Paul Cronin

Meta-analysis: effectiveness of drugs for preventing contrast-induced nephropathy.

Context Contrast-induced nephropathy is a common cause of acute renal failure in hospitalized patients. Clinicians use a variety of contrast agents to reduce the risk for contrast-induced nephropathy, including N-acetylcysteine, theophylline, fenoldopam, dopamine, furosemide, mannitol, and bicarbonate. Contribution Although all of the agents included in this analysis reduced the risk for contrast-induced nephropathy, this meta-analysis of 33 trials involving 3622 patients found the strongest evidence for the effectiveness of N-acetylcysteine, mannitol, and theophylline when compared with periprocedural hydration alone. Caution Available studies examined laboratory end points (such as an increase in serum creatinine levels) rather than clinical end points (such as dialysis or death). The Editors Contrast-induced nephropathy, defined as an increase in serum creatinine greater than 25% or 44.2 mol/L (>0.5 mg/dL) within 3 days of intravascular contrast administration in the absence of an alternative cause, is the third most common cause of new acute renal failure in hospitalized patients (1, 2). Contrast-induced nephropathy develops in 0% to 10% of patients with normal renal function (3). However, the incidence may be as high as 25% in patients with preexisting renal impairment or certain risk factors, such as diabetes, congestive heart failure, advanced age, and concurrent administration of nephrotoxic drugs (3). Large doses of intravenous contrast and use of high-osmolar contrast agents in patients with renal impairment also increase the risk for contrast-induced nephropathy (46). High-osmolar contrast agents are more rarely used now. The risk difference between iso-osmolar agents, such as iodixanol, and low-osmolar agents, such as iopamidol, ioxaglate, or iohexol, is less clear (79). Most episodes of contrast-induced nephropathy are not detected clinically because patients are asymptomatic. However, contrast-induced nephropathy may increase the risk for renal failure and is associated with dialysis, prolonged hospital stay, increased health care costs, potentially irreversible reduction in renal function, and death (10). Use of preprocedural fluids and low-osmolar or iso-osmolar contrast agents has been shown to decrease the risk for contrast-induced nephropathy (1113). These measures suffice for many patients; however, the risk is reduced but not eliminated in some patientseven when iso-osmolar contrast is used (14, 15). Other studies have evaluated the use of N-acetylcysteine, theophylline, fenoldopam, and other agents as preventive strategies in contrast-induced nephropathy; the results have been heterogeneous and are difficult to compare across the different treatment strategies. Given the widespread use of iodinated intravascular contrast agents, an improved understanding of the potential value of these agents has important patient safety and cost implications. We conducted a meta-analysis of the literature to quantify the effects of individual strategies on the prevention of contrast-induced nephropathy and to facilitate comparison of preventive effects across strategies. Methods Study Search Strategy We performed a computerized search by using standard meta-analytic techniques (16) to identify relevant articles in MEDLINE (from 1966 through 3 November 2006), EMBASE (1980 through November 2006), PubMed, Web of Knowledge (Current Contents Connect, Web of Science, BIOSIS Previews, and ISI Proceedings for the latest 5 years), and the Cochrane Library databases. For the MEDLINE search, we used the following combination of keywords: [renal failure or kidney failure to include all subheadings] and [contrast media or iopamidol or iodine or ioxaglic acid or iodine compounds or iohexol or urography or drug hyper sensitivity or tomography, X ray computed or diatrizoate] and [hydration or fluid therapy or water or dehydration or skin or nutritional support or body water] and [clinical trial or randomized, controlled trial] and [prospective trial or prospective studies or clinical trials] and [adult or middle aged or aged] and [N-Acetylcysteine or acetylcysteine] or [theophylline] or [mannitol] or [dopamine] or [fenoldopam] or [bicarbonate]. For the PubMed, Cochrane Library Database, and Web of Knowledge searches, we used the search words renal failure, contrast medium, hydration, randomized, controlled trial, N acetyl cysteine, Theophylline, Mannitol, Fenoldopam, Dopamine and Bicarbonate. We included English-, French-, German-, Spanish- and Italian-language studies and clinical trials and excluded review articles and nonhuman studies. We combined this strategy with a manual search of reference lists from identified articles. Study Selection We included a study if 1 of the treatment groups received N-acetylcysteine, theophylline, fenoldopam, iloprost, statin, dopamine, trimetazidine, bicarbonate, ascorbic acid, furosemide, or mannitol. Criteria for inclusion were randomized, controlled trials that compared treatment with control; used intravenous iodinated contrast; explicitly defined contrast-induced nephropathy; and sufficiently reported data to construct a 22 table and calculate the primary effect measure (relative risk reduction). Where data were missing, we contacted the original authors for the relevant information. Data Extraction One reviewer examined the abstracts to determine whether the study met the inclusion and exclusion criteria. Two reviewers separately abstracted complete articles according to a standardized form for studies meeting criteria. Abstracted information included patient characteristics (mean age, proportion of men and patients with diabetes mellitus or hypertension, and mean baseline creatinine level), type of radiologic or cardiologic imaging, inclusion and exclusion criteria, type of contrast media and dose used, periprocedural hydration, specific definition of contrast-induced nephropathy, prophylactic agent dose and route, and serum creatinine level at baseline and at 48 hours after contrast injection. Analysis of Renoprotective Agents The primary outcome was the development of contrast-induced nephropathy, defined as an absolute increase in baseline serum creatinine greater than 44.2 mol/L (>0.5 mg/dL) or a relative increase greater than 25% at 48 hours after contrast injection. For trials missing this datum, we contacted the original authors to get the number of patients with this outcome. We calculated individual study relative risks and 95% CIs before aggregation. Subsequently, we obtained overall and subgroup summary risk ratios by random-effects modeling of the binary data from the multiple 22 tables. We used the method of DerSimonian and Laird (17), with the estimate of heterogeneity taken from the inverse variance fixed-effect model. We used the metan module in Stata, version 9.0 (Stata, College Station, Texas), to perform data synthesis. We performed subgroup evaluation of each therapeutic regimen. In studies comparing 2 dosage regimens of the same intervention with a single control group (1820), we considered the same-study dosage groups as representing a single intervention to avoid double-counting of shared control observations. When we identified only 1 study that examined a given therapy, we assigned that study to a group termed other and pooled data from all such studies together. This group included 1 study each on the use of iloprost; trimetazidine; mannitol; bicarbonate; ascorbic acid; and combinations of furosemide, dopamine, and mannitol and furosemide and dopamine. We used relative risk ratios to estimate the treatment effects. Assessment of Methodological Quality Criteria for quality assessment included concealment of allocation, similarity of both groups at baseline regarding prognostic indicators, eligibility criteria, blinding of patient, blinding of care provider, blinding of outcome assessor, point estimates and measures of variability for the primary outcome measure, and inclusion of an intention-to-treat analysis (21). Any disagreements in abstracted data between the reviewers were adjudicated by a third reviewer. We explored potential heterogeneity in estimates of treatment efficacy attributable to each quality criterion by using meta-regression. Assessment of Heterogeneity We used Forest plots to visualize the extent of heterogeneity among studies. We also examined I 2, a standard test for heterogeneity that measures the degree of inconsistency across studies. I 2 values, which range from 0% to 100%, describe the proportion of variation in treatment effect estimates that is due to genuine variation rather than sampling error (22). A value of 0% indicates no observed heterogeneity. Higgins and colleagues (22) suggest describing I 2 values of 25%, 50%, and 75% as low, moderate, and high, respectively. We obtained the group-specific and overall I 2 as standard output of the metan program. We performed an Egger precision-weighted linear regression test as a statistical test of funnel plot asymmetry and publication bias (23). All statistical analyses were performed with Stata. Results Study Identification Our initial search yielded 619 citations and references. We excluded 531 studies on the basis of our criteria, including nonclinical trials; trials not conducted on humans; trials not reported in English, French, German, Spanish, or Italian; trials reporting only nonnephropathy outcomes; and trials using nonclinical outcome measures, leaving 88 studies that met the inclusion criteria (Figure 1). We reviewed abstracts from the 88 articles and excluded an additional 23 trials, including nonrandomized clinical trials; trials not conducted on humans; trials not reported in English, French, German, Spanish, or Italian; trials reporting only nonnephropathy outcomes; and trials that used nonclinical outcome measures, leaving 65 studies for full publication review. The full articles were then reviewed, and a further 24 studies were excluded for reasons similar to t

Solitary Pulmonary Nodules: Meta-analytic Comparison of Cross-sectional Imaging Modalities for Diagnosis of Malignancy

PURPOSE To perform a meta-analysis to estimate the diagnostic accuracy of dynamic contrast material-enhanced computed tomography (CT) and magnetic resonance (MR) imaging, fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET), and technetium 99m ((99m)Tc) depreotide single photon emission computed tomography (SPECT) for evaluation of solitary pulmonary nodules (SPNs). MATERIALS AND METHODS Data sources were studies published in PubMed between January 1990 and December 2005. The selected investigations were comparative and noncomparative diagnostic cohort studies to examine the operating characteristics of the four imaging modalities for evaluation of SPNs, involving at least 10 enrolled participants with histologic confirmation and having sufficient data to calculate contingency tables. A random coefficient binary regression model with disease probability conditioned on test results was used to summarize test performance and construct summary receiver operating characteristic (ROC) curves. Sensitivities, specificities, predictive values, diagnostic odds ratios, and areas under the ROC curve were calculated. RESULTS Forty-four studies--10 dynamic CT, six dynamic MR, 22 FDG PET, and seven (99m)Tc-depreotide SPECT--met the inclusion criteria. (One study was included in both the FDG PET and SPECT groups.) Sensitivities, specificities, positive predictive values, negative predictive values, diagnostic odds ratios, and areas under the ROC curve were, respectively, 0.93 (95% confidence interval [CI]: 0.88, 0.97), 0.76 (95% CI: 0.68, 0.97), 0.80 (95% CI: 0.74, 0.86), 0.95 (95% CI: 0.93, 0.98), 39.91 (95% CI: 1.21, 81.04), and 0.93 (95% CI: 0.81, 0.97) for dynamic CT; 0.94 (95% CI: 0.91, 0.97), 0.79 (95% CI: 0.73, 0.86), 0.86 (95% CI: 0.83, 0.89), 0.93 (95% CI: 0.90, 0.96), 60.59 (95% CI: 5.56, 115.62), and 0.94 (95% CI: 0.83, 0.98) for dynamic MR; 0.95 (95% CI: 0.93, 0.98), 0.82 (95% CI: 0.77, 0.88), 0.91 (95% CI: 0.88, 0.93), 0.90 (95% CI: 0.85, 0.94), 97.31 (95% CI: 6.26, 188.37), and 0.94 (95% CI: 0.83, 0.98) for FDG PET; and 0.95 (95% CI: 0.93, 0.97), 0.82 (95% CI: 0.78, 0.85), 0.90 (95% CI: 0.83, 0.97), 0.91 (95% CI: 0.84, 0.98), 84.50 (95% CI: 34.28, 134.73), and 0.94 (95% CI: 0.83, 0.98) for (99m)Tc-depreotide SPECT. CONCLUSION Dynamic CT and MR, FDG PET, and (99m)Tc-depreotide SPECT are noninvasive and accurate in distinguishing malignant from benign SPNs; differences among these tests are nonsignificant.

Breast Cancer : Sentinel Node Identification and Classification after Neoadjuvant Chemotherapy—Systematic Review and Meta Analysis

RATIONALE AND OBJECTIVES Breast cancer is the leading cause of mortality in women worldwide. Lymphatic mapping with sentinel node biopsy has the potential to reduce the morbidity associated with breast cancer staging in women after neoadjuvant therapy. MATERIALS AND METHODS A systematic search of world literature between 1996 and 2007 of sentinel node mapping in patients with early-stage breast carcinoma after chemotherapy was undertaken. Potentially eligible studies were identified using database-specific search strategies incorporating appropriate Boolean combinations of the keywords sentinel node biopsy or sentinel node localization or lymphatic mapping; breast cancer or malignancy or neoplasm; and preoperative or neoadjuvant chemotherapy. The electronic searches were augmented with a manual search of reference lists from identified articles. Successful lymph node mapping, defined as successful identification rate (SIR), and false-negative rate (FNR) was summarized using a bivariate random effects mixed model. The extent of heterogeneity was assessed using the inconsistency statistic. The effect of study level covariates, such as use of immunohistochemistry or dual mapping technique, and individual quality criteria, such as study design or multi-institution participation, on SIR and FNR were analyzed using metaregression. RESULTS A total of 24 trials of 1799 subjects were reported that met eligibility criteria. All studies identified were published between 2000 and 2007. Lymph node involvement was found in 758 patients (37%) and ranged from 25% to 96% across studies. The proportion of patients who had successful lymph node mapping ranged from 63% to 100%, with 79% of studies reporting a rate of less than 95%. The summary successful identification rate was 0.896 (95% confidence interval [CI] 0.860-0.923) with moderate heterogeneity. The summary FNR was 0.084 (95% CI 0.064-0.109) with no significant heterogeneity. Increasing prevalence of lymph node involvement and same-day mapping and lymph node dissection both significantly reduced the FNR. CONCLUSIONS The present systematic review demonstrates robust estimates of successful identification rate and false-negative rates of sentinel lymph node mapping and biopsy after neoadjuvant therapy for early-stage breast cancer patients. With a 90% SIR and 8% FNR, this technique is a reliable tool for planning treatment in this population as an alternative to completion axillary lymph node dissection.

Dual-source computed tomography angiography for diagnosis and assessment of coronary artery disease: Systematic review and meta-analysis

BACKGROUND Development of an accurate test for noninvasive assessment of coronary arteries has been highly desirable. OBJECTIVES We performed a systematic review of diagnostic accuracy of the dual-source computed tomography (DSCT) in the diagnosis of coronary artery disease (CAD). METHODS Eight medical databases were searched for articles published from January 2005 through March 2011. Studies compared DSCT coronary angiography (DSCT-CA) and invasive coronary angiography, as the reference standard, in consecutive patients with suspected or known CAD, and relevant data were extracted by 2 independent reviewers. Summary diagnostic accuracies were calculated, and the effect of covariates on the diagnostic performance was evaluated by meta-regression. RESULTS Twenty-five studies were included. In per-patient analysis (n = 2303), pooled sensitivity was 99% [95% confidence interval (CI), 97%-99%] with specificity of 89% (95% CI, 84%-92%). The summary positive (+LR) and negative (-LR) likelihood ratios were 8.6 (95% CI, 6.4-11.6) and 0.02 (95% CI, 0.01-0.03), respectively. In per-segment analysis (n = 32,615), pooled sensitivity was 94% (95% CI, 92%-96%) with specificity of 97% (95% CI, 96%--98%). Summary +LR and -LR were 30.2 (95% CI, 22.1-43.5) and 0.06 (95% CI, 0.04-0.08), respectively. CONCLUSIONS DSCT-CA seems to be robust to elevate heart rates while maintaining a high level of diagnostic performance.

Challenges, Controversies, and Hot Topics in Pulmonary Embolism Imaging

OBJECTIVE The purpose of this article is to discuss the diagnostic role of pulmonary CT angiography (CTA) in the workup of pulmonary embolism (PE), including specific populations, and issues such as pulmonary CTA combined with indirect CT venography; radiation dose considerations; the management of isolated subsegmental PE; and new technologic developments, such as dual-source/dual-energy pulmonary CTA. CONCLUSION The role of pulmonary CTA will continue to grow with the emergence of MDCT and dual-energy CT and their improved capabilities. However, the need for any given CT examination should always be justified on the basis of the individual patients benefits and risks.

Preoperative MR Angiography in Free Fibula Flap Transfer for Head and Neck Cancer: Clinical Application and Influence on Surgical Decision Making

OBJECTIVE We review the fibular free flap surgical procedure to illustrate the usefulness of preoperative lower limb MR angiography and to show how calf vascular anatomy on MR angiography affects patient surgical management. CONCLUSION With its high positive predictive value and sensitivity, preoperative MR angiography can improve the chances of a successful outcome at the recipient mandibular site. It provides the reconstructive surgeon with a road map, revealing vascular anomalies or disease that could alter or contraindicate surgery.

Solitary pulmonary nodules and masses: a meta-analysis of the diagnostic utility of alternative imaging tests

The purpose was to assess the clinical utility of diagnostic tests for identifying malignancy within a solitary pulmonary nodule (SPN), and to create a nomogram or “look-up” table using clinical data and non-invasive radiology (positive) test results to estimate post-test probability of malignancy. Studies that examined computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET) and single photon emission computed tomography (SPECT) for the evaluation of SPN. Two reviewers independently abstracted data and assessed study quality. Study-specific and overall positive likelihood ratios (LRs) for each diagnostic test confirming a diagnosis of malignancy and negative LR for each diagnostic test excluding a diagnosis of malignancy within an SPN were calculated. Forty-four of 242 articles were included. Positive LRs for diagnostic tests were: CT 3.91 (95% confidence interval 2.42, 5.40), MRI 4.57 (3.03, 6.1), PET 5.44 (3.56, 7.32) and SPECT 5.16 (4.03, 6.30). Negative LRs were: CT 0.10 (0.03, 0.16), MRI 0.08 (0.03, 0.12), PET 0.06 (0.02, 0.09) and SPECT 0.06 (0.04, 0.08). Differences in performance for all tests were negligible; therefore, the clinician may confidently use any of the four tests presented in further evaluating an SPN. Given the low cost and prevalence of the technology, SPECT appears to be the leading choice for additional testing in SPN evaluation.

Aortic Branch Artery Pseudoaneurysms Accompanying Aortic Dissection. Part I. Pseudoaneurysm Anatomy

PURPOSE Small areas of blood flow are sometimes seen within an otherwise thrombosed false lumen on computed tomography (CT) scans of intramural hematomas of the aorta. These are blood-filled spaces that, although they have no apparent communication with the true lumen, appear isodense with the aorta on contrast-enhanced CT scans. The purpose of this report is to describe angiographic and autopsy studies that establish the nature of this entity and describe the principal CT features distinguishing it from a penetrating ulcer. MATERIALS AND METHODS Conventional angiographic and CT aorta findings in two cases with small collections of contrast material within an otherwise thrombosed false lumen of an aortic dissection are discussed. Also examined is another case with pathologic and histologic findings in addition to those of small collections of contrast material within an otherwise thrombosed false lumen of an aortic dissection, which illustrate the pathoanatomy of these lesions. RESULTS Angiographic and necropsy evidence shows that some of these lesions represent branch artery pseudoaneurysms and, as such, are secondary to an intramural hematoma, not the primary cause of it. CONCLUSIONS Difficulty in demonstrating communication between these collections of contrast material and the adjacent true lumen of the aorta on helical CT examinations and the characteristic location of these lesions along the nonpleural portion of the aortic circumference distinguish them from penetrating ulcers and should suggest the diagnosis of branch artery pseudoaneurysm. Demonstration of a branch artery originating from the contrast collection confirms the diagnosis. These branch artery pseudoaneurysms should be distinguished from penetrating atherosclerotic ulcers.

MRI Features of Hidradenitis Suppurativa and Review of the Literature

e describe a case of hidradeni-tis suppurativa in a 31-year-oldwoman with Crohn’s diseasediagnosed by MRI and con-firmed histologically. This disorder is rareand is characterized by recurrent abscesses,sinus tract formation, and scarring. It sharescharacteristics with acne conglobata, dissect-ing cellulitis of the scal p, and pilonidal sinus.The imaging findings include markedthickening of the skin, induration of the sub-cutaneous tissues, and formation of multiplesubcutaneous abscesses. The differential di-agnosis for these findings includes carbun-cles, lymphadenitis, and infected Bartholin’sor sebaceous cysts.Two previous cases are described in the ra-diology literature, with only one report de-scribing the MRI findings. However, these tworeports describe the imaging features of thecomplications of this disease rather than theimaging features of the disease. We describethe MRI features within the skin and subcuta-neous tissues of the typical form of hidradeni-tis suppurativa that, to our knowledge, has notbeen described previously. We also review theliterature. Hidradenitis suppurativa is usuallydiagnosed clinically. This disease may bechronic and progressive; there is no single ef-fective treatment, and surgical debridementmay be required. Our patient eventually re-quired radical surgery for treatment.

2016 SCCT/STR guidelines for coronary artery calcium scoring of noncontrast noncardiac chest CT scans: A report of the Society of Cardiovascular Computed Tomography and Society of Thoracic Radiology

The Society of Cardiovascular Computed Tomography (SCCT) and the Society of Thoracic Radiology (STR) have jointly produced this document. Experts in this subject have been selected from both organizations to examine subject-specific data and write this guideline in partnership. A formal literature review, weighing the strength of evidence has been performed. When available, information from studies on cost was considered. Computed tomography (CT) acquisition, CAC scoring methodologies and clinical outcomes are the primary basis for the recommendations in this guideline. This guideline is intended to assist healthcare providers in clinical decision making. The recommendations reflect a consensus after a thorough review of the best available current scientific evidence and practice patterns of experts in the field and are intended to improve patient care while acknowledging that situations arise where additional information may be needed to better inform patient care.