Comparison of post-COVID-19 symptoms in patients infected with the SARS-CoV-2 variants delta and omicron-results of the Cross-Sectoral Platform of the German National Pandemic Cohort Network (NAPKON-SUEP).

PURPOSE: The influence of new SARS-CoV-2 variants on the post-COVID-19 condition (PCC) remains unanswered. Therefore, we examined the prevalence and predictors of PCC-related symptoms in patients infected with the SARS-CoV-2 variants delta or omicron. METHODS: We compared prevalences and risk factors of acute and PCC-related symptoms three months after primary infection (3MFU) between delta- and omicron-infected patients from the Cross-Sectoral Platform of the German National Pandemic Cohort Network. Health-related quality of life (HrQoL) was determined by the EQ-5D-5L index score and trend groups were calculated to describe changes of HrQoL between different time points. RESULTS: We considered 758 patients for our analysis (delta: n = 341; omicron: n = 417). Compared with omicron patients, delta patients had a similar prevalence of PCC at the 3MFU (p = 0.354), whereby fatigue occurred most frequently (n = 256, 34%). HrQoL was comparable between the groups with the lowest EQ-5D-5L index score (0.75, 95% CI 0.73-0.78) at disease onset. While most patients (69%, n = 348) never showed a declined HrQoL, it deteriorated substantially in 37 patients (7%) from the acute phase to the 3MFU of which 27 were infected with omicron. CONCLUSION: With quality-controlled data from a multicenter cohort, we showed that PCC is an equally common challenge for patients infected with the SARS-CoV-2 variants delta and omicron at least for the German population. Developing the EQ-5D-5L index score trend groups showed that over two thirds of patients did not experience any restrictions in their HrQoL due to or after the SARS-CoV-2 infection at the 3MFU. CLINICAL TRAIL REGISTRATION: The cohort is registered at ClinicalTrials.gov since February 24, 2021 (Identifier: NCT04768998).

Whipple's Disease - delay of diagnosis by immunosuppressive therapy; a case-series report.

BACKGROUND: Risk factors for the development of Whipple's disease (WD) are largely unknown. Case reports, case series, and reviews suggest immunosuppressive therapy as a potential triggering factor in WD. The low incidence of WD and non-specific symptoms at disease onset contribute to the frequent delay of diagnosis. We describe our centre´s experience on differences in the clinical presentation of patients with classic WD compared to patients with "masked" WD because of immunosuppressive therapy. METHODS: In this retrospective case series, 8 patients were included. Diagnosis of WD was confirmed by histological staining of duodenal biopsies revealing T. whipplei within foamy macrophages or by PCR- based detection of specific T. whipplei DNA. Clinical manifestations, laboratory data, and medication have been recorded over a period of 19 years. Subgroup analyses for the two different variants of WD were performed. RESULTS: Seven of eight patients were initially diagnosed with rheumatic disease (polyarthritis, polymyalgia rheumatica). One patient was correctly diagnosed at the beginning without any medication. Three patients were on immunosuppressive therapy and being treated with disease-modifying drugs (DMARDs), three patients were receiving low-dose cortisone in combination with non-steroidal anti- inflammatory drugs (NSAIDs), and one patient was receiving NSAIDs only. All patients presented with increased parameters of inflammation and with clinical and/or laboratory signs of a malabsorption. From the onset of first symptoms, diagnosis of WD took a median of 36 months (range: 6-120 months). The time between onset of joint complaints and onset of gastrointestinal symptoms was 36 months (range: 0-117 months). WD patients receiving immunosuppressive therapy, compared to those not receiving it, had a longer duration of gastrointestinal symptoms (12 months versus 6 months) and reported a greater weight loss (20,3 kg versus 7,8 kg) up to diagnosis of WD. CONCLUSIONS: Immunosuppressive drugs may delay the diagnosis of WD and prolong the course of T. whipplei infection with deterioration of clinical symptoms. If a patient with rheumatic complaints develops gastrointestinal symptoms, diagnosis of WD should be considered and proper diagnostic investigation carried out.

Influence of Artificial Intelligence on the Adenoma Detection Rate throughout the Day.

BACKGROUND: Artificial intelligence systems recently demonstrated an increase in polyp and adenoma detection rate. Over the daytime, the adenoma detection rate decreases as tiredness leads to a lack of attention. It is not clear if a polyp detection system with artificial intelligence leads to constant adenoma detection over the day. METHODS: We performed a database analysis of screening and surveillance colonoscopies with and without the use of AI. In both groups, patients were investigated with the same endoscopy equipment and by the same endoscopists. Only patients with good bowel preparation (BBPS >6) were included. We correlated the daytime, the investigational time, day of the week, and the adenoma and polyp detection. RESULTS: A total of 303 colonoscopies were analyzed. 163 endoscopies in the AI+ group and 140 procedures in the AI- group were included. In both groups, the total adenoma detection rate was equal (AI+ 0.39 vs. AI- 0.43). The adenoma detection rate throughout the day had a significant decreasing trend in the group without the use of AI (p = 0.015), whereas this trend was not present in the investigations that have been performed with AI (p = 0.65). The duration of investigation did not show a significant difference between the groups (8.9 min in both groups). No relevant effect was noticed in adenoma detection between single days of the working week with or without the use of AI. CONCLUSION: AI helps overcome the decay in adenoma detection over the daytime. This may be attributed to a constant awareness caused by the use of the AI system.

The Need of Antimicrobial Stewardship in Post-Operative Infectious Complications of Abdominal Surgery.

Background: Post-operative infection is a common complication following abdominal surgery. The two most common infections are secondary peritonitis and surgical site infections, which lead to increased perioperative morbidity, prolonged hospitalization, higher mortality rates, and increased treatment costs. In addition to surgical procedures, treatment is based on effective antibiotic therapy. Due to increasing antimicrobial resistance, the correct use of antimicrobials is becoming more complex. Many initiatives call for the implementation of an antimicrobial stewardship (AMS) programme to optimize anti-infective therapy. The review article summarizes current recommendations in anti-infective therapy of post-operative peritonitis and surgical site infections and highlights the importance of an AMS programme in abdominal surgery. Summary: Larger studies evaluating the benefit of AMS in abdominal surgery are lacking. However, national and international guidelines have formulated appropriate recommendations for the rational use of antibiotics in post-operative peritonitis and surgical site infections. The rate of post-operative infections can be significantly reduced by perioperative antibiotic prophylaxis. The increase in multidrug-resistant bacteria complicates anti-infective therapy for post-operative infections. Analysis of local susceptibility patterns helps choose an adequate empiric therapy. A high rate of extended-spectrum beta-lactamase-producing bacteria may necessitate the use of other reserve antibiotics in addition to carbapenems, which are approved for the treatment of complicated intra-abdominal infections. A key role for the AMS team is the subsequent de-escalation of antibiotic therapy which limits the use of unnecessary broad-spectrum antibiotics. Key Messages: The increase in multidrug-resistant bacteria poses challenges for abdominal surgery. Post-operative infections should be treated by an interdisciplinary team of surgeons and specialists for AMS.

Can a Polyp Detection and Characterization System Predict Complete Resection?

INTRODUCTION: Artificial Intelligence (AI) is one of the most evolving fields in endoscopy. We aimed to test if a system for polyp detection and polyp characterization can be used to predict complete endoscopic resection of colon adenomas. METHODS: We used the CAD-Eye AI system (Fujifilm Europe) in consecutive patients who received polypectomy using a cold snare. After resection, the submucosal space was flushed with water using an irrigation pump. Images were obtained using the CAD Eye system, and the characterization of the system was noted and afterward compared to histology of the removed specimen. RESULTS: In total, 17 polypectomies were observed, and in no case the AI was able to give information about resection status. First, the resection plane itself was classified as being adenomatous in all cases, while, second, all adenomas were resected completely, thus harboring no potential for overlying misinterpretations in the images. CONCLUSION: An AI system trained to characterize polyps in healthy surrounding colorectal mucosa cannot predict the state of resection after removal of the adenoma. This is explained by the training and programming. Endoscopists using AI from now on should learn about the basics of AI and the pitfalls in interpreting results from AI.

Switching to a NRTI-free 2 drug regimen (2DR) -a sub-analysis of the 48 weeks DUALIS study on metabolic and renal changes.

Background/Aims: Switching from a three-drug regimen (3DR: boosted darunavir [bDRV] and two nucleoside reverse transcriptase inhibitors [NRTIs]) to a two-drug regimen (2DR: bDRV and dolutegravir [DTG]) demonstrated non-inferiority with regard to viral suppression in people living with HIV (PLWH) in the DUALIS study. This sub-analysis focuses on changes in metabolic and renal parameters when sparing the NRTI backbone.Methods: DUALIS was a randomized, open-label, multicenter (27) phase 3-trial. Participants were virologically suppressed (HIV-RNA < 50 copies/mL) on 3DR for at least 24 weeks. Subjects were either switched to DTG 50 mg + bDRV 800 mg (with ritonavir 100 mg) (2DR) or continued their regimen consisting of two NRTIs in combination with ritonavir-bDRV (3DR) once daily. Data of metabolic and renal parameters at baseline and week 48 were compared.Results: The LDL-fraction increased by + 13.3 (-3.0 to +31.3) mg/dL on 2DRs and was stable (-14.0 to +18.0 mg/dL) on 3DRs (p < 0.0010).PLWH gained +2.0 (-0.2 to +4.0) kg and +0.2 (-1.9 to +2.1) kg in body weight on 2DRs and 3DRs, respectively 3 (p = 0.0006).The MDRD eGFR decreased by -7,8 (-17.4 to -0.3) mL/min/1.73m2 and 0.4 (-8.8 to +5.7) mL/min/1.73m2 on 2DRs and 3DRs, respectively (p = 0.0002), while serum levels of cystatin C were stable in both arms (2DR: -0.1 to +0.1 mg/L; 3DR: 0.0 to +0.1 mg/L).Conclusions: While being non-inferior in terms of viral suppression, sparing the NRTI backbone showed a non-favorable profile in metabolic or renal parameters over 48 weeks.

Efficacy and Safety of Switching to Dolutegravir With Boosted Darunavir in Virologically Suppressed Adults With HIV-1: A Randomized, Open-Label, Multicenter, Phase 3, Noninferiority Trial: The DUALIS Study.

BACKGROUND: Dolutegravir (DTG) and boosted darunavir (bDRV) are potent antiretrovirals with a high resistance barrier and might be valuable switch options for people with HIV (PWH). METHODS: DUALIS, a randomized, open-label, phase 3b, noninferiority clinical trial, compared the switch to DTG + bDRV (2DR) with continuation of 2 nucleoside reverse transcriptase inhibitors (2NRTI) + bDRV (3DR). PWH with HIV RNA <50 copies/mL taking 2NRTI + bDRV (3DR) for ≥24 weeks (1 accepted blip <200 copies/mL) were randomized to either switch to DTG 50 mg + DRV 800 mg (boosted with 100 mg of ritonavir) or continue taking 3DR. The primary end point (PE) was the proportion of HIV RNA <50 copies/mL at week (W) 48. Change in NRTI backbone was not classified as failure. The estimated sample size for PE analysis was 292; the noninferiority margin was ≤-10.0%. RESULTS: In total, 263 subjects were randomized and treated (2DR n = 131, 3DR n = 132; 90.1% male; 89.7% Caucasian; median age [interquartile range], 48 [39-54] years). At W48, 86.3% (n = 113/131) of the 2DR subject and 87.9% (n = 116/132) of the 3DR subjects had HIV RNA <50 copies/mL; the difference between arms was -1.6% (95.48% CI, based on the adjusted alpha level accounting for the interim analysis at W24, -9.9% to +6.7%; discontinuations due to adverse events: 2DR, 4.6% [n = 6]; 3DR, 0.8% [n = 1]). Kaplan-Meier estimates of confirmed HIV RNA ≥50 copies/mL at W48 were 1.6% (n = 2) in the 2DR and 3.1% (n = 4) in the 3DR group. Development of treatment-emergent resistance was not observed. CONCLUSIONS: Switching to DTG + bDRV was noninferior to continuing 3DR in subjects already treated with bDRV.

Road Map fluoroscopy successfully guides endoscopic interventions in the esophagus.

BACKGROUND AND STUDY AIMS: Road Map (RM) fluoroscopy is a radiological technique that enables visualization of anatomic structures using image subtraction at peak opacification. RM fluoroscopy has never previously been evaluated for use in endoscopy. The aim of this study was to evaluate the usefulness of RM in guiding endoscopic intervention in the esophagus. PATIENTS AND METHODS: This was a monocentric observational trial of consecutive patients with esophageal strictures in a university hospital. Twenty-seven investigations using RM were performed in 24 patients undergoing esophageal endoscopy. Indications for the procedure were balloon dilatation (n = 7 including 2 pneumatic balloon dilatations for treatment of achalasia), bougie dilatation (n = 7) and diagnostic endoscopy (n = 1). In addition, 12 stents, 7 partially covered and 5 fully covered, were placed using RM as a guide for determination of stent length and diameter. Stents were deployed under RM guidance. RESULTS: In all procedures, RM successfully guided the intervention. Endoscopic control endoscopy confirmed adequate stent placement in all cases. CONCLUSION: RM allows permanent and accurate radiographic imaging of stenoses and esophageal anatomic changes. It is an easy and safe method of guiding endoscopic interventions that require radiological imaging.

Whipple's Disease.

BACKGROUND: Whipple's disease (WD) is rarely the cause of a malabsorption syndrome. The disease is a chronic infection of the intestinal mucosa with the bacterium Tropheryma whipplei, which leads to a lymphostasis with an impaired absorption of the nutrition. Due to its low incidence (1:1,000,000) and the non-specific early symptoms, the disease is often diagnosed only after many years. METHODS: Based on a selective literature review and the clinical experience of the authors, the current knowledge of WD regarding pathogenesis, clinical presentation, diagnosis, and therapy are presented in this paper. RESULTS: Recent studies suggest that a host-specific dysfunction of the intestinal macrophages is responsible for the chronic infection with T. whipplei. Prior to patients reporting symptoms of a malabsorption syndrome (chronic diarrhea/steatorhea, weight loss), they often suffer from non-specific symptoms (polyarthralgia, fever, fatigue) for many years. Misdiagnoses such as seronegative polyarthritis are frequent. Furthermore, neurological, cardiac, ocular, or dermatological symptoms may occur. The standard method concerning diagnosis is the detection of PAS(periodic acid-Schiff)-positive macrophages in the affected tissues. Immunohistochemical staining and PCR(polymerase chain reaction)-based genetic analysis increase the sensitivity and specificity of conventional detection methods. Endoscopically, the intestinal mucosa appears edematous with lymphangiectasias, enlarged villi, and white-yellowish ring-like structures. The German treatment recommendations include a two-week intravenous induction therapy with ceftriaxone, which is followed by a three-month oral maintenance therapy with trimethoprim/sulfamethoxazole. CONCLUSION: WD is rarely responsible for a malabsorption syndrome. However, if WD is not recognized, the disease can be lethal. New diagnostic methods and prospectively approved therapeutic concepts allow an adequate treatment of the patient. Due to the host-specific susceptibility to T. whipplei, a lifelong follow-up is necessary.