Intestinal ex vivo organoid culture reveals altered programmed crypt stem cells in patients with celiac disease

The ex vivo generation of gastrointestinal organoids from crypt stem cells opens up the possibility of new research approaches investigating gastrointestinal diseases. We used this technology to study differences between healthy controls and patients with celiac disease (CD). We noticed distinct dissimilarities in the phenotypes of organoids between our study groups and found considerable variations in their gene expression. Extracellular matrix genes involved in epithelial-mesenchymal transition are expressed most differently. In addition, we demonstrated epigenetic modifications that might be responsible for the different organoid gene expression thus accounting for a deranged crypt/villus axis development in CD. The organoids have proven valuable to demonstrate fundamental differences in duodenal derived organoids between healthy controls and patients with CD and thus are a suitable tool to gain new insights in pathogenesis of CD

Iron Beats Electricity: Resistance Training but Not Whole-Body Electromyostimulation Improves Cardiometabolic Health in Obese Metabolic Syndrome Patients during Caloric Restriction—A Randomized-Controlled Study

Caloric restriction (CR) and exercise are cornerstones in the treatment of obesity and cardiometabolic disorders. Recently, whole body electromyostimulation (WB-EMS) has emerged as a more time-efficient alternative to traditional resistance training (RT). However, the effects of WB-EMS compared to RT on cardiometabolic health in obese metabolic syndrome (MetS) patients performed during CR are still unclear. In total, 118 obese MetS patients (52.7 ± 11.8 years, BMI: 38.1 ± 6.9 kg/m2) undergoing CR over 12 weeks (aim: −500 kcal deficit/day) were randomly allocated to either WB-EMS, single-set RT (1-RT), 3-set RT (3-RT) or an inactive control group (CON). Primary outcome was MetS severity (MetS z-score). Secondary outcomes were body composition, muscle strength and quality of life (QoL). All groups significantly reduced body weight (~3%) and fat mass (~2.6 kg) but only 1-RT and 3-RT preserved skeletal muscle mass (SMM). All exercise groups increased muscle strength in major muscle groups (20–103%). However, only the two RT-groups improved MetS z-score (1-RT: −1.34, p = 0.003; 3-RT: −2.06, p < 0.001) and QoL (1-RT: +6%, p = 0.027; 3-RT: +12%, p < 0.001), while WB-EMS and CON had no impact on these outcomes. We conclude that traditional RT has superior effects on cardiometabolic health, SMM and QoL in obese MetS patients undergoing CR than WB-EMS

Effects of very low volume high intensity versus moderate intensity interval training in obese metabolic syndrome patients: a randomized controlled study

Physical activity is a cornerstone in the treatment of obesity and metabolic syndrome (MetS). Given the leading physical activity barrier of time commitment and safety concerns about vigorous exercise in high-risk groups, this study aimed to investigate the effects of two extremely time-efficient training protocols (< 30 min time effort per week), either performed as high- (HIIT) or moderate-intensity interval training (MIIT) over 12 weeks, in obese MetS patients. In total, 117 patients (49.8 ± 13.6 years, BMI: 38.2 ± 6.2 kg/m2) were randomized to HIIT (n = 40), MIIT (n = 37) or an inactive control group (n = 40). All groups received nutritional counseling to support weight loss. Maximal oxygen uptake (VO2max), MetS severity (MetS z-score), body composition and quality of life (QoL) were assessed pre-and post-intervention. All groups significantly reduced body weight (~ 3%) but only the exercise groups improved VO2max, MetS z-score and QoL. VO2max (HIIT: + 3.1 mL/kg/min, p < 0.001; MIIT: + 1.2 mL/kg/min, p < 0.05) and MetS z-score (HIIT: − 1.8 units, p < 0.001; MIIT: − 1.2 units, p < 0.01) improved in an exercise intensity-dependent manner. In conclusion, extremely low-volume interval training, even when done at moderate intensity, is sufficiently effective to improve cardiometabolic health in obese MetS patients. These findings underpin the crucial role of exercise in the treatment of obesity and MetS

Maximum Heart Rate- and Lactate Threshold-Based Low-Volume High-Intensity Interval Training Prescriptions Provide Similar Health Benefits in Metabolic Syndrome Patients

Exercise is an integral part of metabolic syndrome (MetS) treatment. Recently, low-volume high-intensity interval training (LOW-HIIT) has emerged as a time-efficient approach to improving cardiometabolic health. Intensity prescriptions for LOW-HIIT are typically based on maximum heart rate (HRmax) percentages. However, HRmax determination requires maximal effort during exercise testing, which may not always be feasible/safe for MetS patients. This trial compared the effects of a 12-week LOW-HIIT program based on: (a) HRmax (HIIT-HR), or (b) submaximal lactate threshold (HIIT-LT), on cardiometabolic health and quality of life (QoL) in MetS patients. Seventy-five patients were randomized to HIIT-HR (5 × 1 min at 80–95% HRmax), HIIT-LT (5 × 1 min at 95–105% LT) groups, both performed twice weekly on cycle ergometers, or a control group (CON). All patients received nutritional weight loss consultation. All groups reduced their body weight (HIIT-HR: −3.9 kg, p < 0.001; HTT-LT: −5.6 kg, p < 0.001; CON: −2.6 kg, p = 0.003). The HIIT-HR and HIIT-LT groups similarly, improved their maximal oxygen uptake (+3.6 and +3.7 mL/kg/min, p < 0.001), glycohemoglobin (−0.2%, p = 0.005, and −0.3%, p < 0.001), homeostasis model assessment index (−1.3 units, p = 0.005, and −1.0 units, p = 0.014), MetS z-score (−1.9 and −2.5 units, p < 0.001) and QoL (+10 points, p = 0.029, and +11 points, p = 0.002), while the CON did not experience changes in these variables. We conclude that HIIT-LT is a viable alternative to HIIT-HR for patients who are not able/willing to undergo maximal exercise testing

Very Low-Volume, High-Intensity Interval Training Mitigates Negative Health Impacts of COVID-19 Pandemic-Induced Physical Inactivity

Initially, we aimed to investigate the impact of a one-year worksite low-volume, high-intensity interval training (LOW-HIIT) on cardiometabolic health in 114 sedentary office workers. Due to the COVID-19 pandemic outbreak, LOW-HIIT was discontinued after 6 months and participants were followed up for 6 months to analyze physical activity/exercise behavior and outcome changes during lockdown. Health examinations, including cardiopulmonary exercise testing and the assessment of cardiometabolic markers were performed baseline (T-1), after 6 months (T-2, termination of worksite LOW-HIIT) and 12 months (T-3, follow-up). Cycle ergometer LOW-HIIT (5 × 1 min at 85–95% HRmax) was performed 2×/week. For follow-up analyses, participants were classified into three groups: HIIT-group (continued home-based LOW-HIIT), EX-group (continued other home-based exercises), and NO-EX-group (discontinued LOW-HIIT/exercise). At T-2, VO2max (+1.5 mL/kg/min, p = 0.002), mean arterial blood pressure (MAB, −4 mmHg, p < 0.001), HbA1c (−0.2%, p = 0.005) and self-reported quality of life (QoL, +5 points, p < 0.001) were improved. At T-3, HIIT-group maintained VO2max and QoL and further improved MAB. EX-group maintained MAB and QoL but experienced a VO2max decrease. In NON-EX, VO2max, MAB and QoL deteriorated. We conclude that LOW-HIIT can be considered a promising option to improve cardiometabolic health in real-life conditions and to mitigate physical inactivity-related negative health impacts during lockdowns

Predictive Factors of Mortality After PEG Insertion: Guidance for Clinical Practice

Background: Percutaneous endoscopic gastrostomy (PEG) is considered the preferred route for long-term enteral feeding. The aim of this study was to determine predictors of an increased mortality risk after PEG insertion. Methods: A retrospective study was conducted during a 13-year period in the gastroenterology department of Erlangen University Hospital. The authors completed a questionnaire with details of demographic data, diagnosis, indication for PEG, type of tube, and cause of death. Patients were contacted regularly at scheduled appointments. Results: In total, 787 patients (574 male [72.9%]) underwent PEG placement by the pull technique. The main underlying disease was malignant (75.6%). By the end of the study period, 614 patients had died. The average survival time was 720 days. The 30-, 60-, 90-day and 1-, 3-, and 5-year mortality rates amounted to 6.5%, 9.8%, 13%, 32.1%, 59.3%, and 69.8%, respectively. Predictive factors of increased 30-day mortality were higher age, lower body mass index (BMI), and the presence of diabetes mellitus. The presence of all 3 variables served as an indicator to detect high-risk patients, with a sensitivity of 0.80 and a specificity of 0.64. Conclusion: Mortality predictors for patients after PEG insertion are higher age, lower BMI, and the presence of diabetes mellitus. To avoid unnecessary and dangerous examinations in high-risk patients, the above-mentioned predictive factors of mortality should be checked before PEG placement

Percutaneous Endoscopic Jejunostomy and Jejunal Extension Tube through Percutaneous Endoscopic Gastrostomy: A Retrospective Analysis of Success, Complications and Outcome

Background: Percutaneous access to the jejunum is an important approach if gastrostomy feeding is not possible. Objective: To analyze success, short- and long-term complications (STCs, LTCs) in patients with percutaneous endoscopic jejunostomy (PEJ) and jejunal access through percutaneous endoscopic gastrostomy (Jet-PEG). Methods: A retrospective analysis of endoscopically placed PEJs and Jet-PEGs. Success rates, mortality, STCs and LTCs were investigated for risk factors comprising demographic data, underlying disease, previous surgery and experience of the endoscopist. Results: 205 PEJ and 58 Jet-PEG placements were included in the study. PEJs and Jet-PEGs were successfully placed in 65.4 and 89.7%, respectively. Billroth II surgery predisposed in favor of a significantly higher success rate for PEJ placement (p = 0.014, OR = 2.27). Inexperienced examiners have a significantly (p = 0.040) lower success rate for tube insertion than examiners with a medium level of experience. STCs and LTCs occurred evenly in PEJ and Jet-PEG patients. Dislocation of the tube occurred significantly more frequently in Jet-PEG patients (33.3%, p = 0.005). Aspiration was most common for bedridden patients. Conclusion: PEJ has a significantly lower success rate for insertions, but fewer LTCs. The experience of the endoscopist correlates with the success rate of tube insertion

Proteins from Modern and Ancient Wheat Cultivars: Impact on Immune Cells of Healthy Individuals and Patients with NCGS

In non-celiac gluten sensitivity (NCGS), the elimination of wheat results in a clear symptom improvement, but gluten has still not been proven as (the sole) trigger. Due to the increase in the prevalence of gluten-related diseases, the breeding of high-performance wheat cultivars is discussed as a trigger. To analyze the immune stimulation and signal pathways, the immune cells of healthy subjects and patients with NCGS were stimulated with gliadins from wheat, and the expression and secretion of interleukin 1ß (IL1ß) and interleukin 6 (IL6) were studied. To determine the impact of wheat breeding, the monocyte cell line THP1 and human immune cells were stimulated with gliadin, glutenin, and albumin/globulin fractions of ancient and modern cereals, and expression of inflammatory molecules was checked. Immune cells of patients with NCGS showed an increased expression of IL1ß and IL6 after stimulation with gliadins compared to immune cells of healthy controls. Gliadins caused a strong activation of P-STAT3 in immune cells of healthy controls, and inhibitors of JAK and NFκB pathways considerably reduced this response. In addition to gliadins, we further showed that glutenins and albumin/globulins from all wheat cultivars from the last century, and especially from einkorn and spelt, also markedly induced the expression of inflammatory genes in THP1 and human immune cells. There was no correlation between enhanced immune stimulation and ancient or modern cultivars. This does not support the hypothesis that modern wheat breeding is responsible for the increase in gluten-related diseases. An altered immune situation is suggested in patients with NCGS

Differential Effects of Very-Low-Volume Exercise Modalities on Telomere Length, Inflammation, and Cardiometabolic Health in Obese Metabolic Syndrome Patients: A Subanalysis from Two Randomized Controlled Trials

Oxidative stress (OS) and inflammation are features of metabolic syndrome (MetS) that can contribute to the shortening of telomere length (TL), a marker of cellular ageing. Research indicates that exercise can positively influence MetS-associated conditions and TL. However, the effects of low-volume exercise types on TL are still unknown. We investigated the impact of very-low-volume high-intensity interval training (LV-HIIT), one-set resistance training (1-RT), and whole-body electromyostimulation (WB-EMS) on TL, inflammation, and cardiometabolic indices in 167 MetS patients. Data were derived from two randomized controlled trials where patients were allocated to an exercise group (2 sessions/week, for 12 weeks) or a control group. All groups received standard-care nutritional weight loss counselling. TL was determined as the T/S ratio (telomere to single-copy gene amount). All groups significantly reduced body weight (p &lt; 0.05), but the T/S-ratio (p &lt; 0.001) only increased with LV-HIIT. OS-related inflammatory markers (C-reactive protein, interleukin-6, and lipopolysaccharide-binding protein) only decreased (p &lt; 0.05) following LV-HIIT. The MetS severity z-score improved with LV-HIIT (p &lt; 0.001) and 1-RT (p = 0.014) but not with WB-EMS. In conclusion, very-low-volume exercise modalities have differential effects on telomeres, inflammation, and cardiometabolic health. Only LV-HIIT but not strength-based low-volume exercise increased TL in MetS patients, presumably due to superior effects on OS-related inflammatory markers.</jats:p

Gender-Based Differences in Drug Prescription: Relation to Adverse Drug Reactions

Background/Aim: The female gender appears to suffer from more adverse drug reactions (ADRs) than the male gender. So far, there has been no epidemiologic study analyzing gender-based differences in drug prescribing and its ADR risks. The aim of the present study was to establish a drug risk stratification adjusted to age, number of prescriptions and drug classes with respect to gender differences based on intensive data acquisition methods. Method: A prospective multicenter study was conducted in several departments in Germany and Israel (pediatrics, medicine and geriatrics) enclosing 2,371 inpatients. Results: A total of 25,532 drug prescriptions during hospitalization were evaluated. At least 1 ADR was found in 774 patients (32.6%). Drugs for the cardiovascular system, nervous system, alimentary tract and musculoskeletal system were prescribed most often in females. The following drug classes led significantly more often to ADRs in women as compared to men: alimentary tract (OR 0.5; p = 0.0002), cardiovascular system (OR 0.72; p = 0.0140), musculoskeletal system (OR 0.31; p = 0.0004) and nervous system (OR 0.62; p = 0.0023). After adjustment to age, total number of prescriptions and drug class, only antiinfectives (antibacterials) and musculoskeletal system (antiinflammatory) drugs stand out as causing more ADRs in women. Conclusion: Antibacterials and anti-inflammatory agents cause more ADRs in females as compared to males