Longitudinal evaluation of individuals with severe alpha-1 antitrypsin deficiency (Pi*ZZ genotype).

BACKGROUND AND AIMS: Homozygous Pi*Z mutation in alpha-1 antitrypsin (Pi*ZZ genotype) predisposes to pulmonary loss-of-function and hepatic gain-of-function injury. To facilitate selection into clinical trials typically targeting only one organ, we systematically evaluated an international, multicenter, longitudinal, Pi*ZZ cohort to uncover natural disease course and surrogates for future liver- and lung-related endpoints. METHODS: Cohort 1 recruited 737 Pi*ZZ individuals from 25 different centers without known liver comorbidities that received a baseline clinical and laboratory assessment as well as liver stiffness measurement (LSM). A follow-up interview was performed after at least six months. Cohort 2 consisted of 135 Pi*ZZ subjects without significant liver fibrosis, who received a standardized baseline and follow-up examination at least two years later, both including LSM. RESULTS: During 2634 patient-years of follow-up, 39 individuals died, with liver and lung being responsible for 46% and 36% of deaths, respectively. 41 Pi*ZZ subjects who developed a hepatic endpoint presented with significantly higher baseline liver fibrosis surrogates, i.e., LSM (24 vs. 5 kPa, p<.001) and AST-to-platelet ratio index (APRI, 1.1 vs. 0.3 units, p<.001). Liver-related endpoints within five years were most accurately predicted by LSM (area under the curve [AUC] 0.95) followed by APRI (0.92). Baseline lung parameters displayed only a moderate predictive utility for lung-related endpoints within five years (FEV1 AUC 0.76). Fibrosis progression in those with no/mild fibrosis at baseline was rare and primarily seen in those with preexisting risk factors. CONCLUSIONS: Non-invasive liver fibrosis surrogates accurately stratify liver-related risks in Pi*ZZ individuals. Our findings have direct implications for routine care and future clinical trials of Pi*ZZ patients.

Beyond muscles: Investigating immunoregulatory myokines in acute resistance exercise - A systematic review and meta-analysis.

Myokines, released from the muscle, enable communication between the working muscles and other tissues. Their release during physical exercise is assumed to depend on immune-hormonal-metabolic interactions concerning mode (endurance or resistance exercise), duration, and intensity. This meta-analysis aims to examine the acute changes of circulating myokines inducing immunoregulatory effects caused by a bout of resistance exercise and to consider potential moderators of the results. Based on this selection strategy, a systematic literature search was conducted for resistance exercise intervention studies measuring interleukin (IL-) 6, IL-10, IL-1ra, tumor necrosis factor (TNF-) α, IL-15, IL-7, transforming growth factor (TGF-) ß1, and fractalkines (FKN) before and immediately after resistance exercise in healthy individuals. Random-effects meta-analysis was performed for each myokine. We identified a moderate positive effect of resistance exercise for IL-6 and IL-1ra. Regarding IL-15 and TNF-α, small to moderate effects were found. For IL-10, no significant effect was observed. Due to no data, meta-analyses for IL-7, TGF-ß1, and FKN could not be performed. No moderators (training status, type of exercise, risk of bias, age, sex, time of day, exercise volume, exercise intensity, exercise dose) of the results were detected for all tested myokines. Taken together, this systematic review and meta-analysis showed immediate positive effects of an acute resistance exercise session on IL-6, IL-1ra, TNF-α, and IL-15 levels.

Type-I interferon shapes peritoneal immunity in cirrhosis and drives caspase-5-mediated progranulin release upon infection.

BACKGROUND & AIMS: Gut bacterial translocation contributes to immune dysfunction and spontaneous bacterial peritonitis (SBP) in cirrhosis. We hypothesized that exposure of peritoneal macrophages (PMs) to bacterial DNA results in type-I interferon (IFN) production, shaping subsequent immune responses, inflammasome activation, and the release of damage-associated molecular patterns (DAMPs). METHODS: PMs from patients with cirrhosis were stimulated with E. coli single-stranded DNA (ssDNA), lipopolysaccharide and IFN, or infected with E. coli, S. aureus, and Group B streptococcus in vitro. Cytokine release, inflammasome activation, and DAMP release were quantified by quantitative-PCR, ELISA, western blots, and reporter cells employing primary PMs, monocytes, and caspase-deficient THP-1 macrophages. Serum progranulin concentration was correlated with transplant-free survival in 77 patients with SBP. RESULTS: E. coli ssDNA induced strong type-I IFN activity in PMs and monocytes, priming them for enhanced lipopolysaccharide-mediated tumor necrosis factor production without inducing toll-like receptor 4 tolerance. During in vitro macrophage bacterial infection, type-I IFN release aligned with upregulated expression of IFN-regulatory factors (IRF)1/2 and guanylate binding proteins (GBP)2/5. PMs upregulated inflammasome-associated proteins and type-I IFN upon E. coli ssDNA exposure and released interleukin-1ß upon bacterial infection. Proteomic screening in mouse macrophages revealed progranulin release as being caspase-11-dependent during E. coli infection. PMs and THP-1 macrophages released significant amounts of progranulin when infected with S. aureus or E. coli via gasdermin D in a type-I IFN- and caspase-5-dependent manner. During SBP, PMs upregulated IRF1, GBP2/5 and caspase-5 and higher serum progranulin concentrations were indicative of lower 90-day transplant-free survival after SBP. CONCLUSIONS: Type-I IFN shapes peritoneal immune responses and regulates caspase-5-mediated progranulin release during SBP. IMPACT AND IMPLICATIONS: Patients with cirrhosis exhibit impaired immune responses and increased susceptibility to bacterial infections. This study reveals that type-I interferon responses, triggered by pathogen-associated molecular patterns, are crucial in regulating macrophage activation and priming them for inflammatory responses. Additionally, we elucidate the mechanisms by which type-I interferons promote the release of progranulin from macrophages during spontaneous bacterial peritonitis. Our findings enhance understanding of how bacterial translocation affects immune responses, identify novel biomarkers for inflammasome activation during infections, and point to potential therapeutic targets.

S2k Leitlinie akute infektiöse Gastroenteritis im Säuglings-, Kindes- und Jugendalter ­ Update 2024.

The aim of the interdisciplinary S2k guideline "Acute infectious gastroenteritis in infants, children and adolescents" is to summarise the current state of knowledge on the clinical presentation, diagnosis, treatment, prevention and hygiene of acute infectious gastroenteritis, including nosocomial gastrointestinal infections, in infants, children and adolescents on the basis of scientific evidence, to evaluate it by expert consensus and to derive practice-relevant recommendations from it. The guideline provides a corridor for action for frequent decisions. It also serves the purpose of evidence-based further education and training and is thus intended to improve the medical care of children with acute gastroenteritis. In particular, the guideline aims to avoid unnecessary hospitalisation of children with AGE and to take preventive measures to avoid and spread infection.

Sub-optimal therapy of patients with primary biliary cholangitis (PBC) in the real-life stetting of the German PBC cohort.

Real-world data on the management of patients with primary biliary cholangitis (PBC) are so far scarce in Germany. Therefore, we aimed to establish a nationwide registry and describe the clinical characteristics and therapy of PBC patients.Three different cohorts defined as ursodeoxycholic acid (UDCA) responders, as inadequate responders according to Paris II criteria, and as newly diagnosed patients were prospectively recruited.This manuscript includes the baseline data of the project.In total, 33/77 (43%) contacted centres (58% of university hospitals, 38% of non-university hospitals, and 24% of private practices) recruited 515 patients including 204 UDCA responders, 221 inadequate responders to UDCA, and 90 newly diagnosed patients.All patients were treated with UDCA; however, a UDCA dosage below the recommended dosage of 13 mg/kg/d was observed in 38.5% of individuals after 12 months of treatment. UDCA dosages were lower in nonacademic compared to academic centres.Only 75/219 (38.5%) of inadequate responders to UDCA received a second-line therapy with obeticholic acid (OCA) and/or bezafibrate (BZF). OCA (13% vs. 4.5%) and BZF (14% vs. 6.5%) were significantly more often prescribed by academic vs. nonacademic centres.Pruritus (27% vs. 15.5%), fatigue (23% vs. 4.5%), and sicca syndrome (14% vs. 1%) were significantly more often reported by academic centres.The German PBC registry could be established, which indicates suboptimal therapy in a relevant proportion of patients and shows significant differences between academic and nonacademic centres. Results are fundamental to improving clinical management at different levels of care.

[Post-COVID patients with persistent chemosensory symptoms are rare in the general population]. / Post-COVID-Patienten mit persistierenden chemosensorischen Symptomen sind in der Bevölkerung selten.

OBJECTIVE: The prevalence of long-/post-COVID-associated chemosensory symptoms is reported in the literature to be significantly higher than clinical reality reflects. METHODS: 1. N= 4062 adults acutely infected with SARS-CoV-2 and their symptoms transmitted by the Jena health office to the Robert Koch Institute between March 2020 and September 2021 were evaluated. 2. Part of the same cohort (N = 909 of 4062) answered an extensive questionnaire at least 3 months after the start of the infection, including existing chemosensory post-COVID-associated complaints. 3. Fourteen post-COVID Jena patients with chemosensory symptoms who had become acutely infected during the same period were diagnosed, treated and advised in our ENT specialist outpatient clinic. RESULTS: The prevalence of chemosensory symptoms at the onset of infection was 19% (600/3187). About every second written respondent of the formerly acutely infected (441/890) remembered chemosensory symptoms during their COVID-19 infection. Of these, around 38% (167/441) complained of persistent chemosensory post-COVID symptoms after an average of 14.5 months. Only 2.3% (14/600) of the previously acutely infected patients with chemosensory symptoms sought medical help in a special consultation. Quantitative chemosensory damage could only be objectified in half, i.e. 1.2% (7/600) of the total cohort. CONCLUSIONS: Despite a high prevalence of subjective chemosensory symptoms in acutely and formerly SARS-CoV-2 infected people, there is only a low need for specialized treatment, so that, unlike other post-COVID-associated complaints, the healthcare system as a whole appears to be less significantly burdened.

Visualizing exertional dyspnea in a post-COVID patient using electrical impedance tomography.

PURPOSE AND METHOD: Many post-COVID patients suffer from dyspnea on exertion. To visualize exercise-induced dyspnea, a post-COVID patient and a healthy volunteer underwent an exercise test on a treadmill under stress relevant to everyday life monitored by electrical impedance tomography (EIT). RESULTS: The lung-healthy volunteer showed an even ventilation distribution throughout the assessment, a large ventilated area, and a butterfly-like lung shape with a convex lung rim. The post-COVID patient showed clear differences in the ventilated area compared to the control subject. During exercise, a constantly changing picture of differently ventilated areas is shown. However, especially the anterior regions were under-ventilated and larger areas were partially absent from ventilation. Overall, uncoordinated breathing and an uneven distribution of ventilation dominated the findings. CONCLUSION: EIT is suitable for visualizing disturbed ventilation of the lungs, both at rest and under stress. The potential as a diagnostic tool in dyspnea assessment should be investigated.

Mobile primary healthcare for post-COVID patients in rural areas: a proof-of-concept study.

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 < 2.5th percentile at the 1 min sit-to-stand test compared to age- and sex-matched healthy controls, and 25 patients (20.0%) exhibited a drop in oxygen saturation. A questionnaire given to each patient regarding the mobile unit revealed a very high level of patient satisfaction. 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.

Comparison of fatigue, cognitive dysfunction and psychological disorders in post-COVID patients and patients after sepsis: is there a specific constellation?

BACKGROUND: Sequelae of COVID-19 can be severe and longlasting. We compared frequencies of fatigue, depression and cognitive dysfunction in survivors of SARS-CoV-2-infection and sepsis. METHODS: We performed a prospective cohort study of 355 symptomatic post-COVID patients who visited our out-patient clinic for post-COVID-19 care. We compared them with 272 symptomatic patients from the Mid-German Sepsis Cohort, which investigates the long-term courses of sepsis survivors. Possible predictors for frequent clinical findings (fatigue, signs of depression, cognitive dysfunction) in post-COVID were investigated with multivariable logistic regression. RESULTS: Median age of the post-COVID patients was 51 years (range 17-86), 60.0% were female, and 31.8% required hospitalization during acute COVID-19. In the post-COVID patients (median follow-up time: 163 days) and the post-sepsis patients (180 days), fatigue was found in 93.2% and 67.8%, signs of depression were found in 81.3% and 10.9%, and cognitive dysfunction was found in 23.5% and 21.3%, respectively. In post-COVID, we did not observe an association between fatigue or depression and the severity of acute COVID-19. In contrast, cognitive dysfunction was associated with hospitalization (out-patient versus in-patient) and more frequent in post-COVID patients treated on an ICU compared to the MSC patients. CONCLUSION: In post-COVID patients, fatigue and signs of depression are more common than in sepsis survivors, independent from the acute SARS-CoV-2-infection. In contrast, cognitive dysfunction is associated with hospitalization. Despite the differences in frequencies, owing to the similarity of post-COVID and post-sepsis sequelae, this knowledge may help in implementing follow-up approaches after SARS-CoV-2 infection.

Recurrent Upper Gastrointestinal Bleeding from Isolated Gastric Varices as Primary Symptom of Myelofibrosis: A Case Report on Combining Interventional and Pharmacologic Treatment Options.

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.

Real-World Effectiveness of Piperacillin/Tazobactam with and without Linezolid for Spontaneous Bacterial Peritonitis.

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.

Atezolizumab and bevacizumab with transarterial chemoembolization in hepatocellular carcinoma: the DEMAND trial protocol.

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).

[Inflammatory bowel disease during the COVID-19 pandemic: manifestations and management]. / Chronisch-entzündliche Darmerkrankungen in der COVID-Pandemie: Manifestationen und Management.

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.

SARS-CoV-2 vaccination does not induce relapses of patients with inflammatory bowel disease.

BACKGROUND: 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"). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Peritoneal Level of CD206 Associates With Mortality and an Inflammatory Macrophage Phenotype in Patients With Decompensated Cirrhosis and Spontaneous Bacterial Peritonitis.

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.

Acceptance of SARS-CoV-2 vaccines by liver transplant recipients and candidates.

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; p < 0.001). 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.

Between fear and courage: Attitudes, beliefs, and behavior of liver transplantation recipients and waiting list candidates during the COVID-19 pandemic.

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.

Are CMV-predictive scores in inflammatory bowel disease useful in clinical practice?

BACKGROUND: 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. METHODS: 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. RESULTS: 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 %. CONCLUSIONS: 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.

The ATG16L1 gene variant rs2241880 (p.T300A) is associated with susceptibility to HCC in patients with cirrhosis.

BACKGROUND AND AIMS: Protein and organelle turnover by autophagy is a key component to maintain cellular homeostasis. Loss of the autophagy protein ATG16L1 is associated with reduced bacterial killing and aberrant interleukin-1ß production, perpetuating inflammation and carcinogenesis. Here we hypothesized that the functional p.T300A gene variant in ATG16L1 is associated with an increased risk for hepatocellular carcinoma (HCC) in cirrhosis. METHODS: A case-control study was performed using a prospective derivation cohort (107 patients with HCC and 101 controls) and an independent validation cohort (124 patients with HCC and 108 controls) of patients with cirrhosis of any aetiology. ATG16L1 p.T300A (rs2241880) and PNPLA3 p.I148M (rs738409) variants were determined by real-time PCR. RESULTS: The G allele of the ATG16L1 p.T300A variant was more frequent in patients with HCC compared to controls without HCC in the derivation cohort (0.62 vs. 0.51, P = .022) and in the validation cohort (0.59 vs. 0.50, P = .045). In combined analysis, the odds ratios (OR) were 1.76 (95% CI: 1.07-2.88) for G allele positivity and 2.43 (95% CI: 1.37-4.31) for p.T300A G allele homozygosity. This association was independent from the presence of a PNPLA3 variant, which was also associated with HCC (OR 2.10; 95% CI: 1.20-3.66), and it remained significant after adjustment for male sex, age and aetiology in multivariate analysis. CONCLUSION: The common germ-line ATG16L1 gene variant is a risk factor for HCC in patients with cirrhosis. Personalized strategies employing the genetic risk conferred by ATG16L1 and PNPLA3 may be used for risk-based surveillance in cirrhosis.

Diagnosis of malaria in a traveler 9 months after returning from West Africa by illumigene® LAMP assay: A case report.

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.