[Fecal Microbiota Transfer (FMT) in Germany - Status and Perspective]. / Fäkaler Mikrobiota-Transfer (FMT) in Deutschland ­ Status und Perspektive.

INTRODUCTION: Fecal microbiota transfer (FMT) is a treatment to modulate the gastrointestinal microbiota. Its use in recurrent Clostridioides difficile infection (rCDI) is established throughout Europe and recommended in national and international guidelines. In Germany, the FMT is codeable in the hospital reimbursement system. A comprehensive survey on the frequency of use based on this coding is missing so far. MATERIAL AND METHODOLOGY: Reports of the Institute for Hospital Remuneration (InEK), the Federal Statistical Office (DESTATIS), and hospital quality reports 2015-2021 were examined for FMT coding and evaluated in a structured expert consultation. RESULTS: Between 2015 and 2021, 1,645 FMT procedures were coded by 175 hospitals. From 2016 to 2018, this was a median of 293 (274-313) FMT annually, followed by a steady decline in subsequent years to 119 FMT in 2021. Patients with FMT were 57.7% female, median age 74 years, and FMT was applied colonoscopically in 72.2%. CDI was the primary diagnosis in 86.8% of cases, followed by ulcerative colitis in 7.6%. DISCUSSION: In Germany, FMT is used less frequently than in the European comparison. One application hurdle is the regulatory classification of FMT as a non-approved drug, which leads to significantly higher costs in manufacturing and administration and makes reimbursement difficult. The European Commission recently proposed a regulation to classify FMT as a transplant. This could prospectively change the regulatory situation of FMT in Germany and thus contribute to a nationwide offer of a therapeutic procedure recommended in guidelines.

[Gut microbiota and chronic inflammatory bowel disease]. / Darmmikrobiom und chronisch- entzündliche Darmerkrankung.

Intestinal dysbiosis remains the focus of research into the pathogenesis of chronic inflammatory bowel disease (IBD). The potential role of gut microbiota in the development of IBD includes interaction with the host genome and immune system, as well as various environmental factors, diet, drugs, industrialization, etc. Other organs are negatively affected by intestinal dysbiosis via gut-brain axis. The composition of microbiota and its metabolic activity has a significant impact on the effectiveness of anti-inflammatory therapies. Microbiome-based treatment for IBD includes the use of diet, antibiotics, pre-, pro- and synbiotics, and faecal transplantation (FMT). The development of effective therapies for IBD patients will only be possible once the interactions between the microbiota and its metabolites and the host immune system are better understood.

Microbiota medicine: towards clinical revolution.

The human gastrointestinal tract is inhabited by the largest microbial community within the human body consisting of trillions of microbes called gut microbiota. The normal flora is the site of many physiological functions such as enhancing the host immunity, participating in the nutrient absorption and protecting the body against pathogenic microorganisms. Numerous investigations showed a bidirectional interplay between gut microbiota and many organs within the human body such as the intestines, the lungs, the brain, and the skin. Large body of evidence demonstrated, more than a decade ago, that the gut microbial alteration is a key factor in the pathogenesis of many local and systemic disorders. In this regard, a deep understanding of the mechanisms involved in the gut microbial symbiosis/dysbiosis is crucial for the clinical and health field. We review the most recent studies on the involvement of gut microbiota in the pathogenesis of many diseases. We also elaborate the different strategies used to manipulate the gut microbiota in the prevention and treatment of disorders. The future of medicine is strongly related to the quality of our microbiota. Targeting microbiota dysbiosis will be a huge challenge.

[How does COVID-19 affect intestinal microbiota?] / Wie wirkt sich COVID-19 auf die intestinale Mikrobiota aus?

BACKGROUND: There is a bidirectional interaction between the intestines and lungs, the so-called lung-intestinal axis. METHOD: The review article reports on studies that deal with a possible influence of the intestinal microbiota on the immune response to a SARS-CoV-2 infection. RESULTS AND CONCLUSIONS: Studies have shown that COVID-19 is accompanied by dysbiosis that persists even after successful virus conversion (negative PCR). One study found that the severity of COVID-19 is associated with the intestinal microbiota. A dysbiosis could thus favor the so-called cytokine storm. There is indication that pre- and probiotics could boost the immune response in both the guts and lungs.

Food Intolerance of Unknown Origin: Caused by Mucosal Inflammation? A Pilot Study.

INTRODUCTION: The prevalence of patients with food intolerance (FI) has increased significantly. Immunoglobulin (Ig)E-mediated food allergies (FAs) are detected by determining IgE antibodies and skin prick test. Carbohydrate malabsorptions are clarified with breath tests. However, these diagnostic measures cannot capture all intolerances and have limitations in case of gut-mediated FI. The aims of this pilot study were to evaluate different methods to determine intestinal mucosal IgE in patients with FA and to characterize the intestinal mucosa in patients with FI of unknown origin (FH). METHODS: Patients with FA and FH were compared with healthy controls. To determine the IgE antibodies and the cytokines tumor necrosis factor (TNF)-α and interferon (IFN)-γ of the intestinal mucosal, a lavage was performed as part of an ileocolonoscopy and samples were taken using the cytobrush and biopsy forceps. In a subgroup, mucosal samples were also taken from the duodenum. RESULTS: Data in homogenates of intestinal mucosal samples yielded the highest sensitivity for IgE antibody titers compared with lavage and cytobrush. Patients with FA presented increased intestinal TNF-α and low IFN-γ values. This was in contrast to FH patients, who showed low intestinal IgE antibodies and TNF-α levels, but increased IFN-γ values. DISCUSSION: The determination of IgE antibodies to diagnose intestinal IgE-mediated FA is most reliable in intestinal mucosal samples. Increased TNF-α and low IFN-γ levels in patients with FA characterize an allergic reaction. Decreased TNF-α and increased IFN-γ levels in patients with FH indicate an inflammation-related intolerance reaction (see Visual Abstract, Supplementary Digital Content 1, http://links.lww.com/CTG/A520).

What does a gastroenterologist need to know in the time of SARS-CoV-2 pandemia?

Coronavirus disease 2019 (COVID 19) is an emerging infectious disease caused by a novel coronavirus SARS-CoV2 that was first identified in Wuhan, China 2019 and that led to a worldwide pandemia. In addition to typical respiratory signs (dry cough, shortness of breathing), some patients may develop gastrointestinal and hepatological complications including diarrhea or acute hepatitis, respectively. Due to the close contact to the patient's secretion, the gastroenterologists are at increased risk of getting the infection. Therefore, a proper individual risk stratification before every endoscopic procedure is highly recommended. Endoscopy personnel should reduce exposure hazards by keeping a distance from the patient and using gloves, face masks, face shields and gowns. Taking into the consideration the fact that the virus proliferates in the gastrointestinal (GI) tract, special attention should be given to handling with stool specimens. In patients obtaining FMT for recurrent C. difficile infection, recommended screening measures include donor's medical history and testing for SARS-CoV-2 presence in pharyngeal and stool specimens.

Course of a SARS-COV-2 pneumonia in a middle-aged male patient.

The SARS-CoV-2 infection has recently been declared a pandemic by the WHO. Most fatalities occur in elderly people with comorbidities. However, SARS-CoV-2 pneumonias do also occur in younger patients with no comorbidities or risk factors at all. We report here on one of the "early" cases that occurred in Germany. A 57-year-old man was infected and developed pneumonia after a skiing vacation in Northern Italy. Other members of the travel group also fell ill, but only showed flu-like symptoms. Only a few if any infections originated from the affected person; at this point in time the infection situation in the region could still be grasped. Under supportive measures, the disease developed positively despite impressive radiological findings. The positive course is likely also due to the age of the person affected and the lack of any risk factors. The case does also exemplify that a good health condition does not necessarily protect from acquiring a moderately severe SARS-CoV-2 infection.

Hydroxychloroquine is no miracle cure for covid-19 infection -imaging and clinical course in an elderly female.

The risk for an unfavourable course of SARS-CoV-2 pneumonia rises with age and comorbidities. We report the case of an elderly female where the sum of such factors - together with massive findings in the computed tomography of the lung - led us to a therapy with hydroxychloroquine as a compassionate use. The unfavourable outcome demonstrates that - despite the enthusiasm of some authors - hydroxychloroquine is no miracle drug. The worldwide SOLIDARITY trial will help clinicians to assess the potential of the repurposed antimalarial drugs better.

[Stress and inflammatory bowel disease]. / Stress und chronisch-entzündliche Darmerkrankungen.

Different mechanisms have a negative impact on the course of inflammatory bowel disease. Important mechanisms include amongst others an increased release of pro-inflammatory cytokines, intestinal dysbiosis, increased permeability of the intestinal barrier, increased release of corticotropin-releasing factor (CRF) in the brain, activation of mast cells in the intestinal mucosa and inadequate central pain processing with the consequences of anxiety and depression. All of these factors can increase the inflammatory response in the intestine and lead to acute flare-ups. For this reason, appropriate stress management is extremely important for the success of therapy.

From Donor to Patient: Collection, Preparation and Cryopreservation of Fecal Samples for Fecal Microbiota Transplantation.

Fecal Microbiota Transplantation (FMT) is suggested as an efficacious therapeutic strategy for restoring intestinal microbial balance, and thus for treating disease associated with alteration of gut microbiota. FMT consists of the administration of fresh or frozen fecal microorganisms from a healthy donor into the intestinal tract of diseased patients. At this time, in according to healthcare authorities, FMT is mainly used to treat recurrent Clostridium difficile. Despite the existence of a few existing stool banks worldwide and many studies of the FMT, there is no standard method for producing material for FMT, and there are a multitude of factors that can vary between the institutions. The main constraints for the therapeutic uses of FMT are safety concerns and acceptability. Technical and logistical issues arise when establishing such a non-standardized treatment into clinical practice with safety and proper governance. In this context, our manuscript describes a process of donor safety screening for FMT compiling clinical and biological examinations, questionnaires and interviews of donors. The potential risk of transmission of SARS-CoV-2 virus by the use of fecal microbiota for transplantation must be taken urgently into consideration. We discuss a standardized procedure of collection, preparation and cryopreservation of fecal samples through to the administration of material to patients, and explore the risks and limits of this method of FMT. The future success of medicine employing microbiota transplantation will be tightly related to its modulation and manipulation to combat dysbiosis. To achieve this goal, standard and strict methods need to be established before performing any type of FMT.

An analysis of early morning acth levels in the first case of pembrolizumab-induced adrenalitis as a delayed immune-related event (dire) - case study.

OBJECTIVE: The aim: The levels of adrenocorticotrophic hormone (ACTH) are elevated in primary adrenal failure (Addison's disease) with a peak in the early morning hours. This also occurs under hydrocortisone replacement therapy due to the unphysiological substitution regime. The aim was to study ACTH levels under two different replacement regimens. This is exemplified in a patient with adrenalitis after immunotherapy for malignant melanoma (MM), since (elevated) levels of ACTH and its cleavage product alpha-melanocyte stimulating hormone (α-MSH) raise concerns since receptors for both hormones can be expressed in melanoma cells. PATIENTS AND METHODS: Material and methods: A female with MM had immunotherapy with pembrolizumab and developed adrenalitis with Addison crisis about one year after discontinuation of this therapy (delayed immune-related event = DIRE). ACTH levels were measured hourly (4-8 a.m.) during a "conventional" hydrocortisone replacement therapy and during a therapy with dual-release hydrocortisone. RESULTS: Results: Salient differences between the morning ACTH profiles under the "conventional" hydrocortisone replacement regimen with 10-5-5 mg/die compared to the single-dose regimen with 20 mg dual-release hydrocortisone were not discernible. CONCLUSION: Conclusion: DIRE could be an underestimated problem in immunotherapy and could put the patients at hazard. Especially in case of an endocrinological DIRE concerning the adrenocorticotrophic axis, life-threatening situations can arise for the patients. As for the special situation with M. Addison and MM, where hormonal feedback mechanisms may cause further problems beyond the normal hormonal replacement therapy, we observed no salient differences in the early morning ACTH profiles under different hydrocortisone replacement regimens.

[Intestinal microbiota - a vital "organ" with manifold functions]. / Intestinale Mikrobiota ­ ein lebenswichtiges "Organ" mit vielfältigen Funktionen.

BACKGROUND: The intestinal microbiota must be seen as an elementary component of our health. METHOD: Review article RESULTS AND CONCLUSIONS: An abnormal gut microbiota (dysbiosis) plays an essential role in the pathogenesis of functional and inflammatory bowel diseases. It is often also associated with diseases outside the intestine. The exact causality remains unclear ("chicken and egg problem"). With the help of prebiotics, probiotics or fecal microbiota therapy, relevant therapeutic effects can be achieved in chronic, dysbiosis-associated diseases. The choice of the preparation depends on the clinical symptoms, the duration of the treatment depends on the particular clinical picture.

Humoral Hypercalcemia in a Patient with Cholangiocellular Carcinoma - Effective Therapy with Denosumab.

BACKGROUND Hypercalcemia in cholangiocellular carcinoma is a highly uncommon event, mainly reported in Asian patients. In the absence of bone metastases, humoral hypercalcemia of malignancy (HHM) can be assumed. This is mostly the consequence of an elevated parathormone-related peptide (PTHrP) level. The standard therapeutic options in HHM are sometimes limited by the underlying disease or concomitant diseases. CASE REPORT We report the case of a 65-year-old Caucasian male. A syncope due to a hypercalcemia of 4.16 mmol/L (normal range, 2.19-2.54 mmol/L) was the initial symptom that eventually led to the diagnosis of cholangiocellular carcinoma. He had no metastatic bone disease; HHM was suspected. PTHrP was moderately elevated. Since there were contraindications for the standard therapeutic options, a therapy with 120 mg denosumab was initiated and proved effective, safe, and restored the patient's quality of life for 11 months. CONCLUSIONS The moderate elevation of parathyroid hormone-related peptide (PTHrP) in this case is addressed in context with the recent insights of a substantial underestimation of this parameter by many commercial assays which can explain our observation. Denosumab, a human monoclonal antibody which acts as a RANKL-inhibitor (receptor activator of nuclear factor kappaB ligand) was recently suggested as a therapeutic alternative. In this case, the therapy of the hypercalcemia with denosumab due to contraindications for other therapies led to an effective and long-standing remission of hypercalcemia. Its effectivity should be studied in larger case samples.

Severe metabolic syndrome and primary amenorrhea as main pathophysiological features in a subtype of turner syndrome (46, X, del (X) Q 21).

Turner syndrome can be manifest with a considerable genetic and phenotypic variability. This merely accounts for about 50% of patients who do not have the "classic" 45 X genotype. We report the case of a 42-year-old female patient with a 46, X, del (X) q 21 genotype (deletion on the second X chromosome on the long arm). As the patient displayed a non-typical phenotype and was infertile, a diagnosis was established at the age of 24 with no follow-up treatment. As part of our therapy of the individual due to newly manifested diabetes mellitus, our diagnostic workup revealed a severe metabolic syndrome encompassing fatty liver disease, obstructive sleep apnea syndrome and hyperuricemia. Our observations should sensitize physicians treating female patients for one or more aspects of the metabolic syndrome and its presence in Turner syndrome. These patients have an unfavorable cardiovascular profile, in part due to the metabolic syndrome, but also due to factors intrinsic to Turner syndrome.

Adhesion Ileus after Fecal Microbiota Transplantation in Long-Standing Radiation Colitis.

Fecal microbiota transplantation (FMT) is a novel strategy for the therapy of dysbiosis-associated disorders via modulation of the gut microbiota. Intestinal dysbiosis is associated not only with digestive disorders, but also with a variety of extra-digestive disorders. A worldwide increasing number of FMT can be expected in the future as well as an increase in adverse events. We describe the case of a patient with chronic radiation colitis that developed adhesion ileus 2 days after FMT. Since these problems never occured before and the short time interval favours a causality, we speculate about FMT-induced alterations in gut motility causing a "trapping" of the small intestine in an adhesion and other mechanisms beyond "pure" coincidence.

[Gut-liver axis: How intestinal bacteria affect the liver]. / Leber-Darm-Achse: Wie Darmbakterien die Leber beeinflussen.

BACKGROUND: Liver and intestine are in close contact with each other. The risk of damage to the liver increases, when the intestinal barrier is damaged ("leaky gut") . METHOD: The review article describes how intestinal bacteria influence the pathogenesis of chronic liver diseases and what treatment options are available. RESULTS AND CONCLUSIONS: Intestinal dysbiosis plays an important role in the development of chronic liver diseases such as alcoholic liver disease, nonalcoholic fatty liver disease, primary biliary cholangitis, primary sclerosing cholangitis, and cirrhosis. Intestinal microbial modulating therapy with probiotics, prebiotics or synbiotics shows positive effects. The more precise meaning of this therapeutic approach needs to be clarified in further studies.