Shokoufeh Khalatbari

Contrast Material–induced Nephrotoxicity and Intravenous Low-Osmolality Iodinated Contrast Material: Risk Stratification by Using Estimated Glomerular Filtration Rate

PURPOSE To determine the effect of intravenous (IV) low-osmolality iodinated contrast material (LOCM) on the development of post-computed tomography (CT) acute kidney injury (AKI), stratified by pre-CT estimated glomerular filtration rate (eGFR), in patients with stable renal function. MATERIALS AND METHODS Institutional review board approval was obtained and patient consent waived for this HIPAA-compliant, retrospective study. CT examinations performed over a 10-year period on unique adult inpatients with sufficient serum creatinine (SCr) data and stable renal function (difference between baseline and pre-CT SCr within 0.3 mg/dL and 50% of baseline) were identified. A 1:1 propensity score matched cohort analysis with multivariate analysis of effects was performed with post-CT AKI as the primary outcome measure (8826 nonenhanced and 8826 IV contrast agent-enhanced CT studies in 17 652 patients). Propensity matching was performed with respect to likelihood of receiving IV contrast material (19 tested covariates). Post-CT AKI with Acute Kidney Injury Network SCr criteria was the primary endpoint. A stepwise multivariate conditional logistic regression model was performed to identify the effect of IV LOCM on post-CT AKI. RESULTS After 1:1 propensity matching, IV LOCM had a significant effect on the development of post-CT AKI (P = .04). This risk increased with decreases in pre-CT eGFR (≥ 60 mL/min/1.73 m(2): odds ratio, 1.00; 95% confidence interval: 0.86, 1.16; 45-59 mL/min/1.73 m(2): odds ratio, 1.06; 95% confidence interval: 0.82, 1.38; 30-44 mL/min/1.73 m(2): odds ratio, 1.40; 95% confidence interval: 1.00, 1.97; <30 mL/min/1.73 m(2): odds ratio, 2.96; 95% confidence interval: 1.22, 7.17). CONCLUSION IV LOCM is a nephrotoxic risk factor in patients with a stable eGFR less than 30 mL/min/1.73 m(2), with a trend toward significance at 30-44 mL/min/1.73 m(2). IV LOCM does not appear to be a nephrotoxic risk factor in patients with a pre-CT eGFR of 45 mL/min/1.73 m(2) or greater.

Contrast Material–induced Nephrotoxicity and Intravenous Low-Osmolality Iodinated Contrast Material

PURPOSE To determine whether intravenous low-osmolality iodinated contrast material is associated with post-computed tomography (CT) acute kidney injury (AKI). MATERIALS AND METHODS Institutional review board approval was obtained and patient consent waived for this HIPAA-compliant retrospective study. CT examinations performed over a 10-year period in adult inpatients with sufficient serum creatinine (SCr) data were identified. A one-to-one propensity-matched matched cohort analysis with multivariate analysis of effects was performed with post-CT AKI as the primary outcome measure (10,121 unenhanced and 10,121 intravenous contrast-enhanced CT examinations in 20,242 patients). Propensity matching was performed with respect to likelihood of patient receiving intravenous contrast material (36 tested covariates). The primary endpoint was post-CT AKI by using Acute Kidney Injury Network SCr criteria; the secondary endpoint was post-CT AKI by using traditional SCr criteria for contrast material-induced nephrotoxicity (CIN; SCr increase ≥0.5 mg/dL [44.20 μmol/L] or ≥25%). Multivariate subgroup threshold analysis was performed (SCr <1.5 [<132.60 μmol/L]; ≥1.5 to ≥2.0 mg/dL [≥132.60 to ≥176.80 μmol/L]) and adjusted for assigned propensity scores. RESULTS Intravenous low-osmolality iodinated contrast material had a significant effect on the development of post-CT AKI for patients with pre-CT SCr levels of 1.6 mg/dL (141.44 μmol/L) or greater (odds ratio, 1.45; 95% confidence interval [CI]: 1.11, 1.89;P = .007). This effect strengthened as pre-CT SCr increased. Patients with stable SCr less than 1.5 mg/dL (132.60 μmol/L) were not at risk for developing CIN (P = .25, power > 95%). Both endpoints demonstrated similar results (eg, SCr ≥1.6 mg/dL [141.44 μmol/L] by using traditional CIN criteria: odds ratio, 1.64; 95% CI: 1.18, 2.28; P = .003). Post-CT AKI was prevalent in both the unenhanced and contrast-enhanced CT subgroups, and it increased with increases in pre-CT SCr. Many risk factors contributed to development of post-CT AKI, regardless of iodinated contrast material. CONCLUSION Intravenous low-osmolality iodinated contrast material is a nephrotoxic risk factor, but not in patients with a stable SCr level less than 1.5 mg/dL. Many factors other than contrast material can affect post-CT AKI rates.

Repeatability of Diagnostic Features and Scoring Systems for Hepatocellular Carcinoma by Using MR Imaging

PURPOSE To determine for expert and novice radiologists repeatability of major diagnostic features and scoring systems (ie, Liver Imaging Reporting and Data System [LI-RADS], Organ Procurement and Transplantation Network [OPTN], and American Association for the Study of Liver Diseases [AASLD]) for hepatocellular carcinoma (HCC) by using magnetic resonance (MR) imaging. MATERIALS AND METHODS Institutional review board approval was obtained and patient consent was waived for this HIPAA-compliant, retrospective study. The LI-RADS discussed in this article refers to version 2013.1. Ten blinded readers reviewed 100 liver MR imaging studies that demonstrated observations preliminarily assigned LI-RADS scores of LR1-LR5. Diameter and major HCC features (arterial hyperenhancement, washout appearance, pseudocapsule) were recorded for each observation. LI-RADS, OPTN, and AASLD scores were assigned. Interreader agreement was assessed by using intraclass correlation coefficients and κ statistics. Scoring rates were compared by using McNemar test. RESULTS Overall interreader agreement was substantial for arterial hyperenhancement (0.67 [95% confidence interval {CI}: 0.65, 0.69]), moderate for washout appearance (0.48 [95%CI: 0.46, 0.50]), moderate for pseudocapsule (0.52 [95% CI: 050, 0.54]), fair for LI-RADS (0.35 [95% CI: 0.34, 0.37]), fair for AASLD (0.39 [95% CI: 0.37, 0.42]), and moderate for OPTN (0.53 [95% CI: 0.51, 0.56]). Agreement for measured diameter was almost perfect (range, 0.95-0.97). There was substantial agreement for most scores consistent with HCC. Experts agreed significantly more than did novices and were significantly more likely than were novices to assign a diagnosis of HCC (P < .001). CONCLUSION Two of three major features for HCC (washout appearance and pseudocapsule) have only moderate interreader agreement. Experts and novices who assigned scores consistent with HCC had substantial but not perfect agreement. Expert agreement is substantial for OPTN, but moderate for LI-RADS and AASLD. Novices were less consistent and less likely to diagnose HCC than were experts.

Dose-toxicity relationship of gadoxetate disodium and transient severe respiratory motion artifact.

OBJECTIVE The purpose of this article is to determine whether there is a dose-toxicity relationship between gadoxetate disodium and transient severe respiratory motion artifact. MATERIALS AND METHODS Gadoxetate disodium-enhanced MRI studies (559 studies of 559 patients) using a fixed 20-mL (2 mL/s; n = 112) or 10-mL (1-2 mL/s; n = 447) volume at two health systems were included (dose range, 0.05-0.42 mL/kg; mean, 0.15 mL/kg; above-label dosing, 479 [86%]). Each dynamic phase was assigned a respiratory motion score from 1 (none) to 5 (nondiagnostic). Examinations with an unenhanced score of 1-2, arterial score of 4-5, and venous or late-dynamic scores of 1-3 were labeled as transient severe respiratory motion artifact. Stepwise multivariate logistic regression was performed. RESULTS The overall incidence of transient severe respiratory motion artifact was 12% (67/559; site 1, 15% [35/232]; site 2, 9.8% [32/327]). The administered volume of contrast material had a statistically significant effect (20 mL, 20% [22/112] vs 10 mL, 10%, [45/447]; multivariate p = 0.01; odds ratio, 2.1 [20 vs 10 mL]; 95% CI, 1.2-3.7). There was no dose-toxicity relationship for dose-by-weight (p = 0.61 [multivariate]) or above-label dosing (p = 0.88 [univariate]; 13% [10/80] rate for at- or below-label dosing vs 12% [57/479] rate for above-label dosing). Chronic obstructive pulmonary disease was the only non-dose-related predictor in the multivariate model (p < 0.0001; OR, 5.1 [95% CI, 2.5-11.5]; 39% [12/31] vs 10% [55/528]). CONCLUSION Gadoxetate disodium-associated transient severe respiratory motion artifact is significantly more common after 20-mL administration (2 mL/s) and occurs significantly more often in patients with chronic obstructive pulmonary disease. The volume-related effect suggests a nonallergiclike mechanism.

Interleukin 17 as a novel predictor of vascular function in rheumatoid arthritis

Background Rheumatoid arthritis (RA) is associated with enhanced cardiovascular (CV) risk and subclinical vascular disease. The proinflammatory milieu has been linked to premature atherosclerosis and endothelial dysfunction in RA. While interleukin 17 (IL-17) is considered pathogenic in RA, its role in determining vascular dysfunction in this disease has not been systematically assessed. Objectives To analyse candidate variables that might determine endothelial function in various vascular territories in a cohort of patients with RA receiving treatment with biological agents, with minimal traditional CV risk factors and low disease activity score. Methods Patients with RA (n=50) receiving stable treatment with biological agents underwent measurement of conduit artery endothelial function by brachial artery flow-mediated dilatation; arterial compliance by pulse wave velocity (PWV) assessment; and endothelium-dependent microvascular testing with Endo-Pat2000 device to assess the reactive hyperaemia index (RHI). IL-17 was quantified by ELISA and disease activity was assessed by 28-joint count Disease Activity Score. Results IL-17 was the main determinant of lower RHI in univariate and multivariate analysis. Traditional and non-traditional CV risk variables determined PWV, with a signifi cant positive association with IL-17 in univariate and multivariate analysis. In contrast, conduit endothelial function was mainly determined by rheumatoid factor titres in univariate and multivariate analysis. Anti-cyclic citrullinated peptide titres, specific disease-modifying antirheumatic drugs or biological agents and disease activity did not determine vascular function. Conclusion In patients with RA treated with biological agents, IL-17 is a main predictor of microvascular function and arterial compliance. This study suggests that IL-17 may play a significant role in development of endothelial dysfunction and cardiovascular disease in RA.

“Sweet spot” for endoleak detection: Optimizing contrast to noise using low keV reconstructions from fast-switch kVp dual energy CT

Objective To assess endoleak detection and conspicuity using low–kiloelectron volt (keV) monochromatic reconstructions of single-source (fast-switch kilovolt [peak]) dual-energy data sets. Methods With approval of the institutional review board, multiphasic dual-energy computed tomographic (CT) scans for aortic endograft surveillance were retrospectively reviewed for 39 patients. Two abdominal radiologists each performed 2 separate reading sessions, at 55-keV and standard 75-keV reconstruction, respectively. The readers tabulated endoleak presence, conspicuity on 1-to-5 scale, and type overall and in arterial and venous phases. Originally, dictated reports in medical records were used as criterion standard. Results Original dictations identified 19 endoleaks (9 abdominal and 10 thoracic), 13 of which were type II. The blinded readers (R1 and R2) exhibited good to very good intraobserver and interobserver agreement. Endoleak detection was higher at 55 keV than at 75 keV (sensitivity, 100% (95% confidence interval [CI], 82.4%–100.0%) and 84.2% (95% CI, 60.4–96.6%) at 55 keV vs 79% (95% CI, 54.4–94.0%) and 68.4% (95% CI, 43.5%–87.4%) at 75 keV in venous phase). Further, endoleak conspicuity ratings (where original dictation showed positive leak) were higher at 55 keV than at 75 keV, which was a significant difference for R2 in the overall ratings (P = 0.03) and for both readers in the venous phase ratings (R1, P = 0.01; R2, P = 0.004). There was no difference in endoleak type characterization between the kiloelectron volt levels. Conclusion Sensitivity for endoleak detection and overall endoleak conspicuity ratings were both higher at 55 keV than 75 keV, favoring the inclusion of a lower-energy monochromatic reconstruction for endoleak surveillance protocols with dual-energy computed tomography.

Self-expanding metal stents (SEMS) provide superior outcomes compared to plastic stents for pancreatic cancer patients undergoing neoadjuvant therapy

BACKGROUND Neoadjuvant therapy is increasingly utilized for pancreatic cancer patients to decrease tumor burden in anticipation of later surgical resection. However, infectious complications such as life threatening cholangitis may occur for those with biliary obstruction. We hypothesized that placement of metal rather than plastic stents in such patients results in lower rates of stent-related complications, leading to improved clinical outcomes. METHODS Retrospective cohort of pancreatic cancer patients treated by the University of Michigan Multidisciplinary Pancreatic Cancer Destination Program between January 2005 and June 2010. Only patients undergoing neoadjuvant therapy with one or more biliary stents placed for malignant obstruction were studied. Time to stent complication was compared between metal and plastic stents. The complication rate was estimated as the ratio of complications to total stent exposure time and 95% confidence intervals were calculated. RESULTS 52 patients met inclusion criteria. A total of 113 stents were placed in 52 patients (70 plastic, 43 metal). The complication rate was almost 7 times higher with plastic stents, 0.20 (95% CI, 0.14-0.30), than with metal stents, 0.03 (95% CI, 0.01-0.06). Moreover, the rate of hospitalization for stent-related complications was 3-fold higher in the plastic stent group than the metal stent group. The first quartile estimate of time to stent complication was almost 5 times longer for metal than for plastic stents (44 vs. 200 days) (P<0.0001). CONCLUSION Compelling evidence indicates that self-expanding metal, not plastic stents should be used for malignant biliary obstruction in patients undergoing neoadjuvant therapy for pancreatic cancer.

Effect of Abrupt Substitution of Gadobenate Dimeglumine for Gadopentetate Dimeglumine on Rate of Allergic-like Reactions

PURPOSE To evaluate the effect of abruptly substituting gadobenate dimeglumine for gadopentetate dimeglumine on allergic-like reactions. MATERIALS AND METHODS The institutional review board approved and waived patient consent for this HIPAA-compliant retrospective study. Allergic-like reactions related to gadolinium-based contrast media were assessed 2 years before and 3.5 years after gadobenate dimeglumine was substituted for gadopentetate dimeglumine. Reaction rates and severity were compared by using χ(2) tests, Fisher exact tests, odds ratios (ORs), and confidence intervals (CIs). RESULTS Allergic-like reactions (137 mild, 19 moderate, and six severe) occurred in 162 (0.15%) of 105 607 injections of gadolinium-based contrast media (gadopentetate dimeglumine, 31 540; gadobenate dimeglumine, 66 152; other, 7915). Gadobenate dimeglumine was associated with significantly more overall (0.19% [123 of 66 152] vs 0.08% [24 of 31 540]; OR, 2.4; 95% CI: 1.6, 3.8; P < .0001) and mild (0.16% [107 of 66 152] vs 0.06% [18 of 31 540]; OR, 2.8; 95% CI: 1.7, 4.7; P < .0001) allergic-like reactions than was gadopentetate dimeglumine. The reaction rate for gadobenate dimeglumine peaked (maximum per quarter, 0.38% [16 of 4262]; minimum per quarter, 0.07% [three of 4237]) in the 2nd year after it replaced gadopentetate dimeglumine (maximum per quarter, 0.10% [four of 4122]; minimum per quarter, 0.05% [two of 4222]) and then declined in the 3rd year. The final gadobenate dimeglumine reaction rate (last 3 quarters, 0.12% [17 of 14 387]) did not significantly differ from the original baseline reaction rate with gadopentetate dimeglumine. CONCLUSION After gadobenate dimeglumine was substituted for gadopentetate dimeglumine, a significant transient increase occurred in the frequency of reported allergic-like reactions that demonstrated a temporal pattern suggestive of the Weber effect (a transient increase in adverse event reporting that tends to peak in the 2nd year after a new agent or indication is introduced).

Vitamin D Deficiency, Interleukin 17, and Vascular Function in Rheumatoid Arthritis

Objective. Vitamin D deficiency is associated with increased cardiovascular (CV) disease risk in the general population. We examined the association between vitamin D deficiency and CV risk in rheumatoid arthritis (RA). Methods. We measured large artery compliance by pulse wave velocity and microvascular function by the reactive hyperemia index in patients with stable RA (n = 87). We quantified CV risk factors, serum 25-hydroxyvitamin D [25(OH)D], and interleukin 17 (IL-17), and RA disease activity by Disease Activity Score of 28 joints. We used linear regression to test associations between serum 25(OH)D and CV risk factors. Results. The mean serum 25(OH)D level in the cohort was 27.1 ± SD 13.6 ng/ml. Fifty-nine patients (68%) were vitamin D-insufficient (25(OH)D < 30 ng/ml; mean 20.2 ± 5.9 ng/ml) and of these, 25 (29%) were vitamin D-deficient (25(OH)D < 20 ng/ml; mean 14.4 ± 3.4 ng/ml). In the whole cohort and the vitamin D-insufficient group, serum 25(OH)D was inversely associated with IL-17 (log IL-17; β = −0.83, p = 0.04; β = −0.63, p = 0.004, respectively) by univariate analysis, which persisted after adjustment for season, and in multivariate analysis after adjustment for confounders (log IL-17; β = −0.74, p = 0.04; β = −0.53, p = 0.02). In vitamin D-deficient patients, serum 25(OH)D was positively associated with microvascular function by univariate and multivariate analysis after adjustment for confounders (β = 2.1, p = 0.04; β = 2.7, p = 0.04). Conclusion. Vitamin D deficiency in RA may affect Th17 responses and microvascular function. Maintaining normal serum vitamin D levels may protect against IL-17-mediated inflammation and vascular dysfunction in RA.

The Peroxisome Proliferator Activated Receptor-γ Pioglitazone Improves Vascular Function and Decreases Disease Activity in Patients With Rheumatoid Arthritis

Background Rheumatoid arthritis (RA) is associated with heightened mortality due to atherosclerotic cardiovascular disease (CVD). Inflammatory pathways in RA negatively affect vascular physiology and promote metabolic disturbances that contribute to CVD. We hypothesized that the peroxisome proliferator activated receptor‐γ (PPAR‐γ) pioglitazone could promote potent vasculoprotective and anti‐inflammatory effects in RA. Methods and Results One hundred forty‐three non‐diabetic adult RA patients (76.2% female, age 55.2±12.1 [mean±SD]) on stable RA standard of care treatment were enrolled in a randomized, double‐blind placebo controlled crossover trial of 45 mg daily pioglitazone versus placebo, with a 3‐month duration/arm and a 2‐month washout period. Pulse wave velocity of the aorta (PWV), brachial artery flow mediated dilatation (FMD), nitroglycerin mediated dilatation (NMD), microvascular endothelial function (reactive hyperemia index [RHI]), and circulating biomarkers of inflammation, insulin resistance, and atherosclerosis risk all were quantified. RA disease activity was assessed with the 28‐Joint Count Disease Activity Score (DAS‐28) C‐reactive protein (CRP) and the Short Form (36) Health Survey quality of life questionnaire. When added to standard of care RA treatment, pioglitazone significantly decreased pulse wave velocity (ie, aortic stiffness) (P=0.01), while FMD and RHI remained unchanged when compared to treatment with placebo. Further, pioglitazone significantly reduced RA disease activity (P=0.02) and CRP levels (P=0.001), while improving lipid profiles. The drug was well tolerated. Conclusions Addition of pioglitazone to RA standard of care significantly improves aortic elasticity and decreases inflammation and disease activity with minimal safety issues. The clinical implications of these findings remain to be established. Clinical Trial Registration URL: ClinicalTrials.gov Unique Identifier: NCT00554853.