Bo Zerahn

Cross-talk between the heart and adipose tissue in cachectic heart failure patients with respect to alterations in body composition: A prospective study

OBJECTIVES Cardiac cachexia (CC) is associated with changes in body composition. Lipolysis and increased energy expenditure caused by A- and B natriuretic peptides (NPs) have been suggested to play a role in CC. We tested the hypothesis that neurohormones and adipokines are associated with body composition in CC and that a progressive loss of fat free mass (FFM) and fat mass (FM) takes place. METHODS Body composition with regard to FFM, FM, and body fat distribution was assessed by dual energy X-ray absorptiometry (DXA) in 19 non-diabetic patients with chronic heart failure (CHF) and CC and 38 controls (non-cachectic CHF and individuals with prior myocardial infarction-both n = 19) who were followed for 12 months. Biomarkers of neurohormonal stimulation, inflammation, and endothelial dysfunction were measured. RESULTS N-terminal proBNP (NT-proBNP), midregional proANP (MR-proANP), and total adiponectin were elevated in CHF (p<0.001) and correlated inversely to BMI and FM. An inverse correlation was observed between pro-adrenomedullin (MR-proADM) and FFM. During follow up body weight was unaltered in all groups even though FM increased by 1.35 kg (p<0.05) and FFM decreased by 0.5 kg (p<0.05) in CC patients. The latter correlated inversely to baseline NT-proBNP, MR-proANP, and MR-proADM (p<0.05). No correlation to changes in FM was found. CONCLUSIONS FM was associated with plasma NPs and total adiponectin at baseline; whereas changes in FM and FFM did not correlate to changes in NPs or adiponectin during follow up. Prospectively, FFM decreased but FM increased, despite stable body weight in CC.

Prospective analysis of a first MTP total joint replacement. Evaluation by bone mineral densitometry, pedobarography, and visual analogue score for pain.

BACKGROUND We hypothesized that a total replacement of the first metatarsophalangeal joint (MTP-1) would alter the walking pattern with medialisation of the ground reaction force (GRF) of the foot and subsequently cause an increase in bone mineral density (BMD) in the medial metatarsal bones and a decline of BMD in the lateral metatarsal bones. METHODS Twelve patients receiving total joint replacements (Roto-Glide(®)) of MTP-1 were enrolled in a prospective cohort. BMD and pedobarography of the heel bone and the metatarsal heads were performed preoperatively and at least 12 months postoperatively. RESULTS BMD in the lateral metatarsals and GRF under the lateral column of the operated feet decreased significantly on the operated feet. CONCLUSIONS Total joint replacement of MTP-1 tends to reduce GRF under the lateral column of the foot causing a corresponding decline in BMD and pedobarographic measures. Our findings support the further use of the Roto-Glide(®) prosthesis for osteoarthritis of the first metatarsophalangeal joint.

Incidence rate of symptomatic painless thyroiditis presenting with thyrotoxicosis in Denmark as evaluated by consecutive thyroid scintigraphies

Abstract Background. Painless thyroiditis (PT) is a transient kind of thyrotoxicosis, with lack of uptake on a thyroid scintigraphy in a non-tender thyroid gland, elevated anti-TPO antibodies, no fever, no history of increased iodine intake, and a normal sedimentation rate. The prevalence of PT varies hugely in the literature. Objective. To establish the incidence rate of PT in Denmark as well as to describe the phenotype of PT in more detail. Methods. Tc-99m pertechnetate scintigraphies were performed over a period of 9.75 years on 6022 consecutive patients (2349 had a thyrotoxic episode), and were divided into high or normal (5528), reduced (300) or lack of uptake (194). Patient records were evaluated: 292 with reduced, and 186 with lack of uptake. As a control measure, 230 consecutive thyrotoxic patients were also analyzed. Results. Based on scintigraphies, 12 patients had PT, 10 with lack of uptake and two with reduced, corresponding to an incidence rate of 0.49/100,000 person years. It was predicted, that only one patient among the newly diagnosed consecutive thyrotoxic cohort had PT. This patient was identified. The prevalence of PT among thyrotoxic patients was 0.51% as evaluated by scintigraphy, and 0.43% among the biochemically thyrotoxic patient cohort. Twenty-five percent had more than one thyrotoxic episode, 75% had at least one subsequent hypothyroid episode, and 33% developed permanent hypothyroidism. Conclusions. PT presenting with symptomatic thyrotoxicosis is an extremely rare disease in Denmark. Symptomatic PT presents most often with no uptake on a Tc-99m pertechnetate scintigraphy. Clinical follow-up is essential.

Long-term heart function after adjuvant epirubicin chemotherapy for breast cancer.

Abstract Background. Newer studies raise concern that adjuvant anthracycline treatment for breast cancer (BC) causes long-term heart damage. We aimed to examine whether heart failure or impairment could be demonstrated several years after low-dose epirubicin-based adjuvant treatment. Material and methods. The study-population was a historical cohort comprising 980 women who were randomized to receive one of two adjuvant regimens for treatment for BC: 7–9 cycles of cyclophosphamide-epirubicin-5-fluorouracil [CEF (600 + 60 + 600 mg/m2)] or cyclophosphamide-methotrexate-5- fluorouracil [CMF (600 + 40 + 600 mg/m2)]. We collected information in national registries of death and diagnoses and a sample of 77 survivors was examined with tissue-Doppler imaging (TDI), echocardiography, radionuclide ventriculography and N-terminal-pro-B-type-natriuretic peptide (NT-proBNP), an established marker for heart failure. Results and conclusion. Median follow-up was 12 years (39 days–20 years). Fifty-one percent had died. Incidence of CHF was 2.6/1000/year and equal in the treatment groups. In the sample, individuals who had received CEF showed no cardiac impairment when compared to individuals who received CMF. NT-proBNP-levels were within normal limits but higher in the CEF-group than in the CMF-group (confidence limits 105–226%, p = 0.03). Results of our study seem reassuring regarding the long-term risk of cardiotoxicity following low-dose adjuvant epirubicin treatment. However, larger, longitudinal studies are needed to establish the clinical implications.

Interstudy repeatability of left and right ventricular volume estimations by serial-gated tomographic radionuclide angiographies using a cadmium-zinc-telluride detector gamma camera

Estimation of left ventricular ejection fraction (LVEF) with 99MTc‐HSA equilibrium radionuclide angiography (RA) is frequently used for assessing cardiac function. The purpose of this study was to investigate the interstudy repeatability of left (LV) and right (RV) ventricular volume and ejection fraction estimations, using a cadmium‐zinc‐telluride (CZT) SPECT camera.

Progressive strength training to prevent LYmphoedema in the first year after breast CAncer – the LYCA feasibility study

Abstract Background: Lymphoedema is a common late effect after breast cancer (BC) that has no effective cure once chronic. Accumulating evidence supports progressive strength training (PRT) as a safe exercise modality in relation to the onset and exacerbation of lymphoedema. In the ‘preventive intervention against LYmphoedema after breast CAncer’ (LYCA) feasibility study we examined the feasibility of a program of PRT in the first year after BC to inform a planned randomised controlled trial (RCT). Material and methods: LYCA was a one-group prospective pilot trial inviting women operated with axillary lymph node dissection for unilateral primary BC. Participants exercised three times a week for 50 weeks (20 weeks supervised followed by 30 weeks home-based exercise). The program ensured slow individualised progression during the exercise program. The primary outcome was feasibility measured by eligibility and recruitment rates, as well as questionnaire-assessed satisfaction and adherence to exercise. Furthermore, we assessed arm interlimb volume difference by water displacement, muscle strength by dynamic and isometric muscle testing and range of movement in the shoulder by goniometry. Results: In August 2015, eight of 11 eligible patients accepted participation. Two of them dropped out early due to other health issues. The remaining six participants had high exercise adherence through the supervised period, but only three maintained this through the home exercise period. Program satisfaction was high and no serious adverse events from testing or exercising were reported. One participant presented with lymphoedema at 50-week follow-up. Muscle strength markedly increased with supervised exercise, but was not fully maintained through the home exercise period. Range of shoulder movement was not negatively affected by the program. Conclusion: Recruitment, testing, and exercise in LYCA was safe and feasible. At the 50-week follow-up, there was one case of lymphoedema. The LYCA program will be further tested in a full-scale RCT.

Weekly ascorbic acid infusion in castration-resistant prostate cancer patients: A single-arm phase II trial

Background Ascorbic acid (AA) has in vivo cytotoxic properties at concentrations that can only be achieved through intravenous (IV) administration in humans. Treatment with intravenous AA is widely and increasingly used in complementary medicine despite a lack of clinical evidence for the efficacy of this treatment. Methods This non-comparative, single-center, phase II trial included patients with chemotherapy-naïve, metastatic castration-resistant prostate cancer (mCRPC) from an outpatient clinic to evaluate the efficacy and safety of IV AA therapy. Patients received weekly infusions of AA (week 1, 5 g; week 2, 30 g; and weeks 3–12, 60 g) followed by efficacy evaluation at 12 weeks. The primary endpoint for efficacy was a 50% reduction in the prostate-specific antigen (PSA) level. The secondary endpoints included changes in health-related quality of life (HRQoL), biomarkers of bone metabolism, inflammation and bone scans. Clinicaltrials.gov identifier: NCT01080352. Results Twenty-three patients were enrolled in this study, and 20 completed the efficacy evaluation at 12 weeks. The mean baseline PSA level was 43 µg/L. No patient achieved a 50% PSA reduction; instead, a median increase in PSA of 17 µg/L was recorded at week 12. Among the secondary endpoints, no signs of disease remission were observed. In total, 53 adverse events (AEs) were recorded. Eleven were graded as “serious”. Three AEs were directly related to AA, and all of which were related to fluid load. Conclusions Infusion with 60 g of AA did not result in disease remission. This study does not support the use of intravenous AA outside clinical trials.

The Effect of 99mTc on Dual-Energy X-Ray Absorptiometry Measurement of Body Composition and Bone Mineral Density

Whether the γ-emission by radioisotopes influences the outcome of dual-energy X-ray absorptiometry (DXA) measurements is not fully elucidated. The aim of this study was to evaluate the effect of antecedent administration of 99mTc on DXA measurements regarding body composition and bone mineral density (BMD) using a K-edge filter scanner. The phantom measurements were performed by placing a urinary bladder phantom containing 40 mL of radioisotope solution on the pelvic region of a whole-body phantom. Twenty-seven patients attending our department for a routine examination involving the administration of a tracer marked with 99mTc were included. The patients underwent a whole-body DXA scan before and within 2 h after tracer injection using a GE/Lunar Prodigy scanner. Control scans were performed on 40 volunteers, who had not received any radioactive tracer. In both phantom and patient measurements, we found a significant dose-related decrease in fat mass and BMD and a corresponding increase in fat-free mass (p < 0.001). Based on the linear regression analysis, we suggest upper dose limits for the measurement of BMD at 0.77 μSv/h and body composition at 0.21 μSv/h (dose rate measured at a distance of 1m from the patient). Caution should be taken when interpreting the results of DXA scans performed in close temporal proximity to procedures involving the administration of 99mTc.

Three-phase bone scintigraphy for diagnosis of Charcot neuropathic osteoarthropathy in the diabetic foot – does quantitative data improve diagnostic value?

To investigate whether inclusion of quantitative data on blood flow distribution compared with visual qualitative evaluation improve the reliability and diagnostic performance of 99 mTc‐hydroxymethylene diphosphate three‐phase bone scintigraphy (TPBS) in patients suspected for charcot neuropathic osteoarthropathy (CNO) of the foot.

A suggestion of reference data for flow distribution at ankle and foot level using quantitative 99Tc‐HDP three‐phase bone scintigraphy

Aim:  To determine reference intervals for quantitative 99mTc‐hydroxymethylene diphosphonate (99mTc‐HDP) three‐phase bone scintigraphy regarding flow distribution at ankle and mid‐foot level.