Immunogenicity Parameters of Cancer Patients Receiving the mRNA Vaccine BNT162b2 While Obtaining Radiotherapy: A Longitudinal Cohort Evaluation.

BACKGROUND: Cancer patients are highly prone to infectious diseases. While undergoing antineoplastic treatment, the risk of severe symptoms upon infection increases, necessitating efficient protective measures, such as vaccination. For patients receiving radiotherapy, there is no specific information about humoral immunity. During the COVID-19 pandemic, serial antibody measurements were therefore offered to cancer patients, following SARS-CoV-2 vaccination while obtaining radiotherapy. METHODS: Out of 74 enrolled patients, 46 met the inclusion criteria. Two cohorts were allocated, depending on an association with chemotherapy or pure radiotherapy. An additional healthy control cohort of 16 healthcare workers was enrolled. All participants followed a two-fold BNT162b2 vaccine schedule. SARS-CoV-2 binding antibodies were measured serially in a 7-day cycle for 35 days and over the long-term, using the Elecsys® Anti-SARS-CoV-2 immunoassay. RESULTS: Cancer patients under pure radiotherapy have a comparable humoral vaccination response and long-term persistency of antibodies to healthy controls. Patients receiving additional chemotherapy show a significantly delayed immune response and decreased antibody titers. The vaccine was well tolerated in all cohorts. CONCLUSIONS: Pure radiotherapy in cancer patients does not interfere with the vaccine-induced humoral immune response or other immunogenetic aspects, whereas previous or simultaneous chemotherapy does. Findings are of particular relevance for future epidemic or pandemic scenarios.

Transapical electrosurgical laceration and stabilization of mitral clips followed by transcatheter mitral valve replacement-A one-stop shop.

Objective: Electrosurgical laceration and stabilization of mitral clips (ELASTA-CLIP) is a bail-out technique to recreate a single-orifice mitral valve after transcatheter edge-to-edge repair (TEER) with subsequent transcatheter mitral valve replacement (TMVR). This technique is a novel option for patients with significant residual mitral regurgitation after TEER with high risk for conventional surgery. The original ELASTA CLIP procedure features a transseptal approach, whereas the TMVR with the Tendyne bioprosthesis has a transapical access. Hereby we tested the hypothesis that a modified transapical ELASTA CLIP technique can be safely applied transapically allowing a straightforward one-stop shop access strategy. Methods: We developed the procedural steps in a porcine passive-beating heart model and applied the modified technique with subsequent TMVR in 2 consecutive patients with severe mitral regurgitation after previous TEER. Patients were followed up to 30 days. Results: The modified transapical ELASTA CLIP procedure was successful in both patients. The mean total procedure time was 118 minutes, and the mean fluoroscopy duration 22 minutes. At 30 days' follow-up, both patients were alive without bleeding complications, reintervention, or prosthetic valve dysfunction. Conclusions: The modified transapical ELASTA CLIP procedure is technically feasible and safe at 30 days. Procedure times are lower compared with previous reports of the original transseptal approach.

[Other specific types of diabetes and exocrine pancreatic insufficiency (update 2023)]. / Andere spezifische Diabetesformen und exokrine Pankreasinsuffizienz (Update 2023).

The heterogenous category "specific types of diabetes due to other causes" encompasses disturbances in glucose metabolism due to other endocrine disorders such as acromegaly or hypercortisolism, drug-induced diabetes (e.g. antipsychotic medications, glucocorticoids, immunosuppressive agents, highly active antiretroviral therapy (HAART), checkpoint inhibitors), genetic forms of diabetes (e.g. Maturity Onset Diabetes of the Young (MODY), neonatal diabetes, Down­, Klinefelter- and Turner Syndrome), pancreatogenic diabetes (e.g. postoperatively, pancreatitis, pancreatic cancer, haemochromatosis, cystic fibrosis), and some rare autoimmune or infectious forms of diabetes. Diagnosis of specific diabetes types might influence therapeutic considerations. Exocrine pancreatic insufficiency is not only found in patients with pancreatogenic diabetes but is also frequently seen in type 1 and long-standing type 2 diabetes.

[Obesity and type 2 diabetes (Update 2023)]. / Adipositas und Typ-2-Diabetes (Update 2023).

The body mass index (BMI) is a very crude measure of body fatness in individuals. Even normal weight persons can have too much body fat in cases of a lack of muscle mass (sarcopenia), which is why additional measurements of waist circumference and body fatness, e.g. bioimpedance analysis (BIA), are recommended. Lifestyle management including nutrition modification and increase in physical activity are important measures for the prevention and treatment of diabetes. Regarding the treatment of type 2 diabetes, body weight is increasingly used as a secondary target parameter. The choice of anti-diabetic treatment and additional concomitant therapies is increasingly influenced by body weight. The importance of modern GLP­1 agonists and dual GLP­1 GIP agonists increases since these drugs target obesity and type 2 diabetes. Bariatric surgery is at present indicated with a BMI > 35 kg/m2 with concomitant risk factors, such as diabetes and can lead at least to partial diabetes remission but has to be incorporated into an appropriate lifelong care concept.

[Diabetes education and counseling in adult patients with diabetes (Update 2023)]. / Diabetesschulung und -beratung bei Erwachsenen mit Diabetes (Update 2023).

Diabetes education and self-management play a critical role in diabetes care. Patient empowerment aims to actively influence the course of the disease by self-monitoring and subsequent treatment modification as well as the ability of patients to integrate diabetes into their daily life and to appropriately adapt diabetes to their life style situation. Diabetes education has to be made accessible for all persons with the disease. In order to be able to provide a structured and validated education program, adequate personnel as well as space, organizational and financial prerequisites are required. Besides an increase in knowledge about the disease it has been shown that a structured diabetes education is able to improve diabetes outcome as measured by parameters, such as blood glucose, HbA1c, lipids, blood pressure and body weight in follow-up evaluations. Modern education programs emphasize the ability of patients to integrate diabetes into everyday life, stress physical activity besides healthy eating as important components of life style therapy and use interactive methods in order to increase the acceptance of personal responsibility. Specific situations (e.g. impaired hypoglycemia awareness, illness, travel), the occurrence of diabetic complications and the use of technical devices such as glucose sensor systems and insulin pumps require additional educational measures supported by adequate electronic tools (diabetes apps and diabetes web portals). New data demonstrate the effect of telemedicine and internet-based services for diabetes prevention and management.

[Position statement: surgery and diabetes mellitus (Update 2023)]. / Positionspapier: Operation und Diabetes mellitus (Update 2023).

This position statement reflects the perspective of the Austrian Diabetes Association concerning the perioperative management of people with diabetes mellitus based on the available scientific evidence. The paper covers necessary preoperative examinations from an internal/diabetological point of view as well as the perioperative metabolic control by means of oral antihyperglycemic and/or insulin therapy.

Glucose and lipopolysaccharide differentially regulate fibroblast growth factor 21 in healthy male human volunteers - A prospective cross-over trial.

Fibroblast growth factor 21 (FGF21) affects the regulation of metabolism. Additionally, anti-inflammatory properties are attributed to FGF21, and studies in animals and humans show conflicting results. This study aimed to investigate how FGF21 is affected by glucose and lipopolysaccharide (LPS) in humans. Therefore, FGF21 was measured eight times at different time points within 48 h in this prospective cross-over trial after glucose and LPS on two different study days. The study included ten healthy, non-smoking male subjects aged 18-40. Repeated measures analysis of variance and paired t-test as post hoc analysis were applied. The administration of glucose and LPS resulted in a significant difference in regulating FGF21 (p < 0.001). After glucose administration, FGF21 declined sharply at 360 min, with a subsequent steep increase that exceeded baseline levels. LPS induced a drop in FGF21 after 180 min, while the baseline concentrations were not reached. After 180 min and 24 h, a statistically significant difference was demonstrated after adjusting the Bonferroni-Holm method. So, our results support the hypothesis that glucose and LPS differentially affect the human expression of FGF21 over 48 h.

Intravenous administration of LPS activates the kynurenine pathway in healthy male human subjects: a prospective placebo-controlled cross-over trial.

BACKGROUND: Administration of lipopolysaccharide (LPS) from Gram-negative bacteria, also known as the human endotoxemia model, is a standardized and safe model of human inflammation. Experimental studies have revealed that peripheral administration of LPS leads to induction of the kynurenine pathway followed by depressive-like behavior and cognitive dysfunction in animals. The aim of the present study is to investigate how acute intravenous LPS administration affects the kynurenine pathway in healthy male human subjects. METHODS: The present study is a prospective, single-blinded, randomized, placebo-controlled cross-over study to investigate the effects of intravenously administered LPS (Escherichia coli O113, 2 ng/kg) on tryptophan and kynurenine metabolites over 48 h and their association with interleukin-6 (IL-6) and C-reactive protein (CRP). The study included 10 healthy, non-smoking men (18-40 years) free from medication. Statistical differences in tryptophan and kynurenine metabolites as well as associations with IL-6 and CRP in LPS and placebo treated subjects were assessed with linear mixed-effects models. RESULTS: Systemic injection of LPS was associated with significantly lower concentrations of plasma tryptophan and kynurenine after 4 h, as well as higher concentrations of quinolinic acid (QUIN) after 48 h compared to the placebo injection. No differences were found in kynurenic acid (KYNA) or picolinic acid plasma concentrations between LPS or placebo treatment. The KYNA/kynurenine ratio peaked at 6 h post LPS injection while QUIN/kynurenine maintained significantly higher from 3 h post LPS injection until 24 h. The kynurenine/tryptophan ratio was higher at 24 h and 48 h post LPS treatment. Finally, we report an association between the kynurenine/tryptophan ratio and CRP. CONCLUSIONS: Our findings strongly support the concept that an inflammatory challenge with LPS induces the kynurenine pathway in humans, activating both the neurotoxic (QUIN) and neuroprotective (KYNA) branch of the kynurenine pathway. TRIAL REGISTRATION: This study is based on a study registered at ClinicalTrials.gov, NCT03392701 . Registered 21 December 2017.

[Diabetes mellitus, coronary artery disease und heart disease (Update 2019)]. / Diabetes mellitus, koronare Herzkrankheit und Herzinsuffizienz (Update 2019).

Diabetes mellitus, cardiovascular disease and heart failure are interacting dynamically. Patients being diagnosed with cardiovascular disease should be screened for diabetes mellitus. Enhanced cardiovascular risk stratification based on biomarkers, symptoms and classical risk factors should be performed in patients with pre-existing diabetes mellitus. In patients with previously diagnosed arterosclerotic cardiovascular disease an agent proven to reduce major adverse cardiovascular events or cardiovascular mortality is recommended after therapy failure of metformin.

[Diabetes education and counselling in adult patients with diabetes (Update 2019)]. / Diabetesschulung und -beratung bei Erwachsenen mit Diabetes (Update 2019).

Diabetes education and self-management play a critical role in diabetes care. Patient empowerment aims to actively influence the course of the disease by self-monitoring and subsequent treatment modification as well as the ability of patients to integrate diabetes into their daily life and to appropriately adapt it to their life style situation. Diabetes education has to be made accessible for all persons with the disease. In order to be able to provide a structured and validated education program, adequate personnel as well as space, organizational and financial prerequisites are required. Besides an increase in knowledge about the disease it has been shown that a structured diabetes education is able to improve diabetes outcome as measured by parameters, such as blood glucose, HbA1c, blood pressure and body weight in follow-up evaluations. Modern education programs emphasize the ability of patients to integrate diabetes into everyday life, stress physical activity besides healthy eating as important components of life style therapy and use interactive methods in order to increase the acceptance of personal responsibility. Specific situations (e. g. impaired hypoglycemia awareness, illness, travel) and technical innovations, such as glucose sensor systems and insulin pumps require additional educational measures by information exchange in small groups supported by adequate electronic tools (diabetes apps and diabetes web portals).

[Other specific types of diabetes and exocrine pancreatic insufficiency (Update 2019)]. / Andere spezifische Diabetesformen und exokrine Pankreasinsuffizienz (Update 2019).

The heterogenous catagory "specific types of diabetes due to other causes" encompasses disturbances in glucose metabolism due to other endocrine disorders such as acromegaly or hypercortisolism, drug-induced diabetes (e. g. antipsychotic medications, glucocorticoids, immunosuppressive agents, highly active antiretroviral therapy (HAART)), genetic forms of diabetes (e. g. Maturity Onset Diabetes of the Young (MODY), neonatal diabetes, Down Syndrome, Klinefelter Syndrome, Turner Syndrome), pancreatogenic diabetes (e. g. postoperatively, pancreatitis, pancreatic cancer, haemochromatosis, cystic fibrosis), and some rare autoimmune or infectious forms of diabetes. Diagnosis of specific diabetes types might influence therapeutic considerations. Exocrine pancreatic insufficiency is not only found in patients with pancreatogenic diabetes but is also frequently seen in type 1 and long-standing type 2 diabetes.

[Position statement: surgery and diabetes mellitus (Update 2019)]. / Positionspapier: Operation und Diabetes mellitus (Update 2019).

This position statement reflects the opinion of the Austrian Diabetes Association concerning the perioperative management of patients with diabetes mellitus based on the available scientific evidence. The paper covers necessary preoperative examinations from an internal/diabetological point of view as well as the perioperative metabolic control by means of oral antidiabetics and/or insulin therapy.

Unrecognised cardiovascular disease in type 2 diabetes: is it time to act earlier?

Cardiovascular disease (CVD) is the most significant prognostic factor in individuals with type 2 diabetes (T2D). However, a significant number of individuals may develop CVD that does not present with the classic angina-related or heart failure symptoms. In these cases, CVD may seem to be 'silent' or 'asymptomatic', but may be more accurately characterised as unrecognised diabetic cardiac impairment. An initial step to raise awareness of unrecognised CVD in individuals with T2D would be to reach a consensus regarding the terminology used to describe this phenomenon. By standardising the terminologies, and agreeing on the implementation of an efficient screening program, it is anticipated that patients will receive an earlier diagnosis and appropriate and timely treatment. Given the availability of anti-diabetic medications that have been shown to concomitantly reduce CV risk and mortality, it is imperative to improve early identification and initiate treatment as soon as possible in order to enable as many patients with T2D as possible to benefit.

Growth differentiation factor 15 increases following oral glucose ingestion: effect of meal composition and obesity.

OBJECTIVE: Growth differentiation factor 15 (GDF15) is a cardiovascular biomarker belonging to the transforming growth factor-ß superfamily. Increased GDF15 concentrations are associated with insulin resistance, diabetes and obesity. We investigated the physiological effects of meal composition and obesity on the regulation of systemic GDF15 levels. DESIGN: Lean (n = 8) and obese (n = 8) individuals received a carbohydrate- or fat-rich meal, a 75 g oral glucose load (OGTT) or short-term fasting. OGTTs were performed in severely obese patients (n = 6) pre- and post-bariatric surgery. METHODS: Circulating serum GDF15 concentrations were studied in lean and obese individuals in response to different meals, OGTT or short-term fasting, and in severely obese patients pre- and post-bariatric surgery. Regulation of GDF15 mRNA levels and protein release were evaluated in the human hepatic cell line HepG2. RESULTS: GDF15 concentrations steadily decrease during short-term fasting in lean and obese individuals. Carbohydrate- and fat-rich meals do not influence GDF15, whereas an OGTT leads to a late increase in GDF15 levels. The positive effect of OGTT on GDF15 levels is also preserved in severely obese patients, pre- and post-bariatric surgery. We further studied the regulation of GDF15 mRNA levels and protein release in HepG2, finding that glucose and insulin independently stimulate both GDF15 transcription and secretion. CONCLUSION: In summary, high glucose and insulin peaks upregulate GDF15 transcription and release. The nutrient-induced increase in GDF15 levels depends on rapid glucose and insulin excursions following fast-digesting carbohydrates, but not on the amount of calories taken in.

GDF-15 Is Associated with Cancer Incidence in Patients with Type 2 Diabetes.

BACKGROUND: Diabetes has been linked epidemiologically to increased cancer incidence and mortality. Growth differentiation factor 15 (GDF-15) is increased in patients with diabetes and has recently been linked to the occurrence of cancer. We investigated whether circulating GDF-15 concentrations can predict the incidence of malignant diseases in a diabetic patient cohort already facing increased risk for cancer. METHODS: We prospectively enrolled a total of 919 patients with type 2 diabetes and no history of malignant disease, who were clinically followed up for 60 months. GDF-15, N-terminal pro-B-type natriuretic peptide and troponin T were measured at baseline; an additional 4 cardiovascular biomarkers were determined for a subpopulation (n = 259). Study end point was defined as the first diagnosis of any type of cancer during the follow-up period. RESULTS: During a median follow-up of 60 months, 66 patients (7.2%) were diagnosed with cancer. Baseline circulating GDF-15 concentrations were higher in patients that developed cancer over the follow-up period when compared to cancer-free patients. Increased GDF-15 concentrations were significantly associated with cancer incidence [crude hazard ratio (HR) per 1-IQR (interquartile range) increase 2.13, 95% CI 1.53-2.97, P < 0.001]. This effect persisted after multivariate adjustment with an adjusted HR of 1.86 (95% CI 1.22-2.84; P = 0.004). Among the 4 additionally tested cardiovascular markers in the subpopulation, only troponin T and C-terminal proendothelin-1 showed a significant association with future cancer incidence with unadjusted HRs of 1.71 (95% CI 1.28-2.28, P < 0.001) and 1.68 (95% CI 1.02-2.76, P = 0.042), respectively. CONCLUSIONS: Increased circulating concentrations of GDF-15 are associated with increased cancer incidence in patients with type 2 diabetes.

Cardiovascular safety of metformin and sulfonylureas in patients with different cardiac risk profiles.

OBJECTIVES/BACKGROUND: Based on previous experiences, the Food and Drug Administration and the European Medicines Agency recommend that clinical trials for novel antidiabetic drugs are powered to detect increased cardiovascular risk. In this context, data concerning licensed drugs such as metformin and sulfonylureas are conflicting. The influence of baseline cardiovascular risk on any treatment effect appears obvious but has not been formally proven. We therefore evaluated association of metformin and sulfonylureas with cardiovascular events in patients with different cardiovascular risk profiles indicated by N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) levels. METHODS: 2024 patients with diabetes mellitus were included in this observational study. The primary endpoint was defined as a combination of cardiovascular events and death. Association of metformin and sulfonylureas was assessed using Cox regression models. Possible differences of these associations in patients with different NT-proBNP levels were studied by stratifying and through interaction analysis. RESULTS: During a median follow-up of 60 months, the primary endpoint occurred in 522 (26%) of patients. The median age was 63 years. A Cox regression analysis was adjusted for site of treatment, concomitant medication, age, gender, body mass index, glycated haemoglobin, duration of diabetes, glomerular filtration rate, cholesterol, and history of smoking and cardiac disease. Metformin was associated with a decreased risk in the cohort with elevated NT-proBNP ≥300 pg/mL (HR 0.70, p=0.014) and a similar association was found for the interaction between metformin and NT-proBNP (p=0.001). There was neither an association for sulfonylureas nor a significant interaction between sulfonylureas and NT-proBNP. CONCLUSIONS: Metformin is associated with beneficial cardiovascular outcomes in patients with diabetes only when (sub)clinical cardiovascular risk defined by NT-proBNP levels is present.

[Exocrine pancreatic insufficiency and diabetes mellitus]. / Exokrine Pankreasinsuffizienz und Diabetes mellitus.

Exocrine pancreatic insufficiency (EPI) in diabetic patients is frequent. Studies based on fecal elastase-1 measurement give prevalence rates of 10‒30 % of severe and 22‒56 % of moderate EPI in type 1 and rates of 5‒46 % in type 2 diabetic patients. Nevertheless, not all patients report typical symptoms like diarrhea, steatorrhea and weight loss. For noninvasive testing the determination of fecal elastase-1 has the highest sensitivity and specificity. This test should be performed at least in all symptomatic patients. As differential diagnosis celiac disease (with a prevalence of about 3-5 % of type 1 diabetic patients), autonomic neuropathy, but also diseases like irritable bowel syndrome and gastrointestinal tumors have to be taken into account. Patients with symptoms and a fecal elastase-1 < 100 µg/g should be treated with pancreatic enzymes in adequate daily doses administered at main meals. Treatment improves symptoms significantly, supply with fat soluble vitamins is normalised, risk for osteoporosis is reduced. However, improvement of glucose metabolism has not been demonstrated consistently. A pancreatogenic diabetes, also termed as type 3c diabetes, has not necessarily to be treated with insulin, often-at least initially-treatment with oral antidiabetic drugs is sufficient.

[Position statement: surgery and diabetes mellitus]. / Positionspapier: Operation und Diabetes mellitus.

This position statement reflects the opinion of the Austrian Diabetes Association concerning the perioperative management of patients with diabetes mellitus based on the available scientific evidence. The paper covers necessary preoperative examinations from an internal/diabetological point of view as well as the perioperative metabolic control by means of oral antidiabetics and/or insulin therapy.

[Diabetes education in adult diabetic patients]. / Diabetesschulung bei Erwachsenen mit Diabetes.

Diabetes education and self management has gained a critical role in diabetes care. Patient empowerment aims to actively influence the course of the disease by self-monitoring and treatment modification, as well as integration of diabetes in patients' daily life to achieve changes in lifestyle accordingly.Diabetes education has to be made accessible for all patients with the disease. To be able to provide a structured and validated education program adequate personal as well as space, organizational and financial background are required. Besides an increase in knowledge about the disease it has been shown that structured diabetes education is able to improve diabetes outcome measured by parameters like blood glucose, HbA1c, blood pressure and body weight in follow-up evaluations. Modern education programs emphasize the ability of patients to integrate diabetes in everyday life and stress physical activity besides healthy eating as a main component of lifestyle therapy and use interactive methods in order to increase the acceptance of personal responsibility.

[Diabetes mellitus, coronary artery disease and heart disease]. / Diabetes mellitus, koronare Herzkrankheit und Herzinsuffizienz.

Diabetes mellitus, cardiovascular disease and heart failure are interacting dynamically. Patients being diagnosed with cardiovascular disease should be screened for diabetes mellitus. Enhanced cardiovascular risk stratification based on biomarkers, symptoms and classical risk factors should be performed in patients with pre-existing diabetes mellitus.