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Introduction Post-COVID syndrome is increasingly recognized as a new clinical entity after SARS-CoV-2 infection. Patients living in rural areas may have to travel long with subjectively great effort to be examined using all necessary interdisciplinary tools. This problem could be addressed with mobile outpatient clinics. Methods In this prospective observational study, we investigated physical fitness, fatigue, depression, cognitive dysfunction, and dyspnea in patients with post-COVID syndrome in a mobile interdisciplinary post-COVID outpatient clinic. Upon referral from their primary care physician, patients were offered an appointment at a mobile post-COVID outpatient clinic close to their home. Results We studied 125 patients (female, n = 79; 63.2%) in our mobile unit. All patients reported symptoms lasting for more than 12 weeks after acute infection. 88.3% and 64.1% of patients reported significant impairment in physical and mental quality of life. Patients reported a median of three symptoms. The most frequently reported symptoms were fatigue (86.4%), cognitive dysfunction (85.6%), and dyspnea (37.6%). 56.0% of patients performed at Conclusion There is an increasing need for high-quality and locally available care for patients with post-COVID syndrome. A mobile post-COVID outpatient clinic is a new concept that may be particularly suitable for use in rural regions. Patients’ satisfaction following visits in such units is very high.

A relevant proportion of patients suffer from long-lasting impairments following an acute SARS-CoV-2 infection. The proposed post-COVID syndrome (PCS) score may improve comparison in the course and classification of affected patients. A prospective cohort of 952 patients presenting to the post-COVID outpatient clinic at Jena University Hospital, Germany, was enrolled. Patients received a structured examination. PCS score was calculated per visit. A total of 378 (39.7%) and 129 (13.6%) patients of the entire population visited the outpatient clinic two or three times, respectively (female: 66.4%; age: 49.5 (SD = 13) years). The initial presentation took place, on average, 290 (SD = 138) days after acute infection. The most frequently reported symptoms were fatigue (80.4%) and neurological impairments (76.1%). The mean PCS scores of patients with three visits were 24.6 points (SD = 10.9), 23.0 points (SD = 10.9) and 23.5 points (SD = 11.5) (p = 0.407), indicating moderate PCS. Female sex (p < 0.001), preexisting coagulation disorder (p = 0.021) and coronary artery disease (p = 0.032) were associated with higher PCS scores. PCS is associated with a multitude of long-lasting problems. The PCS score has proven its capability to objectify and quantify PCS symptoms in an outpatient setting. The influence of therapeutic measures on various PCS aspects should be the subject of further analyses.

BackgroundMyokines, released from the contracting muscle, enable communication between the working muscles and other tissue. Their release during physical exercise is assumed to depend on mode, duration, and intensity.ObjectiveThe aim is to examine the acute changes in circulating levels of the myokines IL-6, IL-10, and IL-1ra induced by a bout of resistance exercise and to consider potential moderators of the results.MethodsSystematic literature search was conducted for resistance exercise intervention studies measuring IL-6, IL-10, or IL-1ra before and immediately after resistance exercise in healthy individuals. Random effects meta-analysis was performed for each myokine.ResultsA small to moderate positive effect of resistance exercise for IL-6 and a moderate to large positive effect for IL-1ra were detected. This could not be shown for IL-10. No moderators of the results were detected.ConclusionThis systematic review and meta-analysis clearly showed the immediate positive effects of an acute resistance exercise session on IL-6 and IL-1ra levels.

Zusammenfassung Einleitung Persistierende und neu-auftretende Beschwerden nach einer SARS-CoV-2-Infektion (sog. Long/Post-COVID-Syndrom) stellen eine große Herausforderung für unser Gesundheitssystem dar. Analysen zu Bedürfnissen von Betroffenen an die primäre Behandlung und Versorgungsplanung sind rar, sodass die gezielte Lenkung von Patientenströmen und letztlich auch die Patientenversorgung deutlich erschwert ist. Methoden Die JenUP-Studie (Jenaer Untersuchung zum populations-basierten Auftreten von Post-COVID-Beschwerden) ist eine fragebogenbasierte Untersuchung aller Erwachsenen der Stadt Jena, welche zwischen März 2020 und September 2021 mit einer RT-PCR-bestätigte SARS-CoV-2-Infektion durch das Gesundheitsamt Jena registriert wurden. Ein Teil dieser Studie beschäftigt sich mit der ärztlichen Betreuung von Betroffenen mit prolongierten/persistierenden Symptomen sowie deren subjektiven Schwierigkeiten im Rahmen dieser Behandlung. Ergebnisse Insgesamt beantworten 1,008 der 4,209 angeschriebenen Personen den zugesendeten Fragebogen, wobei 922 (91,5%) über das Auftreten von mindestens einem Long/Post-COVID-assoziierten Symptom berichteten. 85,6% dieser Personen (790/922) gaben zudem detaillierte Auskünfte über Kontakte mit Einrichtungen und Personen des Gesundheitswesens. Drei von vier Personen (590/790) stellten sich im Zusammenhang mit ihren Beschwerden hausärztlich vor, 155/790 (19,6%) konsultierten, meist zusätzlich, Fachspezialist:innen (am häufigsten Internist:innen – 7,1% (55/790). Schwierigkeiten eine subjektiv benötigte Therapie zu erhalten, wurden von 22,6% (162/718) der Befragten angegeben. Als Gründe wurden vornehmlich das patientenseitige Gefühl scheinbar „nicht krank genug zu sein“ (69/162) und ein fehlender Ansprechpartner (65/162) angeführt. 27% (247/919) aller Probanden mit Long/Post-COVID-Beschwerden äußerten den Wunsch nach einem konkreten Ansprechpartner. Schlussfolgerung Die hausärztliche Betreuung stellt eine zentrale Säule der ambulanten Versorgung von Long/Post-COVID-Patienten dar. Zudem sollten gemäß der nationalen S1-Leitlinie flächendeckende Strukturen zur interdisziplinären Betreuung aufgebaut werden. Die Analyse wahrgenommener Barrieren bei der ärztlichen Betreuung und der Wünsche für die Versorgung stellen einen ersten Schritt zur Verbesserung der ambulanten Versorgung von Long/Post-COVID-Patienten dar.

The combination of the anti-PD-L1 antibody atezolizumab and the anti-VEGF bevacizumab is the first approved immunotherapeutic regimen for first-line therapy in patients with unresectable hepatocellular carcinoma (HCC), currently approved in more than 80 countries. The efficacy and tolerability of this regimen suggest that the use of atezolizumab + bevacizumab could be extended to the treatment of patients with intermediate-stage HCC in combination with transarterial chemoembolization (TACE). The authors describe the rationale and design of the DEMAND study. This investigator-initiated, multicenter, randomized phase II study is the first trial to evaluate the safety and efficacy of atezolizumab + bevacizumab prior to or in combination with TACE in patients with intermediate-stage HCC. The primary end point is the 24-month survival rate; secondary end points include objective response rate, progression-free survival, safety and quality of life. Clinical Trial Registration: NCT04224636 (ClinicalTrials.gov).

ZusammenfassungDie COVID-19-Pandemie beeinflusst das Leben von Patient*innen mit chronisch-entzündlichen Darmerkrankungen (CED) in erheblicher Weise. Betroffene und Angehörige haben zahlreiche Fragen zum Erkrankungsrisiko, zum Verlauf einer möglichen SARS-CoV-2-Infektion oder auch zum Einfluss der CED-spezifischen Therapie. Auch bestehen bei vielen CED-Patient*innen zusätzliche Fragen zu Sicherheit und Wirksamkeit einer Impfung gegen SARS-CoV-2. Ziel dieser Übersicht ist die Zusammenfassung der neusten Erkenntnisse zu COVID-19 und CED, aber auch die Diskussion zum Impfansprechen (humoral/zellulär), zum Einfluss laufender Therapie auf die Impfantwort sowie zur Häufigkeit von Nebenwirkungen und zur Bedeutung der Booster-Immunisierungen zu führen und für das Gespräch mit Patient*innen eine Evidenz-basierte Grundlage zu schaffen.

Vaccination against SARS-CoV-2 is a promising strategy to protect immunocompromised IBD patients from a severe course of COVID-19. As these patients were excluded from initial clinical vaccination trials, patients frequently express concerns regarding the safety of these vaccines, especially whether vaccination might trigger IBD flares ("hit-and-run-hypothesis").In order to assess the risk of an IBD flare after vaccination against SARS-CoV-2, an anonymous survey was performed at five German IBD centers and one patient organization (Deutsche Morbus Crohn/Colitis ulcerosa Vereinigung (DCCV) e.V.) in August and October 2021.The questionnaire was answered by 914 patients, 781 of whom reported a previous vaccination against SARS-CoV-2 (85.4%). Vaccination against SARS-CoV-2 was not associated with an increased risk of IBD flares (p=0.319) or unscheduled visits to the IBD physician (p=0.848). Furthermore, typical symptoms of an IBD flare including abdominal pain, increases in stool frequency, or rectal bleeding were not influenced by the vaccination.Vaccination against SARS-CoV-2 is safe in IBD patients. These results may help to reduce fears regarding the vaccination in IBD patients. Our results can help to reduce fears in IBD patients regarding the SARS-CoV-2 vaccine. A close communication between patients and physicians before and after the vaccination may be beneficial.Die Impfung gegen SARS-CoV-2 kann immunkompromittierte Patienten mit einer chronisch-entzündlichen Darmerkrankung (CED) vor einem schweren Verlauf einer COVID-19-Erkrankung schützen. Da diese Patientengruppe in den Zulassungsstudien nicht eingeschlossen wurde, werden vielfach von Patienten Sorgen im Hinblick auf die Sicherheit geäußert, insbesondere bestehen Ängste vor der Auslösung eines akuten CED-Schubs.Zwischen August und Oktober 2021 wurde eine retrospektive Umfrage an 5 deutschen CED-Zentren und unter den Mitgliedern der „Deutschen Morbus Crohn/Colitis ulcerosa Vereinigung (DCCV) e.V.“ durchgeführt, um das Auftreten eines Schubs nach SARS-CoV-2-Impfung zu erfassen.Der Fragebogen wurde von 914 Patienten beantwortet. Von diesen haben 781 (85,4%) berichtet, mindestens eine Impfung gegen SARS-CoV-2 erhalten zu haben. Die Vakzinierung gegen SARS-CoV-2 war nicht mit einer erhöhten Frequenz an CED-Schüben (p=0,319) oder ungeplanten Vorstellungen beim CED-Behandler (p=0,848) assoziiert. Des Weiteren war die Impfung nicht mit einer erhöhten Stuhlfrequenz, vermehrten abdominellen Schmerzen oder rektalen Blutabgängen assoziiert.Die Vakzinierung gegen SARS-CoV-2 war in unserem Kollektiv nicht mit einer nachfolgend gesteigerten Krankheitsaktivität der CED assoziiert. Unsere Resultate können helfen, Ängste von CED-Patienten vor einer Impfung gegen SARS-CoV-2 zu reduzieren.

Background Vaccination is a promising strategy to protect vulnerable groups like immunocompromised inflammatory bowel disease [IBD] patients from an infection with SARS-CoV-2. These patients may have lower immune responses. Little is known about the cellular and humoral immune response after a SARS-CoV-2 vaccination in IBD patients. Methods Totals of 28 patients with IBD and 27 age- and sex-matched healthy controls were recruited at Jena University Hospital. Blood samples were taken before, after the first, and in a subgroup of 11 patients after second dose of a SARS-CoV-2 vaccination. Cellular immune response, including IFN-γ and TNF-α response and antibody titres, were analysed. Results Overall, 71.4% of the IBD patients and 85.2% of the controls showed levels of anti-SARS-CoV-2 antibodies above the cutoff of 33.8 BAU/ml [p = 0.329] after the first dose. Even in the absence of SARS-CoV-2 antibodies, IBD patients showed significant T cell responses after first SARS-CoV-2 vaccination compared with healthy controls, which was not influenced by different immunosuppressive regimens. Associated with the vaccination, we could also detect a slight increase of the TNF production among SARS-CoV-2-reactive TH cells in healthy donorsn [HD] and IBD patients. After the second dose of vaccination, in IBD patients a further increase of humoral immune response in all but one patient was observed. Conclusions Already after the first dose of a SARS-CoV-2 vaccination, cellular immune response in IBD patients is comparable to controls, indicating a similar efficacy. However, close monitoring of long-term immunity in these patients should be considered.

Portal hypertension leads to pronounced venous collateralization and development of varices. Besides manifest liver cirrhosis, primarily left-sided portal hypertension is causal for the development of gastric varices. We present a case of a 36-year-old female patient with splenomegaly, underlying primary myelofibrosis, and detection of somatic Janus-kinase-2 driver-mutation JAK2V617F. Following first upper gastrointestinal bleeding, isolated gastric varices could be detected as a result of underlying left-sided portal hypertension. Within a few months, repeated life-threatening bleedings with transfusion requirements and frequent hospitalizations occurred. Despite multiple injections of cyanoacrylates, the proven therapy of choice, varices could not be stabilized. Combination of targeted JAK-inhibitor therapy in conjunction with the use of EUS-guided application of coils with subsequent cyanoacrylate injection resulted in acute and long-term bleeding control.

Neuropsychiatric symptoms are the most common sequelae of long-COVID. As accumulating evidence suggests an impact of survived SARS-CoV-2-infection on brain physiology, it is necessary to further investigate brain structural changes in relation to course and neuropsychiatric symptom burden in long-COVID. To this end, the present study investigated 3T-MRI scans from long-COVID patients suffering from neuropsychiatric symptoms (n = 30), and healthy controls (n = 20). Whole-brain comparison of gray matter volume (GMV) was conducted by voxel-based morphometry. To determine whether changes in GMV are predicted by neuropsychiatric symptom burden and/or initial severity of symptoms of COVID-19 and time since onset of COVID-19 stepwise linear regression analysis was performed. Significantly enlarged GMV in long-COVID patients was present in several clusters (spanning fronto-temporal areas, insula, hippocampus, amygdala, basal ganglia, and thalamus in both hemispheres) when compared to controls. Time since onset of COVID-19 was a significant regressor in four of these clusters with an inverse relationship. No associations with clinical symptom burden were found. GMV alterations in limbic and secondary olfactory areas are present in long-COVID patients and might be dynamic over time. Larger samples and longitudinal data in long-COVID patients are required to further clarify the mediating mechanisms between COVID-19, GMV and neuropsychiatric symptoms.

Purpose Some patients experience long-term sequelae after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, despite a present post-COVID condition, defined as “any symptom lasting longer than 12 weeks,” only a subset of patients search for medical help and therapy. Method We invited all adults with a positive real-time polymerase chain reaction (RT-PCR) for SARS-CoV-2 between March 2020 and September 2021 (n = 4091) in the city of Jena to answer a standardized questionnaire including demographic information, the course of the acute infection and current health status. K-means-clustering of quality of life (QoL) was used to explore post-COVID subgroups. Results A total of 909 participants at a median interval of 367 (IQR 291/403) days after acute infection were included in the analysis. Of those, 643 (70.7%) complained of having experienced persistent symptoms at the time of the survey. Cluster analysis based on QoL revealed two subgroups of people with persistent post-COVID symptoms. Whereas 189/643 participants (29.4%) showed markedly diminished QoL, normal QoL was detected in 454/643 individuals (70.6%). Conclusion Despite persistent symptoms being reported by nearly three quarters of participants, only one-third of these described a significant reduction in QoL (cluster 1), whereas the other two-thirds reported a near-normal QoL (cluster 2), thus indicating a differentiation between “post-COVID disease” and “post-COVID condition”. The prevalence of clinically relevant post-COVID disease was at least 20.7%. Health policies should focus on this subset.

Patients with chronic liver disease and patients after solid organ transplantation (SOT) are vulnerable to severe coronavirus disease 2019 (COVID-19). We evaluated fears, attitudes, and opinions associated with COVID-19 in 365 SOT recipients (95% liver, 5% pancreas/kidney), 112 SOT candidates, and 394 immediate household contacts in 2 German transplant centers. Seven (1.5%) patients and 10 (2.5%) controls had contact with confirmed COVID-19 cases. Fear of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was expressed by 65% of SOT recipients and by 55% of SOT candidates. SOT recipients had higher levels of fear of infection and more often wore personal protective gear than household controls. Female sex, steroid treatment, and using the local newspaper as a primary source of information were independently associated with expressed fear of infection in SOT recipients. Younger age and more recent transplantation correlated with concerns about severe COVID-19 expressed by patients and with concerns about worse medical care expressed by household controls. One third of the patients expressed fear that immunosuppression could worsen COVID-19 but only 15% used the transplantation center as a source of information. These data show that fears associated with the SARS-CoV-2 pandemic are frequently expressed but measures to prevent infection are regularly followed by patients before and after SOT.

Concurrent cytomegalovirus (CMV) in inflammatory bowel disease (IBD)-related colitis is an important scenario associated with high rates of colectomy and other morbidity. Due to the low incidence of CMV, testing of all patients is associated with an unacceptably high consumption of resources and delay in treatment. Therefore, several predictive scores have been developed to identify patients at risk for a CMV infection. We performed a retrospective single center study in a German University hospital including all IBD patients with available data on CMV-PCR analysis in whole blood between 2010 and 2018 and evaluated 2 prognostic scores for CMV infection for their diagnostic accuracy. In the study, 907 patients with IBD and CMV-PCR were identified. Of them, 21 patients (2.3 %) had a positive CMV-PCR (≥ 1000 copies/mL), 14 of them in ulcerative colitis and 7 in Crohn's disease. The Berlin Score identified 667 patients (73.1 %) as potentially CMV-positive, resulting in a positive predictive value of 2.5 % and a negative predictive value of 98.3 %. In contrast, the Münster Score identified 60 patients as potentially CMV-positive, resulting in a PPV of 20 % and an NPV of 99.4 %. Scoring systems can help to identify patients at risk for a CMV infection and minimize resource consumption and delay in treatment. Due to low incidence, a 2-step-algorithm, consisting of the Münster Score followed by a CMV-PCR if the score indicates a CMV infection, is preferable. Eine Infektion mit dem Cytomegalovirus (CMV) bei Patienten mit einer chronisch-entzündlichen Darmerkrankung (CED) ist eine wichtige Differentialdiagnose eines Schubes. Aufgrund der niedrigen Inzidenz ist die Testung aller Patienten mit einem inakzeptabel hohen Ressourcen-Verbrauch verbunden. Daher wurden verschiedene prädiktive Scores entwickelt um Risiko-Patienten zu identifizieren. An unserer Universitätsklinik erfolgte eine retrospektive Analyse aller CED-Patienten, bei denen zwischen 2010 und 2018 eine CMV-PCR im Blut bestimmt wurde Die diagnostische Präzision zweier publizierter Scores wurde analysiert. 907 Patienten mit CED und CMV-PCR wurden identifiziert. 21 Patienten (2,3 %) hatten eine positive CMV-PCR (≥ 1000 Kopien/ml), 14 mit Colitis ulcerosa und 7 mit Morbus Crohn. Der Berlin Score identifizierte 667 Patienten (73.1 %) als potentiell CMV-positiv, was einem positiv-prädiktiven Werte von 2,5 % entspricht und einem negativ-prädiktiven Wert von 98.3 %. Im Gegensatz dazu identifizierte der Münster Score 60 Patienten als potentiell CMV-positiv, entsprechend einem PPV von 20 % und einem NPV von 99,4 %. Scoring Systeme können helfen, Patienten mit einem hohen Risiko für eine CMV-Infektion zu identifizieren und den Ressourcen-Verbrauch zu minimieren. Aufgrund der geringen Inzidenz erscheint ein zweistufiges Verfahren aus dem Münster Score, gefolgt von einer CMV-PCR bei positivem Score, am sinnvollsten.

Zusammenfassung Clostridioides-difficile-Infektionen (CDI) sind typische Komplikationen einer Antibiotikatherapie. Wenn auch die durch C. diff. verursachten Krankheitsbilder bis zum toxischen Megakolon mit letalen Verläufen reichen können, sind leichte Verlaufsformen mit unkomplizierter Diarrhoe bei Weitem am häufigsten. Auch die Behandlung dieser Krankheitsbilder sollte leitliniengerecht erfolgen. Die zurzeit gültigen internationalen Leitlinien sind bezüglich der Therapie der leichten Infektion mit Metronidazol aber widersprüchlich. Vor diesem Hintergrund erfolgte eine selektive Literaturrecherche zu Leitlinien und Behandlungsstudien zum Einsatz von Metronidazol bei leichter CDI. Die Auswertung randomisierter kontrollierter Studien zeigt eine statistische Überlegenheit von Vancomycin gegenüber Metronidazol (NNT 16). Unter Einbeziehung großer Kohortenstudien reduziert sich dieser Unterschied in der Effektivität auf 2,5 % (NNT 40). Inkonsistente Kriterien zur Definition einer leichten CDI, unterschiedliche Dosierungen, Applikationen und Zeitintervalle (z. B. zusätzliche Gabe von Metronidazol i. v.) sowie der retrospektive Charakter mancher Studien verhindern das Erkennen möglicher Einflüsse von Störgrößen bei dieser Bewertung. Dennoch kann eine leichte CDI erfolgreich mit Metronidazol behandelt werden; andere Empfehlungen insbesondere amerikanischer Gesellschaften sollten deshalb kritisch bewertet werden. Wichtig ist, dass diese Therapieempfehlung nicht für Patienten mit chronisch entzündlichen Darmerkrankungen oder andere Patienten mit relevanten Komorbiditäten gilt.

Background & Aims Peritoneal macrophages (PMs) regulate inflammation and control bacterial infections in patients with decompensated cirrhosis. We aimed to characterize PMs and associate their activation with outcomes of patients with spontaneous bacterial peritonitis (SBP). Methods We isolated PMs from ascites samples of 66 patients with decompensated cirrhosis (19 with SBP) and analyzed them by flow cytometry, quantitative real-time polymerase chain reaction, functional analysis, and RNA microarrays. We used ascites samples of a separate cohort of 111 patients with decompensated cirrhosis (67 with SBP) and quantified the soluble form of the mannose receptor (CD206) and tumor necrosis factor by enzyme-linked immunosorbent assay (test cohort). We performed logistic regression analysis to identify factors associated with 90-day mortality. We validated our findings using data from 71 patients with cirrhosis and SBP. Data from 14 patients undergoing peritoneal dialysis for end-stage renal disease but without cirrhosis were included as controls. Results We used surface levels of CD206 to identify subsets of large PMs (LPM) and small PMs (SPM), which differed in granularity and maturation markers, in ascites samples from patients with cirrhosis. LPMs vs SPMs from patients with cirrhosis had different transcriptomes; we identified more than 4000 genes that were differentially regulated in LPMs vs SPMs, including those that regulate the cycle, metabolism, self-renewal, and immune cell signaling. LPMs had an inflammatory phenotype, were less susceptible to tolerance induction, and released more tumor necrosis factor than SPMs. LPMs from patients with cirrhosis produced more inflammatory cytokines than LPMs from controls. Activation of PMs by Toll-like receptor agonists and live bacteria altered levels of CD206 on the surface of LPMs and release of soluble CD206. Analysis of serial ascites fluid from patients with SBP revealed loss of LPMs in the early phase of SBP, but levels increased after treatment. In the test and validation cohorts, patients with SBP and higher concentrations of soluble CD206 in ascites fluid (>0.53 mg/L) were less likely to survive for 90 days than those with lower levels. Conclusions Surface level of CD206 can be used to identify mature, resident, inflammatory PMs in patients with cirrhosis. Soluble CD206 is released from activated LPMs and increased concentrations in patients with cirrhosis and SBP indicate reduced odds of surviving for 90 days.

Background & Aims: Recurrence of primary biliary cholangitis (PBC) after liver transplantation (LT) is frequent and can impair graft and patient survival. Ursodeoxycholic acid (UDCA) is the current standard therapy for PBC. We investigated the effect of preventive exposure to UDCA on the incidence and long-term consequences of PBC recurrence after LT. Methods: We performed a retrospective cohort study in 780 patients transplanted for PBC, between 1983–2017 in 16 centers (9 countries), and followed-up for a median of 11 years. Among them, 190 received preventive UDCA (10–15 mg/kg/day). The primary outcome was histological evidence of PBC recurrence. The secondary outcomes were graft loss, liver-related death, and all-cause death. The association between preventive UDCA and outcomes was quantified using multivariable-adjusted Cox and restricted mean survival time (RMST) models. Results: While recurrence of PBC significantly shortened graft and patient survival, preventive exposure to UDCA was associated with reduced risk of PBC recurrence (adjusted hazard ratio [aHR] 0.41; 95% CI 0.28–0.61; p

Background & Aims Mucosal-associated invariant T (MAIT) cells are depleted from blood in patients with advanced liver disease and show features of immune dysfunction. Because circulating MAIT cells differ from organ-resident MAIT cells, we aimed to investigate the frequency, phenotype, and function of peritoneal MAIT cells from patients with cirrhosis and spontaneous bacterial peritonitis (SBP). Methods MAIT cells in blood and ascitic fluid from patients with cirrhosis were characterized using flow cytometry. Healthy individuals and noncirrhotic patients undergoing peritoneal dialysis served as controls. MAIT cell migration was studied in transwell assays. Cytokine release in response to infected ascitic fluid and bacterial products was assessed in vitro. Results Peritoneal CD3+ CD161hi Vα7.2+ T cells had an inflammatory, tissue retention phenotype, expressing the alpha E integrin, the chemokine receptors CCR5 and CXCR3, and the activation marker CD69 at higher levels than their circulating equivalents. Seventy-seven percent bound to MR1 tetramers loaded with the pyrimidine intermediate 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil. The ratio of peritoneal to blood MAIT cell frequency increased from 1.3 in the absence of SBP to 2.6 at diagnosis and decreased by day 3. MAIT cells migrated toward infected ascitic fluid containing CCL5 and CCL20 and released cytokines in an MR1-restricted fashion. Whereas the depleted circulating MAIT cell pool displayed features of immune exhaustion, peritoneal MAIT cells remained competent producers of inflammatory cytokines in response to bacterial products. Peritoneal MAIT activation correlated with systemic inflammation, suggesting a possible link between peritoneal and systemic immunity. Conclusions Peritoneal MAIT cells phenotypically and functionally differ from circulating MAIT cells in decompensated cirrhosis and redistribute to the peritoneum during SBP., Graphical abstract

The COVID-19 pandemic is significantly affecting the lives of patients with inflammatory bowel disease (IBD). Those affected and their relatives have numerous questions about the risk of the disease, the course of a possible SARS-CoV-2 infection or the influence of CED-specific therapy on these. Many IBD patients also have additional questions about the safety and effectiveness of a vaccination against SARS-CoV-2. The aim of this review is to summarize the latest findings on COVID-19 and IBD, but also to discuss vaccine response (humoral/cellular), the influence of ongoing therapy on the vaccine response as well as the frequency of side effects and the importance of booster immunizations and to create an evidence-based basis for discussion with patients.Die COVID-19-Pandemie beeinflusst das Leben von Patient*innen mit chronisch-entzündlichen Darmerkrankungen (CED) in erheblicher Weise. Betroffene und Angehörige haben zahlreiche Fragen zum Erkrankungsrisiko, zum Verlauf einer möglichen SARS-CoV-2-Infektion oder auch zum Einfluss der CED-spezifischen Therapie. Auch bestehen bei vielen CED-Patient*innen zusätzliche Fragen zu Sicherheit und Wirksamkeit einer Impfung gegen SARS-CoV-2. Ziel dieser Übersicht ist die Zusammenfassung der neusten Erkenntnisse zu COVID-19 und CED, aber auch die Diskussion zum Impfansprechen (humoral/zellulär), zum Einfluss laufender Therapie auf die Impfantwort sowie zur Häufigkeit von Nebenwirkungen und zur Bedeutung der Booster-Immunisierungen zu führen und für das Gespräch mit Patient*innen eine Evidenz-basierte Grundlage zu schaffen.

The assessment of cancer patient care during the COVID-19 pandemic has been mainly reported from a physician’s perspective. Patients with rare tumor entities such as neuroendocrine tumors (NET), which require a complex and specialized care infrastructure, were highly affected by the COVID-19 crisis. Using a structured questionnaire consisting of a general section on the disease and a special COVID-19 section to record medical care, vaccination behavior as well as social and psycho-emotional parameters were collected from NET patients. The survey was distributed via direct medical contact and via the patient organization NETZWERK NeT. A total of 684 patients participated in the survey and 79.2% (n = 542) of the participants answered the questionnaire completely (54 questions). Patient characteristics were comparable to those in large NET registries. The majority of participants were patients with pancreatic and small bowel NET on somatostatin analogue (SSA) therapy. Medical care under COVID-19 was adequate and appointment cancellations and postponements were not common. Nevertheless, the majority of patients were worried about adequate treatment for their tumor disease during the crisis. Most of the participants considered themselves to be at risk of severe COVID-19 infection and were therefore very concerned. This was accompanied by an extremely high vaccination readiness rate of 90%. Increased distress in the social and psycho-emotional domains in the course of the crisis reflected a need for optimization in the medical care of NET patients, although the rate of COVID-19 positive participants was low (3.7%). Therefore, patient-reported measurements are required to identify and address all areas of medical care. Overall, our survey provides an essential contribution to the care of NET patients during the COVID-19 pandemic from the patient’s perspective.

Background & Aims V-set Ig-domain-containing 4 (VSIG4) is an immunomodulatory macrophage complement receptor modulating innate and adaptive immunity and affecting the resolution of bacterial infections. Given its expression on peritoneal macrophages (PMs), we hypothesised a prognostic role of peritoneal VSIG4 concentrations in patients with spontaneous bacterial peritonitis (SBP). Methods We isolated PMs from patients with cirrhosis and analysed VSIG4 expression and release by flow cytometry, quantitative real-time PCR, ELISA, and confocal microscopy. We measured soluble VSIG4 concentrations in ascites from 120 patients with SBP and 40 patients without SBP and investigated the association of soluble VSIG4 in ascites with 90-day survival after SBP using Kaplan–Meier statistics, Cox regression, and competing-risks regression analysis. Results VSIG4 expression was high on resting, large PMs, which co-expressed CD206, CD163, and tyrosine-protein kinase Mer (MERTK). VSIG4 gene expression in PMs decreased in patients with SBP and normalised after resolution. During SBP, VSIG4hi PMs were depleted (25% vs. 57%; p, Graphical abstract, Highlights • VSIG4 expression is high on human resting, large peritoneal macrophages (PMs) that co-express CD206, CD163, and MERTK. • PM activation by TLR agonists or infection results in the loss of surface VSIG4 and release of soluble VSIG4 (sVSIG4). • Ascites sVSIG4 correlates with organ dysfunction and inflammation during SBP. • Higher ascitic fluid sVSIG4 concentrations indicated increased risk of 90-day mortality in 120 patients with SBP. • Addition of an antibody binding to the extracellular domain of VSIG4 enhanced phagocytosis of bacteria in vitro.

Background: Guidelines recommend empirical therapy with piperacillin/tazobactam (TZP) for spontaneous bacterial peritonitis (SBP) with low risk of multidrug-resistant organisms. Whether coverage of beta-lactam-resistant Gram-positive bacteria, such as ampicillin-resistant Enterococcus faecium, provides clinical benefit in such situations is unknown. Methods: In this observational study, we investigated the real-world effectiveness of empirical therapy with TZP monotherapy versus TZP plus linezolid (LZD) combination therapy in patients with SBP from two centers. Treatment failure, defined as the need to escalate antibiotic therapy due to in vitro resistance, lack of neutrophil decrease in ascitic fluid, or clinical decision, and 30-day survival were retrospectively assessed. Results: In the first cohort, 100 SBP episodes were empirically treated with TZP + LZD combination therapy (n = 50) or TZP monotherapy (n = 50). Treatment failure was recorded in 48% with TZP monotherapy compared with 16% with TZP + LZD combination therapy (p = 0.001), and this difference persisted after stratification for community-acquired versus hospital-acquired SBP. Although treatment failure after TZP therapy was associated with lower 30-day survival (56% vs. 82%; p = 0.04), 30-day survival with empirical TZP + LZD combination therapy was not different from empirical TZP monotherapy (Kaplan-Meier estimates 74% vs. 69%; p = 0.87). TZP concentrations in ascitic fluid were >32 mg/L in 94% samples after continuous administration. In a second cohort of 41 patients empirically treated with TZP, treatment failure was observed in 37%, which was also higher than in episodes treated with TZP + LZD in cohort 1 (p = 0.03). Conclusion: In this retrospective analysis, empirical TZP + LZD combination therapy for SBP was associated with fewer treatment failures without impact on short-term survival.

Guidelines recommend vaccination against SARS-CoV-2 in transplant recipients, candidates, and their household contacts. However, little is known about the acceptance of COVID-19 vaccines in these groups.In March 2021, we surveyed 826 liver transplant recipients, candidates, and their household contacts to determine acceptance rates and factors influencing the acceptance of the COVID-19 vaccine; 341 patients (40%) and 237 household contacts (28%) returned the questionnaire. Ninety percent of patients returning the survey reported they were willing to receive the vaccine within the next 6 months or had already started vaccination. Only 2% of patients and 4% of household contacts reported refusing the vaccine, and 8% of patients and 9% of household contacts wanted to postpone vaccination because of concerns about side effects. Having received the influenza vaccine in the last 2 seasons was the strongest indicator of acceptance to receive the SARS-CoV-2 vaccine within 6 months (odds ratio 5.11; 95% confidence interval 2.43-10.74; p0.001). Thirty-two percent of responding patients reported fear of side effects as a reason for having refused vaccination before.Although the acceptance of the SARS-CoV-2 vaccine was particularly high among German liver transplant recipients, candidates, and household contacts in this survey, transplant physicians are encouraged to discuss safety concerns with patients who have refused the seasonal influenza vaccine in the past.Aktuelle Leitlinien empfehlen die Impfung gegen SARS-CoV-2 bei Patienten nach einer Organtransplantation, Patienten auf Wartelisten und bei Haushaltskontakten. Allerdings ist bislang wenig über die Akzeptanz dieser Impfung bei den Betroffenen bekannt.Wir haben daher im März 2021 in zwei deutschen Transplantationszentren an 826 Patienten nach Lebertransplantation, auf der Warteliste für eine Lebertransplantation und ihre Angehörige einen Fragebogen versandt, um die Akzeptanz der Impfung und Faktoren, die diese beeinflussen, zu erfragen. Es wurden 341 Fragebögen von Patienten (40%) und 237 von Angehörigen (28%) beantwortet. 90% der Patienten, die den Fragebogen beantwortet haben, gaben an, dass sie sich gegen SARS-CoV-2 innerhalb von 6 Monaten impfen lassen möchten oder bereits geimpft sind. Lediglich 2% der Patienten und 4% der Angehörigen gaben an, keine Impfung zu wollen, weitere 8 bzw. 9% wollen die Impfung aus Angst vor Nebenwirkungen verschieben. Der stärkste prädiktive Faktor für die Bereitschaft zur SARS-CoV-2 Impfung war eine durchgeführte Influenza-Impfung innerhalb der letzten 2 Jahre (OR 5,11, 95% Konfidenzintervall 2,43–10,74; p0,001). Der Hauptgrund für die Ablehnung einer Influenza-Impfung war bei 32% der Patienten ohne Impfung die Angst vor Nebenwirkungen.Auch wenn die Akzeptanz der SARS-CoV-2-Impfung unter den Befragten sehr hoch war, so sollten durch die Ärzte in den Transplantationszentren die Ängste vor Nebenwirkungen aktiv angesprochen und diskutiert werden, insbesondere bei Patienten, die bislang auch eine Influenza-Impfung abgelehnt haben.

Loop-mediated isothermal amplification (LAMP) is a rapid molecular technique that has been introduced into malaria diagnosis. The test is easy to perform and offers high sensitivity. We report a 53-year-old male patient who was hospitalized with fever attacks, chills, and headache caused 9 months after returning from Africa. During his stay in Africa, he used malaria chemoprophylaxis. Microscopy of thin and thick blood films and rapid diagnostic antigen testing remained negative for three times. The EDTA blood samples were tested using the Meridian illumigene® malaria LAMP assay that gave a positive result for Plasmodium spp. Diagnosis of malaria was subsequently specified as P. ovale infection by real-time PCR. Ovale malaria often manifests with delay and low parasitemia. The patient was treated with atovaquone-proguanil, followed by primaquine for prophylaxis of relapse. This case illustrates the usefulness of the illumigene® malaria LAMP assay for initial screening of malaria parasites.

Background & Aims Based on positive results from small single center studies, granulocyte-colony stimulating factor (G-CSF) is being widely used for the treatment of patients with acute-on-chronic liver failure (ACLF). Herein, we aimed to evaluate the safety and efficacy of G-CSF in patients with ACLF. Methods In this multicenter, prospective, controlled, open-label phase II study, 176 patients with ACLF (EASL-CLIF criteria) were randomized to receive G-CSF (5 μg/kg daily for the first 5 days and every third day thereafter until day 26) plus standard medical therapy (SMT) (n = 88) or SMT alone. The primary efficacy endpoint was 90-day transplant-free survival analyzed by Cox regression modeling. The key secondary endpoints were overall and transplant-free survival after 360 days, the development of ACLF-related complications, and the course of liver function scores during the entire observation period. Results Patients treated with G-CSF had a 90-day transplant-free survival rate of 34.1% compared to 37.5% in the SMT group (hazard ratio [HR] 1.05; 95% CI 0.711–1.551; p = 0.805). Transplant-free and overall survival at 360 days did not differ between the 2 arms (HR 0.998; 95% CI 0.697–1.430; p = 0.992 and HR 1.058; 95% CI 0.727–1.548; p = 0.768, respectively). G-CSF did not improve liver function scores, the occurrence of infections, or survival in subgroups of patients without infections, with alcohol-related ACLF, or with ACLF defined by the APASL criteria. Sixty-one serious adverse events were reported in the G-CSF+SMT group and 57 were reported in the SMT group. In total, 7 drug-related serious adverse reactions occurred in the G-CSF group. The study was prematurely terminated due to futility after conditional power calculation. Conclusions In contrast to previous findings, G-CSF had no significant beneficial effect on patients with ACLF in this multicenter controlled trial, which suggests that it should not be used as a standard treatment for ACLF. ClinicalTrials.gov number NCT02669680 Lay summary Granulocyte-colony stimulating factor was considered as a novel treatment for acute-on-chronic liver failure (ACLF). We performed the first randomized, multicenter, controlled phase II trial, which showed that G-CSF did not improve survival or other clinical endpoints in patients with ACLF. Therefore, G-CSF should not be used to treat liver disease outside clinical studies.

Zusammenfassung Einleitung Der Einfluss einer SARS-CoV-2-Infektion auf chronisch entzündliche Darmerkrankungen (CED) ist bislang nicht gut charakterisiert, und es ist unklar, ob diese eine Anpassung der immunsuppressiven Therapie erfordert. Methodik Für die retrospektive Dokumentation klinischer Parameter und Veränderungen einer immunsuppressiven Therapie von mit SARS-CoV-2 infizierten CED-Patienten wurde ein nationales Melderegister etabliert. Ergebnisse Insgesamt wurden nur 3 von 185 CED-Patienten (1,6 %) wegen abdomineller Symptome auf eine SARS-CoV-2-Infektion getestet. Im COVID-19-Krankheitsverlauf entwickelten 43,5 % Durchfall, abdominelle Schmerzen oder Hämatochezie (Hospitalisierungsrisiko mit vs. ohne abdominelle Symptome: 20,0 % vs. 10,6 %, p Diskussion Bei mit SARS-CoV-2 infizierten CED-Patienten traten häufig neue abdominelle Symptome bei Infektion auf. Diese führten aber nur selten zur SARS-CoV-2-Testung. Eine hohe CED-Aktivität zum Zeitpunkt des SARS-CoV-2-Nachweises war mit einem erhöhten Hospitalisierungsrisiko assoziiert.

LINKED CONTENT This article is linked to Taxonera et al and Reuken et al papers. To view these articles, visit https://doi.org/10.1111/apt.15804 and https://doi.org/10.1111/apt.16087