Tina M. Gunderson

AKI after Transcatheter or Surgical Aortic Valve Replacement

Transcatheter aortic valve replacement (TAVR) is an alternative to surgical aortic valve replacement (SAVR) for patients with symptomatic severe aortic stenosis who are at high risk of perioperative mortality. Previous studies showed increased risk of postoperative AKI with TAVR, but it is unclear whether differences in patient risk profiles confounded the results. To conduct a propensity-matched study, we identified all adult patients undergoing isolated aortic valve replacement for aortic stenosis at Mayo Clinic Hospital in Rochester, Minnesota from January 1, 2008 to June 30, 2014. Using propensity score matching on the basis of clinical characteristics and preoperative variables, we compared the postoperative incidence of AKI, defined by Kidney Disease Improving Global Outcomes guidelines, and major adverse kidney events in patients treated with TAVR with that in patients treated with SAVR. Major adverse kidney events were the composite of in-hospital mortality, use of RRT, and persistent elevated serum creatinine ≥200% from baseline at hospital discharge. Of 1563 eligible patients, 195 matched pairs (390 patients) were created. In the matched cohort, baseline characteristics, including Society of Thoracic Surgeons risk score and eGFR, were comparable between the two groups. Furthermore, no significant differences existed between the TAVR and SAVR groups in postoperative AKI (24.1% versus 29.7%; P=0.21), major adverse kidney events (2.1% versus 1.5%; P=0.70), or mortality >6 months after surgery (6.0% versus 8.3%; P=0.51). Thus, TAVR did not affect postoperative AKI risk. Because it is less invasive than SAVR, TAVR may be preferred in high-risk individuals.

Wall Apposition Is a Key Factor for Aneurysm Occlusion after Flow Diversion: A Histologic Evaluation in 41 Rabbits

BACKGROUND AND PURPOSE: Robust wall apposition for flow-diverter stents may be important for endothelialization. Using a large series of experimental aneurysms treated with the Pipeline Embolization Device, the objectives of this study were to 1) assess interobserver agreement for the evaluation of wall apposition on posttreatment DSA and evaluate its association with aneurysm occlusion, and 2) measure the relationship between wall apposition assessed with histology and aneurysm occlusion rate after treatment. MATERIALS AND METHODS: Saccular aneurysms were created in 41 rabbits and treated with the Pipeline Embolization Device. DSA was performed just after the deployment of the device and at follow-up. Three investigators independently graded wall apposition on posttreatment DSA as good or poor. A histopathologist blinded to the angiographic results graded the wall apposition on histologic samples. We examined the correlation between angiographic occlusion and wall apposition with histology and angiography. RESULTS: Wall apposition evaluated on histology was strongly associated with saccular aneurysm occlusion. Sensitivity and specificity of wall apposition to predict complete occlusion at follow-up were 76.9% and 84.0%, respectively, with an overall accuracy of 81.6%. In this experimental study, DSA was suboptimal to assess flow-diverter apposition, with moderate interobserver agreement and low accuracy. CONCLUSIONS: Good wall apposition is strongly associated with complete occlusion after flow-diverter therapy. In this study, DSA was suboptimal for assessing wall apposition of flow-diverter stents. These findings suggest that improved tools for assessing flow diverter–stent wall apposition are highly relevant.

Association between Obstructive Sleep Apnea and Acute Kidney Injury in Critically Ill Patients: A Propensity-Matched Study

Background/Aims: Obstructive sleep apnea (OSA) is a known risk factor for chronic kidney disease (CKD); however, its association with acute kidney injury (AKI) is not well documented. We aimed to study whether OSA is associated with the risk of AKI in the intensive care unit (ICU) setting. Methods: All consecutive adult Olmsted County, MN residents who were admitted in Mayo Clinic ICUs from January 1, 2010 to December 31, 2010 were screened. Chronic and acute risk factors were collected within the first 48 h of ICU admission. Logistic regression and propensity score matching were used to examine crude and adjusted associations of OSA with AKI. Results: Among 1,259 enrolled ICU patients, 183 patients had a diagnosis of OSA prior to the index ICU admission. Compared with non-OSA patients, the incidence of AKI in OSA patients was more frequent (41 vs. 57%, p < 0.001). In univariate analysis, it was found that CKD, age, gender, Caucasian race, congestive heart failure, cerebrovascular disease, diabetes mellitus, body mass index, and OSA were associated with AKI. In the multivariate model, following adjustment for age, gender, race, and chronic and acute risk factors, OSA was found to have an independent association with AKI (OR 1.53; 95% CI 1.04-2.24; p = 0.031). Among 176 propensity score matched pairs, there was a significant difference in the incidence of AKI between the OSA and non-OSA groups (OR 1.54; 95% CI 1.01-2.35; p = 0.04). Conclusions: The history of OSA diagnosed by polysomnography is associated with higher risk of AKI in critically ill patients.

First PET Imaging Studies With 63Zn-Zinc Citrate in Healthy Human Participants and Patients With Alzheimer Disease:

Abnormalities in zinc homeostasis are indicated in many human diseases, including Alzheimer disease (AD). 63Zn-zinc citrate was developed as a positron emission tomography (PET) imaging probe of zinc transport and used in a first-in-human study in 6 healthy elderly individuals and 6 patients with clinically confirmed AD. Dynamic PET imaging of the brain was performed for 30 minutes following intravenous administration of 63Zn-zinc citrate (∼330 MBq). Subsequently, body PET images were acquired. Urine and venous blood were analyzed to give information on urinary excretion and pharmacokinetics. Regional cerebral 63Zn clearances were compared with 11C-Pittsburgh Compound B (11C-PiB) and 18F-fluorodeoxyglucose (18F-FDG) imaging data. 63Zn-zinc citrate was well tolerated in human participants with no adverse events monitored. Tissues of highest uptake were liver, pancreas, and kidney, with moderate uptake being seen in intestines, prostate (in males), thyroid, spleen, stomach, pituitary, and salivary glands. Moderate brain uptake was observed, and regional dependencies were observed in 63Zn clearance kinetics in relationship with regions of high amyloid-β plaque burden (11C-PiB) and 18F-FDG hypometabolism. In conclusion, zinc transport was successfully imaged in human participants using the PET probe 63Zn-zinc citrate. Primary sites of uptake in the digestive system accent the role of zinc in gastrointestinal function. Preliminary information on zinc kinetics in patients with AD evidenced regional differences in clearance rates in correspondence with regional amyloid-β pathology, warranting further imaging studies of zinc homeostasis in patients with AD.

Early Intravascular Events Are Associated with Development of Acute Respiratory Distress Syndrome. A Substudy of the LIPS-A Clinical Trial

Rationale: Acute respiratory distress syndrome (ARDS) is a devastating illness with limited therapeutic options. A better understanding of early biochemical and immunological events in ARDS could inform the development of new preventive and treatment strategies. Objectives: To determine select peripheral blood lipid mediator and leukocyte responses in patients at risk for ARDS. Methods: Patients at risk for ARDS were randomized as part of a multicenter, double‐blind clinical trial of aspirin versus placebo (the LIPS‐A [Lung Injury Prevention Study with Aspirin] trial; NCT01504867). Plasma thromboxane B2 (TXB2), aspirin‐triggered lipoxin A4 (15‐epi‐LXA4, ATL), and peripheral blood leukocyte number and activation were determined on enrollment and after treatment with either aspirin or placebo. Measurements and Main Results: Thirty‐three of 367 subjects (9.0%) developed ARDS after randomization. Baseline ATL levels, total monocyte counts, intermediate monocyte counts, and monocyte‐platelet aggregates were associated with the development of ARDS. Peripheral blood neutrophil count and monocyte‐platelet aggregates significantly decreased over time. Of note, nine subjects developed ARDS after randomization yet before study drug initiation, including seven subjects assigned to aspirin treatment. Subjects without ARDS at the time of first dose demonstrated a lower incidence of ARDS with aspirin treatment. Compared with placebo, aspirin significantly decreased TXB2 and increased the ATL/TXB2 ratio. Conclusions: Biomarkers of intravascular monocyte activation in at‐risk patients were associated with development of ARDS. The potential clinical benefit of early aspirin for prevention of ARDS remains uncertain. Together, results of the biochemical and immunological analyses provide a window into the early pathogenesis of human ARDS and represent potential vascular biomarkers of ARDS risk. Clinical trial registered with www.clinicaltrials.gov (NCT01504867).

Validity of the Meyer Scale for Assessment of Coiled Aneurysms and Aneurysm Recurrence

BACKGROUND AND PURPOSE: Both the Meyer and Raymond scales are commonly used to report angiographic outcomes following coil embolization of intracranial aneurysms. The objectives of this study were the following: 1) to assess the interobserver agreement of the Meyer and Raymond scales, and 2) to evaluate and compare their performance in predicting major recurrence at follow-up. MATERIALS AND METHODS: A retrospective series of 120 coiled aneurysms was included. Four investigators independently graded DSA images immediately posttreatment and at follow-up according to the Meyer and Raymond scales. On follow-up DSA, readers also evaluated recurrence outcome. Interobserver agreement was assessed via the intraclass correlation coefficient. The ability of posttreatment Meyer and Raymond scales to predict major recurrence was modeled by using logistic regression and assessed by using receiver operating characteristic analysis. RESULTS: For the Meyer scale, interobserver intraclass correlation coefficients were 0.58 (95% CI, 0.46–0.68) on posttreatment and 0.78 (95% CI, 0.72–0.83) on follow-up evaluations. For the Raymond scale, interobserver intraclass correlation coefficients were 0.50 (95% CI, 0.39–0.61) and 0.69 (95% CI, 0.62–0.76), respectively, for posttreatment and follow-up. The areas under the curve for the receiver operating characteristic analyses regarding the performance to predict major recurrence at follow-up were 0.69 (95% CI, 0.60–0.79) for the Meyer and 0.70 (95% CI, 0.61–0.78) for the Raymond scale. CONCLUSIONS: The Meyer scale appears consistent and reliable with observer agreement as high or higher than that of the Raymond scale. Performance of both scales in predicting the risk of major recurrence at follow-up is adequate, with no statistical difference between the scales.

Accumulation of Gadolinium in Human Cerebrospinal Fluid after Gadobutrol-enhanced MR Imaging: A Prospective Observational Cohort Study

Purpose To determine whether gadolinium accumulates within cerebrospinal fluid (CSF) in patients recently exposed to the macrocyclic agent gadobutrol and identify factors that may affect this accumulation. Materials and Methods In this prospective observational cohort study, gadolinium was quantified by using inductively coupled plasma mass spectrometry of CSF samples from patients who underwent gadobutrol-enhanced magnetic resonance (MR) imaging followed by lumbar puncture within 30 days (gadobutrol group) or patients who underwent lumbar puncture without history of gadolinium-enhanced MR imaging (control group). CSF total protein level of 35 mg/dL or lower was used as a surrogate marker of an intact blood-brain barrier (BBB). Associations between gadolinium CSF concentration and patient characteristics were examined by using log (e)-linear regression models. Results A total of 82 patients (68 in gadobutrol group, 14 in control group; 42 male and 40 female patients; median age, 47 years [interquartile range, 25-65 years]) were included in this study. Gadolinium was detected in the CSF of all 68 patients in the gadobutrol group (100% [95% confidence interval: 94.7, 100]; range, 0.2-1494 ng/mL). CSF total protein level higher than 35 mg/dL and patient age of at least 18 years were associated with higher gadolinium concentrations (estimate: 1.1, with standard error [SE] of 0.26 [P < .001] and 0.91, with SE of 0.37 [P = .02], respectively). Conclusion Intravenous administration of the macrocyclic agent gadobutrol results in gadolinium accumulation within the CSF, even in the setting of normal renal function and no BBB dysfunction.

Association between hospital volume and mortality of patients with metastatic non-small cell lung cancer

BACKGROUND Prior studies have shown superior surgical outcomes of stage I-III non-small cell lung cancer (NSCLC) in centers with higher patient volumes. However, there is a lack of such information in stage IV NSCLC. PATIENTS AND METHODS This is a retrospective study of stage IV NSCLC patients diagnosed between 2004 and 2014 using the National Cancer Data Base (NCDB). We classified the total number of patients treated at facilities into quartiles: quartile 1 (Q1): ≤23; quartile 2 (Q2): 24-36, quartile 3 (Q3): 37-55, and quartile 4 (Q4): ≥56 cases/year. Cox regression was used to assess whether risk of death differed between quartiles after adjusting for demographics, insurance type, Charlson-Deyo score, and type of therapy received. RESULTS There were 338, 445 patients with stage IV NSCLC treated at 1326 facilities. We included the patients who received any form of therapy in the survival analysis. The unadjusted median overall survival by facility volume was: Q1: 6 months, Q2: 6 months, Q3: 7 months, and Q4: 8 months (p < .001). Multivariable analysis showed that facility volume was independent predictor of all-cause mortality. Compared with patients treated at Q4 facilities, patients treated at lower-quartile facilities had a small but significantly higher risk of death (Q3 hazard ratio [HR], 1.05 [95%CI, 1.04-1.06]; Q2 HR, 1.12 [95%CI, 1.11-1.14]; Q1 HR, 1.11 [95%CI, 1.10-1.12]). CONCLUSIONS Patients who were treated for stage IV NSCLC at highest-volume facilities had less risk of all-cause mortality compared with those who were treated at lower-volume facilities. Although the survival advantage of being treated at highest-volume facilities appeared small, the results of this study suggest differences in cancer care delivery models among various facilities, and may become more relevant in the future era of personalized treatment of stage IV NSCLC.

Percutaneous image guided nodal biopsy after C-11 Choline PET/CT for Biochemically Recurrent Prostate Cancer: Imaging Predictors of Disease and Clinical Implications

Purpose Management of recurrent prostate cancer necessitates timely diagnosis and accurate localization of the sites of recurrent disease. The purpose of this study was to assess predictors of histologic outcomes after 11C-choline positron emission tomography/computed tomography (CholPET) to increase the positive predictive value and specificity of CholPET in identifying imaging predictors of malignant and benign nodal disease to better inform clinical decision making regarding local therapy planning. Materials and Methods Retrospective review of patients undergoing CholPET followed by percutaneous core needle biopsy between January 1, 2010 and January 1, 2016. A total of 153 patients were identified who underwent 166 biopsy procedures. Patient, CholPET, procedural, and pathologic characteristics were recorded. Results A total of 157 biopsies were technically successful, and 110 (70.1%; 95% confidence interval, 62.2-77.1) yielded histologic results abnormal for metastatic prostate cancer. Lesion location, lesion maximum standardized uptake value (SUVmax), SUV ratio (calculated as the ratio of SUVmax to SUV mean in the right atrium), prostate-specific antigen, lesion short axis length, total Gleason score, and castration resistance were all associated with abnormal biopsy results (P values <.001, <.001, <.001, .02, .02, .02, and .015, respectively). External iliac, common iliac, and inguinal sites were associated with much lower rates of histologic positivity (mean [95% confidence interval], 51.2% [35.1-67.1], 46.2% [19.2-74.9], and 33.3% [7.5-70.1]), respectively. Conclusions In a cohort of patients in whom core needle biopsy was performed after CholPET, characteristics of choline localization including node location, SUVmax, lesion–to–blood pool SUV ratio, prostate-specific antigen, total Gleason score, and castration resistance were significantly associated with abnormal biopsy results for metastatic disease on CholPET. Relatively high false positive rates were found in common iliac, external iliac, and inguinal lymph node locations. Histologic confirmation of these sites should be strongly considered in the appropriate clinical scenario before designing additional local therapy plans.

Incidence of major hemorrhage after aggressive image-guided liver mass biopsy in the era of individualized medicine

PurposeTo analyze a large volume of image-guided liver mass biopsies to assess for an increased incidence of major hemorrhage after aggressive liver mass sampling, and to determine if coaxial technique reduces major hemorrhage rate.MethodsPatients who underwent image-guided liver mass biopsy over a 15-year period (December 7, 2001–September 22, 2016) were retrospectively identified. An aggressive biopsy was defined as a biopsy event in which ≥ 4 core needle passes were performed. Association of major hemorrhage after aggressive liver mass biopsy and other potential risk factors of interest were assessed using logistic regression analysis. For the subset of aggressive biopsies, Fisher’s exact test was used to compare the incidence of major hemorrhage using coaxial versus noncoaxial techniques.ResultsAggressive biopsies constituted 11.6% of biopsy events (N =579/5011). The incidence of major hemorrhage with <4 passes was 0.4% (N =18/4432) and with ≥4 passes 1.2% (N =6/579). In univariable models, aggressive biopsy was significantly associated with major hemorrhage (OR 3.0, 95% CI 1.16–6.92, p =0.025). After adjusting for gender and platelet count, the association was not significant at the p =0.05 level (OR 2.58, 95% CI 0.927–6.24, p =0.067). The rate of major hemorrhage in the coaxial biopsy technique group was 1.4% (N =3/209) compared to 1.1% (N =4/370) in the noncoaxial biopsy technique group, which was not a significant difference (p =0.707).ConclusionsAlthough aggressive image-guided liver mass biopsies had an increased incidence of major hemorrhage, the overall risk of bleeding remained low. The benefit of such biopsies will almost certainly outweigh the risk in most patients.