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.

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.

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 Do Gut Bacteria Influence the Liver?

Chronic liver diseases are a major cause of morbidity and mortality worldwide. Recently, gut dysbiosis was identified as an important factor in the pathogenesis of liver diseases. The relationship between gut microbiota and the liver is still not well understood; however, dysfunction of the gut mucosal barrier ("leaky gut") and increased bacterial translocation into the liver via the gut⁻liver axis probably play crucial roles in liver disease development and progression. The liver is an important immunological organ, and, after exposure to gut-derived bacteria via portal circulation, it responds with activation of the innate and adaptive immune system, leading to hepatic injury. A better understanding of the pathophysiological links among gut dysbiosis, the integrity of the gut barrier, and the hepatic immune response to gut-derived factors is essential for the development of new therapies to treat chronic liver diseases.

Acute-onset diabetes mellitus with ketoacidosis in a nivolumab-treated patient with hepatocellular carcinoma.

The therapy with immune checkpoint inhibitors (Programmed cell death-1 and programmed cell death-ligand-1 inhibitors) is a novel and promising approach in cancer treatment. The mode of action can cause serious adverse advents, mainly immune-related ones. The case of a 65 year old caucasian female is reported. She suffers from hepatocellular carcinoma since 2012. She underwent several surgeries, was treated with sorafenib and had transcatheter arterial chemoembolizations. As part of an individual healing trial, the patient was treated with nivolumab every 2 or 3 weeks since September 2017 and has no recurrence of the tumor ever since. Eight months after onset of the therapy she rapidly developed an insulin-dependent diabetes with ketoacidosis. She had no previous history of diabetes. She had no type 1 diabetes-related autoantibodies or a common HLA-genotype associated with a higher risk to develop type 1 diabetes mellitus. This adverse event during therapy with an immune checkpoint inhibitor is yet reported to be rare. Cases with a rapid-onset diabetes with ketoacidosis have also been reported under treatment with other immune checkpoint inhibitors. The pathomechanism is not clear yet and which patients are at an elevated risk. An increasing use of immune checkpoint inhibitor therapy can be expected. This may cause a concurrent increase of the side effect diabetes. Glucose monitoring and sensitizing the patients for this adverse event seems reasonable.

Emphysematous pyelonephritis - a rare complication of diabetes mellitus.

Emphysematous pyelonephritis is a rare form of acute necrotizing pyelonephritis. It is a gas-producing, necrotizing infection involving the renal parenchyma and surrounding tissues. It is associated with high mortality and morbidity. In the majority of cases, patients with long-standing diabetes and poor glycemic control are affected. We report the case of a 67 yr old female who survived severe sepsis due to emphysematous pyelonephritis. Potential therapeutic strategies in the aftermath from a diabetologist's point of view are discussed.

Pretreatment with obestatin inhibits the development of acetic acid-induced colitis in rats.

INTRODUCTION: Obestatin is a 23-amino acid peptide derived from proghrelin, a common prohormone for ghrelin and obestatin. Previous studies have shown that obestatin exhibits some protective and therapeutic effects in the pancreas and stomach. The aim of this study was to examine the effect of pretreatment with obestatin on the development of acetic acid-induced colitis. MATERIAL AND METHODS: Studies were performed on Wistar rats. Before induction of colitis, rats were treated intraperitoneally with saline or obestatin, administered twice at a dose of 4, 8 or 16 nmol/kg/dose. The first dose of saline or obestatin was administered 8 h before the induction of colitis, the second one 7 h after the first dose. Colitis was induced by enema with 1 ml of 4% acetic acid solution. The severity of colitis was assessed 1 or 24 h after administration of enema. RESULTS: Pretreatment with obestatin administered at a dose of 8 or 16 nmol/kg/dose significantly reduced the area of mucosal damage evoked by enema with acetic acid (p < 0.05). This effect was accompanied by an improvement of mucosal blood flow and DNA synthesis in the colon. Moreover, obestatin administered at a dose of 8 or 16 nmol/kg/dose significantly reduced mucosal concentration of IL-1ß and activity of myeloperoxidase (p < 0.05). CONCLUSIONS: Pretreatment with obestatin exhibited a protective effect in the colon, leading to a reduction of colonic damage in acetic acid-induced colitis. This effect was associated with an improvement of mucosal blood flow, an increase in mucosal cell proliferation, and a decrease in local inflammation.

The Role of Gut Microbiota in Obesity and Type 2 and Type 1 Diabetes Mellitus: New Insights into "Old" Diseases.

The investigation of the human microbiome is the most rapidly expanding field in biomedicine. Early studies were undertaken to better understand the role of microbiota in carbohydrate digestion and utilization. These processes include polysaccharide degradation, glycan transport, glycolysis, and short-chain fatty acid production. Recent research has demonstrated that the intricate axis between gut microbiota and the host metabolism is much more complex. Gut microbiota—depending on their composition—have disease-promoting effects but can also possess protective properties. This review focuses on disorders of metabolic syndrome, with special regard to obesity as a prequel to type 2 diabetes, type 2 diabetes itself, and type 1 diabetes. In all these conditions, differences in the composition of the gut microbiota in comparison to healthy people have been reported. Mechanisms of the interaction between microbiota and host that have been characterized thus far include an increase in energy harvest, modulation of free fatty acids—especially butyrate—of bile acids, lipopolysaccharides, gamma-aminobutyric acid (GABA), an impact on toll-like receptors, the endocannabinoid system and “metabolic endotoxinemia” as well as “metabolic infection.” This review will also address the influence of already established therapies for metabolic syndrome and diabetes on the microbiota and the present state of attempts to alter the gut microbiota as a therapeutic strategy.

Synergic Interaction of Rifaximin and Mutaflor (Escherichia coli Nissle 1917) in the Treatment of Acetic Acid-Induced Colitis in Rats.

Background. Inflammatory bowel disease results from the dysregulation of immune response to environmental and microbial agents in genetically susceptible individuals. The aim of the present study was to examine the effect of rifaximin and/or Mutaflor (Escherichia coli Nissle 1917, EcN) administration on the healing of acetic acid-induced colitis. Methods. Colitis was induced in male Wistar rats by rectal enema with 3.5% acetic acid solution. Rifaximin (50 mg/kg/dose) and/or Mutaflor (10(9) CFU/dose) were given intragastrically once a day. The severity of colitis was assessed at the 8th day after induction of inflammation. Results. Treatment with rifaximin significantly accelerated the healing of colonic damage. This effect was associated with significant reversion of the acetic acid-evoked decrease in mucosal blood flow and DNA synthesis. Moreover, administration of rifaximin significantly reduced concentration of proinflammatory TNF-α and activity of myeloperoxidase in colonic mucosa. Mutaflor given alone was without significant effect on activity of colitis. In contrast, Mutaflor given in combination with rifaximin significantly enhanced therapeutic effect of rifaximin. Moreover, Mutaflor led to settle of the colon by EcN and this effect was augmented by pretreatment with rifaximin. Conclusion. Rifaximin and Mutaflor exhibit synergic anti-inflammatory and therapeutic effect in acetic acid-induced colitis in rats.

The malabsorption of commonly occurring mono and disaccharides: levels of investigation and differential diagnoses.

BACKGROUND: Adverse food reactions (AFR) have has recently attracted increased attention from the media and are now more commonly reported by patients. Its classification, diagnostic evaluation, and treatment are complex and present a considerable challenge in clinical practice. Non-immune-mediated types of food intolerance have a cumulative prevalence of 30% to 40%, while true (immune-mediated) food allergies affect only 2% to 5% of the German population. METHOD: We selectively searched the literature for pertinent publications on carbohydrate malabsorption, with special attention to published guidelines and position papers. RESULTS: Carbohydrate intolerance can be the result of a rare, systemic metabolic defect (e.g., fructose intolerance, with a prevalence of 1 in 25,000 persons) or of gastrointestinal carbohydrate malabsorption. The malabsorption of simple carbohydrates is the most common type of non-immune-mediated food intolerance, affecting 20% to 30% of the European population. This condition is caused either by deficient digestion of lactose or by malabsorption of fructose and/or sorbitol. Half of all cases of gastrointestinal carbohydrate intolerance have nonspecific manifestations, with a differential diagnosis including irritable bowel syndrome, intolerance reactions, chronic infections, bacterial overgrowth, drug side effects, and other diseases. The diagnostic evaluation includes a nutritional history, an H2 breath test, ultrasonography, endoscopy, and stool culture. CONCLUSION: The goals of treatment for carbohydrate malabsorption are to eliminate the intake of the responsible carbohydrate substance or reduce it to a tolerable amount and to assure the physiological nutritional composition of the patient's diet. In parallel with these goals, the patient should receive extensive information about the condition, and any underlying disease should be adequately treated.

Leptin, obestatin and apelin levels in patients with obstructive sleep apnoea syndrome.

BACKGROUND: Recent studies suggest that adipose tissue hormones are involved in the pathogenesis of obstructive sleep apnoea syndrome (OSAS). The role of leptin, obestatin and apelin still needs to be established. MATERIAL/METHODS: Ten patients with newly diagnosed OSAS (AHI >10/h and ESS >10 points) were enrolled in the study as well as ten healthy volunteers as controls. All underwent measurements for Leptin, Obestatin and Apelin in four hour intervals during diagnostic polysomnography for 24 h and the patients also three months after onset of CPAP treatment. Furthermore the HOMA-index and body composition were quantified. RESULTS: Plasma apelin levels in the patients decreased under CPAP therapy, but showed no significant difference in patients and volunteers. We found a positive correlation to AHI, BMI in the therapy group at all observation points. Leptin plasma levels were higher in the patient group and decreased after onset of CPAP therapy. Leptin plasma levels were positively correlated to the BMI, min. 02 and AHI in the patient group before therapy. Plasma obestatin levels did not differ significantly in these three observation groups, but were partly correlated to AHI and weight in the newly diagnosed OSAS group. CONCLUSIONS: In agreement with previous investigations, we could demonstrate a difference in leptin plasma levels between healthy volunteers and patients with newly diagnosed OSAS. Apelin decreases under CPAP therapy, but not significantly. Obestatin remains unchanged after onset of CPAP. We further found a linkage between leptin plasma levels and BMI, AHI and weight in the untreated patient group.

Successful interventional treatment of postoperative bile duct leakage after Billroth II resection by unusual procedure using double balloon enteroscopy.

BACKGROUND: Endoscopic treatment of advanced biliary disorders and their complications following surgical procedures is often difficult especially after Billroth II gastric resection. In such cases, endoscopic access to the papilla and neopapilla is often low, and access to the choledocho- or hepaticojejunostomy is often difficult. Thus, percutaneous cholangiodrainage or re-operation is therefore indicated when endoscopic access to the papilla failed. But both of those methods are much more invasive and more likely to be followed by complications than use of a purely endoscopic approach. CASE REPORT: The present case report describes endoscopic access to the papilla with both push enteroscopy and double-balloon enteroscopy (DBE, push-and-pull enteroscopy) in a female patient after Billroth II resection with bile leakage following cholecystectomy. Successful closure of the bile duct fistula could be achieved via an unusual abdominal-biliary-jejunal cannulation way after several attempts of modern enteroscopy and in this way re-operation was avoided. CONCLUSIONS: Modern enteroscopy by experienced investigators using push-and-pull enteroscopes can provide access to the papilla even in complex postoperative anatomic rearrangements. Push-and-pull enteroscopes offer a further option for successful cannulation of the papilla and therapeutic interventions via additional stabilization with balloons and the modern enteroscopic approach by push-and-pull enteroscopy appears to provide more patient comfort, requires less analgo-sedation and examination time and in cases with intra-abdominal drainage this external access may be used as an additional aid for exploration and intervention in complex individual cases with extremely difficult treatable bile duct injuries.

Experiences with a long-term treatment of a massive gluteal acne inversa with infliximab in Crohn's disease.

BACKGROUND: In 40% of all cases of Crohn's disease fistulas emerge during the course of disease. Nevertheless, acne inversa has to be taken into account as an infrequent differential diagnosis. Infliximab as an antibody against the pro-inflammatory mediator TNF-alpha is active in cases of acute Crohn's disease, concomitant fistulas and cutaneous manifestations. CASE REPORT: We report on the case of a 54-year-old patient suffering for five years from a severe suppurative fistuling cutaneous disease concomitant to Crohn's disease. At the start of treatment the histological findings of a specimen presented chronically fibrosing lymphoplasmacellular dermatitis with both a very high number of plasma cells and a burrow-like fistula system. Due to superinfection the treatment was at first based on the administration of intravenous and oral doses of antibiotic agents, followed by a treatment course of 14 months with methotrexate and seven applications of infliximab. During the Crohn's disease, which was accompanied by persisting concomitant discomforts, an extensive surgical sanitation of the fistulous tracts was performed. Acne inversa was diagnosed in the subsequent histological analysis of the operative specimen. CONCLUSIONS: Acne inversa is a very rare cutaneous disease. Several case reports describe the successful treatment of acne inversa concomitant to Crohn's disease using anti-TNF-alpha-antibodies. The long-term course of the case presented here shows that the non-response to infliximab might be caused by both the long duration and the distinct grade of seriousness of the acne inversa.