COVID-19 - more than respiratory disease: a gastroenterologist's perspective.

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV2) outbreak is the most dramatic event since World War II. Originating as a cluster of unexplained cases of pneumonia, it turned out that this viral disease termed COVID-19 is not only a respiratory infection, but a systemic disease associated with a number of extrapulmonary complications. One of the medical disciplines that is strongly affected by this viral infection is gastroenterology. COVID-19 causes in some patients typical symptoms of enteritis such as diarrhea or abdominal pain. There is also evidence that this infection may lead to liver and pancreatic injury. Since the SARS-CoV2 virus was detected in stool, a fecal-oral route of transmission is possible. Moreover, viral receptor angiotensin converting enzyme 2 (ACE2) is highly expressed in the gastrointestinal tract and enables the invasion of the gastrointestinal epithelium as demonstrated in vitro and in vivo. COVID-19 pandemic has an impact on the daily practice and the workflows in endoscopy leading to a dramatic decrease of screening and surveillance procedures. COVID-19 impacts the therapy of patients with inflammatory bowel disease (IBD), particularly those using high doses of corticosteroids, immunosuppressive agents and biologics. Patients with preexisting liver disease, especially metabolic associated liver fatty disease (MALFD) with fibrosis or liver cirrhosis, are at high risk for severe COVID-19. As long as no active vaccine against SARS-CoV2 is available, gastroenterologists have to be aware of these problems that affect their daily routine practice.

Hypoglycemic side effects of sulfonylureas and repaglinide in ageing patients - knowledge and self-management.

Insulinotropic oral antidiabetics (OAD) such as sulfonylureas and (SU) glinides are among the frequently prescribed OAD. Side effects are the potential to induce hypoglycemias and weight gain. The aim was to assess the self-managing skills in case of a hypoglycemic event in an elderly type 2 diabetic patient population. In a 2-year period, 160 hospitalized patients (mean age 77.4 years) under insulinotrophic OAD were interviewed using a standardized questionnaire. Additionally, possible dementia was evaluated by using the Mini-Mental State Examination (MMSE) and the Clock-Drawing Test (CDT). The mean HbA1c was 7.6%. MMSE and CDT did intraindividually correlate well and 23.8% of the patients had moderate dementia (10 - 20 points MMSE), 13.1% had severe dementia (0 - 10 points MMSE) at the time of the survey. When under treatment with a sulfonylurea, only 16.0% of patients were aware of the potential hypoglycemia-inducing side effect. Moreover, only 11.8% of patients treated with a combination of a sulfonylurea and insulin knew this side effect of the OAD. The awareness of the side effects of repaglinide was 21.6% (without insulin therapy) versus 21.4% in the insulin-comedicated group. Only 42.6% of patients treated with sulfonylureas or repaglinide knew how to act in the case of hypoglycemia. Even under comedication with insulin, only in 41.2% of the respondents in the comedicated group knew how to take action if they were to experience hypoglycemia. Our findings raise concerns and demonstrate, that the self-managing skills in an elderly patient group are not good, which may become an increasing problem in an ageing population. The prescription or the re-prescription of insulinotropic OAD needs to be adapted to the current cognitive situation and re-evaluated regularly.

Gastric ulcer healing and stress-lesion preventive properties of pioglitazone are attenuated in diabetic rats.

Diabetes mellitus increases susceptibility to acute gastric injury and impairs ulcer healing. Pioglitazone as an agonist of peroxisome proliferator-activated receptor gamma (PPARgamma) is used as anti-diabetic drug and has additionally gastroprotective activities. However, the effect of pioglitazone on the protection and healing of gastric mucosa under diabetic conditions is poorly understood. The aim of the present study was: 1) to compare the effects of treatment with PPARg ligand (pioglitazone) on healing of acetic acid-induced gastric ulcers and prevention of acute water immersion and restraint stress (WRS)-induced gastric lesions in normal rats and those with streptozotocin (STZ)-induced diabetes mellitus; 2) to assess the effects of pioglitazone on the mRNA expression of cyclooxygenase-2 (COX-2), c-NOS, interleukin-1beta and hypoxia inducible factor-1 alpha (HIF-1alpha) in the gastric mucosa of rats with or without STZ-induced diabetes mellitus; 3) to investigate the involvement of endogenous NO and proinflammatory cytokines (IL-1beta, TNF-alpha) in healing of chronic gastric ulcers and in prevention of acute stress lesions by pioglitazone in rats with or without STZ-induced diabetes mellitus. Diabetes was induced in rats by single injection of STZ (70 mg/kg i.p.) four weeks prior to production of gastric ulcers by acetic acid method or induction of stress lesions by 3.5 hours of WRS. Non-diabetic rats were used as controls. Two major animal groups (A and B) were tested; A) diabetic and non-diabetic rats with chronic gastric ulcers treated with 1) pioglitazone (40 mg/kg-d i.g.), 2) pioglitazone in combination of blocker of NO synthase (L-NNA 20 mg/kg-d i.p.), and 3) saline (vehicle-control); and B) diabetic and non-diabetic rats exposed to 3.5 hours of WRS and pretreated with 1) pioglitazone (40 mg/kg i.g.), 2) pioglitazone in combination of blocker of NO synthase (L-NNA 20 mg/kg i.p.), and 3) saline (vehicle-control). The gastric mucosal blood flow was assessed by H(2)-gas clearance method. The area of chronic acetic acid ulcers and number of acute WRS-induced gastric lesions were assessed by planimetry or by counting of number of lesions, respectively. In rats with chronic ulcers, the mRNA expression of HIF-1alpha, IL-1beta and COX-2 was assessed by RT-PCR and protein expression of platelet endothelial cell adhesion molecule-1 (PECAM-1), COX-2 and cNOS was examined by Western blot. In rats with stress lesions, the protein expression of COX-2, cNOS, catalase, PPAR and heat shock protein 70 (HSP70) was examined by Western blot. In diabetic rats, a marked delay in ulcer healing and increased susceptibility to WRS lesions were observed and these effects were accompanied by a significant decrease in GBF. Pioglitazone significantly increased healing of chronic gastric ulcers and exerted a strong protective effect against WRS-induced lesions, but these effects were attenuated by NO-inhibition with L-NNA. Interestingly, the ulcer healing and gastroprotective effects of pioglitazone were weak under diabetic conditions, and this effect on ulcer healing was accompanied by impaired angiogenesis due to decreased PECAM-1 expression, attenuated expression of COX-2 and the increased expression of proinflammatory cytokines compared to those in diabetic rats treated with vehicle. We conclude that: 1) experimental diabetes in rats impairs healing of chronic ulcers and enhances acute stress lesions due to an increase in the expression and release of proinflammatory cytokines such as TNF-alpha and IL-1beta; 2) the ulcer healing effect of pioglitazone, which is, at least in part, mediated by endogenous NO, is significantly attenuated by L-NNA in diabetic rats despite increased COX-2 expression at the ulcer edge; 3) the formation of acute gastric lesions induced by WRS is also attenuated by pretreatment with pioglitazone due to increased GBF probably mediated by NO, as the administration of L-NNA reversed, in part, the preventive action induced by this PPARgamma ligand, and 4) pioglitazone is effective both in healing of chronic ulcers and protection against WRS lesions though its action under diabetic conditions seems to be attenuated, possibly due to reduction in NOS-NO system, angiogenesis and increased expression and release of proinflammatory cytokines.

[38 year-old patient with suspected congenital hormonal dysfunction]. / 38-jähriger Patient mit Verdacht auf eine angeborene hormonelle Störung.

We present the case of a patient with suspected congenital hypopituitarism first diagnosed at the age of 38 years. Despite partial insufficiency of all pituitary-regulated hormonal axes, the patient never suffered from severe health problems. However, the patient was disfigured, and his intellectual and physical capacities were clearly impaired. The initiation of a hormone replacement therapy with hydrocortisone and thyroid hormones is essential in such a patient, but the substitution of sex hormones can create ethical problems.

[33-year-old male patient with recurrent syncopes and orthostatic hypotension]. / 33-jähriger Patient mit rezidivierenden Synkopen und orthostatischer Hypotension.

We describe the case of a 33 year old male patient with severe orthostatic hypotension, which was at times even in upright (sitting) position not tolerated, thus leading to complete immobilisation. The diagnostic measurements pointed to the group of primary autonomic degenerative disorders, the so-called "synucleinopathies". The clinical presentation und laboratory values confirmed the diagnosis of "pure autonomic failure". Finally, we describe the differential diagnosis of autonomic dysfunction.

[Unexplained weight gain in a 41-year-old woman]. / Unklare Gewichtszunahme bei einer 41-jährigen Frau.

A 41-year-old female was admitted to our clinic due to weight gain and facial edema. The patient also reported hair loss, amenorrhea and the formation of striae. The laboratory diagnostics ensured the diagnosis of Cushing's syndrome. Unfortunately, the patient was among the 5-10% of patients in whom neither laboratory testing nor imaging revealed the source of the cortisol excess. Due to the dramatic decrease of her general condition, and the appearance of hypertension and diabetes mellitus we chose to refer the patient to bilateral minimally invasive adrenalectomy. The advantage of this therapeutic approach is, that it is a definitive treatment that provides immediate control of hypercortisolism. As disadvantage, the resultant permanent hypoadrenalism requires a lifelong glucocorticoid and mineralocorticoid replacement therapy. Furthermore, given that the problem was caused by occult pituitary microadenoma, Nelson's syndrome has to be considered. As only one adrenal could be excised due to technical reasons, the underlying pathology is thus not solved. In spite of this, the patient's general condition improved dramatically without need for replacement therapy. As the mortality of patients with persistent moderate hypercortisolism is increased 3,8- to 5 fold, mainly due to cardiovascular reasons, thorough surveillance for signs of recurrence is mandatory to be ready for quick intervention.

[Metabolical characteristics in patients with multiple symmetrical lipomatosis]. / Metabolische Besonderheiten bei Patienten mit Multipler Symmetrischer Lipomatose.

BACKGROUND AND OBJECTIVE: Multiple symmetrical lipomatosis (MSL) is a rare cause of obesity. As the cause is unknown the therapeutic options are unsatisfactory. This study was undertaken to elucidate whether there are singular metabolic and endocrine characteristics in such patients. PATIENTS AND METHODS: Data were collected from 15 patients with MSL who had been referred to our clinic during the last ten years. Various metabolic and endocrine parameters as well as bone density were measured. The possible presence of an obstructive sleep apnoea syndrome was also looked for. RESULTS: Five of the 15 patients fulfilled the International Diabetes Federation's criteria of a metabolic syndrome. The parathormone level was elevated in seven patients, but there were no other endocrine abnormalities. DISCUSSION: No endocrine abnormalities other than an elevation of parathormone (of no clinical significance) are associated with MSL. But the prevalence of the (cardio)metabolic syndrome is relatively high. Thus an elevated risk of cardiovascular disease in these patients is likely.

[A 67-year-old patient with recurrent hypoglycemia]. / 67-jährige Patientin mit rezidivierenden Hypoglykämien.

A 67 year old female patient was admitted to our clinic with recurrent hypoglycemia in December 2006. Laboratory findings revealed an elevated insulin, and C-peptide. Imaging techniques revealed a tumor of the pancreas involving the spleen with metastases of the liver, expressing somatostatin receptors. Ultrasound-guided biopsy was performed and confirmed the suspected insulinoma. Since the hypoglycemias could not sufficiently be controlled by subcutaneous administration of octreotide and by oral glucose intake, surgical debulking was performed in a palliative intention. After resection the patient was free of hypoglycemia. In case of diagnosed insulinoma, underlying MEN (multiple endocrine neoplasia) should be considered. Excision of the tumor is recommended in patients with benign solitary insulinomas. If complete excision is impossible, there are several therapeutic options that aim at preventing hypoglycemia. Thus, in contrast to other extended tumors, surgery is reasonable in malignant insulinoma even in case of metastatic disease.

Reduced frequency of peripheral dendritic cells in type 2 diabetes.

OBJECTIVE: It is a common clinical experience that type 2 diabetic patients are susceptible to opportunistic infections. The underlying reasons for this immune deficiency are not yet understood. Dendritic cells (DC) play a key role in initiating innate and adapted immune responses. DESIGN: In order to investigate changes in the DC compartment in the peripheral blood in type 2 diabetes, we analyzed blood from patients under poor and good metabolic control and compared them to healthy controls. PATIENTS: 5 mls of blood were collected from 15 healthy controls, 15 diabetic patients with an HbA1c <7.0 and 15 patients with an HbA1c >9.5%. Age range was 44-80 years. Patients were age-matched with the control group. MEASUREMENT: Blood DC were enumerated by flow cytometry after staining with antibodies against the blood dendritic cells antigens 1-3 (BDCA 1-3). This allows quantification of the DC subtypes: myeloid dendritic cells type 1 (mDC1, mDC2) and plasmacytoid dendritic cells (pDC). RESULTS: The relative and absolute frequency for both mDC1 and pDC was clearly diminished in patients with poor metabolic control as compared to healthy controls. In patients with good metabolic control the reduction of DC was less pronounced but still significant, particularly for mDC1. CONCLUSION: Hyperglycemic metabolism does affect the pool of peripheral DCs and leads to a reduction of both, mDC1 and pDC. Even patients considered to be under good metabolic control appear to have a reduced peripheral pool of DC.

Adiponectin, resistin and subclinical inflammation--the metabolic burden in Launois Bensaude Syndrome, a rare form of obesity.

The aim of the study was to investigate, whether the degree of metabolic risk factors for atherosclerotic complications in a very rare kind of obesity, the Multiple Symmetrical Lipomatosis, also known as the Launois-Bensaude Syndrome (LBS), are comparable or different from "simple" truncal obesity. 10 patients with LBS (Body mass index 34.4 +/- 1.8 kg/m(2), age: 62 +/- 3 yrs) were compared with 19 BMI - matched patients with "simple" truncal obesity and obstructive sleep apnoea syndrome (OSAS) and 20 BMI- matched patients with "simple" truncal obesity without OSAS. Markers of subclinical inflammation and thrombocyte activation (sCD62p = soluble p-selectin, highly sensitive C-Reactive protein = CRP, Interleukin-6 = IL-6, ICAM-1 = Intracellular Adhesion Molecule-1, Vascular Cell Adhesion Molecule = VCAM -1, leptin), as well as adiponectin and resistin were studied. The prevalence of atherogenic risk factors as hypertension (80%), type 2 diabetes (30%), OSAS (50%), smoking (30%) and alcohol abuse (80%) was high in the (obese) LBS group. The markers of subclinical inflammation and thrombocyte activation showed an indifferent picture with lower levels of circulating IL-6 and sCD62p, comparable CRP and higher ICAM-1 and VCAM-1 than in controls. Leptin and adiponectin were higher than in controls. However, the accumulation of "classic" cardiovascular risk factors in the LBS group was well reflected by the presence of symptomatic cardiovascular disease in 3 of the 10 LBS patients, putting LBS patients - if obese - at an atherosclerotic risk at least comparable to obese persons.

Increase in serum resistin during weight loss in overweight subjects is related to lipid metabolism.

OBJECTIVE: Human resistin has been stated to influence preadipocyte cell numbers and to stimulate adipocyte triglyceride lipolysis in vivo and in vitro. However, its role in human obesity remains unclear. DESIGN: Cross-sectional study for comparisons of lean and obese subjects, and subsequent longitudinal 4-month weight loss intervention study in obese subjects. SUBJECTS: Healthy subjects, lean (n=20, BMI<25) and overweight (n=43, BMI>or=25). MEASUREMENTS: Serum resistin, body weight, body fat, waist-to-hip ratio, as well as markers of insulin resistance and lipid metabolism at baseline and after 4 months of intervention. RESULTS: Serum resistin was positively correlated to HOMA-IR (partial r=0.288; P=0.055), serum fructosamines (partial r=0.280; P=0.062), serum NEFA (partial r=0.276; P=0.066) and negatively to age (partial r=-0.349; P=0.019) and serum apolipoprotein A-1 (partial r=-0.363; P=0.014). During the intervention, serum resistin increased significantly (P<0.001). The increase was inversely related to changes in waist-to-hip ratio (P=0.025) and positively to serum apolipoprotein B (P=0.011). In males only, the increase in resistin during weight loss was predicted by total serum cholesterol at baseline (r=0.703, P=0.007). No relation was observed between changes in resistin and changes in HOMA-IR. CONCLUSION: The present study indicates an association between serum resistin and markers of abdominal fat distribution as well as the regulation of lipid metabolism. However, human resistin is unlikely to play an independent role in the regulation of glucose metabolism.

[Unspecified gain of weight?]. / Unklare Gewichtszunahme?

In the case of a 49 year old patient, a weight gain of 37 kg occurred during the first weeks of the year 2003, accompanied by a painless increase in the diameter of the upper arms and thighs. This process did spontaneously cease in the summer of 2003, but weight reduction could not be achieved. The diagnosis of multiple symmetrical lipomatosis, also known as Launois-Bensaude syndrome, the first authors to describe the condition in detail in 1898, could be established due to the unique appearance of the patient. Typical features of the disease are the accumulation of multiple lipomata in the shoulder girdle, upper arms, thorax and thighs, whereas the face, the forearms and the shanks are typically excluded. The etiology of the disease is obscure, dietetic intervention is futile, surgical approaches are liposuction or excision of the lipomata. Cessation of alcohol consumption may also be helpful, since the condition is typically associated with present or past alcohol abuse. The disease is usually reported to be rare, but there is reason enough to assume, that it is frequently misdiagnosed as simple truncal obesity.

[Recurrent bouts of fever accompanied by abdominal pain and emesis]. / Rezidivierende Fieberschübe mit abdominellen Schmerzen und Emesis.

A 34 year-old Turkish patient was admitted to hospital several times with the same symptoms of abdominal pain, fever up to 39.2 degrees C and vomiting. The diagnosis always was an acute attack of chronic pancreatitis. The inflammation scores in the blood were high and he had a moderate increase in pancreatic enzymes. He always got well in a few days on a strict diet and regime of analgesics. Taking these symptoms and his ethnic affiliation into consideration, differential diagnosis should include familial Mediterranean fever (FMF). Therapy with colchicine should be initiated even if genetic testing does not reveal the mutation characteristics for FMF. Immediate and consistent therapy helps to avoid amyloid nephropathy as the most dangerous complication of this disease.

Adiponectin in patients with obstructive sleep apnea syndrome: course and physiological relevance.

BACKGROUND: Adiponectin is an adipocyte-derived hormone with anti-inflammatory and insulin-sensitizing properties. Insulin resistance is a typical feature of the obstructive sleep apnea syndrome (OSAS). OBJECTIVES: Since nasal continuous positive airway pressure (nCPAP) treatment improves insulin sensitivity in patients with OSAS, we investigated serum adiponectin levels before and during nCPAP treatment to clarify possible interactions between the adiponectin levels and insulin sensitivity in patients with OSAS. METHODS: Thirty nondiabetic, obese patients with OSAS (mean age 56.4 +/- 11.1 years; apnoea-hypopnoea index (AHI) 46.03 +/- 19.57) underwent CPAP treatment. Adiponectin levels and the levels of proinflammatory cytokines and proteins reflecting platelet activation [regulated on activation normally T cell expressed and secreted (RANTES) and soluble P-selectin (sCD62p)], as well as the insulin sensitivity index were measured before, and after 2 days and 3 months of CPAP treatment. RESULTS: Insulin sensitivity increased significantly under nCPAP treatment, whereas adiponectin levels decreased after 2 days of nCPAP treatment, but returned to baseline levels after 3 months of nCPAP treatment. The increase in insulin sensitivity was more pronounced in patients with the highest adiponectin levels at baseline (p = 0.021) after adjustment for body fat (p = 0.003). During treatment, changes in adiponectin levels were highly predictable by the insulin sensitivity index. CONCLUSIONS: We found a significant relation between adiponectin and the insulin sensitivity index in overweight patients with OSAS. The lack of a long-lasting change in adiponectin may be explained by the overwhelming influence of the body mass index on adiponectin secretion, which was unchanged during nCPAP treatment.

Leptin and ghrelin levels in patients with obstructive sleep apnoea: effect of CPAP treatment.

Serum leptin and ghrelin levels were investigated in patients with obstructive sleep apnoea (OSA) syndrome before and during continuous positive airways pressure (CPAP) treatment and compared with body mass index (BMI)-matched controls without OSA. Male patients (n=30) with OSA (apnoea/hypopnoea index=58+/-16, BMI=32.6+/-5.3 kg x m(-2)) underwent CPAP treatment. Fasting leptin and ghrelin were measured at baseline and 2 days, and in the case of leptin 2 months after initiation of treatment. Baseline plasma ghrelin levels were significantly higher in OSA patients than in controls. After 2 days of CPAP treatment, plasma ghrelin decreased in almost all OSA patients (n=9) to levels that were only slightly higher than those of controls (n=9). Leptin levels did not change significantly from baseline after 2 days of CPAP treatment, but were higher than in the control group. After 8 weeks, leptin levels decreased significantly, although the BMI of the patients showed no change. The decrease in leptin levels was more pronounced in patients with a BMI <30 kg x m(-2). These data indicate that the elevated leptin and ghrelin levels are not determined by obesity alone, since they rapidly decreased during continuous positive airways pressure therapy.