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Focal liver lesions are detected in about 15% of abdominal ultrasound examinations. The diagnosis of frequent benign lesions can be determined reliably based on the characteristic B-mode appearance of cysts, hemangiomas, or typical focal fatty changes. In the case of focal liver lesions which remain unclear on B-mode ultrasound, contrast-enhanced ultrasound (CEUS) increases diagnostic accuracy for the distinction between benign and malignant liver lesions. Artificial intelligence describes applications that try to emulate human intelligence, at least in subfields such as the classification of images. Since ultrasound is considered to be a particularly examiner-dependent technique, the application of artificial intelligence could be an interesting approach for an objective and accurate diagnosis. In this systematic review we analyzed how artificial intelligence can be used to classify the benign or malignant nature and entity of focal liver lesions on the basis of B-mode or CEUS data. In a structured search on Scopus, Web of Science, PubMed, and IEEE, we found 52 studies that met the inclusion criteria. Studies showed good diagnostic performance for both the classification as benign or malignant and the differentiation of individual tumor entities. The results could be improved by inclusion of clinical parameters and were comparable to those of experienced investigators in terms of diagnostic accuracy. However, due to the limited spectrum of lesions included in the studies and a lack of independent validation cohorts, the transfer of the results into clinical practice is limited.

Marcel Vetter1 12 2, Timo Rath1 12 2, Jürgen Siebler1 12 2, Maximilian Waldner1 12 2, Markus F Neurath1 12 2, Lukas Pfeifer3 3 1Department of Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany; 2Deutsches Zentrum Immuntherapie, DZI, Erlangen, Germany; 3Department of Gastroenterology and Interventional Endoscopy, Krankenhaus Barmherzige Brüder, Regensburg, GermanyCorrespondence: Lukas PfeiferDepartment of Gastroenterology and Interventional Endoscopy, Krankenhaus Barmherzige Brüder, Prüfeninger Straße 86, Regensburg, Bavaria, 93049, GermanyTel +49 941 369 2051Fax +49 941 369 2055Email Lukas.Pfeifer@barmherzige-regensburg.deBackground: Ingestion of alkaline fluids is a common problem, which can lead to perforations, strictures and malignancy. We present a rare case series of several patients who accidentally ingested the same alkaline substance in different doses.Methods: We investigated four patients with accidental ingestion of dishwashing liquid. All patients underwent gastroscopy within 24h after inpatient admission. Gastroesophageal lesions were classified according to the Zargar classification for corrosive ingestions.Results: Esophagogastric lesions were predominantly found at the distal esophagus and the small curvature of the stomach. The severity of these lesions ranged from mild erosions (Zargar 2A) to marked necrosis (Zargar 3A). Our data suggest that the degree of these lesions correlated with the amount of ingested toxin and duration of the inpatient stay. However, a low symptom severity or inconspicuous otolaryngologic examination did not exclude severe gastroesophageal lesions.Conclusion: Our data suggest that the severity of gastroesophageal lesions correlates with the amount of ingested alkaline substance. Symptom burden and an otolaryngologic examination are not sufficiently predictive for the severity of gastroesophageal lesions. The composition and quantity of the swallowed liquid should be determined.Keywords: alkali ingestion, gastroscopy, toxin dose, case series

COVID‐19 is a life‐threatening disease leading to bilateral pneumonia and respiratory failure. The underlying reasons why a smaller percentage of patients present with severe pulmonary symptoms whereas the majority is only mildly affected are to date not well understood. Comparing the immunological phenotype in healthy donors and patients with mild versus severe COVID‐19 shows that in COVID‐19 patients, NK‐/B‐cell activation and proliferation are enhanced independent of severity. As an important precondition for effective antibody responses, T‐follicular helper cells and antibody secreting cells are increased both in patients with mild and severe SARS‐CoV‐2 infection. Beyond this, T cells in COVID‐19 patients exhibit a stronger activation profile with differentiation toward effector cell phenotypes. Importantly, when looking at the rates of pulmonary complications in COVID‐19 patients, the chemokine receptor CCR4 is higher expressed by both CD4 and CD8 T cells of patients with severe COVID‐19. This raises the hypothesis that CCR4 upregulation on T cells in the pathogenesis of COVID‐19 promotes stronger T‐cell attraction to the lungs leading to increased immune activation with presumably higher pulmonary toxicity. Our study contributes significantly to the understanding of the immunological changes during COVID‐19, as new therapeutic agents, preferentially targeting the immune system, are highly warranted., Patients with mild COVID‐19 after SARS‐CoV2 infection exhibit increased T‐cell activation and induction of T‐cell exhaustion. During severe COVID‐19 patients show massive T‐cell activation and upregulation of homing receptors promoting hyperinflammation and increased lung trafficking.

Introduction: Histological alterations in primary biliary cholangitis (PBC) are heterogeneously distributed throughout the liver. Thus, the quality of histological staging is probably dependent on the available amount of liver tissue. The goals of this study were to test this hypothesis and to define biopsy conditions for obtaining sufficient tissue. Methods: In this retrospective analysis, we investigated 34 patient cases who fulfilled the criteria of the European Association for the Study of the Liver (EASL) for PBC and underwent a mini-laparoscopic liver biopsy between 2011 and 2018 using 16 or 18G needles. For histological assessment of fibrosis, we used the Ishak score, and the amount of tissue was measured by the number of portal fields. Histological staging was compared with the macroscopic mini-laparoscopic fibrosis score (MLFS), and non-invasive liver stiffness measurements using acoustic radiation force impulse (ARFI) imaging and the FIB-4 score. Results: Biopsy was successful in 33 of 34 patients (97%). Fibrosis assessment by MLFS and ARFI correlated strongly with each other (r = 0.7088, p = 0.000017). However, the correlation of both methods with the histological staging was weaker (MLFS vs. histology: r = 0.4231, p = 0.0142; ARFI vs. histology: r = 0.3564, p = 0.0577). The correlation of ARFI and MLFS with the histological staging was better in the subgroup of biopsies with at least 10 portal fields (= SG≥10PF) (MLFS vs. histology: r = 0.6369, p = 0.006; ARFI vs. histology: r = 0.7538, p = 0.0012). FIB-4 correlated weakly with the histological staging, which was statistically not significant (all samples: r = 0.2693, p = 0.1296; SG≥10PF: r = 0.2244, p = 0.3866). The number of portal fields correlated well with the length of the samples (r = 0.6436, p = 0.00012). The probability to attain at least 10 portal fields depended on the needle diameter and number of samples (1 × 16G or 18G [n = 10]: 30.0%; 2 × 18G [n = 15]: 53.3%; 2 × 16G [n = 5]: 100%; p = 0.0414). Conclusion: ARFI and MLFS are probably well suited for the assessment of liver fibrosis in patients with PBC. A minimum of 10 portal fields could improve the histological assessment in PBC and can probably be achieved by obtaining two 16G biopsies.

In the current pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; COVID-19), a better understanding of the underlying mechanisms is essential to reduce morbidity and mortality and treat post-COVID-19 disease. Here, we analyzed alterations of sphingolipids and their metabolizing enzymes in 125 men and 74 women tested positive for SARS-CoV-2 and hospitalized with mild, moderate or severe symptoms or after convalescence.The activities of acid and neutral sphingomyelinases (ASM, NSM), which hydrolyze sphingomyelin to ceramide, were significantly increased in COVID-19 patients, while the activity of neutral ceramidase (NC), which hydrolyzes ceramide to sphingosine, was reduced. These alterations could each contribute to elevated ceramide levels in patients. Accordingly, liquid chromatography tandem-mass spectrometry (LC-MS/MS) yielded increased levels of ceramides 16:0 and 18:0 with highest levels in severely affected patients and similar effects for dihydroceramides 16:0 and 18:0, whereas levels of (dihydro-)ceramides 24:0 were reduced. Furthermore, sphingomyelin 20:0; 22:0 and 24:0 as substrates of ASM and NSM as well as their dihydrosphingomyelin counterparts were reduced in patients as well as sphingosine-1-phosphate further downstream of NC activity. Effects of NSM, NC, ceramides and sphingomyelins remained significant after Bonferroni correction. SARS-CoV-2 antibody levels in convalescent patients were associated with age but none of the sphingolipid parameters. Based on our data, COVID-19 is associated with a dysregulation of sphingolipid homeostasis in a severity-dependent manner, particularly focused around a reduction of sphingomyelins and an accumulation of ceramides by increased enzyme activities leading to ceramide elevation (ASM, NSM) combined with a decreased activity of enzymes (NC) reducing ceramide levels. The potential of a combined sphingolipid/enzyme pattern as a diagnostic and prognostic marker and therapeutic target deserves further exploration.

SARS-CoV-2 antibody assays are used for epidemiological studies and for the assessment of vaccine responses in highly vulnerable patients. So far, data on cross-reactivity of SARS-CoV-2 antibody assays is limited. Here, we compared four enzyme-linked immunosorbent assays (ELISAs; Vircell SARS-CoV-2 IgM/IgA and IgG, Euroimmun SARS-CoV-2 IgA and IgG) for detection of anti-SARS-CoV-2 antibodies in 207 patients with COVID-19, 178 patients with serological evidence of different bacterial infections, 107 patients with confirmed viral respiratory disease, and 80 controls from the pre-COVID-19 era. In COVID-19 patients, the assays showed highest sensitivity in week 3 (Vircell-IgM/A and Euroimmun-IgA: 78.9% each) and after week 7 (Vircell-IgG: 97.9%; Euroimmun-IgG: 92.1%). The antibody indices were higher in patients with fatal disease. In general, IgM/IgA assays had only limited or no benefit over IgG assays. In patients with non-SARS-CoV-2 respiratory infections, IgG assays were more specific than IgM/IgA assays, and bacterial infections were associated with more false-positive results than viral infections. The specificities in bacterial and viral infections were 68.0 and 81.3% (Vircell-IgM/IgA), 84.8 and 96.3% (Euroimmun-IgA), 97.8 and 86.0% (Vircell-IgG), and 97.8 and 99.1% (Euroimmun-IgG), respectively. Sera from patients positive for antibodies against Mycoplasma pneumoniae, Chlamydia psittaci, and Legionella pneumophila yielded particularly high rates of unspecific false-positive results in the IgM/IgA assays, which was revealed by applying a highly specific flow-cytometric assay using HEK 293 T cells expressing the SARS-CoV-2 spike protein. Positive results obtained with anti-SARS-CoV-2 IgM/IgA ELISAs require careful interpretation, especially if there is evidence for prior bacterial respiratory infections.

Treatment with convalescent plasma has been shown to be safe in coronavirus disease in 2019 (COVID‐19) infection, although efficacy reported in immunocompetent patients varies. Nevertheless, neutralizing antibodies are a key requisite in the fight against viral infections. Patients depleted of antibody‐producing B cells, such as those treated with rituximab (anti‐CD20) for hematological malignancies, lack a fundamental part of their adaptive immunity. Treatment with convalescent plasma appears to be of general benefit in this particularly vulnerable cohort. We analyzed clinical course and inflammation markers of three B‐cell‐depleted patients suffering from COVID‐19 who were treated with convalescent plasma. In addition, we measured serum antibody levels as well as peripheral blood CD38/HLA‐DR‐positive T‐cells ex vivo and CD137‐positive T‐cells after in vitro stimulation with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)‐derived peptides in these patients. We observed that therapy with convalescent plasma was effective in all three patients and analysis of CD137‐positive T‐cells after stimulation with SARS‐CoV‐2 peptides showed an increase in peptide‐specific T‐cells after application of convalescent plasma. In conclusion, we here demonstrate efficacy of convalescent plasma therapy in three B‐cell‐depleted patients and present data that suggest that while application of convalescent plasma elevates systemic antibody levels only transiently, it may also boost specific T‐cell responses., Treatment of B‐cell depleted patients suffering from COVID‐19 with convalescent plasma led to viral clearance and was followed by an increase in peptide‐specific CD4+ T‐cells suggesting that transient antibody titers promoted specific cellular immunity in these patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a worldwide health threat. Here, we report that low plasma interleukin-3 (IL-3) levels were associated with increased severity and mortality during SARS-CoV-2 infections. IL-3 promoted the recruitment of antiviral circulating plasmacytoid dendritic cells (pDCs) into the airways by stimulating CXCL12 secretion from pulmonary CD123+epithelial cells. This study identifies IL-3 as a predictive disease marker and potential therapeutic target for SARS-CoV-2 infections.

The COVID-19 pandemic represents a challenge for rheumatologists: how activity of rheumatological diseases or disease-modifying therapies may affect the outcome of SARS-CoV-2 infection is only beginning to be understood. Gianfrancesco et al provided important insights in this regard by evaluating the hospitalisation rate of 600 patients with rheumatological diseases from 40 different countries.1 They found that glucocorticoid treatment in doses equivalent with prednisolone 10 mg/day or higher was associated with an increased hospitalisation rate. Here, we describe the case of a 50-year-old man who was diagnosed with Lofgren syndrome in January 2019 presenting with cough, bilateral ankle joint swelling and mediastinal lymphadenopathy. ACE (37.3 U/L, normal range

Background: Crohn’s disease (CD) is a chronic immune-mediated disorder of the gastrointestinal tract. The pathophysiological understanding of this disease is limited and no curative therapy is available so far. Therefore, most patients require long-lasting or even life-long immunosuppressive therapies for the suppression of symptoms to improve quality of life and reduction of long-term risks. However, in a relevant subgroup of patients, these therapeutic goals cannot be sufficiently attained. Summary: Clinically established therapies in active CD comprise corticosteroids and immunosuppressants such as azathioprine. After the introduction of anti-TNFα (Tumor necrosis factor alpha) antibodies, other biologicals (e.g., vedolizumab and ustekinumab) have also been approved. New drugs in the pipeline like filgotinib, upadacitinib, risankizumab or rifaximin could improve the therapy of CD in the near future. Thus, an individualized therapy management, based on optimal selection of therapeutic agents will become more important. Additionally, the local application of mesenchymal stem cells might be helpful in the management of fistulas. Key Messages: The targeted biological therapeutic agents (anti-TNFα antibodies, vedolizumab, ustekinumab) are well established for therapy in CD. There are several new substances in the pipeline with promising results in phase II trials (filgotinib, rifaximin, risankizumab, upadacitinib). The upcoming extension of the therapeutic arsenal will require methods for an optimized selection of substances, thus enabling a more individualized therapy.

Background The vast majority of COVID-19 patients experience a mild disease. However, a minority suffers from critical disease with substantial morbidity and mortality. Objectives To identify individuals at risk of critical COVID-19, the relevance of a seroreactivity against seasonal human coronaviruses was analyzed. Methods We conducted a multi-center non-interventional study comprising 296 patients with confirmed SARS-CoV-2 infections from four tertiary care referral centers in Germany and France. The ICU group comprised more males, whereas the outpatient group contained a higher percentage of females. For each patient, the serum or plasma sample obtained closest after symptom onset was examined by immunoblot regarding IgG antibodies against the nucleocapsid protein (NP) of HCoV 229E, NL63, OC43 and HKU1. Results Median age was 60 years (range 18-96). Patients with critical disease (n=106) had significantly lower levels of anti-HCoV OC43 nucleocapsid protein (NP)-specific antibodies compared to other COVID-19 inpatients (p=0.007). In multivariate analysis (adjusted for age, sex and BMI), OC43 negative inpatients had an increased risk of critical disease (adjusted odds ratio (AOR) 2.68 [95% CI 1.09 - 7.05]), higher than the risk by increased age or BMI, and lower than the risk by male sex. A risk stratification based on sex and OC43 serostatus was derived from this analysis. Conclusions Our results suggest that prior infections with seasonal human coronaviruses can protect against a severe course of COVID-19. Therefore, anti-OC43 antibodies should be measured for COVID-19 inpatients and considered as part of the risk assessment for each patient. Hence, we expect individuals tested negative for anti-OC43 antibodies to particularly benefit from vaccination against SARS-CoV-2, especially with other risk factors prevailing.

Wichtigstes Mittel fur die Diagnose eines Morbus Crohn und die Beurteilung der entzundlichen Aktivitat ist die Endoskopie mit histologischer Begutachtung. Da diese Methode aufwandig und oft problematisch ist, wurden in den letzten Jahren zunehmend nicht-invasive Methoden (fort)entwickelt. Hierbei spielen Biomarker eine bedeutende Rolle.

A preliminary study suggests that intestinal-wall assessment by means of noninvasive multispectral optoacoustic tomography may distinguish remission from active disease in patients with Crohn’s disease.

Introduction. Gastrointestinal bleeding represents the main indication for emergency endoscopy (EE). Lately, several hemostatic powders have been released to facilitate EE.Methods. We evaluated all EE in which Hemospray was used as primary or salvage therapy, with regard to short- and long-term hemostasis and complications.Results. We conducted 677 EE in 474 patients (488 examinations in 344 patients were upper GI endoscopies). Hemospray was applied during 35 examinations in 27 patients (19 males), 33 during upper and 2 during lower endoscopy. It was used after previous treatment in 21 examinations (60%) and in 14 (40%) as salvage therapy. Short-term success was reached in 34 of 35 applications (97.1%), while long-term success occurred in 23 applications (65.7%). Similar long-term results were found after primary application (64,3%) or salvage therapy (66,7%). Rebleeding was found in malignant and extended ulcers. One major adverse event (2.8%) occurred with gastric perforation after Hemospray application.Discussion. Hemospray achieved short-term hemostasis in virtually all cases. The long-term effect is mainly determined by the type of bleeding source, but not whether it was applied as first line or salvage therapy. But, even in the failures, patients had benefit from hemodynamic stabilization and consecutive interventions in optimized conditions.

For proper evaluation of capsule endoscopy (CE), a complete examination is necessary.We evaluated risk factors of an incomplete CE with focus on patient hospitalization.We retrospectively evaluated 161 consecutive patients who underwent CE between 01.07.2013 and 13.03.2016. Main indications were active bleeding, iron deficiency anemia (IDA), inflammatory bowel disease (IBD), abdominal pain, and familial adenomatous polyposis (FAP).We report the results of 103 in-patients and 56 out-patients. Eighty-two patients were male, average age was 58.9 years (range 18-90). Indications for CE were active bleeding (103 patients), IDA and IBD (16 patients), and FAP, abdominal pain and others (eight examinations each). All FAP patients were out-patients, but showed the longest small bowel transit time (SBTT) of 443.6min (p=0.0001). The shortest SBTT was found in out-patients without FAP (267.5min, p0.05). In the in-patient group, nine endoscopies did not record the entire small bowel (8.7%) due to battery depletion, compared with only one incomplete examination in the out-patients (1.8%, p=0.036). We found pathologic lesions in the last 30min of the SBTT in 43 patients, and this indicates the necessity for complete examination. Thirteen of these 43 patients showed major lesions such as ulcers or angiodysplasia in this last region alone.In-patients might require special treatment to ensure complete examination, since a considerable amount of pathologies can only be found in the ileum.

Mesenchymal stromal cells (MSCs) from human bone marrow serve as a resource for cell-based therapies in regenerative medicine. Clinical applications require standardized protocols according to good manufacturing practice (GMP) guidelines. Donor variability as well as the intrinsic heterogeneity of MSC populations must be taken into consideration. The composition of the culture medium is a key factor in successful MSC expansion. The aim of this study was to comparatively assess the efficiency of xeno-free human platelet lysate (HPL)-based cell expansion with two commercially available media—StemPro MSC SFM CTS (for human ex vivo tissue and cell culture processing applications) and MSCGM (non-GMP-compliant, for research only)—in an academic setting as the first optimization step toward GMP-compliant manufacturing. We report the feasibility of MSC expansion up to the yielded cell number with all three media. MSCs exhibited the typical fibroblastoid morphology, with distinct differences in cell size depending on the medium. The differentiation capacity and characteristic immunophenotype were confirmed for all MSC populations. Proliferation was highest using StemPro MSC SFM CTS, whereas HPL medium was more cost-effective and its composition could be adjusted individually according to the respective needs. In summary, we present a comprehensive evaluation of GMP-compatible culture media for MSC expansion. Both StemPro and HPL medium proved to be suitable for clinical application and allowed sufficient cell proliferation. Specific differences were observed and should be considered according to the intended use. This study provides a detailed cost analysis and tools that may be helpful for the establishment of GMP-compliant MSC expansion.