Renal complications in chronic hypoparathyroidism – a systematic cross-sectional assessment

ContextAlthough renal long-term complications are acknowledged in chronic hypoparathyroidism (HPT), standardized investigations are scarce.ObjectiveTo systematically investigate renal complications and their predictors in hypoparathyroid patients compared to matched individuals.DesignProspective observational study in 161 patients with chronic HPT.MethodsPatients received renal ultrasound, clinical and laboratory assessments. An individual 1:3 matching with participants from the German population-based Study of Health in Pomerania was performed.ResultsOf 161 patients (92% postoperative HPT), prevalence of eGFR <60ml/min/1.73m2 was 21%, hypercalciuria 41%. Compared to healthy individuals, HPT patients had a significantly lower eGFR (74.2 vs. 95.7 ml/min/1.73m², p<0.01). Renal ultrasound revealed calcifications in 10% (nephrocalcinosis in 7% and calculi in 3%). Patients with renal calcifications had higher levels of 24-hour urine calcium excretion (8.34 vs. 5.08 mmol/d, p=0.02), spot urine calcium excretion (4.57 vs. 2.01 mmol/L, p=0.01) and urine calcium-to-creatinine ratio (0.25 vs. 0.16, p<0.01) than patients without calcifications. Albumin-corrected calcium, phosphate, calcium-phosphate product, 25-hydroxyvitamin D in serum, eGFR, daily calcium intake or disease duration were not significantly different between these two groups. Including patients receiving rhPTH therapy, a lower serum phosphate concentration (odds ratio 1.364 [95% confidence interval (CI) 1.049-1.776], p<0.05) and a longer disease duration of HPT (odds ratio 1.063 [95% CI 1.021-1.106], p<0.01) were significant predictors for renal calcifications. Excluding patients receiving rhPTH therapy, a higher 24-hour urine calcium excretion (odds ratio 1.215 [95% CI 1.058-1.396], p<0.01) was a significant predictor for renal calcifications but not serum magnesium or disease duration.ConclusionsPrevalence of impaired renal function among patients with chronic HPT is increased and independent from visible renal calcifications. Depending on exclusion of patients with rhPTH therapy, regression analysis revealed disease duration and serum phosphate or disease duration and 24-hour urinary calcium excretion as predictors for renal calcifications.Clin Trials IdentifierNCT0558559

Changes in Plasma Metabolomic Profile Following Bariatric Surgery, Lifestyle Intervention or Diet Restriction—Insights from Human and Rat Studies

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

Computed tomography-3D-volumetry: a valuable adjunctive diagnostic tool after bariatric surgery

Aim: After bariatric surgery, a variety of complaints may arise. Identification of the causes of such symptoms is often challenging due to the postoperatively modified anatomy. While standard examinations with upper endoscopy and upper gastrointestinal series might miss the three-dimensional anatomic nature of the problem, quantitative three-dimensional computed tomography volumetry (3D-CT) of the upper gastrointestinal tract offers a novel, adjunctive examination, revealing the detailed anatomy. The aim of this study was to analyse the clinical value of 3D-CT in post-bariatric patients.Methods: Prospective data of 279 patients, who underwent 3D-CT due to complications after different bariatric procedures, were retrospectively analysed. Directly before examination, the surgical-modified stomach was distended with an effervescent-powder. CT images were 3D-reconstructed and, further, gastric volume was calculated.Results: In total, 279 patients were examined. Time between surgery and examination was significantly different between Roux-en-Y gastric bypass (n = 168) (54.3 ± 38.6 months) and sleeve gastrectomy (n = 78) (27.8 ± 21.7 months) (P = 0.0001). Others, less numerous, but included procedures were one-anastomosis/mini gastric bypass (n = 11), and dated procedures, such as the vertical banded gastrostomy. The examination allowed calculation of the gastric volume, and the 3D-reconstructions depicted accurately the pivotable anatomic details of the modified upper gastrointestinal tract with 360° view. As a robust result, patients with a higher gastric volume showed more weight regain after sleeve gastrectomy.Conclusion: 3D-CT is easy-to-perform and facilitates identification of the post-surgical three-dimensional gastric anatomy. It represents a valuable additional diagnostic tool in post-bariatric patients with post-procedural complications. 3D-CT might be an important preoperative tool prior to revisional surgery. In addition, this is the only exact and reproducible calculation of the gastric volume

Fast-track rescue weight reduction therapy to achieve rapid technical operability for emergency bariatric surgery in patients with life-threatening inoperable severe obesity - A proof of concept study

Background and aims: Severe obesity (BMI >= 60 kg/m(2)) in multimorbid patients can be acutely life-threatening. While emergency weight-loss surgery is urgently needed to preserve life, most patients are in an inoperable state. Pre-surgical bridging therapy is required to achieve technical operability through weight reduction. Standard bridging using an intragastric balloon (IB) can achieve operability in 6 months but is unsuitable for some patients in a critical condition. A non-invasive fast-track rescue therapy to achieve very rapid operability is urgently needed. We investigated whether a rescue weight reduction therapy (RWR) consisting of liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, a leucine-rich amino acid infusion and a hypocaloric diet, can accelerate readiness for emergency surgery in patients with acutely life-threatening severe obesity. Methods: In this proof-of-concept study, prospective data from patients treated with RWR (intervention group 1, n = 26) were mathematically matched with retrospective biometric data of 26 patients with severe obesity (historic control group 2) who underwent standard 6-month bridging with IB. A rating scale was developed to identify patients needing urgent fast-track bridging. Results: Rapid weight loss was observed in all patients on the RWR therapy. All achieved operability after a mean RWR bridging duration of 20.7 +/- 6.9 days. Baseline weight was 236.3 +/- 35.8 kg in group 1 compared with 230.1 +/- 32.7 kg in group 2. Mean body weight loss during RWR was 27.5 +/- 14.1 kg, compared with 20.9 +/- 10.5 kg in group 2 (P = 0.0629). Conclusions: Pre-operative bridging using liraglutide in combination with a leucine-rich amino acid infusion and hypocaloric diet was effective in all cases of acutely life-threatening severe obesity, achieving technical operability within only ca. 2-4 weeks. This therapy has potential as a life-saving rescue therapy for multimorbid patients with severe obesity who were previously untreatable. (C) 2022 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved

The German CaRe high registry for familial hypercholesterolemia – Sex differences, treatment strategies, and target value attainment

Background and aims: Familial hypercholesterolemia (FH) is among the most common genetic disorders in primary care. However, only 15% or less of patients are diagnosed, and few achieve the goals for low-density lipoprotein cholesterol (LDL-C). In this analysis of the German Cascade Screening and Registry for High Cholesterol (CaRe High), we examined the status of lipid management, treatment strategies, and LDL-C goal attainment according to the ESC/EAS dyslipidemia guidelines. Methods: We evaluated consolidated datasets from 1501 FH patients diagnosed clinically and seen either by lipid specialists or general practitioners and internists. We conducted a questionnaire survey of both the recruiting physicians and patients. Results: Among the 1501 patients, 86% regularly received lipid-lowering drugs. LDL-C goals were achieved by 26% and 10% of patients with atherosclerotic cardiovascular disease (ASCVD) according to the 2016 and 2019 ESC/EAS dyslipidemia guidelines, respectively. High intensity lipid-lowering was administered more often in men than in women, in patients with ASCVD, at higher LDL-C and in patients with a genetic diagnosis of FH. Conclusions: FH is under-treated in Germany compared to guideline recommendations. Male gender, genetic proof of FH, treatment by a specialist, and presence of ASCVD appear to be associated with increased treatment intensity. Achieving the LDL-C goals of the 2019 ESC/EAS dyslipidemia guidelines remains challenging if pre-treatment LDL-C is very high

Combination chemotherapy in advanced adrenocortical carcinoma

BACKGROUND: Adrenocortical carcinoma is a rare cancer that has a poor response to cytotoxic treatment. METHODS: We randomly assigned 304 patients with advanced adrenocortical carcinoma to receive mitotane plus either a combination of etoposide (100 mg per square meter of body-surface area on days 2 to 4), doxorubicin (40 mg per square meter on day 1), and cisplatin (40 mg per square meter on days 3 and 4) (EDP) every 4 weeks or streptozocin (streptozotocin) (1 g on days 1 to 5 in cycle 1; 2 g on day 1 in subsequent cycles) every 3 weeks. Patients with disease progression received the alternative regimen as second-line therapy. The primary end point was overall survival. RESULTS: For first-line therapy, patients in the EDP–mitotane group had a significantly higher response rate than those in the streptozocin–mitotane group (23.2% vs. 9.2%, P<0.001) and longer median progression-free survival (5.0 months vs. 2.1 months; hazard ratio, 0.55; 95% confidence interval [CI], 0.43 to 0.69; P<0.001); there was no significant between-group difference in overall survival (14.8 months and 12.0 months, respectively; hazard ratio, 0.79; 95% CI, 0.61 to 1.02; P=0.07). Among the 185 patients who received the alternative regimen as second-line therapy, the median duration of progression-free survival was 5.6 months in the EDP–mitotane group and 2.2 months in the streptozocin–mitotane group. Patients who did not receive the alternative second-line therapy had better overall survival with first-line EDP plus mitotane (17.1 month) than with streptozocin plus mitotane (4.7 months). Rates of serious adverse events did not differ significantly between treatments. CONCLUSIONS: Rates of response and progression-free survival were significantly better with EDP plus mitotane than with streptozocin plus mitotane as first-line therapy, with similar rates of toxic events, although there was no significant difference in overall survival. (Funded by the Swedish Research Council and others; FIRM-ACT ClinicalTrials.gov number, NCT00094497.)Martin Fassnacht... David J. Torpy... et al