Morten Jørgensen

The impact of involved node, involved field and mantle field radiotherapy on estimated radiation doses and risk of late effects for pediatric patients with Hodgkin lymphoma

The use of radiotherapy (RT) is debated for pediatric patients with Hodgkin lymphoma (HL) due to the late effects of treatment. Radiation doses to the thyroid, heart, lungs, and breasts are compared with the extensive mantle field (MF), Involved Field RT (IFRT), Modified IFRT (mIFRT), and Involved Node RT (INRT) and the risk of radiation‐induced cardiovascular disease, secondary cancers, and the corresponding Life Years Lost (LYL) is estimated with each technique.

Safety and Efficacy of Liraglutide in Patients With Type 2 Diabetes and End-Stage Renal Disease: An Investigator-Initiated, Placebo-Controlled, Double-Blind, Parallel-Group, Randomized Trial.

OBJECTIVE To evaluate parameters related to safety and efficacy of liraglutide in patients with type 2 diabetes and dialysis-dependent end-stage renal disease (ESRD). RESEARCH DESIGN AND METHODS Twenty-four patients with type 2 diabetes and ESRD and 23 control subjects with type 2 diabetes and normal kidney function were randomly allocated to 12 weeks of double-blind liraglutide (titrated to a maximum dose of 1.8 mg) or placebo treatment (1:1) injected subcutaneously once daily as add on to ongoing antidiabetic treatment. Dose-corrected plasma trough liraglutide concentration was evaluated at the final trial visit as the primary outcome measure using a linear mixed model. RESULTS Twenty patients with ESRD (1:1 for liraglutide vs. placebo) and 20 control subjects (1:1) completed the study period. Dose-corrected plasma trough liraglutide concentration at the final visit was increased by 49% (95% CI 6–109, P = 0.02) in the group with ESRD compared with the control group. Initial and temporary nausea and vomiting occurred more frequently among liraglutide-treated patients with ESRD compared with control subjects (P < 0.04). Glycemic control tended to improve during the study period in both liraglutide-treated groups as assessed by daily blood glucose measurements (P < 0.01), and dose of baseline insulin was reduced in parallel (P < 0.04). Body weight was reduced in both liraglutide-treated groups (−2.4 ± 0.8 kg [mean ± SE] in the group with ESRD, P = 0.22; −2.9 ± 1.0 kg in the control group, P = 0.03). CONCLUSIONS Plasma liraglutide concentrations increased during treatment in patients with type 2 diabetes and ESRD, who experienced more gastrointestinal side effects. Reduced treatment doses and prolonged titration period may be advisable.

Gastrointestinal factors contribute to glucometabolic disturbances in nondiabetic patients with end-stage renal disease

Nondiabetic patients with end-stage renal disease (ESRD) have disturbed glucose metabolism, the underlying pathophysiology of which is unclear. To help elucidate this, we studied patients with ESRD and either normal or impaired glucose tolerance (10 each NGT or IGT, respectively) and 11 controls using an oral glucose tolerance test and an isoglycemic intravenous glucose infusion on separate days. Plasma glucose, insulin, glucagon, and incretin hormones were measured repeatedly, and gastrointestinal-mediated glucose disposal (GIGD) based on glucose amounts utilized, and incretin effect based on incremental insulin responses, were calculated. The GIGD was significantly reduced in both ESRD groups compared with controls. Incretin effects were 69% (controls), 55% (ESRD with NGT), and 41% (ESRD with IGT), with a significant difference between controls and ESRDs with IGT. Fasting concentrations of glucagon and incretin hormones were significantly increased in patients with ESRD. Glucagon suppression was significantly impaired in both groups with ESRD compared with controls, while the baseline-corrected incretin hormone responses were unaltered between groups. Thus, patients with ESRD had reduced GIGD, a diminished incretin effect in those with IGT, and severe fasting hyperglucagonemia that seemed irrepressible in response to glucose stimuli. These factors may contribute to disturbed glucose metabolism in ESRD.

Elimination and Degradation of Glucagon-like Peptide-1 and Glucose-Dependent Insulinotropic Polypeptide in Patients with End-Stage Renal Disease

CONTEXT The affect of the kidneys in elimination and degradation of intact incretin hormones and their truncated metabolites is unclear. OBJECTIVE To evaluate elimination and degradation of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) in patients with dialysis-dependent kidney failure. SETTING AND DESIGN Twelve non-diabetic patients treated with chronic hemodialysis and 12 control subjects were examined in a double-blind, randomized, matched observational study at the Department of Nephrology, Rigshospitalet, University of Copenhagen, Denmark. Over 4 separate study days, synthetic human GIP or GLP-1 was infused with or without concurrent inhibition of dipeptidyl peptidase 4 using sitagliptin or placebo. Plasma concentrations of glucose, insulin, glucagon, and intact and total forms of GLP-1 or GIP were measured repeatedly. Plasma half-life (T1/2), metabolic clearance rate (MCR), area under curve, and volume of distribution for intact and metabolite levels of GLP-1 and GIP were calculated. RESULTS Fasting concentrations of intact GLP-1 and GIP were increased in dialysis patients (P < .001) whereas fasting levels of GLP-1 and GIP metabolites did not differ between groups (P > .738). MCRs of intact GLP-1 and GIP, and the GLP-1 metabolite were reduced in dialysis patients on the placebo day (P < .009), and T1/2 of intact and metabolite forms of GLP-1 and GIP were comparable between groups (P > .121). CONCLUSIONS Unexpectedly, degradation and elimination of the intact and metabolite forms of GLP-1 and GIP seemed preserved, although reduced, in patients with dialysis-dependent kidney failure.

Safety and efficacy of liraglutide in patients with type 2 diabetes and end-stage renal disease: protocol for an investigator-initiated prospective, randomised, placebo-controlled, double-blinded, parallel intervention study

Introduction Diabetes is the leading cause of end-stage renal disease (ESRD). Owing to renal clearance, several antidiabetic agents cannot be used in patients with ESRD. The present protocol describes an investigator-initiated trial aiming to test safety and efficacy of treatment with the glucagon-like peptide-1 receptor agonist liraglutide in patients with type 2 diabetes and dialysis-dependent ESRD. Methods and analysis Twenty patients with type 2 diabetes and ESRD will be compared with 20 matched patients with type 2 diabetes and normal kidney function in a randomised, parallel, placebo-controlled (1 : 1), double-blinded setting. All participants will receive 12 weeks of daily treatment with liraglutide/placebo in an individually titrated dose of 0.6, 1.2 or 1.8 mg. Over nine visits, plasma liraglutide, glycaemic control, β-cell response, cardiovascular parameters, various biomarkers and adverse events will be assessed. The primary endpoint will be evaluated from dose-corrected plasma trough liraglutide concentration at the final trial visit to determine potential accumulation in the ESRD group. Ethics and dissemination The study has been approved by the Danish Medicines Agency, the Scientific-Ethical Committee of the Capital Region of Denmark and the Danish Data Protection Agency. An external monitoring committee (The Good Clinical Practice Unit at Copenhagen University Hospitals) will oversee the study. The results of the study will be presented at national and international scientific meetings, and publications will be submitted to peer-reviewed journals. Trial registration ClinicalTrials.gov Identifier: NCT01394341

Postprandial responses of incretin and pancreatic hormones in non-diabetic patients with end-stage renal disease

BACKGROUND Patients with end-stage renal disease (ESRD) have glucometabolic disturbances resulting in a high prevalence of prediabetes. The underlying pathophysiology remains unclear, but may prove important for the strategies employed to prevent progression to overt diabetes. Meal-induced release of the insulinotropic gut-derived incretin hormones and pancreatic hormones play a critical role in the maintenance of a normal postprandial glucose tolerance. METHODS We studied patients with ESRD and either normal (n = 10) or impaired (n = 10) glucose tolerance, and control subjects (n = 11). Plasma concentrations of glucose, insulin, glucagon, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and paracetamol were measured repeatedly during a standardized 4-h liquid meal including 1.5 g paracetamol (added for evaluation of gastric emptying). RESULTS Fasting glucose and postprandial glucose responses were comparable between groups (P > 0.082). Patients with ESRD exhibited higher fasting levels of GIP and glucagon compared with controls (P < 0.001). Baseline-corrected GLP-1 and glucagon responses were enhanced (P < 0.002), baseline-corrected insulin responses and insulin excursions were reduced (P < 0.035), and paracetamol excursions were delayed (P < 0.024) in patients with ESRD compared with controls. None of the variables differed between the two ESRD subgroups. CONCLUSIONS Non-diabetic patients with ESRD were characterized by reduced postprandial insulin responses despite increased secretion of the insulinotropic incretin hormone GLP-1. Fasting levels and baseline-corrected responses of glucagon were elevated and gastric emptying was delayed in the ESRD patients. These perturbations seem to be caused by uraemia per se and may contribute to the disturbed glucose metabolism in ESRD patients.

A Retrospective Evaluation of the Benefit of Referring Pediatric Cancer Patients to an External Proton Therapy Center

Pediatric cancer patients requiring radiation therapy (RT) have been routinely assessed and referred to proton therapy (PT) at an external institution. The benefit of the delivered PT compared to the state‐of‐the‐art intensity modulated x‐ray RT (XT) at the home institution was evaluated.

Contrasting groups’ standard setting for consequences analysis in validity studies: reporting considerations

BackgroundThe contrasting groups’ standard setting method is commonly used for consequences analysis in validity studies for performance in medicine and surgery. The method identifies a pass/fail cut-off score, from which it is possible to determine false positives and false negatives based on observed numbers in each group. Since groups in validity studies are often small, e.g., due to a limited number of experts, these analyses are sensitive to outliers on the normal distribution curve.MethodsWe propose that these shortcomings can be addressed in a simple manner using the cumulative distribution function.ResultsWe demonstrate considerable absolute differences between the observed false positives/negatives and the theoretical false positives/negatives. In addition, several important examples are given.ConclusionsWe propose that a better reporting strategy is to report theoretical false positives and false negatives together with the observed false positives and negatives, and we have developed an Excel sheet to facilitate such calculations.Trial registrationNot relevant.

Clearance of glucoregulatory peptide hormones during haemodialysis and haemodiafiltration in non-diabetic end-stage renal disease patients

BACKGROUND Patients with end-stage renal disease (ESRD) have increased fasting concentrations and disturbed postprandial responses of several glucoregulatory hormones. We aimed to evaluate the impact of high-flux haemodialysis (HD) and high-volume haemodiafiltration (HDF) on fasting and postprandial plasma levels of glucoregulatory pancreatic and gut peptide hormones in ESRD patients. METHODS Ten non-diabetic HD-treated ESRD patients were included to undergo a 3-h standardized liquid mixed meal test 1 h into an HD and an HDF, respectively. On a third, optional, examination day, the meal test was performed without concurrent dialysis treatment. Concentrations of glucose, C-peptide, insulin, glucagon, glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide were measured in plasma and dialysate. RESULTS Ten participants completed the meal test during HD, eight completed the meal test during HDF and four completed the optional meal test without dialysis. All plasma hormone concentrations declined significantly during the first fasting hour of dialysis with no differences between HD and HDF. Significant clearance of the investigated hormones was observed for both dialysis modalities with significantly higher clearance of insulin, C-peptide and GIP during HDF compared with HD. The fractional appearance of hormones entering the utilized dialysate was higher during HDF. Both dialysis modalities reduced postprandial plasma hormone concentrations in a similar manner. CONCLUSIONS Our findings show that HD and HDF, respectively, significantly remove glucoregulatory peptide hormones from plasma of non-diabetic ESRD patients; a phenomenon which may affect the glucose metabolism in dialysis-treated ESRD patients.

A review of nasal, paranasal, and skull base tumors invading the orbit

Tumors that invade the orbit are uncommon. The majority are meningiomas arising from the sphenoid ridge (66%). Others are bone and cartilage tumors arising from the surrounding bones of the orbit, pituitary adenomas, and epithelial tumors arising from the paranasal sinuses and nasal cavity. Meningiomas occur more often in women, whereas epithelial tumors have a predilection for men. Meningiomas and epithelial tumors typically present in the sixth decade of life, whereas bone tumors tend to affect individuals in their third decade of life. Patients often present with a combination of ophthalmological and otorhinolaryngological symptoms, including proptosis, pain, decreased visual acuity, restrictions in motility of the eye, epistaxis, and nasal obstruction. Sarcomas and benign bone and cartilage tumors arise from surrounding structures, whereas carcinomas usually arise from the paranasal sinuses. Surgery is the mainstay of treatment. Depending on the aggressiveness and histology of the tumor, surgery may be combined with radiation and chemotherapy. The prognosis is generally poor, but varies depending on histology and cell origin, size of the tumor, and degree of invasion. Meningiomas and benign bone tumors have the best prognoses. Sinonasal undifferentiated carcinomas, small-cell neuroendocrine carcinomas, osteosarcomas, and rhabdomyosarcomas have poorer prognoses.