically integrated, facilitating pre-POEM and post-POEM comparisons. Treatment response was evaluated by changes in volumetric and pressure indices for the TE and the LES before as well as 3 and 12 months after POEM. In addition, these values were compared with normal value indices of non-achalasia patients.Results 50 treatment-naive achalasia patients were enrolled prospectively. The mean TE index decreased significantly (p

Barrett’s esophagus is associated with an increased risk of adenocarcinoma. Thorough screening during endoscopic surveillance is crucial to improve patient prognosis. Detecting and characterizing dysplastic or neoplastic Barrett’s esophagus during routine endoscopy are challenging, even for expert endoscopists. Artificial intelligence-based clinical decision support systems have been developed to provide additional assistance to physicians performing diagnostic and therapeutic gastrointestinal endoscopy. In this article, we review the current role of artificial intelligence in the management of Barrett’s esophagus and elaborate on potential artificial intelligence in the future.

Background/Aims Endoscopic submucosal dissection (ESD) has been established as a treatment modality for superficial esophageal squamous cell carcinoma (ESCC). Long-term follow-up data are lacking in Western countries. The aim of this study was to analyze long-term survival in a Western center. Methods Patients undergoing ESD for ESCC were included. The analysis was performed retrospectively using a prospectively collected database. Results R0 resection rate was 96.7% (59/61 lesions in 58 patients). Twenty-seven patients (46.6%) fulfilled the curative resection criteria (M1/M2) (group A), 11 patients (19.0%) had M3 lesions without lymphovascular invasion (LVI) (group B), and 20 patients (34.5%) had lesions with submucosal invasion or LVI (group C). Additional treatment was recommended after non-curative resection. It was not performed in 20/31 patients (64.5%), mainly because of comorbidities (75%). Twenty-nine out of 58 (50.0%) patients died during a mean follow-up of 3.7 years. Death was related to ESCC in 17.2% (5/29) of patients. The disease-specific survival rate after curative resection was 100%. Overall survival rates after 5 years were 61.5%, 63.6% and 28.1% for groups A, B, and C, respectively. The overall survival was significantly worse after non-curative resection (p=0.038). Conclusions Non-curative resection is frequent after ESD for ESCC in Western patients. The long-term prognosis is limited and mainly determined by comorbidity. Early diagnosis and pre-interventional assessments need to be improved.

Abstract The endoscopic features associated with eosinophilic esophagitis (EoE) may be missed during routine endoscopy. We aimed to develop and evaluate an Artificial Intelligence (AI) algorithm for detecting and quantifying the endoscopic features of EoE in white light images, supplemented by the EoE Endoscopic Reference Score (EREFS). An AI algorithm (AI-EoE) was constructed and trained to differentiate between EoE and normal esophagus using endoscopic white light images extracted from the database of the University Hospital Augsburg. In addition to binary classification, a second algorithm was trained with specific auxiliary branches for each EREFS feature (AI-EoE-EREFS). The AI algorithms were evaluated on an external data set from the University of North Carolina, Chapel Hill (UNC), and compared with the performance of human endoscopists with varying levels of experience. The overall sensitivity, specificity, and accuracy of AI-EoE were 0.93 for all measures, while the AUC was 0.986. With additional auxiliary branches for the EREFS categories, the AI algorithm (AI-EoE-EREFS) performance improved to 0.96, 0.94, 0.95, and 0.992 for sensitivity, specificity, accuracy, and AUC, respectively. AI-EoE and AI-EoE-EREFS performed significantly better than endoscopy beginners and senior fellows on the same set of images. An AI algorithm can be trained to detect and quantify endoscopic features of EoE with excellent performance scores. The addition of the EREFS criteria improved the performance of the AI algorithm, which performed significantly better than endoscopists with a lower or medium experience level.

Introduction: Invasive listeriosis most often presents as bacteremia or neurolisteriosis. Cerebral infection mostly manifests as meningitis or meningoencephalitis, but cerebral abscesses are a rare manifestation. Case presentation: We present the rare case of a 51-year old patient with progressive right sided hemiparesis caused by a cerebral abscess due to Listeria monocytogenes infection. The initially suspected cerebral ischemia or bleeding was ruled out. Magnetic resonance imaging led to the suspected diagnosis of an angiocentric lymphoma. An open cerebral biopsy revealed an intracranial abscess formation. After abscess evacuation and identification of Listeria monocytogenes, anti-infective treatment with ampicillin and gentamicin was started. After repeated cerebral imaging with signs of ongoing tissue inflammation after 6 weeks we chose to prolong the therapy with oral amoxicillin until resolution of signs of intracerebral inflammation after 12 weeks, documented by repeated cerebral magnetic resonance imaging. During hospitalization, the patient was diagnosed with diabetes mellitus type II and treatment was initiated. The patient was discharged without any persistent neurologic deficits. Discussion: For the treatment of bacterial brain abscesses, 4–6 weeks of intravenous antimicrobial treatment after surgical drainage are recommended. However, first line therapy of invasive cerebral listeriosis is not well established. We decided to use a combined treatment using ampicillin and gentamicin, followed by prolonged oral treatment due to ongoing tissue inflammation. Conclusion: No evidence-based treatment recommendations are available for brain abscess caused by Listeria monocytogenes. We report a case with favorable outcome after anti-infective ampicillin- and gentamicin-based therapy. Systematic assessment of treatment would be desirable.

Abstract Objectives The gold standard for diagnosing an infection with SARS-CoV-2 is detection of viral RNA by nucleic acid amplification techniques. Test capacities, however, are limited. Therefore, numerous easy-to-use rapid antigen tests based on lateral flow technology have been developed. Manufacturer-reported performance data seem convincing, but real-world data are missing. Methods We retrospectively analysed all prospectively collected antigen tests results performed between 23.06.2020 and 26.11.2020, generated by non-laboratory personnel at the point-of-care from oro- or nasopharyngeal swab samples at the University Hospital Augsburg and compared them to concomitantly (within 24 h.) generated results from molecular tests. Results For a total of 3630 antigen tests, 3110 NAAT results were available. Overall, sensitivity, specificity, NPV and PPV of antigen testing were 59.4%, 99.0%, 98.7% and 64.8%, respectively. Sensitivity and PPV were lower in asymptomatic patients (47.6% and 44.4%, respectively) and only slightly higher in patients with clinical symptoms (66.7% and 85.0%, respectively). Some samples with very low Ct-values (minimum Ct 13) were not detected by antigen testing. 31 false positive results occurred. ROC curve analysis showed that reducing the COI cut-off from 1, as suggested by the manufacturer, to 0.9 is optimal, albeit with an AUC of only 0.66. Conclusion In real life, performance of lateral-flow-based antigen tests are well below the manufacturer's specifications, irrespective of patient’s symptoms. Their use for detection of individual patients infected with SARS-CoV2 should be discouraged. This does not preclude their usefulness in large-scale screening programs to reduce transmission events on a population-wide scale.

Abstract Background Despite the worldwide burden of diverticular disease, the connections between diverticular disease and dietary habits remain poorly understood, particularly in an asymptomatic representative sample. We investigated the association between asymptomatic diverticular disease as assessed by magnetic resonance imaging (MRI) and dietary habits in a Western study cohort. Methods Participants from a cross-sectional sample of a population-based cohort study underwent whole-body 3T-MRI including an isotropic VIBE-Dixon sequence. The presence and extent of diverticular disease was assessed in blinded fashion. Habitual dietary intake was recorded using a blended approach, applying 24-h food lists and a food-frequency questionnaire. Traditional cardiometabolic risk factors were obtained by interviews and medical examination. Univariate and multivariate associations were calculated. Results A total of 308 subjects were included in this analysis (56% male, 56.4 ± 9.1 years). 39.9% had any form of diverticular disease and 15.3% had advanced asymptomatic diverticular disease. After adjustment for age, sex and total energy intake a higher intake of fiber and vegetables was associated with a lower odds for asymptomatic diverticular disease (fiber: OR 0.68 95% CI [0.48, 0.95]; vegetables: OR 0.72 95% CI [0.53, 0.97]) and an increased intake of meat was associated with an approximately two-fold higher odds for advanced asymptomatic diverticular disease (OR 1.84 95% CI [1.13, 2.99]). However, after additional adjustment for body-mass-index (BMI), alcohol consumption, smoking behavior and physical activity only a high fiber and vegetables intake remained significantly associated with lower odds of asymptomatic diverticular disease. Conclusion Our results indicate that a high-fiber diet and increased intake of vegetables is associated with lower odds of having asymptomatic diverticular disease, independent of age, sex, total energy intake, BMI and other life-style factors.

Endoscopic submucosal dissection (ESD) is a well-established method for the treatment of early-stage gastrointestinal neoplasms. Adequate submucosal exposure is one of the most significant factors related to an effective and safe dissection. The aim of this systematic review was to evaluate the effcacy and safety of various methods that assist traction during ESD of precancerous and earlystage neoplastic lesions of the gastrointestinal tract. We performed an electronic search of the MEDLINE and the Cochrane Controlled Trials Register databases for relevant studies published up to May 2019. Trials exclusively recruiting patients undergoing ESD for superficial gastrointestinal cancer were considered eligible for inclusion. Thirty-three articles including 3,134 patients met the inclusion criteria. The studies evaluated different approaches for widening the endoscopic view, including magnetic anchor-guided ESD (3 studies), use of a second endoscope (5 studies), clip-involving technique (21 studies), and miscellaneous methods (4 studies). Among them, only 6 were randomized controlled trials evaluating different approaches. Overall, the implementation of methods that assist traction during ESD significantly improved the operating time and R0 resection rate and decreased the rate of complications (bleeding and perforation). Interventions that assist traction seem effcacious in improving tissue traction, thus facilitating ESD performance.

Background and study aims The European Society of Gastrointestinal Endoscopy (ESGE) has defined COVID-19 infection prevention and control strategies within the endoscopy unit. These include pre-endoscopic questionnaire-based risk-stratification as well as pre-procedure viral testing. Real-life data on the effectiveness of these measures are presented here. Patients and methods Data from the outpatient endoscopic unit of the University Hospital Augsburg between July 1, 2020 and December 31, 2020 including the second pandemic wave were reviewed retrospectively. All patients were assessed with a pre-endoscopic risk-stratification questionnaire as well as viral testing using an antigen point-of-care test (Ag-POCT) in conjunction with a standard polymerase chain reaction (PCR) test. Highly elective procedures were postponed. The theoretically expected number of SARS-CoV-2-positive patients was simulated and compared with the actual number. In addition, endoscopy staff was evaluated with a rapid antibody test to determine the number of infections among the personnel. Results In total, 1029 procedures, 591 questionnaires, 591 Ag-POCTs, and 529 standard PCR tests were performed in 591 patients. 247 procedures in 142 patients were postponed. One Ag-POCT was positive but with a negative PCR test, while one PCR test was positive but with a negative Ag-POCT. This was lower than the theoretically expected number of COVID-19-positive patients (n = 15). One of 43 employees (2.3 %) in the outpatient endoscopy unit was seropositive. Conclusions Pre-endoscopic risk management including questionnaire-based risk stratification and viral testing seems to be an effective tool in combination with personal protective equipment for SARS-CoV-2 infection prevention and control within the endoscopy unit even in a high-prevalence setting.

Artificial intelligence is gaining increasing relevance in the field of radiology. This study retrospectively evaluates how a commercially available deep learning algorithm can detect pneumonia in chest radiographs (CR) in emergency departments. The chest radiographs of 948 patients with dyspnea between 3 February and 8 May 2020, as well as 15 October and 15 December 2020, were used. A deep learning algorithm was used to identify opacifications associated with pneumonia, and the performance was evaluated by using ROC analysis, sensitivity, specificity, PPV and NPV. Two radiologists assessed all enrolled images for pulmonal infection patterns as the reference standard. If consolidations or opacifications were present, the radiologists classified the pulmonal findings regarding a possible COVID-19 infection because of the ongoing pandemic. The AUROC value of the deep learning algorithm reached 0.923 when detecting pneumonia in chest radiographs with a sensitivity of 95.4%, specificity of 66.0%, PPV of 80.2% and NPV of 90.8%. The detection of COVID-19 pneumonia in CR by radiologists was achieved with a sensitivity of 50.6% and a specificity of 73%. The deep learning algorithm proved to be an excellent tool for detecting pneumonia in chest radiographs. Thus, the assessment of suspicious chest radiographs can be purposefully supported, shortening the turnaround time for reporting relevant findings and aiding early triage.

Background and Aims. Flexible endoscopic treatment plays an important role in the treatment of Zenker’s diverticulum (ZD). This study analyzes long-term symptom control and the rate of adverse events in treatment-naïve patients and patients with recurrence, using the stag beetle knife junior (sb knife jr). Methods. From August 2013 to May 2019, 100 patients with symptomatic ZD were treated with flexible endoscopy using the sb knife jr. Before treatment, as well as 1 and 6 months afterwards, symptoms were obtained by a nine-point questionnaire, with symptoms weighted from 0 to 4. Results. Overall, 126 interventions were performed. The median follow-up period was 41 months (range 7-74). For the three most frequent symptoms, regurgitation, dysphagia, and dry cough, a significant reduction of the mean score could be achieved, from 2.85/3.45/2.85 before the initial treatment to 0.56/1.09/0.98 6 months later. 17 patients were retreated because of recurrence. Out of these, 12 patients underwent a 2nd, 4 patients a 3rd, and 1 patient a 4th session, respectively. The mean dysphagia score for successfully treated patients could be reduced from initially 2.34 to 0.49/0.33/0.67 after the 1st/2nd/3rd session, the frequency of dysphagia from 3.45 to 0.92/1.00/1.33, and the score for regurgitations from 2.85 to 0.35/1.00/0.67. In first-line treatment, as well as in retreatment, no severe adverse event occurred. Conclusion. Patients with ZD can be treated safely and effectively with the sb knife jr. Retreatment leads to equal symptom relief as compared to a successful first-line treatment and is not associated with a higher rate of adverse events.

Background and study aims There are no data showing the outcome of ESD during live endoscopy events (LEE). ESD performed during the Augsburg Endo-Update LEE were compared with matched routine procedures with the aim of demonstrating non-inferiority of LEE ESD. Patients and methods ESD performed during the Endo-Update between 2006 and 2018 were reviewed. The controls were routine procedures matched according to age, location and lesion size. Resection, recurrence, survival and complication rates, procedure time and propofol sedation were assessed. Clinically relevant margins were assumed for resection and complication rates, procedure time and propofol sedation quantity. Results Thirty-eight ESD were performed in the given time period, and were compared with 38 matched routine ESD. En bloc and curative resection rates in the LEE group and in the control group were 100 % and 87 % as well as 84 % and 71 % respectively, while procedure times were 135 and 125 minutes, respectively. Non-inferiority was demonstrated for resection rates and procedure time. The complication rate was lower in the LEE group as compared with the control group (5 % vs 13 %) while propofol sedation was similar in both groups (863 mg vs 872 mg). Recurrence and 5-year survival rates for both groups were 4 % vs 0 % and 70 % vs 65% respectively. Conclusions The resection rate and procedure time of ESD during LEE was non-inferior to those of routine ESD procedures. Comparison of the complication rates, however, was inconclusive owing to the low patient number and complication risk in both groups.

Background and aim The growing number of publications on the application of artificial intelligence (AI) in medicine underlines the enormous importance and potential of this emerging field of research. In gastrointestinal endoscopy, AI has been applied to all segments of the gastrointestinal tract most importantly in the detection and characterization of colorectal polyps. However, AI research has been published also in the stomach and esophagus for both neoplastic and non-neoplastic disorders. The various technical as well as medical aspects of AI, however, remain confusing especially for non-expert physicians. This physician-engineer co-authored review explains the basic technical aspects of AI and provides a comprehensive overview of recent publications on AI in gastrointestinal endoscopy. Finally, a basic insight is offered into understanding publications on AI in gastrointestinal endoscopy.

Background and study aims It is unclear if the clinical success rate of the over-the-scope-clip (OTSC) in peptic ulcer bleeding (PUB) is comparable when it is used in the first- or in the second-line of treatment. Patients and methods Data on endoscopic treatment (first- vs. second-line) in PUB with OTSC and clinical data were analyzed. The primary outcome was the clinical success of hemostasis, defined as the absence of recurrent bleeding or further intervention. Secondary outcomes were factors associated with OTSC failure. Results From April 2014 to March 2018, 100 patients (age 72 [20 – 98] y, female 36 %) with PUB in the stomach or the duodenum were treated endoscopically with the OTSC. The OTSC was used as a first-line procedure (primary-OTSC) in 66 pts. Successful hemostasis could be achieved in 90.9 %. After failure of an initial endoscopic treatment, 34 patients were treated with the OTSC (secondary-OTSC) and the treatment was successful in 94.1 %. Recurrent bleeding occurred in n = 10 for primary-OTSC (16.7 %) and in n = 7 pts in the secondary-OTSC (21.9 %) (P = 0.81). Clinical success in the primary-OTSC was 75.8 % and 73.5 % in the secondary-OTSC respectively. Conclusions The OTSC has a high rate of initial bleeding control in first- and second line treatment of PUB. OTSC failure occurs more often in the duodenum than in the stomach and results in longer intensive care unit stay, higher amount of transfusions, and a higher reimbursement per case.

Background and study aims Mapping of pathologic specimens after endoscopic submucosal dissection (ESD) is common practice in Asian countries, especially in Japan. However, there is a lack of awareness for this technique in Europe. In this report, we demonstrate the feasibility and benefits of topographic mapping in a Western setting.

Introduction. Endoscopic resection (ER) exceeding ≥75% of the esophageal circumference is accompanied with a high stricture risk regardless of the resection method. The ideal strategy for stricture prevention is not well defined today. Different approaches have been reported but data are limited to the resection of squamous cell neoplasia. The aim of this study was to assess the efficacy of an individualized oral steroid regimen to prevent strictures after extensive ER in neoplastic Barrett’s esophagus (NBE). Materials and Methods. Over a 50-month period, endoscopic submucosal dissection (ESD) was performed in 193 patients with NBE. 23 patients with resections exceeding 75% of the circumference were included. 19 resection ulcers were noncircumferential (NCR) while 4 were circumferential (CR). Stricture prevention was performed using oral prednisolone starting with a daily dose of 50 mg and standard tapering over 8 weeks (50/40/30/25/20/15/10/5 mg). Tapering was individualized according to the ulcer healing process (assessed endoscopically in the first tapering period and before stopping the steroids). Data were analyzed retrospectively. Results. Stricture rates were 5.3% (1/19) for NCR and 100% (4/4) for CR (p

Background and study aims The ideal treatment strategy for rectal neoplasia extending to the dentate line (RNDL) is not well defined. Endoscopic mucosal resection (EMR) and submucosal dissection (ESD) compete with surgical techniques such as transanal endoscopic microsurgery (TEM). Non-Asian data and prospective data on ESD are lacking. The study aim was to evaluate the role of ESD in treatment of RNDL in a Western center. Patients and methods Eighty-six patients with rectal adenomas were included. ESD was performed in 86 rectal adenomas including 24 RNDLs (27.9 %) and 62 lesions distant from the dentate line (72.1 %). Results En bloc resection rate was comparable (91.7 % vs. 93.5 %, P = 0.670) between ESD for RNDL and non-RNDL. R0 resection rate was significantly lower in ESD for RNDL compared to that for non-RNDL (70.8 % vs 88.7 %; P = 0.039), but most non-R0 resection was unclear margin (Rx) and was not obvious positive margin (R1). Accordingly, the recurrence rate after ESD for RNDL (4.5 %) was not statistically different from that for non-RNDL (0 %, P = 0.275) and was lower than that previously reported for EMR. Median procedure time was 127 vs. 110 minutes (P = 0.182). Risk of delayed bleeding (20.8 % vs. 0 %, P = 0.001) and postinterventional pain (33.3 % vs. 14.5 %, P = 0.07) increased in RNDL cases, but they were managed conservatively. Incidence of stricture (4.2 % vs. 1.6 %, P = 0.483) and perforation (0 % vs. 1.6 %, P = 1.000) were similar. Conclusions ESD is a feasible and safe resection technique for RNDLs. A randomized controlled trial comparing ESD to other methods (EMR or transanal surgery) is warranted.

Background and study aims The endoscopic submucosal dissection (ESD) of cancerous and precancerous lesions in the gastrointestinal (GI) tract is an effective but difficult-to-learn procedure, especially for Western endoscopists. We developed a step-up training protocol and evaluated its outcome on a single endoscopist using specific performance measures. Patients and methods The training protocol included a 12-month period of 50 observational and supervised ESD cases as well as 24 animal procedures. After completion of the protocol, ESD competency was evaluated in the first 30 independent ESD cases. Majority of lesions were located in the stomach and rectum. Performance measures included R0-resection rate, complication rate and resection speed. Results R0 resection rate was 93 %, complication rate was 7 % and median resection speed was 6,77 cm2/h. 1 case of delayed perforation with subsequent hemicolectomy occurred in the descending colon. Conclusion The ESD step-up training protocol used in this study on a single endoscopist showed excellent outcomes for lesions in the rectum and stomach. However, ESD training in the upper colon remains a challenge.