Metabolic and hormonal response to intermittent high-intensity and continuous moderate intensity exercise in individuals with type 1 diabetes: a randomised crossover study.

AIMS/HYPOTHESIS To investigate exercise-related fuel metabolism in intermittent high-intensity (IHE) and continuous moderate intensity (CONT) exercise in individuals with type 1 diabetes mellitus. METHODS In a prospective randomised open-label cross-over trial twelve male individuals with well-controlled type 1 diabetes underwent a 90 min iso-energetic cycling session at 50% maximal oxygen consumption ([Formula: see text]), with (IHE) or without (CONT) interspersed 10 s sprints every 10 min without insulin adaptation. Euglycaemia was maintained using oral (13)C-labelled glucose. (13)C Magnetic resonance spectroscopy (MRS) served to quantify hepatocellular and intramyocellular glycogen. Measurements of glucose kinetics (stable isotopes), hormones and metabolites complemented the investigation. RESULTS Glucose and insulin levels were comparable between interventions. Exogenous glucose requirements during the last 30 min of exercise were significantly lower in IHE (p = 0.02). Hepatic glucose output did not differ significantly between interventions, but glucose disposal was significantly lower in IHE (p < 0.05). There was no significant difference in glycogen consumption. Growth hormone, catecholamine and lactate levels were significantly higher in IHE (p < 0.05). CONCLUSIONS/INTERPRETATION IHE in individuals with type 1 diabetes without insulin adaptation reduced exogenous glucose requirements compared with CONT. The difference was not related to increased hepatic glucose output, nor to enhanced muscle glycogen utilisation, but to decreased glucose uptake. The lower glucose disposal in IHE implies a shift towards consumption of alternative substrates. These findings indicate a high flexibility of exercise-related fuel metabolism in type 1 diabetes, and point towards a novel and potentially beneficial role of IHE in these individuals. TRIAL REGISTRATION ClinicalTrials.gov NCT02068638 FUNDING: Swiss National Science Foundation (grant number 320030_149321/) and R&A Scherbarth Foundation (Switzerland)

Molecular Cytogenetic Profiling Reveals Similarities and Differences Between Localized Nodal and Systemic Follicular Lymphomas

Recently, we have developed novel highly promising gene expression (GE) classifiers discriminating localized nodal (LFL) from systemic follicular lymphoma (SFL) with prognostic impact. However, few data are available in LFL especially concerning hotspot genetic alterations that are associated with the pathogenesis and prognosis of SFL. A total of 144 LFL and 527 SFL, enrolled in prospective clinical trials of the German Low Grade Lymphoma Study Group, were analyzed by fluorescence in situ hybridization to detect deletions in chromosomes 1p, 6q, and 17p as well as BCL2 translocations to determine their impact on clinical outcome of LFL patients. The frequency of chromosomal deletions in 1p and 17p was comparable between LFL and SFL, while 6q deletions and BCL2 translocations more frequently occurred in SFL. A higher proportion of 1p deletions was seen in BCL2-translocation–positive LFL, compared with BCL2-translocation–negative LFL. Deletions in chromosomes 1p, 6q, and 17p predicted clinical outcome of patients with SFL in the entire cohort, while only deletions in chromosome 1p retained its negative prognostic impact in R-CHOP–treated SFL. In contrast, no deletions in one of the investigated genetic loci predicted clinical outcome in LFL. Likewise, the presence or absence of BCL2 translocations had no prognostic impact in LFL. Despite representing a genetic portfolio closely resembling SFL, LFL showed some differences in deletion frequencies. BCL2 translocation and 6q deletion frequency differs between LFL and SFL and might contribute to distinct genetic profiles in LFL and SFL

Identity matters - perceptions of inter-professional feedback in the context of workplace-based assessment in Diabetology training: a qualitative study

Background Inter-professional collaboration is acknowledged as essential for quality patient-care. However, little is known about receptiveness to inter-professional feedback in the postgraduate training. This study explores, in light of social identity theory, the perceptions of residents, supervising physicians and allied health care professionals regarding inter-professional feedback in the context of workplace-based assessment. Methods For 6 months, residents in Diabetology at the University Hospital of Bern performed formative workplace-based assessments under direct observation of a supervising physician and an allied health care professional. Feedback from both observers was given to the resident after every assessment. Subsequently, focus group discussions were conducted to collect the participants’ perceptions of inter- and intra-professional feedback. Transcripts were analyzed qualitatively using a thematic analysis approach. Results We identified four main themes: (1) Identity and hierarchy; (2) Interdependence of feedback source and feedback content; (3) Impact on collaboration and patient-care; (4) Logistical and organizational requirements. While different social identities are the source of inter-professional hierarchies, they did not impede the receptiveness to feedback. Perceived trustworthiness of the feedback was attributed with more importance than professional affiliations, whereas intra-professional hierarchies between physicians led to the perception of a more summative nature of the feedback and rather impeded receptiveness. According to the participants, inter-professional feedback raised awareness of the working reality of other team members and had a positive impact on communication between the different professional groups. Moreover, participants reported positive response from patients regarding the inter-professional collaboration they experienced. Considerable organizational effort is required to enable the parallel observation of a resident’s consultation by a supervising physician and an allied health care professional. Conclusions Feedback from allied health care professionals can be a valuable learning resource for residents, given its role outside the sometimes conflicting area of intra-professional hierarchies. Inter-professional feedback in the context of workplace-based assessment carries the potential to strengthen collaboration between the different professional groups

How Identity Matters: A Qualitative Study of Perceptions of Interprofessional Feedback in Diabetology Training

Background: Little is known about receptiveness to interprofessional feedback in a postgraduate setting. This study explores, in light of social identify theory, the perceptions of residents, senior physicians and allied health care professionals regarding interprofessional feedback in the context of workplace-based assessment.Summary of Work: Residents in diabetology at the University Hospital of Bern, Switzerland, performed formative workplace-based assessments under direct observation of a senior physician and an allied health care professional. Feedback of both observers was given after every assessment to the resident. Focus group discussions were conducted to analyze the perception of participants, using a constructivist grounded theory approach.Summary of Results:While different social identities are the source of interprofessional hierarchies, they do not hinder the receptivity to feedback. Perceived trustworthiness of the feedback is given more importance than professional affiliations, whereas intraprofessional hierarchies between physicians led to the perception of a more summative character of the feedback and rather hindered receptivity. Interprofessional feedbacks strengthened collaboration but organizational support is required to promote such activities.Discussion and Conclusions:Despite disposing of a firm professional identity, residents in a postgraduate training in diabetology retained a positive attitude towards interprofessional feedback in the context of workplace-based assessments. Perceived credibility of the feedback source was crucial for acceptability of feedback. Interprofessional workplace-based assessments require institutional support, but might be a promotor for improving interprofessional collaboration.Take-home Messages: Interprofessional feedback from allied health care professionals can be a powerful resource for residents in the setting of a postgraduate subspecialty training, taking its role outside the sometimes conflicting area of intraprofessional hierarchies

Endokrinologische Notfälle

Die meisten Krankheitsbilder in der Endokrinologie zeichnen sich durch ein schleichendes Auftreten aus. Entsprechend besteht bei der Diagnosestellung und Therapieeinleitung meist keine Eile. Dennoch gibt es endokrinologische Notfallsituationen, in denen ein sofortiges Handeln nötig ist und die auch den Allgemeininternisten bekannt sein sollten. Für viele der hier vorgestellten Notfallsituationen gibt es keine prospektiv randomisierten, kontrollierten Studien. Die hier abgegebenen Empfehlungen beruhen daher auch auf Expertenmeinungen und Guidelines der einschlägigen Fachgesellschaften

Successful Treatment of Pituitary Germinoma with Etoposide, Cisplatin, Vincristine, Methotrexate and Bleomycin Chemotherapy Without Radiotherapy.

We report on the case of a 25-year-old man with pituitary germinoma. The patient had noticed polydipsia, reduced sexual function, and loss of body hair. Laboratory investigations confirmed panhypopituitarism including diabetes insipidus. Magnetic resonance imaging of the brain showed a 14×8.4 mm enhancing lesion of the pituitary stalk and histopathology of the neurosurgical biopsy confirmed pituitary germinoma. The patient was treated with 3 cycles of chemotherapy, consisting of 150 mg/m2 etoposide and 75 mg/m2 cisplatin, with the administration of intrathecal 12.5 mg methotrexate, on day one, alternating every 10 to 11 days with 1 mg/m2 vincristine, 1,000 mg/m2 methotrexate on day 1 and 30 mg/m2 bleomycin on day 2. MRI scans showed lasting complete remission more than a year after completion of chemotherapy. Intracranial germinomas are exquisitely sensitive to radiation. However, due to concerns of side-effects (radiation-associated tumour, relapse outside the radiation field, mental and pituitary hormonal dysfunction), and after discussing both approaches carefully with the patient, the decision was made to treat his pituitary germinoma with chemotherapy alone. Further studies should address the question as to whether a modulated approach, using radiotherapy only as a salvage in patients with relapse, might result in a better overall outcome, given the potentially harmful long-term side-effects of radiotherapy to the brain

A rare cause of a 46, XY disorder of sex development diagnosed in an adult patient

The defective conversion of testosterone to dihydrotestosterone due to a steroid 5-alpha-reductase 2 deficiency results in a unique form of 46, XY disorder of sexual development (DSD). Dihydrotestosterone is essential for the embryonic differentiation of the external male genitalia and the prostate. Steroid 5-alpha-reductase 2 deficiency is an autosomal recessive disorder in which genetic males have a predominantly female phenotype with female external genitalia but male internal urogenital tract. We describe the case of an adult patient having migrated from Pakistan to Switzerland in whom a steroid 5-alpha-reductase 2 deficiency was diagnosed at the age of 29. Molecular genetic analysis identified a homozygous point mutation in exon 4 of the 5-alpha-reductase 2 gene, leading to an amino acid change from glutamic acid to lysine. To our knowledge, this is the second case of this mutation in the steroid 5-alpha-reductase 2 gene (SRD5A2) which was first described in 1997 (Anwar et al.)

Round-robin test for the cell-of-origin classification of diffuse large B-cell lymphoma—a feasibility study using full slide staining

Diffuse large B-cell lymphoma (DLBCL) is subdivided by gene expression analysis (GEP) into two molecular subtypes named germinal center B-cell-like (GCB) and activated B-cell-like (ABC) after their putative cell-of-origin (COO). Determination of the COO is considered mandatory in any new-diagnosed DLBCL, not otherwise specified according to the updated WHO classification. Despite the fact that pathologists are free to choose the method for COO classification, immunohistochemical (IHC) assays are most widely used. However, to the best of our knowledge, no round-robin test to evaluate the interlaboratory variability has been published so far. Eight hematopathology laboratories participated in an interlaboratory test for COO classification of 10 DLBCL tumors using the IHC classifier comprising the expression of CD10, BCL6, and MUM1 (so-called Hans classifier). The results were compared with GEP for COO signature and, in a subset, with results obtained by image analysis. In 7/10 cases (70%), at least seven laboratories assigned a given case to the same COO subtype (one center assessed one sample as not analyzable), which was in agreement with the COO subtype determined by GEP. The results in 3/10 cases (30%) revealed discrepancies between centers and/or between IHC and GEP subtype. Whereas the CD10 staining results were highly reproducible, staining for MUM1 was inconsistent in 50% and for BCL6 in 40% of cases. Image analysis of 16 slides stained for BCL6 (N = 8) and MUM1 (N = 8) of the two cases with the highest disagreement in COO classification were in line with the score of the pathologists in 14/16 stainings analyzed (87.5%). This study describes the first round-robin test for COO subtyping in DLBCL using IHC and demonstrates that COO classification using the Hans classifier yields consistent results among experienced hematopathologists, even when variable staining protocols are used. Data from this small feasibility study need to be validated in larger cohorts

Metabolic Effects of Glucose-Fructose Co-Ingestion Compared to Glucose Alone during Exercise in Type 1 Diabetes

This paper aims to compare the metabolic effects of glucose-fructose co-ingestion (GLUFRU) with glucose alone (GLU) in exercising individuals with type 1 diabetes mellitus. Fifteen male individuals with type 1 diabetes (HbA1c 7.0% ± 0.6% (53 ± 7 mmol/mol)) underwent a 90 min iso-energetic continuous cycling session at 50% VO2max while ingesting combined glucose-fructose (GLUFRU) or glucose alone (GLU) to maintain stable glycaemia without insulin adjustment. GLUFRU and GLU were labelled with 13C-fructose and 13C-glucose, respectively. Metabolic assessments included measurements of hormones and metabolites, substrate oxidation, and stable isotopes. Exogenous carbohydrate requirements to maintain stable glycaemia were comparable between GLUFRU and GLU (p = 0.46). Fat oxidation was significantly higher (5.2 ± 0.2 vs. 2.6 ± 1.2 mg·kg−1·min−1, p &lt; 0.001) and carbohydrate oxidation lower (18.1 ± 0.8 vs. 24.5 ± 0.8 mg·kg−1·min−1 p &lt; 0.001) in GLUFRU compared to GLU, with decreased muscle glycogen oxidation in GLUFRU (10.2 ± 0.9 vs. 17.5 ± 1.0 mg·kg−1·min−1, p &lt; 0.001). Lactate levels were higher (2.2 ± 0.2 vs. 1.8 ± 0.1 mmol/L, p = 0.012) in GLUFRU, with comparable counter-regulatory hormones between GLUFRU and GLU (p &gt; 0.05 for all). Glucose and insulin levels, and total glucose appearance and disappearance were comparable between interventions. Glucose-fructose co-ingestion may have a beneficial impact on fuel metabolism in exercising individuals with type 1 diabetes without insulin adjustment, by increasing fat oxidation whilst sparing glycogen

Tumour cell characteristics and microenvironment composition correspond to clinical presentation in newly diagnosed nodular lymphocyte-predominant Hodgkin lymphoma

Different studies have characterized the microenvironment and its prognostic impact in classic Hodgkin lymphoma whereas such analyses are pending for nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). We thus investigated characteristics of tumour cells and microenvironment in NLPHL and evaluated possible correlations with the clinical presentation. Lymph node samples from 152 NLPHL patients who had first-line treatment within the randomized German Hodgkin Study Group HD16-HD18 trials were available and analysed with regard to IgD status and nuclear size of the tumour cells as well as presence of PD1-positive follicular T helper cells and CD163-positive macrophages in the microenvironment. While large tumour cell nuclei and high numbers of PD1-positive follicular T helper cells in the microenvironment were more common in patients presenting with early/intermediate stages than in patients with advanced-stage disease (p < 0.0001, unpaired t-test; p = 0.0022, Mann-Whitney test), no differences between risk groups were observed in terms of the IgD status of the tumour cells and the content of CD163-positive macrophages in the microenvironment. PD1-positive follicular T helper cells were present in both cases with typical and variant growth patterns and rosetting around the tumour cells was observed in 96% of patients, indicating an important role of PD1-positive follicular T helper cells in NLPHL