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Although bariatric surgery is known to change the metabolome, it is unclear if this is specific for the intervention or a consequence of the induced bodyweight loss. As the weight loss after Roux-en-Y Gastric Bypass (RYGB) can hardly be mimicked with an evenly effective diet in humans, translational research efforts might be helpful. A group of 188 plasma metabolites of 46 patients from the randomized controlled Würzburg Adipositas Study (WAS) and from RYGB-treated rats (n = 6) as well as body-weight-matched controls (n = 7) were measured using liquid chromatography tandem mass spectrometry. WAS participants were randomized into intensive lifestyle modification (LS, n = 24) or RYGB (OP, n = 22). In patients in the WAS cohort, only bariatric surgery achieved a sustained weight loss (BMI −34.3% (OP) vs. −1.2% (LS), p ≤ 0.01). An explicit shift in the metabolomic profile was found in 57 metabolites in the human cohort and in 62 metabolites in the rodent model. Significantly higher levels of sphingolipids and lecithins were detected in both surgical groups but not in the conservatively treated human and animal groups. RYGB leads to a characteristic metabolomic profile, which differs distinctly from that following non-surgical intervention. Analysis of the human and rat data revealed that RYGB induces specific changes in the metabolome independent of weight loss.

After bariatric surgery lifelong follow-up is recommended. Evidence of the consequences and reasons for being lost to follow-up (LTFU) is sparse. In this prospective study follow-up data of all patients who underwent bariatric surgery between 2008 and 2017 at a certified obesity centre were investigated. LTFU patients were evaluated through a structured telephone interview. Overall, 573 patients (female/male 70.9%/29.1%), aged 44.1 ± 11.2 years, preoperative BMI 52.1 ± 8.4 kg/m2 underwent bariatric surgery. Out of these, 33.2% had type 2 diabetes mellitus and 74.4% had arterial hypertension. A total of 290 patients were LTFU, of those 82.1% could be reached. Baseline characteristics of patients in follow-up (IFU) and LTFU were comparable, but men were more often LTFU (p = 0.01). Reported postoperative total weight loss (%TWL) and improvements of comorbidities were comparable, but %TWL was higher in patients remaining in follow-up for at least 2 years (p = 0.013). Travel issues were mentioned as the main reason for being LTFU. A percentage of 77.6% of patients reported to regularly supplement micronutrients, while 71.0% stated regular monitoring of their micronutrient status, mostly by primary care physicians. Despite comparable reported outcomes of LTFU to IFU patients, the duration of the in-centre follow-up period affected %TWL. There is a lack of sufficient supplementation and monitoring of micronutrients in a considerable number of LTFU patients.

BackgroundVenous thromboembolism (VTE) is the most frequent 30-day complication in patients with morbid obesity undergoing bariatric surgery. Therefore, there is a need for optimized low molecular weight heparin (LMWH) thromboprophylaxis dosing strategies in order to avoid VTE-associated morbidity and mortality in this patient population.ObjectiveThe primary goal was to evaluate if a pre-specified enoxaparin dosing regimen in patients undergoing bariatric surgery reaches anti-factor Xa (aFXa) levels in the defined target range (0.2–0.4 U/ml). Second, we aimed to identify biometric and laboratory parameters that might influence the aFXa value.MethodsA prospective database of 236 patients with obesity who received thromboprophylaxis with enoxaparin was established. These patients were divided into two weight-adjusted groups (group 1 < 150 kg, group 2 ≥ 150 kg). Enoxaparin was administered twice daily; dosing was determined by weight (group 1, 2 × 40 mg/day; group 2, 2 × 60 mg/day). In both groups, the peak aFXa serum level was evaluated 3 days after initiating the thromboprophylaxis.ResultsIn group 1 (body mass index (BMI) 42.94 ± 6.84 kg/m2, weight of 121.7 ± 17.49 kg), seventy-one of the included 124 patients (57.25%) reached the aFXa target range of 0.2 to 0.4 U/m. In group 2 (BMI 63.21 ± 10.05 kg/m2, weight of 191.66 ± 33.37 kg), 68 of 112 (60.71%) patients scored prophylactic aFXa range. Multiple regression of the biometric and laboratory parameters showed significance for weight, waist-to-hip ratio, glomerular filtration rate (GFR), creatinine, and HbA1c exclusively in group 1. There was no case of VTE within 3 months after surgery and no case of severe perioperative bleeding in those patients who underwent surgery.ConclusionsMeasurement of the aFXa level helps to define the real prophylactic thromboprophylaxis status in patients with obesity, especially in those with a weight above 150 kg. In patients at risk, the measurement of aFXa should be considered in routine clinical practice.

Abstract Introduction: Almost 25% of German adults have obesity and numbers are rising, making it an important health issue. Bariatric-metabolic surgery reduces body weight and complications for persons with obesity, but therapeutic success requires long-term postoperative care. Since no German standards for follow-up by family physicians exist, follow-up is provided by surgical obesity centers, but they are reaching their limits. The ACHT study, funded by the German Innovation Fund, is designed to establish and evaluate the follow-up program, with local physicians following patients supported remotely by obesity centers. Methods: ACHT is a multicenter, prospective, non-randomized control group study. The 18-month ACHT follow-up program is a digitally supported, structured, cross-sectoral, and close-to-home program to improve success after bariatric-metabolic surgery. Four groups are compared: intervention group 1 starts the program immediately (3 weeks) after Roux-en-Y gastric bypass or sleeve gastrectomy (months 1–18 postoperatively), intervention group 2 begins the program 18 months after surgery (months 19–36 postoperatively). Intervention groups are compared to respective control groups that had surgery 18 and 36 months previously. In total, 250 patients, enrolled in the intervention groups, are compared with 360 patients in the control groups, who only receive standard care. Results: The primary endpoint to compare intervention and control groups is the adapted King’s score, a composite tool evaluating physical, psychological, socioeconomic, and functional health status. Secondary endpoints include changes in care structures and care processes for the intervention groups. Multivariate regression analyses adjusting for confounders (including the type of surgery) are used to compare intervention and control groups and evaluate determinants in longitudinal analyses. The effect of the intervention on healthcare costs will be evaluated based on health insurance billing data of patients who had bariatric-metabolic surgery in the 3 years prior to the start of the study and of patients who undergo bariatric-metabolic surgery during the study period. Conclusions: ACHT will be the one of the first evaluated structured, close-to-home follow-up programs for bariatric surgery in Germany. It will evaluate the effectiveness of the implemented program regarding improvements in health status, mental health, quality of life, and the feasibility of such a program outside of specialized obesity centers.

This retrospective analysis assessed the efficacy of adjuvant mitotane treatment in prolonging recurrence-free survival in adrenocortical cancer, which carries a high risk of recurrence. Survival was significantly prolonged in patients receiving mitotane, as compared with those who did not. Adjuvant mitotane may prolong recurrence-free survival in patients with radically resected adrenocortical carcinoma. This retrospective analysis assessed the efficacy of adjuvant mitotane treatment in prolonging recurrence-free survival in adrenocortical cancer. Survival was significantly prolonged in patients receiving mitotane, as compared with those who did not. Adrenocortical carcinoma is a rare neoplasm characterized by a dismal prognosis, with only 16 to 38% of patients surviving for more than 5 years after diagnosis. 1 – 3 Although a majority of patients have resectable disease at presentation, 4 – 6 as many as 75 to 85% have a relapse after radical resection. 7 , 8 This high recurrence rate has prompted investigators to consider the use of adjuvant therapy, 1 – 3 , 9 and mitotane (a synthetic derivative of the insecticide dichlorodiphenyltrichloroethane [DDT]) has been widely used for this purpose. 10 – 21 However, available studies do not provide data as to whether adjuvant mitotane is efficacious, mainly . . .

The extraneuronal monoamine transporter from rat (EMTr) was heterologously expressed by stable transfection in human embryonic kidney 293 cells and characterized in radiotracer experiments. EMTr‐mediated uptake of 1‐methyl‐4‐phenylpyridinium (MPP+) was saturable, with a Km of 151 μmol l−1 and Vmax of 7.5 nmol min−1 mg protein−1. Compared to the human orthologue EMTh (gene symbol SLC22A3), EMTr was about two orders of magnitude more resistant to most inhibitors, including disprocynium24 and corticosterone. Strikingly, inhibitors and substrates at low concentration stimulated EMTr‐mediated transport above control level with MPP+ and noradrenaline as substrate, but not with cimetidine. Results were confirmed with EMT from mouse. With different IC50‐values for different substrates, the standard method to calculate Ki‐values is not applicable. Our experiments suggest that activation is not caused by changes in membrane potential or trans‐stimulation. Since the extent of activation depends markedly on the chemical structure of the monitored substrate, involvement of a receptor‐mediated signalling pathway or recruitment of transporter reserve are implausible. To explain activation, we present a kinetic model which assumes two binding sites for substrate or inhibitor per transporter entity, possibly resulting from the assembly of homodimers. Activation explains previous reports about inhibitor‐insensitive catecholamine transport in rat brain. We speculate that activation may serve to keep the transporter working for specific substrates in the face of inhibitors. British Journal of Pharmacology (2002) 137, 910–918. doi:10.1038/sj.bjp.0704926

Introduction: Almost 25% of German adults have obesity and numbers are rising, making it an important health issue. Bariatric-metabolic surgery reduces body weight and complications for persons with obesity, but therapeutic success requires long-term post-operative care. Since, no German standards for follow-up by family physicians exist, follow-up is provided by surgical obesity centers, but they are reaching their limits. The ACHT study, funded by the German Innovation Fund, is designed to establish and evaluate the follow-up program, with local physicians following patients supported remotely by obesity centers. Methods: ACHT is a multicenter, prospective, non-randomized control-group study. The 18-month ACHT follow-up program is a digitally supported, structured, cross-sectoral, and close-to-home program to improve success after bariatric-metabolic surgery. Four groups are compared: intervention group 1 starts the program immediately (3 weeks) after Roux-en-Y gastric-bypass or sleeve-gastrectomy (months 1-18 postoperatively), intervention group 2 begins the program 18-months after surgery (months 19-36 postoperatively). Intervention groups are compared to corresponding control groups that had surgery 18 respectively 36 months previously. In total, 250 patients, enrolled in the intervention groups, are compared with 360 patients in the control groups, who only receive standard care. Results: The primary endpoint to compare intervention and control groups is the adapted King’s Score, a composite tool evaluating physical, psychological, socio-economic and functional health status. Secondary endpoints include changes in care structures and care processes for the intervention groups. Multivariate regression analyses adjusting for confounders (including the type of surgery) are used to compare intervention and control groups and to evaluate determinants in longitudinal analyses. The effect of the intervention on healthcare costs will be evaluated based on health insurance billing data of patients who had bariatric-metabolic surgery in the three years prior to the start of the study and of patients who undergo bariatric-metabolic surgery during the study period. Conclusions: ACHT will be the one of the first evaluated structured, close-to-home follow-up programs for bariatric surgery in Germany. It will evaluate the effectiveness of the implemented program regarding improvements in health status, mental health, quality of life and the feasibility of such a program outside of specialized obesity centers.

AimThe PERI-DYS study aims to characterize two groups of patients with dyslipidaemia at very high CV risk: PCSK9i receivers and patients qualifying for but not receiving PCSK9i.MethodsThis is an observational study by office-based and clinic-based physicians, mainly cardiologists and other internists in Germany, with data extracted from patient charts. ClinicalTrials.gov identifier NCT03110432.ResultsA total of 1659 patients were enrolled across 70 sites. The majority of patients (91.0%) were reported as having mixed dyslipidaemia or non-familial or heterozygous familial hypercholesterolemia. At enrolment, 794 (47.9%) of patients were PCSK9i receivers (of these 65.9% ongoing, and 34.1% newly treated within 30 days before their baseline visit). Among PCSK9i receivers, the majority had evolocumab 140 mg (n = 632, 38.1% of total). PCSK9i receivers compared to non-receivers were about 2 years younger and had a lower proportion of males. In terms of comorbidities, they had (statistically significantly) more often CAD, and less often PAD, diabetes mellitus, arterial hypertension and chronic renal disease. The calculated untreated median LDL-C was 187 mg/dl (IQR 127; 270) in ongoing PCSK9i receivers, 212 mg/dl (IQR 132; 277) in newly treated PCSK9i receivers, and 179 mg/dl (IQR 129; 257) in non-receivers. Physician-reported statin intolerance was much more common in the two PCSK9i receiver groups as compared to non-receivers (67.3% versus 15.3%). Consequently, patients in the PCSK9i groups received fewer concomitant statins. Mean total cholesterol (143 vs. 172 mg/dl) and LDL-C (69 vs. 99 mg/dl) were considerably lower in ongoing PCSK9i receivers compared to non-receivers.ConclusionsPCSK9i receivers are characterized by higher baseline LDL-C and a higher portion of statin intolerance compared to those qualified for but not-receiving PCSK9i treatment. On-treatment, LDL-C was lower in PCSK9i receivers. Ongoing follow-up will determine the prognostic importance of these findings.