Jeffrey D Blume

Accuracy of FDG-PET to diagnose lung cancer in areas with infectious lung disease: A meta-analysis

IMPORTANCE Positron emission tomography (PET) combined with fludeoxyglucose F 18 (FDG) is recommended for the noninvasive diagnosis of pulmonary nodules suspicious for lung cancer. In populations with endemic infectious lung disease, FDG-PET may not accurately identify malignant lesions. OBJECTIVES To estimate the diagnostic accuracy of FDG-PET for pulmonary nodules suspicious for lung cancer in regions where infectious lung disease is endemic and compare the test accuracy in regions where infectious lung disease is rare. DATA SOURCES AND STUDY SELECTION Databases of MEDLINE, EMBASE, and the Web of Science were searched from October 1, 2000, through April 28, 2014. Articles reporting information sufficient to calculate sensitivity and specificity of FDG-PET to diagnose lung cancer were included. Only studies that enrolled more than 10 participants with benign and malignant lesions were included. Database searches yielded 1923 articles, of which 257 were assessed for eligibility. Seventy studies were included in the analysis. Studies reported on a total of 8511 nodules; 5105 (60%) were malignant. DATA EXTRACTION AND SYNTHESIS Abstracts meeting eligibility criteria were collected by a research librarian and reviewed by 2 independent reviewers. Hierarchical summary receiver operating characteristic curves were constructed. A random-effects logistic regression model was used to summarize and assess the effect of endemic infectious lung disease on test performance. MAIN OUTCOME AND MEASURES The sensitivity and specificity for FDG-PET test performance. RESULTS Heterogeneity for sensitivity (I2 = 87%) and specificity (I2 = 82%) was observed across studies. The pooled (unadjusted) sensitivity was 89% (95% CI, 86%-91%) and specificity was 75% (95% CI, 71%-79%). There was a 16% lower average adjusted specificity in regions with endemic infectious lung disease (61% [95% CI, 49%-72%]) compared with nonendemic regions (77% [95% CI, 73%-80%]). Lower specificity was observed when the analysis was limited to rigorously conducted and well-controlled studies. In general, sensitivity did not change appreciably by endemic infection status, even after adjusting for relevant factors. CONCLUSIONS AND RELEVANCE The accuracy of FDG-PET for diagnosing lung nodules was extremely heterogeneous. Use of FDG-PET combined with computed tomography was less specific in diagnosing malignancy in populations with endemic infectious lung disease compared with nonendemic regions. These data do not support the use of FDG-PET to diagnose lung cancer in endemic regions unless an institution achieves test performance accuracy similar to that found in nonendemic regions.

Safety and Efficacy of 68Ga-DOTATATE PET/CT for Diagnosis, Staging and Treatment Management of Neuroendocrine Tumors

Our purpose was to evaluate the safety and efficacy of 68Ga-DOTATATE PET/CT compared with 111In-pentetreotide imaging for diagnosis, staging, and restaging of pulmonary and gastroenteropancreatic neuroendocrine tumors. Methods: 68Ga-DOTATATE PET/CT and 111In-pentetreotide scans were obtained for 78 of 97 consecutively enrolled patients with known or suspected pulmonary or gastroenteropancreatic neuroendocrine tumors. Safety and toxicity were measured by comparing vital signs, serum chemistry values, or acquisition-related medical complications before and after 68Ga-DOTATATE injection. Added value was determined by changes in treatment plan when 68Ga-DOTATATE PET/CT results were added to all prior imaging, including 111In-pentetreotide. Interobserver reproducibility of 68Ga-DOTATATE PET/CT scan interpretation was measured between blinded and nonblinded interpreters. Results: 68Ga-DOTATATE PET/CT and 111In-pentetreotide scans were significantly different in impact on treatment (P < 0.001). 68Ga-DOTATATE PET/CT combined with CT or liver MRI changed care in 28 of 78 (36%) patients. Interobserver agreement between blinded and nonblinded interpreters was high. No participant had a trial-related event requiring treatment. Mild, transient events were tachycardia in 1, alanine transaminase elevation in 1, and hyperglycemia in 2 participants. No clinically significant arrhythmias occurred. 68Ga-DOTATATE PET/CT correctly identified 3 patients for peptide-receptor radiotherapy incorrectly classified by 111In-pentetreotide. Conclusion: 68Ga-DOTATATE PET/CT was equivalent or superior to 111In-pentetreotide imaging in all 78 patients. No adverse events requiring treatment were observed. 68Ga-DOTATATE PET/CT changed treatment in 36% of participants. Given the lack of significant toxicity, lower radiation exposure, and improved accuracy compared with 111In-pentetreotide, 68Ga-DOTATATE imaging should be used instead of 111In-pentetreotide imaging where available.

Smaller Prostate Size Predicts High Grade Prostate Cancer at Final Pathology

PURPOSE Prostate size may influence the likelihood of detecting high grade prostate cancer at final pathology. We evaluated the association between prostate size and high grade (Gleason score 7 or greater) cancer. MATERIALS AND METHODS We analyzed data from 2,880 patients who underwent surgical treatment of prostate cancer between January 2000 and June 2008. Prostate size measured at prostatectomy was compared across a strata of clinical variables (age, body mass index, prostate specific antigen, biopsy Gleason score, clinical stage and year of surgery) and pathological outcomes (final Gleason score, extraprostatic extension, positive surgical margin, seminal vesicle invasion and lymph node involvement). Multivariate logistic regression was used to assess prostate size as a predictor of high grade cancer. RESULTS Older age, higher prostate specific antigen and later year of surgery were associated with larger gland size. Small prostate size was associated with high grade prostate cancer as well as extraprostatic extension and positive surgical margins on univariate and adjusted analysis. The probability of high grade disease decreased approximately 15% across the lowest vs highest prostate sizes. On multivariate analysis adjusted for age, race, prostate specific antigen, clinical stage, biopsy Gleason score and date of surgery prostate size was an important predictor of high grade disease (OR 0.94; 95% CI 0.92, 0.97 per 2 gm increments, p <0.001). The area under the ROC curve was 0.82 (95% CI 0.81, 0.84). CONCLUSIONS Prostate size was inversely associated with the risk of high grade cancer at final pathology. The ability to predict high grade disease could have implications for the management of prostate cancer.

Racial Variation in the Quality of Surgical Care for Prostate Cancer

PURPOSE Difference in the quality of care may contribute to the less optimal prostate cancer treatment outcomes among black men compared with white men. We determined whether a racial quality of care gap exists in surgical care for prostate cancer, as evidenced by racial variation in the use of high volume surgeons and facilities, and in the quality of certain outcome measures of care. MATERIALS AND METHODS We performed cross-sectional and cohort analyses of administrative data from the Healthcare Cost and Utilization Project all-payer State Inpatient Databases, encompassing all nonfederal hospitals in Florida, Maryland and New York State from 1996 to 2007. Included in analysis were men 18 years old or older with a diagnosis of prostate cancer who underwent radical prostatectomy. We compared the use of surgeons and/or hospitals in the top quartile of annual volume for this procedure, inpatient blood transfusion, complications, mortality and length of stay between black and white patients. RESULTS Of 105,972 patients 81,112 (76.5%) were white, 14,006 (13.2%) were black, 6,999 (6.6%) were Hispanic and 3,855 (3.6%) were all other. In mixed effects multivariate models, black men had markedly lower use of high volume hospitals (OR 0.73, 95% CI 0.70-0.76) and surgeons (OR 0.67, 95% CI 0.64-0.70) compared to white men. Black men also had higher odds of blood transfusion (OR 1.08, 95% CI 1.01-1.14), longer length of stay (OR 1.07, 95% CI 1.06-1.07) and inpatient mortality (OR 1.73, 95% CI 1.02-2.92). CONCLUSIONS Using an all-payer data set, we identified concerning potential quality of care gaps between black and white men undergoing radical prostatectomy for prostate cancer.

Acute Kidney Injury as a Risk Factor for Delirium and Coma during Critical Illness.

Rationale: Acute kidney injury may contribute to distant organ dysfunction. Few studies have examined kidney injury as a risk factor for delirium and coma. Objectives: To examine whether acute kidney injury is associated with delirium and coma in critically ill adults. Methods: In a prospective cohort study of intensive care unit patients with respiratory failure and/or shock, we examined the association between acute kidney injury and daily mental status using multinomial transition models adjusting for demographics, nonrenal organ failure, sepsis, prior mental status, and sedative exposure. Acute kidney injury was characterized daily using the difference between baseline and peak serum creatinine and staged according to Kidney Disease Improving Global Outcomes criteria. Mental status (normal vs. delirium vs. coma) was assessed daily with the Confusion Assessment Method for the ICU and Richmond Agitation‐Sedation Scale. Measurements and Main Results: Among 466 patients, stage 2 acute kidney injury was a risk factor for delirium (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.07‐2.26) and coma (OR, 2.04; 95% CI, 1.25‐3.34) as was stage 3 injury (OR for delirium, 2.56; 95% CI, 1.57‐4.16) (OR for coma, 3.34; 95% CI, 1.85‐6.03). Daily peak serum creatinine (adjusted for baseline) values were also associated with delirium (OR, 1.35; 95% CI, 1.18‐1.55) and coma (OR, 1.44; 95% CI, 1.20‐1.74). Renal replacement therapy modified the association between stage 3 acute kidney injury and daily peak serum creatinine and both delirium and coma. Conclusions: Acute kidney injury is a risk factor for delirium and coma during critical illness.

Trends in Estradiol During Critical Illness Are Associated with Mortality Independent of Admission Estradiol

BACKGROUND We have previously demonstrated that elevated serum estradiol (E(2)) at intensive care unit (ICU) admission is associated with death in the critically ill, regardless of sex. However, little is known about how changes in initial E(2) during the course of care might signal increasing patient acuity or risk of death. We hypothesized that changes from baseline serum E(2) during the course of critical illness are more strongly associated with mortality than a single E(2) level at admission. STUDY DESIGN A prospective cohort of 1,408 critically ill or injured nonpregnant adult patients requiring ICU care for ≥48 hours with admission and subsequent E(2) levels was studied. Demographics, illness severity, and E(2) levels were examined, and the probability of mortality was modeled with multivariate logistic regression. Changes in E(2) were examined by both analysis of variance and logistic regression. RESULTS Overall mortality was 14.1% [95% confidence interval (CI) 12.3% to 16%]. Both admission and subsequent E(2) levels were independently associated with mortality [admission E(2) odds ratio 1.1 (CI 1.0 to 1.2); repeat estradiol odds ratio 1.3 (CI 1.2 to1.4)], with subsequent values being stronger. Changes in E(2) were independently associated with mortality [odds ratio 1.1 (CI 1.0 to 1.16)] and improved regression model performance. The regression model produced an area under the receiver operating characteristic curve of 0.80 (CI 0.77 to 0.83). CONCLUSIONS Although high admission levels of E(2) are associated with mortality, changes from baseline E(2) in critically ill or injured adults are independently associated with mortality. Future studies of E(2) dynamics may yield new indicators of patient acuity and illuminate underlying mechanisms for targeted therapy.

The fellowship effect: how the establishment of a fellowship in female pelvic medicine and reconstructive surgery affected resident vaginal hysterectomy training

OBJECTIVE We report on trends in resident-performed vaginal hysterectomies before and after the establishment of a female pelvic medicine and reconstructive surgery fellowship at Vanderbilt University Medical Center. STUDY DESIGN We examined medical records and resident self-reports concerning all hysterectomies at our institution in an 8-year period: 4 years before fellowship and 4 years after. Route of hysterectomy, resident and fellow involvement, and division of attending surgeon were recorded from the electronic medical record. Resident Accreditation Council for Graduate Medical Education (ACGME) case log data were used to estimate the number of hysterectomies where residents reported themselves as the primary surgeon. RESULTS During the 8-year period of this study, 3317 hysterectomies were performed at our institution, 41% (1371) before and 59% (1946) after fellowship. Prior to fellowship, 29% (393) were vaginal, 56% (766) were abdominal, and 15% (212) were laparoscopic/robotic. After addition of fellowship, 23% (449) were vaginal, 31% (597) were abdominal, and 46% (900) were laparoscopic/robotic. Of the total vaginal hysterectomies (TVH), there was resident involvement in 98.0% (385) cases before fellowship and 98.2% (441) cases after fellowship. From the ACGME case log data, the resident identified himself/herself as the primary surgeon in 388 cases before and 393 cases after fellowship. During this time period, medical records indicate a fellow was involved in 42% (189) of TVH, with resident involvement in all but 5 of these procedures. CONCLUSION Frequency of resident involvement in TVH cases, either as primary surgeon or team member, remained constant after the addition of the female pelvic medicine and reconstructive surgery fellowship.

High‐Density Lipoprotein Cholesterol Concentration and Acute Kidney Injury After Cardiac Surgery

Background Acute kidney injury (AKI) after cardiac surgery is associated with increased short‐ and long‐term mortality. Inflammation, oxidative stress, and endothelial dysfunction and damage play important roles in the development of AKI. High‐density lipoproteins (HDLs) have anti‐inflammatory and antioxidant properties and improve endothelial function and repair. Statins enhance HDLs anti‐inflammatory and antioxidant capacities. We hypothesized that a higher preoperative HDL cholesterol concentration is associated with decreased AKI after cardiac surgery and that perioperative statin exposure potentiates this association. Methods and Results We tested our hypothesis in 391 subjects from a randomized clinical trial of perioperative atorvastatin to reduce AKI after cardiac surgery. A 2‐component latent variable mixture model was used to assess the association between preoperative HDL cholesterol concentration and postoperative change in serum creatinine, adjusted for known AKI risk factors and suspected confounders. Interaction terms were used to examine the effects of preoperative statin use, preoperative statin dose, and perioperative atorvastatin treatment on the association between preoperative HDL and AKI. A higher preoperative HDL cholesterol concentration was independently associated with a decreased postoperative serum creatinine change (P=0.02). The association between a high HDL concentration and an attenuated increase in serum creatinine was strongest in long‐term statin‐using patients (P=0.008) and was further enhanced with perioperative atorvastatin treatment (P=0.004) and increasing long‐term statin dose (P=0.003). Conclusions A higher preoperative HDL cholesterol concentration was associated with decreased AKI after cardiac surgery. Preoperative and perioperative statin treatment enhanced this association, demonstrating that pharmacological potentiation is possible during the perioperative period. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique Identifier: NCT00791648.

SCN5A (NaV1.5) Variant Functional Perturbation and Clinical Presentation: Variants of a Certain Significance

Background: Accurately predicting the impact of rare nonsynonymous variants on disease risk is an important goal in precision medicine. Variants in the cardiac sodium channel SCN5A (protein NaV1.5; voltage-dependent cardiac Na+ channel) are associated with multiple arrhythmia disorders, including Brugada syndrome and long QT syndrome. Rare SCN5A variants also occur in ≈1% of unaffected individuals. We hypothesized that in vitro electrophysiological functional parameters explain a statistically significant portion of the variability in disease penetrance. Methods: From a comprehensive literature review, we quantified the number of carriers presenting with and without disease for 1712 reported SCN5A variants. For 356 variants, data were also available for 5 NaV1.5 electrophysiological parameters: peak current, late/persistent current, steady-state V1/2 of activation and inactivation, and recovery from inactivation. RESULTS: We found that peak and late current significantly associate with Brugada syndrome (P<0.001; &rgr;=−0.44; Spearman rank test) and long QT syndrome disease penetrance (P<0.001; &rgr;=0.37). Steady-state V1/2 activation and recovery from inactivation associate significantly with Brugada syndrome and long QT syndrome penetrance, respectively. Continuous estimates of disease penetrance align with the current American College of Medical Genetics classification paradigm. Conclusions: NaV1.5 in vitro electrophysiological parameters are correlated with Brugada syndrome and long QT syndrome disease risk. Our data emphasize the value of in vitro electrophysiological characterization and incorporating counts of affected and unaffected carriers to aid variant classification. This quantitative analysis of the electrophysiological literature should aid the interpretation of NaV1.5 variant electrophysiological abnormalities and help improve NaV1.5 variant classification.

Latent variable modeling improves AKI risk factor identification and AKI prediction compared to traditional methods

BackgroundAcute kidney injury (AKI) is diagnosed based on postoperative serum creatinine change, but AKI models have not consistently performed well, in part due to the omission of clinically important but practically unmeasurable variables that affect creatinine. We hypothesized that a latent variable mixture model of postoperative serum creatinine change would partially account for these unmeasured factors and therefore increase power to identify risk factors of AKI and improve predictive accuracy.MethodsWe constructed a two-component latent variable mixture model and a linear model using data from a prospective, 653-subject randomized clinical trial of AKI following cardiac surgery (NCT00791648) and included established AKI risk factors and covariates known to affect serum creatinine. We compared model fit, discrimination, power to detect AKI risk factors, and ability to predict AKI between the latent variable mixture model and the linear model.ResultsThe latent variable mixture model demonstrated superior fit (likelihood ratio of 6.68 × 1071) and enhanced discrimination (permutation test of Spearman’s correlation coefficients, p < 0.001) compared to the linear model. The latent variable mixture model was 94% (−13 to 1132%) more powerful (median [range]) at identifying risk factors than the linear model, and demonstrated increased ability to predict change in serum creatinine (relative mean square error reduction of 6.8%).ConclusionsA latent variable mixture model better fit a clinical cohort of cardiac surgery patients than a linear model, thus providing better assessment of the associations between risk factors of AKI and serum creatinine change and more accurate prediction of AKI. Incorporation of latent variable mixture modeling into AKI research will allow clinicians and investigators to account for clinically meaningful patient heterogeneity resulting from unmeasured variables, and therefore provide improved ability to examine risk factors, measure mechanisms and mediators of kidney injury, and more accurately predict AKI in clinical cohorts.