Frank Stam

Hyperhomocysteinaemia in chronic kidney disease: focus on transmethylation

Abstract Hyperhomocysteinaemia almost invariably occurs in patients with end-stage renal disease (ESRD), but there is debate whether, within the group of ESRD patients, higher or lower plasma homocysteine concentrations are related to an increased risk of vascular disease. Homocysteine is thought to be vasculotoxic in high concentrations, but it may also lead to elevated levels of its precursor, S-adenosylhomocysteine (AdoHcy), which is a potent inhibitor of the transmethylation pathway, in which S-adenosylmethionine (AdoMet) donates its methyl group to a variety of acceptors. Impairment of this transmethylation pathway in ESRD patients has been suggested by high AdoHcy levels, decreased AdoMet/AdoHcy ratios, decreased protein repair requiring methyltransferases, and by DNA hypomethylation. Stable isotope techniques using labelled methionine have indeed demonstrated a decreased whole body transmethylation flux in ESRD patients. These studies have also shown that folic acid treatment is capable of restoring transmethylation rates to normal values. The remaining hyperhomocysteinaemia after folic acid treatment in ESRD is probably due to a persistent impairment of homocysteine clearance through transsulphuration. DNA hypomethylation with its concurrent alterations in gene expression is largely improved by folate treatment. The adverse effects of hyperhomocysteinaemia in ESRD may thus be related to impaired transmethylation. Normalisation of plasma homocysteine does not seem to be required to restore transmethylation to normal levels in ESRD patients.

18F-Fluorodeoxyglucose Positron Emission Tomography in Elderly Patients with an Elevated Erythrocyte Sedimentation Rate of Unknown Origin

Patients with an elevated erythrocyte sedimentation rate (ESR) and non-specific symptoms often pose a diagnostic dilemma. PET/CT visualises infection, inflammation and malignancy, all of which may cause elevated ESR. The objective of this study was to determine the contribution of 18F-fluorodeoxglucose positron emission tomography (PET/CT) in the diagnostic work-up of referred patients with an elevated ESR, in whom initial routine evaluation did not reveal a diagnosis. We conducted a combined retrospective (A) and prospective (B) study in elderly (>50 years) patients with a significantly elevated ESR of≥50 mm/h and non-specific complaints. In study A, 30 patients were included. Malignancy (8 patients), auto-inflammatory disease (8 patients, including 5 with large-vessel vasculitis) and infection (3 patients) were suggested by PET/CT. Two scans showed non-specific abnormalities and 9 scans were normal. Of the 21 abnormal PET/CT results, 12 diagnoses were independently confirmed and two alternative diagnosis were made. Two diagnoses were established in patients with a normal scan. In study B, 58 patients in whom a prior protocolised work-up was non-diagnostic, were included. Of these, 25 PET/CT-scans showed suspected auto-inflammatory disease, particularly large-vessel vasculitis (14 cases). Infection and malignancy was suspected in 5 and 3 cases, respectively. Seven scans demonstrated non-specific abnormalities, 20 were normal. Of the 40 abnormal PET/CT results, 22 diagnoses were confirmed, 3 alternative diagnoses were established. Only one diagnosis was established in the 20 patients with a normal scan. In both studies, the final diagnosis was based on histology, clinical follow-up, response to therapy or additional imaging. In conclusion, PET/CT may be of potential value in the diagnostic work-up of patients with elevated ESR if routine evaluation reveals no diagnosis. In particular, large-vessel vasculitis appears to be a common finding. A normal PET/CT scan in these patients suggests that it is safe to follow a wait-and-see policy.

The need for information among patients with hematological malignancies: Psychometric analyses of the 62-item Hematology Information Needs Questionnaire (HINQ-62)

The purpose of this study was to investigate the psychometric characteristics (content validity, internal consistency, and subscale structure) of the Hematology Information Needs Questionnaire-62 (HINQ-62), a patient reported outcome measure (PROM) for assessing the need for information among patients with hematological malignancies (HM-patients). Baseline data were used from a prospective study on the need for information which 336 newly diagnosed HM-patients had completed. In phase 1 (design phase), data from the first 135 patients were used and in phase 2 (validation phase), data from the remaining 201 HM patients were used. Content validity was analyzed by examining irrelevance of items. Items were considered irrelevant if more than 10% of the patients scored totally disagree on that item. The subscale structure of the HINQ-62 was investigated with Factor analysis (FA) (exploratory FA in phase 1 and confirmatory FA in phase 2). Cronbach’s α was computed for the different subscales and >.70 was considered as good internal consistency. None of the 62 HINQ-items were irrelevant. Exploratory FA identified five subscales: “Disease, symptoms, treatment and side-effects”, “Etiology, sleep and physical changes”, “Self-care”, “Medical tests and prognosis”, and “Psychosocial”. Root Mean Square Error of Approximation (RMSEA) among patients was 0.037 in phase 1 and 0.045 in phase 2. The comparative fit index (CFI)/Tucker-Lewis index -non-normed fit index among patients was 0.984/0.983 and 0.948/0.946, in phase 1 and 2 respectively. The internal consistency of the subscales was good, with Cronbach’s α 0.82–0.99. The HINQ is a valid PROM for assessing the need for information among Dutch HM-patients at diagnosis.

Long-term follow-up of the randomized (BIOMArCS-2) glucose trial

In the BIOMArCS-2 Glucose (Randomized Trial to Evaluate the Clinical Value of Intensive Glucose Monitoring and Regulation in Myocardial Infarction) trial, intensive glucose control (IGC) did not reduce myocardial infarction (MI) size in ST-segment–elevation MI or non–ST-segment–elevation MI patients presenting with hyperglycemia. In fact, IGC was associated with excess in-hospital death or MI (8 versus 1 event).1 Because these findings were unexpected, we executed a longer-term extension of the original trial cohort. In BIOMArCS-2 Glucose, 280 MI patients with admission blood glucose 140 to 288 mg/dL were randomly assigned to either IGC with intravenous insulin for 48 hours aiming for plasma levels of 85 to 110 mg/dL versus conventional management (control).1 The protocol was approved by the local Medical Ethics committee, and all patients provided written informed consent. In January 2016, median follow-up was 5.1 years (interquartile range, 4.0–6.2). We obtained data on vital status from municipal registries and on MI by reviewing medical records. MI was defined as typical chest pain accompanied by a rise of troponins. Follow-up on all-cause death and MI was 99.3% and 97.5% of patients, respectively. Patients with incomplete follow-up data were censored after their last hospital …

FRI0485 18f-fluorodeoxyglucose positron emission tomography in elderly patients with an elevated erythrocyte sedimentation rate of unknown origin

Background Patients with an elevated erythrocyte sedimentation rate (ESR) and non-specific symptoms often pose a diagnostic dilemma. PET/CT visualises infection, inflammation and malignancy, all of which may cause elevated ESR. Objectives To determine the contribution of 18F-fluorodeoxglucose positron emission tomography (PET/CT) in the diagnostic work-up of referred patients with an elevated ESR, in whom initial routine evaluation did not reveal a diagnosis, in order to detect large vessel vasculitis, among other diseases. Methods In a combined retrospective (A) and prospective (B) study PET/CT was performed in elderly patients (> 50 years of age) who presented with a significantly elevated ESR (≥ 50 mm/h) and non-specific complaints. In addition, a protocolised work-up (including chest X-ray, abdominal ultrasound and protein electrophoresis) was used in study B. In both studies, the final diagnosis was based on histology, clinical follow-up, response to therapy and/or additional imaging. Results In study A, 30 patients were included. PET/CT results suggested malignancy (8 patients), inflammatory disease (8 patients, including 5 with large-vessel vasculitis) and infection (3 patients). In 2 patients, non-specific abnormalities were found. Of the 21 patients with abnormal PET/CT results, final diagnoses were in accordance with PET/CT results in 12 patients (including 5 with large-vessel vasculitis). In 9 patients, abnormalities detected by PET/CT did not contribute to the final diagnosis. Two diagnoses (tendinitis and acute myeloid leukaemia) were established in 9 patients with a normal scan. In study B, 58 patients were included. PET/CT results suggested inflammatory disease (25 patients), particularly large-vessel vasculitis (14 cases), infection (5 patients) and malignancy (3 patients). 7 scans demonstrated non-specific abnormalities. Of the 40 patients with abnormal PET/CT results, final diagnoses were in accordance with PET/CT results in 22 patients (including 14 with large-vessel vasculitis). In 18 patients PET/CT abnormalities did not contribute to a final diagnosis. One final diagnosis (PMR) was established in 20 patients with a normal scan. Conclusions PET/CT may be of potential value in the diagnostic work-up of patients with non-specific complaints and an elevated ESR. In particular, large-vessel vasculitis appears to be a common finding. A normal PET/CT scan in these patients suggests that it is safe to follow a wait-and-see policy. Disclosure of Interest None Declared