Symptoms and Severity of COVID-19 in Patients with Immune-Mediated Inflammatory Diseases: Experience of a University Medical Center.

Background: The pandemic situation of the novel coronavirus (severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) and its associated disease (coronavirus disease 2019 (COVID-19)) represents a challenging condition with a plethora of aspects. The course of COVID-19 in patients with immune-mediated inflammatory diseases (IMID) such as inflammatory bowel disease (IBD) and rheumatic diseases (RD) is not well known. Our study is one step toward closing this gap by collecting data on vaccination rates, infection-free survival, and individual symptom severity. Methods: We conducted a prospective questionnaire-based study between April 2022 and October 2022 at our university hospital. Outward patients over the age of 18 years were screened for participation and reported about their infection/infection-free survival since the start of the pandemic. Results: Finally, 156 patients were included in the study, 117 (75.0%) of which had inflammatory bowel disease and 39 (25.0%) patients with rheumatic disease. Altogether, 143 (91.7%) persons had received at least one vaccination against SARS-CoV-2. A total of 153 patients provided information regarding their COVID-19 history: 81 patients (52.0%) self-reported about their SARS-CoV-2 infection. In general, courses of infection were mild: only two patients (2.5% of patients with reported COVID-19) were hospitalized due to COVID-19 with one (1.2%) of the two needing intensive care. Asymptomatic COVID-19 had been described by 7 persons (8.6% of patients with reported COVID-19). Acute COVID-19 was accompanied by fatigue/tiredness in 58 persons (71.6% of patients with history of COVID-19) as the most frequent symptom. Other complaints were common cold (55 patients = 67.9%), cough (51 patients = 63.0%), headache (44 patients = 54.3%), and fever (35 patients = 43.2%). Stratified by vaccination status (unvaccinated vs. at least once vaccinated), the time to infection differed significantly (logrank test: p = 0.04, Chi2 4.1). At least once vaccinated people had a median COVID-19-free survival of 28.5 months (confidence interval (CI): 23.6 months-not reached). Without any vaccination, the estimated time to infection was 25.1 months (CI: 23.6 months-not reached). Conclusion: Our IMID patients have a high rate of vaccination against SARS-CoV-2. Data show a significantly longer infection-free survival in vaccinated IMID patients as compared to unvaccinated patients. Discrimination between symptoms of COVID-19 and a concomitant inflammatory disease is difficult as complaints might be overlapping. This trial is registered with DRKS00028880.

Visual acuity prediction on real-life patient data using a machine learning based multistage system.

In ophthalmology, intravitreal operative medication therapy (IVOM) is a widespread treatment for diseases related to the age-related macular degeneration (AMD), the diabetic macular edema, as well as the retinal vein occlusion. However, in real-world settings, patients often suffer from loss of vision on time scales of years despite therapy, whereas the prediction of the visual acuity (VA) and the earliest possible detection of deterioration under real-life conditions is challenging due to heterogeneous and incomplete data. In this contribution, we present a workflow for the development of a research-compatible data corpus fusing different IT systems of the department of ophthalmology of a German maximum care hospital. The extensive data corpus allows predictive statements of the expected progression of a patient and his or her VA in each of the three diseases. For the disease AMD, we found out a significant deterioration of the visual acuity over time. Within our proposed multistage system, we subsequently classify the VA progression into the three groups of therapy "winners", "stabilizers", and "losers" (WSL classification scheme). Our OCT biomarker classification using an ensemble of deep neural networks results in a classification accuracy (F1-score) of over 98%, enabling us to complete incomplete OCT documentations while allowing us to exploit them for a more precise VA modelling process. Our VA prediction requires at least four VA examinations and optionally OCT biomarkers from the same time period to predict the VA progression within a forecasted time frame, whereas our prediction is currently restricted to IVOM/no therapy. We achieve a final prediction accuracy of 69% in macro average F1-score, while being in the same range as the ophthalmologists with 57.8 and 50 ± 10.7 % F1-score.

Development, evaluation, and overview of standardized training phantoms for abdominal ultrasound-guided interventions.

PURPOSE: Ultrasound (US) represents the primary approach for abdominal diagnosis and is regularly used to guide diagnostic and therapeutic interventions (INVUS). Due to possible serious INVUS complications, structured training concepts are required. Phantoms can facilitate teaching, but their use is currently restricted by complex manufacturing and short durability of the materials. Hence, the aim of this study was the development and evaluation of an optimized abdominal INVUS phantom. MATERIALS AND METHODS: Phantom requirements were defined in a structured research process: Skin-like surface texture, homogeneous matrix with realistic tissue properties, implementation of lesions and abscess cavities in different sizes and depths as well as a modular production process allowing for customized layouts. The phantom prototypes were evaluated in certified ultrasound courses. RESULTS: In accordance with the defined specifications, a new type of matrix was developed and cast in multiple layers including different target materials. The phantom structure is based on features of liver anatomy and includes solid focal lesions, vessels, and abscess formations. For a realistic biopsy procedure, ultrasound-proof material was additionally included to imitate bone. The evaluation was performed by US novices (n=40) and experienced participants (n=41). The majority (73/81) confirmed realistic visualization of the lesions. The 3D impression was rated as "very good" in 64% of cases (52/81) and good in 31% (25/81). Overall, 86% (70/81) of the participants certified high clinical relevance of the phantom. CONCLUSION: The presented INVUS phantom concept allows standardized and realistic training for interventions.

Improving OCT Image Segmentation of Retinal Layers by Utilizing a Machine Learning Based Multistage System of Stacked Multiscale Encoders and Decoders.

Optical coherence tomography (OCT)-based retinal imagery is often utilized to determine influential factors in patient progression and treatment, for which the retinal layers of the human eye are investigated to assess a patient's health status and eyesight. In this contribution, we propose a machine learning (ML)-based multistage system of stacked multiscale encoders and decoders for the image segmentation of OCT imagery of the retinal layers to enable the following evaluation regarding the physiological and pathological states. Our proposed system's results highlight its benefits compared to currently investigated approaches by combining commonly deployed methods from deep learning (DL) while utilizing deep neural networks (DNN). We conclude that by stacking multiple multiscale encoders and decoders, improved scores for the image segmentation task can be achieved. Our retinal-layer-based segmentation results in a final segmentation performance of up to 82.25±0.74% for the Sørensen-Dice coefficient, outperforming the current best single-stage model by 1.55% with a score of 80.70±0.20%, given the evaluated peripapillary OCT data set. Additionally, we provide results on the data sets Duke SD-OCT, Heidelberg, and UMN to illustrate our model's performance on especially noisy data sets.

Cystic fibrosis transmembrane conductance regulator function in patients with chronic pancreatitis.

BACKGROUND: Pathogenesis of chronic pancreatitis (CP) is still not entirely understood with many patients probably having more than 1 underlying etiology. Besides toxic-metabolic factors, genetics contribute to disease development. Mutations in cystic fibrosis transmembrane conductance regulator (CFTR) are shown to increase risk for CP. Activity of CFTR can easily be accessed in vivo by measurement of nasal potential difference (PD). METHODS: We compared in this monocentric study 17 CP patients from the outpatient unit of our university hospital with 30 healthy controls regarding nasal PDs by using a superfusion protocol. Additionally, demographic and lifestyle data of all persons were recorded. RESULTS: Seventeen patients (12% female, median age 48 years) with CP and 30 healthy volunteers (47% female, 25 years) were included in the study. Patients with CP had a significant higher proportion of CFTR dysfunction (P = .04). Furthermore, demographics differed between the 2 groups with CP patients being older (P < .001). There were differences in daily alcohol consumption (P = .001) and smoking habits (smokers vs nonsmokers: P = .01, pack years: P = .002). CONCLUSIONS: PD measurement is an easily accessible way to show CFTR dysfunction as an etiological factor of CP. Cigarette smoking might impair CFTR function and therefore be 1 preventable cause of CP evolution.

Successful endoscopic recanalization of complete pharyngoesophageal obstruction after therapy of head and neck cancer.

BACKGROUND: Neopharyngeal obstruction after therapy of head and neck cancer is a frequent and clinically challenging problem without evidence-based guideline recommendations. CASE: We present two cases of complete esophageal obstruction after treatment for head and neck cancer. Due to complete obstruction of long distance stricture standard dilatation procedures were impossible to perform. In both cases, recanalization was achieved by combining an antegrade with a retrograde maneuver. In one patient endoscopic cutting with a papillotome was needed. CONCLUSION: Even in complex cases of post-therapeutic stenosis an endoscopic approach may offer a feasible alternative to surgical therapy, especially in the subset of frail patients.

Endoscopic findings and outcome in caustic ingestion of acidic and alkaline agents in adults: A retrospective analysis.

Caustic ingestion in adults is a rare but potentially life-threatening problem. It remains controversial whether endoscopic findings and mortality differ between acid and alkali ingestion. We compared ingestion of these agents and evaluated prediction parameters for survival and complications.Adult patients who presented with caustic ingestion were analyzed from 2005 to 2016. Mucosal injury was graded endoscopically by Zargar's score. Age, gender, intent of ingestion, caustic agents, comorbidities, management, complications, and mortality were examined.Thirty-one patients met inclusion criteria and were divided into acid (n = 10) and alkali group (n = 21). Ingestion of alkali resulted in higher grades (≥III) of esophageal (56% vs 24%, P = .01) and stomach injuries (43% vs 13%, P = .05) and was mostly done with suicidal intent (76% vs 30%, P = .003). Patients in the alkali group received more often surgical interventions, mechanical ventilation and tracheotomy. Overall complications including Zargar's-score ≥ grade III, mediastinitis, and aspiration pneumonia were higher in alkali group but all showed no statistical significance (P = .73). Mortality (acid: 1 (10%), alkali: 4 (19%), P = .52), age, gender, comorbidities, and intensive care management did not differ significantly between the groups. Chronic renal failure and mediastinitis were promising prediction parameters for mortality but did not reach statistical significance. No independent risk factors for the development of esophageal stenosis were identified.Alkaline agents caused a higher mucosal injury severity and were more often used in suicidal intent. Mediastinitis and chronic renal failure might be potential prediction parameters for survival but need to be evaluated in larger studies.

Endoscopic suturing as a less invasive approach for the treatment of anastomotic leakage after esophagogastrostomy - a case report.

Anastomotic leakage is a frequent complication after gastrointestinal (GI) surgery and is associated with high morbidity and mortality. Endoluminal therapy offers numerous advantages compared to surgical revision. We present the case of a 74-year-old female patient with anastomotic leakage after esophagogastrostomy. The defect was closed using the OverStitch endoscopic suturing system with immediate technical and clinical success. Hereby, an example of the feasibility of this novel technique in a case of anastomotic leakage is presented and provides an outlook for the rising importance of endoscopic therapy.

Endoscopic treatment of obesity and complications after bariatric surgery.

Prevalence and incidence of obesity in the population has been increasing for decades. Due to associated comorbidities, treatment of obesity has become a global health topic and should be addressed with multimodal strategies. As conservative treatment has high rates of failure, bariatric surgery is often performed, especially in cases of severe obesity. However, interventional endoscopic options are gaining importance as less invasive approach. Intragastric balloons and duodenojejunal bypass liners are the most frequent applied endoscopic therapies. Besides primary bariatric intervention, endoscopy may also help bridging towards surgery. Management of postsurgical adverse events (e.g. leakage, stenosis) can be handled endoscopically as well. This article summarizes current knowledge and available endoscopic treatment options for obesity.

Cyclin D1 in ASM Cells from Asthmatics Is Insensitive to Corticosteroid Inhibition.

Hyperplasia of airway smooth muscle (ASM) is a feature of the remodelled airway in asthmatics. We examined the antiproliferative effectiveness of the corticosteroid dexamethasone on expression of the key regulator of G(1) cell cycle progression-cyclin D1-in ASM cells from nonasthmatics and asthmatics stimulated with the mitogen platelet-derived growth factor BB. While cyclin D1 mRNA and protein expression were repressed in cells from nonasthmatics in contrast, cyclin D1 expression in asthmatics was resistant to inhibition by dexamethasone. This was independent of a repressive effect on glucocorticoid receptor translocation. Our results corroborate evidence demonstrating that corticosteroids inhibit mitogen-induced proliferation only in ASM cells from subjects without asthma and suggest that there are corticosteroid-insensitive proliferative pathways in asthmatics.

A novel docking domain interface model predicting recombination between homoeologous modular biosynthetic gene clusters.

An in silico model for homoeologous recombination between gene clusters encoding modular polyketide synthases (PKS) or non-ribosomal peptide synthetases (NRPS) was developed. This model was used to analyze recombination between 12 PKS clusters from Streptomyces species and related genera to predict if new clusters might give rise to new products. In many cases, there were only a limited number of recombination sites (about 13 per cluster pair), suggesting that recombination may pose constraints on the evolution of PKS clusters. Most recombination events occurred between pairs of ketosynthase (KS) domains, allowing the biosynthetic outcome of the recombinant modules to be predicted. About 30% of recombinants were predicted to produce polyketides. Four NRPS clusters from Streptomyces strains were also used for in silico recombination. They yielded a comparable number of recombinants to PKS clusters, but the adenylation (A) domains contained the largest proportion of recombination events; this might be a mechanism for producing new substrate specificities. The extreme G + C-content, the presence of linear chromosomes and plasmids, as well as the lack of a mutSL-mismatch repair system should favor production of recombinants in Streptomyces species.