Henrik S. Thomsen

Sucrose-sweetened beverages increase fat storage in the liver, muscle, and visceral fat depot: a 6-mo randomized intervention study

BACKGROUND The consumption of sucrose-sweetened soft drinks (SSSDs) has been associated with obesity, the metabolic syndrome, and cardiovascular disorders in observational and short-term intervention studies. Too few long-term intervention studies in humans have examined the effects of soft drinks. OBJECTIVE We compared the effects of SSSDs with those of isocaloric milk and a noncaloric soft drink on changes in total fat mass and ectopic fat deposition (in liver and muscle tissue). DESIGN Overweight subjects (n = 47) were randomly assigned to 4 different test drinks (1 L/d for 6 mo): SSSD (regular cola), isocaloric semiskim milk, aspartame-sweetened diet cola, and water. The amount of intrahepatic fat and intramyocellular fat was measured with (1)H-magnetic resonance spectroscopy. Other endpoints were fat mass, fat distribution (dual-energy X-ray absorptiometry and magnetic resonance imaging), and metabolic risk factors. RESULTS The relative changes between baseline and the end of 6-mo intervention were significantly higher in the regular cola group than in the 3 other groups for liver fat (132-143%, sex-adjusted mean; P < 0.01), skeletal muscle fat (117-221%; P < 0.05), visceral fat (24-31%; P < 0.05), blood triglycerides (32%; P < 0.01), and total cholesterol (11%; P < 0.01). Total fat mass was not significantly different between the 4 beverage groups. Milk and diet cola reduced systolic blood pressure by 10-15% compared with regular cola (P < 0.05). Otherwise, diet cola had effects similar to those of water. CONCLUSION Daily intake of SSSDs for 6 mo increases ectopic fat accumulation and lipids compared with milk, diet cola, and water. Thus, daily intake of SSSDs is likely to enhance the risk of cardiovascular and metabolic diseases. This trial is registered at clinicaltrials.gov as NCT00777647.

Pharmacokinetics of gadodiamide injection in patients with severe renal insufficiency and patients undergoing hemodialysis or continuous ambulatory peritoneal dialysis

RATIONALE AND OBJECTIVES The authors performed this study to evaluate the pharmacokinetics, dialysability, and safety of gadodiamide injection in patients with severely reduced renal function not treated with renal replacement therapy and patients undergoing hemodialysis or continuous ambulatory peritoneal dialysis. MATERIALS AND METHODS Twenty-seven patients--nine with severely reduced renal function (glomerular filtration rate, 2-10 mL/min), nine undergoing hemodialysis, and nine undergoing continuous ambulatory peritoneal dialysis--were followed up for 5, 8, and 22 days, respectively, after receiving gadodiamide injection (0.1 mmol per kilogram body weight). RESULTS Gadodiamide injection caused no changes in renal function. In patients with severely reduced renal function, the elimination half-life of gadodiamide injection was prolonged (34.3 hours +/- 22.9) compared with data in healthy volunteers (1.3 hours +/- 0.25). An average of 65% of the gadodiamide injected was eliminated during a hemodialysis session. After 22 days of continuous ambulatory peritoneal dialysis, 69% of the total amount of gadodiamide was excreted; this reflects the low peritoneal clearance. In all patients, no metabolism or transmetallation of gadodiamide was found. There were no contrast material-related adverse events. CONCLUSION Gadodiamide is dialysable and can safely be used in patients with severely impaired renal function or those undergoing hemodialysis or continuous ambulatory peritoneal dialysis. No precautions to increase the elimination are necessary.

MRI bone oedema is the strongest predictor of subsequent radiographic progression in early rheumatoid arthritis. Results from a 2-year randomised controlled trial (CIMESTRA)

Objective: To identify predictors of radiographic progression in a 2-year randomised, double-blind, clinical study (CIMESTRA) of patients with early rheumatoid arthritis (RA). Methods: Patients with early RA (n = 130) were treated with methotrexate, intra-articular betamethasone and ciclosporin/placebo-ciclosporin. Baseline magnetic resonance imaging (MRI) of the wrist (wrist-only group, n = 130) or MRI of wrist and metacarpophalangeal (MCP) joints (wrist+MCP group, n = 89) (OMERACT RAMRIS), x-ray examination of hands, wrists and forefeet (Sharp/van der Heijde Score (TSS)), Disease Activity Score (DAS28), anti-cyclic citrullinated peptide antibodies (anti-CCP), HLA-DRB1-shared epitope (SE) and smoking status were assessed. Multiple regression analysis was performed with delta-TSS (0–2 years) as dependent variable and baseline DAS28, TSS, MRI bone oedema score, MRI synovitis score, MRI erosion score, anti-CCP, smoking, SE, age and gender as explanatory variables. Results: Baseline values: median DAS28 5.6 (range 2.4–8.0); anti-CCP positive 61%; radiographic erosions 56%. At 2 years: DAS28 2.0 (0.5–5.7), in DAS remission: 56%, radiographic progression 26% (wrist+MCP group, similar for wrist-only group). MRI bone oedema score was the only independent predictor of delta-TSS (wrist+MCP group: coefficient = 0.75 (95% CI 0.55 to 0.94), p<0.001; wrist-only group: coefficient = 0.59 (95% CI 0.40 to 0.77), p<0.001). Bone oedema score explained 41% of the variation in the progression of TSS (wrist+MCP group), 25% in wrist-only group (Pearson’s r = 0.64 and r = 0.50, respectively). Results were confirmed by sensitivity analyses. Conclusion: In a randomised controlled trial aiming at remission in patients with early RA, baseline RAMRIS MRI bone oedema score of MCP and wrist joints (and of wrist only) was the strongest independent predictor of radiographic progression in hands, wrists and forefeet after 2 years. MRI synovitis score, MRI erosion score, DAS28, anti-CCP, SE, smoking, age and gender were not independent risk factors. Trial registration number: NCT00209859.

High prevalence of nephrogenic systemic fibrosis in chronic renal failure patients exposed to gadodiamide, a gadolinium-containing magnetic resonance contrast agent.

Objective:Nephrogenic systemic fibrosis (NSF) is a serious disease affecting renal failure patients. It may be caused by some gadolinium (Gd)-containing contrast agents, including gadodiamide. The study aimed at estimating the prevalence of NSF after gadodiamide exposure for patients with chronic kidney disease (CKD). Materials and Methods:Retrospective cohort study of 190 consecutive nephrological patients in different categories of kidney function referred for gadodiamide-enhanced magnetic resonance imaging in the period January 1, 2004 to March 21, 2006. Results:Eighteen patients (18/190; 10%, 95% CI: 6%–15%) were diagnosed with NSF within a mean follow-up period of 29 months (range 16–43 months). All 18 cases had stage 5 CKD (ie, estimated glomerular filtration rate less than 15 mL/min/1.73 m2 or in dialysis therapy) at the time of their gadodiamide exposure. The prevalence of NSF among patients with stage 5 CKD at exposure (n = 102) was 18% (95% CI: 11%–27%). No cases were seen among 88 gadodiamide-exposed patients who had milder degrees of renal insufficiency (prevalence 0%, 95% CI: 0%–4%). Conclusions:The risk of NSF is unacceptably high among stage 5 CKD patients exposed to gadodiamide.

Ultrasonography of the metacarpophalangeal and proximal interphalangeal joints in rheumatoid arthritis: a comparison with magnetic resonance imaging, conventional radiography and clinical examination.

Signs of inflammation and destruction in the finger joints are the principal features of rheumatoid arthritis (RA). There are few studies assessing the sensitivity and specificity of ultrasonography in detecting these signs. The objective of the present study was to investigate whether ultrasonography can provide information on signs of inflammation and destruction in RA finger joints that are not available with conventional radiography and clinical examination, and comparable to the information provided by magnetic resonance imaging (MRI). The second to fifth metacarpophalangeal and proximal interphalangeal joints of 40 RA patients and 20 control persons were assessed with ultrasonography, clinical examination, radiography and MRI. With MRI as the reference method, the sensitivity, specificity and accuracy of ultrasonography in detecting bone erosions in the finger joints were 0.59, 0.98 and 0.96, respectively; they were 0.42, 0.99 and 0.95 for radiography. The sensitivity, specificity and accuracy of ultrasonography, with signs of inflammation on T1-weighted MRI sequences as the reference method, were 0.70, 0.78 and 0.76, respectively; they were 0.40, 0.85 and 0.72 for the clinical examination. With MRI as the reference method, ultrasonography had higher sensitivity and accuracy in detecting signs of inflammation and destruction in RA finger joints than did clinical and radiographic examinations, without loss of specificity. This study shows that ultrasonography has the potential to improve assessment of patients with RA.

Contrast-induced nephropathy in patients with chronic kidney disease undergoing computed tomography: a double-blind comparison of iodixanol and iopamidol.

Background:Based on a single clinical trial, it has been suggested that the contrast agent iodixanol, which is isotonic to human plasma, may be less nephrotoxic than other nonionic contrast agents in renally impaired patients after intra-arterial injection. We compared the effects on renal function of iopamidol-370 injection (796 mOsm/kg) and iodixanol-320 (290 mOsm/kg) in patients with chronic kidney disease undergoing contrast-enhanced multidetector computed tomography (CE-MDCT) examinations using a multicenter, double-blind, randomized, parallel-group design. Methods:A total of 166 patients with stable moderate-to-severe chronic kidney disease (screening and baseline serum creatinine, SCr, ≥1.5 mg/dL and/or creatinine clearance, CrCl, ≤60 mL/min) who were undergoing CE-MDCT of the liver or peripheral arteries were randomized to receive equi-iodine IV doses (40 gI) of either iopamidol-370 (370 mgI/mL) or iodixanol-320 (320 mgI/mL) at 4 mL/s. SCr and CrCl were obtained at screening, baseline, and at 48–72 ± 6 hours after dose (mean, 57.4 hours). Contrast-induced nephropathy (CIN) was defined as an absolute increase ≥0.5 mg/dL (44.2 &mgr;mol/L) and/or a relative increase in SCr ≥25% from baseline. Results:A total of 153 patients were included in the final analysis (13 patients excluded because of lack of follow-up, hemodialysis to remove contrast, average daily CrCl variation >1% at screening). The 2 study groups were comparable with regard to age, gender distribution, the presence of diabetes, concomitant medications, hydration, and contrast dose. Mean predose SCr was 1.6 ± 0.4 mg/dL in both groups (P = 0.9). An absolute increase ≥0.5 mg/dL (44.2 &mgr;mol/L) in SCr was observed in none of the patients receiving iopamidol-370 and in 2.6% (2/76) of patients receiving iodixanol-320 (95% confidence interval −6.2, 1.0, P = 0.2). A relative increase ≥25% in SCr occurred in 4% (3/77) of patients receiving iopamidol-370 and in 4% (3/76) of the patients receiving iodixanol-320 (95% confidence interval −6.2, 6.1, P = 1.0). Conclusion:The rate of CIN was similarly low in risk patients after intravenous administration of iopamidol-370 or iodixanol-320 for CE-MDCT.

Are bone erosions detected by magnetic resonance imaging and ultrasonography true erosions? A comparison with computed tomography in rheumatoid arthritis metacarpophalangeal joints

The objective of the study was, with multidetector computed tomography (CT) as the reference method, to determine whether bone erosions in rheumatoid arthritis (RA) metacarpophalangeal (MCP) joints detected with magnetic resonance imaging (MRI) and ultrasonography (US), but not with radiography, represent true erosive changes. We included 17 RA patients with at least one, previously detected, radiographically invisible MCP joint MRI erosion, and four healthy control individuals. They all underwent CT, MRI, US and radiography of the 2nd to 5th MCP joints of one hand on the same day. Each imaging modality was evaluated for the presence of bone erosions in each MCP joint quadrant. In total, 336 quadrants were examined. The sensitivity, specificity and accuracy, respectively, for detecting bone erosions (with CT as the reference method) were 19%, 100% and 81% for radiography; 68%, 96% and 89% for MRI; and 42%, 91% and 80% for US. When the 16 quadrants with radiographic erosions were excluded from the analysis, similar values for MRI (65%, 96% and 90%) and US (30%, 92% and 80%) were obtained. CT and MRI detected at least one erosion in all patients but none in control individuals. US detected at least one erosion in 15 patients, however, erosion-like changes were seen on US in all control individuals. Nine patients had no erosions on radiography. In conclusion, with CT as the reference method, MRI and US exhibited high specificities (96% and 91%, respectively) in detecting bone erosions in RA MCP joints, even in the radiographically non-erosive joints (96% and 92%). The moderate sensitivities indicate that even more erosions than are seen on MRI and, particularly, US are present. Radiography exhibited high specificity (100%) but low sensitivity (19%). The present study strongly indicates that bone erosions, detected with MRI and US in RA patients, represent a loss of calcified tissue with cortical destruction, and therefore can be considered true bone erosions.

The Active Trial: Comparison of the Effects on Renal Function of Iomeprol-400 and Iodixanol-320 in Patients With Chronic Kidney Disease Undergoing Abdominal Computed Tomography

Background:We performed a multicenter, double-blind, randomized, parallel-group study to compare the renal effects of iomeprol-400 and iodixanol-320 in patients with preexisting chronic kidney disease undergoing contrast-enhanced multidetector computed tomography of the liver. Methods:One hundred forty-eight patients with moderate-to-severe chronic kidney disease, ie, serum creatinine (SCr) ≥1.5 mg/dL (132.6 &mgr;mol/L) and/or calculated creatinine clearance (CrCl) <60 mL/min, undergoing contrast-enhanced multidetector computed tomography of the liver were randomized to equi-iodine doses (40 gI) of either the low-osmolar agent iomeprol-400 (400 mgI/mL, 726 mOsm/kg, N = 76) or the isotonic agent iodixanol-320 (320 mgI/mL, 290 mOsm/kg, N = 72), injected intravenously at 4 mL/S, followed by a bolus of 20 mL normal saline solution at the same rate. SCr was obtained at screening, baseline and at 48 to 72 hours postdose. SCr measurements and CrCl calculations were performed by a central laboratory. Contrast-induced nephropathy (CIN) was defined as an absolute SCr increase of ≥0.5 mg/dL (44.2 &mgr;mol/L) from baseline to 48 to 72 hours postdose. Mean SCr changes from baseline were also assessed. A Renal Safety Review Board comprised 3 medical experts reviewed the renal safety data, demographics, medical history, CIN risk factors, concomitant medications, and hydration status of each subject in a blinded manner. Results:The 2 study groups were comparable with regard to age, gender distribution, concomitant nephrotoxins, hydration status, and total iodine dose; however, the iomeprol-400 group showed a significantly higher proportion of patients with diabetes mellitus (P = 0.02). Baseline SCr was 1.7 ± 0.6 mg/dL (150.3 ± 53.0 &mgr;mol/L) in the iomeprol-400 group and 1.7 ± 0.7 mg/dL (150.3 ± 61.9 &mgr;mol/L) in the iodixanol-320 group (P = 0.87). Predose CrCl was 41.5 ± 13.1 mL/Min in the iomeprol-400 group and 43.0 ± 13.3 mL/Min in the iodixanol-320 group (P = 0.49). Five of 72 patient receiving iodixanol-320 (6.9%) and none of the patients receiving iomeprol-400 showed an increase of ≥0.5 mg/dL (44.2 &mgr;mol/L) from baseline [P = 0.025, 95% CI (−12.8%, −1.1%)]. The mean SCr change from baseline was significantly higher (P = 0.017 ANCOVA) after iodixanol-320 (0.06 ± 0.27) than after iomeprol-400 (−0.04 ± 0.19). Conclusions:The incidence of CIN was significantly higher after IV administration of iodixanol-320 than iomeprol-400. The mean rise in SCr from baseline was also higher in patients receiving iodixanol.

Prednisolone treatment affects the performance of the QuantiFERON gold in-tube test and the tuberculin skin test in patients with autoimmune disorders screened for latent tuberculosis infection†‡

Background: During screening for latent tuberculosis infection (LTBI), before anti‐tumor‐necrosis‐factor‐&agr; treatment, most patients are already receiving immunosuppressive therapy. The objective was to evaluate the performance of the QuantiFERON Gold In‐Tube (QFT‐IT) and the Tuberculin Skin Test (TST). Methods: A prospective multicenter study included 248 patients with ulcerative colitis (39), Crohns disease (54), rheumatoid arthritis (111), and spondylo‐arthropathy (44). Results: QFT‐IT was positive in 7/248 (3%), negative in 229 (92%), and indeterminate in 12 (5%). TST was positive in 54/238 (23%) patients. Chest x‐ray was suspect for tuberculosis in 5/236 (2%), and 35/167 (21%) had ≥1 risk‐factors for infection with Mycobacterium tuberculosis. The main finding was a pronounced negative effect on QFT‐IT and TST performance associated with prednisolone treatment. During prednisolone treatment interferon gamma (IFN‐&ggr;) response to mitogen stimulation was impaired (median IFN‐&ggr; response 4.9 IU/mL; interquartile range [IQR] 0.8 to ≥10.0) compared to patients 1) not receiving corticosteroids (median ≥10.0; IQR 5.0 to ≥10.0; P = 0.0015) or 2) receiving long‐acting corticosteroids (median >10.0; IQR 9.7 to >10.0; P = 0.0058). Prednisolone treatment was strongly associated with negative TST, adjusted odds ratio (AOR) 0.22 (0.1–0.8; P = 0.018), and with an increased risk of indeterminate QFT‐IT results AOR 16.1 (4.1–63.2; P < 0.001), whereas no negative effect was found for long‐acting corticosteroids. Doses of ≥10 mg prednisolone were associated with a 27% risk of indeterminate results. Single use of azathioprine, methotrexate, or 5‐aminosalicylate (5‐ASA) did not affect the test results. Conclusions: Oral prednisolone severely suppressed QFT‐IT and TST performance, whereas the long‐acting corticosteroids methotrexate, azathioprine, and 5‐ASA did not have a similar detrimental effect. Patients should be screened for LTBI with QFT‐IT or TST prior to initiation of prednisolone therapy and negative QFT‐IT or TST results interpreted with caution in patients treated with any corticosteroid until further data are available. (Inflamm Bowel Dis 2011;)

Contrast-Induced Nephropathy: The Wheel Has Turned 360 Degrees

Contrast-induced nephropathy (CIN) has been a hot topic during the last 5 years due its association with increased morbidity and mortality. CIN is an important complication, particularly in patients with advanced chronic kidney disease (CKD) associated with diabetes mellitus. Methods to diminish the incidence of CIN have been highly contentious. They include choice of contrast, pharmacologic manipulation, and volume expansion. The pathophysiology of this complication remains uncertain, but reduction in renal blood flow and direct toxicity of tubular cells has been implicated. More than 900 publications under the heading CIN have been published during the last 5 years. Fewer than 5% of these publications are randomized prospective controlled studies. In spite of the large number of reports on CIN, very little has been changed. The use of the smallest possible dose of low- or iso-osmolar contrast media, volume expansion, stopping nephrotoxic drugs, and avoiding repeat contrast injections within 48 hours remain the most effective approach to reduce the risk of CIN.