Longterm course of neuropsychological symptoms and ME/CFS after SARS-CoV-2-infection: a prospective registry study.

A significant proportion of patients after SARS-CoV-2 infection suffer from long-lasting symptoms. Although many different symptoms are described, the majority of patients complains about neuropsychological symptoms. Additionally, a subgroup of patients fulfills diagnostic criteria for ME/CFS. We analyzed a registry of all patients presenting in the out-patients clinic at a German university center. For patients with more than one visit, changes in reported symptoms from first to second visit were analyzed. A total of 1022 patients were included in the study, 411 of them had more than one visit. 95.5% of the patients reported a polysymptomatic disease. At the first visit 31.3% of the patients fulfilled ME/CFS criteria after a median time of 255 days post infection and and at the second visit after a median of 402 days, 19.4% still suffered from ME/CFS. Self-reported fatigue (83.7-72.7%) and concentration impairment (66.2-57.9%) decreased from first to second visit contrasting non-significant changes in the structured screening. A significant proportion of SARS-CoV-2 survivors presenting with ongoing symptoms present with ME/CFS. Although the proportion of subjective reported symptoms and their severity reduce over time, a significant proportion of patients suffer from long-lasting symptoms necessitating new therapeutic concepts.

The JAK1/2 inhibitor ruxolitinib in patients with COVID-19 triggered hyperinflammation: the RuxCoFlam trial.

Dysregulated hyperinflammatory response is key in the pathogenesis in patients with severe COVID-19 leading to acute respiratory distress syndrome and multiorgan failure. Whilst immunosuppression has been proven to be effective, potential biological targets and optimal timing of treatment are still conflicting. We sought to evaluate efficacy and safety of the Janus Kinase 1/2 inhibitor ruxolitinib, employing the previously developed COVID-19 Inflammation Score (CIS) in a prospective multicenter open label phase II trial (NCT04338958). Primary objective was reversal of hyperinflammation (CIS reduction of ≥25% at day 7 in ≥20% of patients). In 184 patients with a CIS of ≥10 (median 12) ruxolitinib was commenced at an initial dose of 10 mg twice daily and applied over a median of 14 days (range, 2-31). On day 7, median CIS declined to 6 (range, 1-13); 71% of patients (CI 64-77%) achieved a ≥25% CIS reduction accompanied by a reduction of markers of inflammation. Median cumulative dose was 272.5 mg/d. Treatment was well tolerated without any grade 3-5 adverse events related to ruxolitinib. Forty-four patients (23.9%) died, all without reported association to study drug. In conclusion, ruxolitinib proved to be safe and effective in a cohort of COVID-19 patients with defined hyperinflammation.

[German S1 Guideline Long-/Post-COVID]. / S1-Leitlinie Long-/Post-COVID.

The German Society of Pneumology initiated 2021 the AWMF S1 guideline Long COVID/Post-COVID. In a broad interdisciplinary approach, this S1 guideline was designed based on the current state of knowledge.The clinical recommendations describe current Long COVID/Post-COVID symptoms, diagnostic approaches, and therapies.In addition to the general and consensus introduction, a subject-specific approach was taken to summarize the current state of knowledge.The guideline has an explicit practical claim and will be developed and adapted by the author team based on the current increase in knowledge.

T Cell Response After SARS-CoV-2 Vaccination in Immunocompromised Patients with Inflammatory Bowel Disease.

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.

Clinical characteristics and outcome of patients with enterococcal liver abscess.

Epidemiology of bacteria isolated from pyogenic liver abscesses change, and an increase in enterococci has been reported in European hospitals. The aim of this study was to investigate the clinical characteristics and outcome of enterococcal PLA. We performed a retrospective analysis of patients with microbiologically confirmed PLA at three German university centers. Indicators of enterococcal PLA were determined using binary logistic regression, and survival analysis was performed using Kaplan-Meier statistics and Cox regression analysis. Enterococci were isolated in 51/133 (38%) patients with PLA. Patients with enterococcal PLA had smaller abscess diameter (4.8 vs. 6.7 cm, p = 0.03) than patients with non-enterococcal PLA, but had more frequent polymicrobial culture results. In univariate logistic regression analysis, alcohol abuse (OR 3.94, 95% CI 1.24-12.49, p = 0.02), hepatobiliary malignancies (OR 3.90, 95% CI 1.86-8.18, p < 0.001) and cirrhosis (OR 6.36, 95% CI 1.27-31.96, p = 0.02) were associated with enterococcal PLA. Patients with enterococcal PLA had a higher mortality than patients with non-enterococcal PLA (hazard ratio 2.92; 95% confidence interval 1.09-7.80; p = 0.03), which remained elevated even after excluding patients with hepatobiliary malignancies, cirrhosis, and transplant recipients in a sensitivity analysis. The increased mortality was associated with non-fecal enterococci but not in patients with Enterococcus faecalis. In this retrospective, multicenter study, enterococcal PLA was common and indicated an increased risk of mortality, underscoring the need for close clinical monitoring and appropriate treatment protocols in these patients.

Inflammatory Bowel Disease in the COVID-19 Pandemic: the Patients' Perspective.

BACKGROUND: The coronavirus disease 2019 [COVID-19] pandemic is affecting lives worldwide. The influence of inflammatory bowel disease [IBD] medication and IBD itself on COVID-19 is controversial. Additionally, IBD-focused guidance is scarce. OBJECTIVE: Our aims were to determine COVID-19 prevalence/exposure, perception and information sources, medication compliance, patient behaviour and physician contact among patients with IBD compared with non-IBD controls. METHODS: A cross-sectional anonymous survey of patients with IBD [N = 415] at one university IBD clinic and one gastroenterology practice, matched 4:1 with control participants [N = 116], was performed. RESULTS: Patients with IBD had a high fear of infection. This was more pronounced in patients taking immunosuppressants and it extended to hospitals, private practices and public places, such as supermarkets. IBD patients reported leaving their homes less frequently than their peers without IBD. A total of 90% of patients with IBD reported washing their hands more frequently. Patients taking immunosuppressants were concerned about interactions between medication and COVID-19, whereas patients taking 5-aminosalicylates were not. Nonetheless, 96.4% of patients adhered to continuing their medication. Patients sought guidance primarily from television and internet news sites. Video consultations were found to be a suitable solution for a subset of patients who are young, have a high level of fear and leave their home less frequently than their peers, whereas overall acceptance of video consultations was limited. CONCLUSION: Patients with IBD are significantly more affected by the COVID-19 pandemic than their non-IBD peers, but they continue to adhere to their medication regimens. IBD-focused COVID-19 information should be actively conveyed.

[Clostridium difficile in the intensive care unit]. / Clostridium difficile auf der Intensivstation.

Clostridium difficile infections (CDI) are encountered in about 1-2% of patients in the intensive care unit (ICU) and pose a special challenge to those who provide care. Only little data regarding severity and management of CDI in ICU patients in Europe are available. Extrapolation of results from one patient population to another is often difficult. The comorbidities of those patients often limit the application of general recommendations concerning diagnosis and therapy. In addition, there are a relevant percentage of patients (10-20%) with asymptomatic C. difficile colonization. The relevance for the patient and for the risk of patient to patient infection is not yet fully understood. Based on available data, we give an overview of current challenges in the diagnosis, assessment of disease course, primary management options, and alternatives in special cases and treatment failures of CDI. We also discuss prevention of new CDI in the intensive care unit.

[Aspects of pulmonary involvement in inflammatory bowel disease]. / Lungenbeteiligung bei chronisch-entzündlichen Darmerkrankungen.

The incidence of pulmonary manifestations of inflammatory bowel disease (IBD) appears to be much higher than previously assumed. In prospective studies, subclinical pulmonary interstitial infiltrates or pathological lung function were found in 40%-60% of IBD patients, both in children and adults. Pulmonary disorders can affect any part of the respiratory system, the most frequent pattern being inflammation of the large airways often associated with bronchiectasis. The differential diagnosis should include drug-related pulmonary disease and infectious causes when receiving immunosuppressive therapy. The diagnostic approach consists of a thorough history and clinical status as well as lung function tests including body plethysmography and high-resolution computed tomography of the thorax. Bronchoscopy with broncheoalveolar lavage and sample collection for histology as well as exclusion of pulmonary embolism may be indicated. Pulmonary disease in association with IBD can develop at any time during the course of IBD: in rare cases, symptoms can evolve even before gastrointestinal symptoms appear. On the other hand, there are frequent reports on the occurrence of pulmonary inflammation after proctocolectomy in patients with ulcerative colitis. The pathophysiologic background is largely unknown, but there seems to be an interaction between gastrointestinal and pulmonary inflammation. The mainstay of therapy are inhaled or systemic corticosteroids. Most patterns of pulmonary involvement in IBD respond well to corticosteroid therapy. Rarely, serious and persisting complications occur, such as strictures or stenosis of the large airways.

Microbial Spectrum of Intra-Abdominal Abscesses in Perforating Crohn's Disease: Results from a Prospective German Registry.

BACKGROUND: Intra-abdominal abscesses [IAAs] are common life-threatening complications in patients with Crohn's disease [CD]. In addition to interventional drainage and surgical therapy, empirical antibiotic therapy represents a cornerstone of treatment, but contemporary data on microbial spectra and antimicrobial resistance are scarce. METHODS: We recruited 105 patients with CD and IAAs from nine German centres for a prospective registry in order to characterize the microbiological spectrum, resistance profiles, antibiotic therapy and outcome. RESULTS: In 92 of 105 patients, microbial investigations of abscess material revealed pathogenic microorganisms. A total of 174 pathogens were isolated, with a median of 2 pathogens per culture [range: 1-6]. Most frequently isolated pathogens were E. coli [45 patients], Streptococcus spp. [28 patients], Enterococci [27 patients], Candida [13 patients] and anaerobes [12 patients]. Resistance to third-generation cephalosporins, penicillins with beta-lactamase inhibitors and quinolones were observed in 51, 36 and 35 patients, respectively. Seven patients had multiple-drug-resistant bacteria. Thirty patients received inadequate empirical treatment, and this was more frequent in patients receiving steroids or immunosuppression [37%] than in patients without immunosuppression [10%: p = 0.001] and was associated with a longer hospital stay [21 days vs 13 days, p = 0.003]. CONCLUSION: Based on antimicrobial resistance profiles, we herein report a high rate of inadequate empirical first-line therapy for IAAs in CD, especially in patients receiving immunosuppression, and this is associated with prolonged hospitalization.

Vedolizumab in the treatment of chronic, antibiotic-dependent or refractory pouchitis.

BACKGROUND: The most common complication after ileal pouch anal anastomosis in up to 50% of patients is an acute pouchitis. The majority of patients respond to antibiotic treatment. However, 10%-15% develops chronic antibiotic-dependent or refractory pouchitis which is usually hard to treat. AIM: To evaluate the effectiveness of vedolizumab in patients with chronic pouchitis. METHODS: Patients with chronic antibiotic-dependent or refractory pouchitis were treated with vedolizumab (300 mg at week 0, 2, 6 and 10) in 10 IBD centres and retrospectively registered. Data were recorded until week 14 of vedolizumab treatment. In total 20 patients (12 male, median age 43 years) were included for analysis. The effectiveness was measured using the Oresland Score (OS) at week 2, 6, 10 and 14 and the pouch disease activity index (PDAI) at week 0 and 14. RESULTS: The mean OS declined from 6.8 (range 2-12) to 3.4 (range 0-11). Concordantly, the mean PDAI after 14 weeks of treatment dropped from 10 (range 5-18) to 3 (range 0-10). Only three patients reported moderate side effects. No serious side effects were recorded. In addition, symptomatic co-medication such as loperamide and tincture of opium could be terminated in 8 out of 12 patients as well as antibiotic treatment could be stopped in 17 out of 19 patients. CONCLUSION: Our data indicate that vedolizumab could be an option in the treatment of patients with chronic, antibiotic-dependent or refractory pouchitis.

Treatment of refractory ascites with an automated low-flow ascites pump in patients with cirrhosis.

BACKGROUND: Refractory ascites (RA) is a frequent complication of cirrhosis, requiring large volume paracentesis or placement of a transjugular intrahepatic portosystemic shunt (TIPSS). The automated low-flow ascites pump (alfapump, Sequana Medical AG, Zurich, Switzerland) is an innovative treatment option for patients with RA. AIM: To assess safety and efficacy of this treatment in patients with a contraindication to TIPSS. METHODS: Fifty-six patients (43 males; mean age 62 years) from centres in Germany, Switzerland, UK and Spain were included and followed for up to 24 months. Complications, device deficiencies, paracentesis frequency and patient survival were recorded. RESULTS: At the time of this analysis, 3 patients completed the 24-month observation period, monitoring of 3 was ongoing, 9 underwent liver transplantation, 17 patients were withdrawn due to serious adverse events and 23 patients died. Most frequently observed technical complication was blocking of the peritoneal catheter. Twenty-three pump-related reinterventions (17 patients) and 12 pump exchanges (11 patients) were required during follow-up. The pump system was explanted in 48% of patients (in 17 patients due to serious adverse events, in 9 at the time of liver transplantation and in 1 due to recovery from RA). Median frequency of paracentesis dropped from 2.17 to 0.17 per month. CONCLUSIONS: The alfapump can expand therapeutic options for cirrhotic patients with RA. Continuous drainage of ascites in a closed loop automated system led to significant reduction in paracentesis frequency. Technical and procedural improvements are required to reduce the rate of adverse events and reinterventions. https://clinicaltrials.gov/ct2/show/NCT01532427.

Consensus report: faecal microbiota transfer - clinical applications and procedures.

BACKGROUND: Faecal microbiota transplantation or transfer (FMT) aims at replacing or reinforcing the gut microbiota of a patient with the microbiota from a healthy donor. Not many controlled or randomised studies have been published evaluating the use of FMT for other diseases than Clostridium difficile infection, making it difficult for clinicians to decide on a suitable indication. AIM: To provide an expert consensus on current clinical indications, applications and methodological aspects of FMT. METHODS: Well-acknowledged experts from various countries in Europe have contributed to this article. After literature review, consensus has been achieved by repetitive circulation of the statements and the full manuscript among all authors with intermittent adaptation to comments (using a modified Delphi process). Levels of evidence and agreement were rated according to the GRADE system. Consensus was defined a priori as agreement by at least 75% of the authors. RESULTS: Key recommendations include the use of FMT in recurrent C. difficile infection characterised by at least two previous standard treatments without persistent cure, as well as its consideration in severe and severe-complicated C. difficile infection as an alternative to total colectomy in case of early failure of antimicrobial therapy. FMT in inflammatory bowel diseases (IBD), irritable bowel syndrome (IBS) and metabolic syndrome should only be performed in research settings. CONCLUSIONS: Faecal microbiota transplantation or transfer is a promising treatment for a variety of diseases in which the intestinal microbiota is disturbed. For indications other than C. difficile infection, more evidence is needed before more concrete recommendations can be made.