Publications

2021

Markezana, Aurelia, Nahum Goldberg, Gaurav Kumar, Elina Zorde-Khvalevsky, Svetlana Gourevtich, Nir Rozenblum, Eithan Galun, and Muneeb Ahmed. (2021) 2021. “Incomplete Thermal Ablation of Tumors Promotes Increased Tumorigenesis.”. International Journal of Hyperthermia : The Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group 38 (1): 263-72. https://doi.org/10.1080/02656736.2021.1887942.

PURPOSE: While systemic tumor-stimulating effects can occur following ablation of normal liver linked to the IL-6/HGF/VEGF cytokinetic pathway, the potential for tumor cells themselves to produce these unwanted effects is currently unknown. Here, we study whether partially treated tumors induce increased tumor growth post-radiofrequency thermal ablation (RFA).

METHODS: Tumor growth was measured in three immunocompetent, syngeneic tumor models following partial RFA of the target tumor (in subcutaneous CT26 and MC38 mouse colorectal adenocarcinoma, N = 14 each); and in a distant untreated tumor following partial RFA of target subcutaneous R3230 rat breast adenocarcinoma (N = 12). Tumor cell proliferation (ki-67) and microvascular density (CD34) was assessed. In R3230 tumors, in vivo mechanism of action was assessed following partial RFA by measuring IL-6, HGF, and VEGF expression (ELISA) and c-Met protein (Western blot). Finally, RFA was performed in R3230 tumors with adjuvant c-Met kinase inhibitor or VEGF receptor inhibitor (at 3 days post-RFA, N = 3/arm, total N = 12).

RESULTS: RFA stimulated tumor growth in vivo in residual, incompletely treated surrounding CT26 and MC38 tumor at 3-6 days (p < 0.01). In R3230, RFA increased tumor growth in distant tumor 7 days post treatment compared to controls (p < 0.001). For all models, Ki-67 and CD34 were elevated (p < 0.01, all comparisons). IL-6, HGF, and VEGF were also upregulated post incomplete tumor RFA (p < 0.01). These markers were suppressed to baseline levels with adjuvant c-MET kinase or VEGF receptor inhibition.

CONCLUSION: Incomplete RFA of a target tumor can sufficiently stimulate residual tumor cells to induce accelerated growth of distant tumors via the IL-6/c-Met/HGF pathway and VEGF production.

Gaube, Susanne, Harini Suresh, Martina Raue, Alexander Merritt, Seth J Berkowitz, Eva Lermer, Joseph F Coughlin, John Guttag V, Errol Colak, and Marzyeh Ghassemi. (2021) 2021. “Do As AI Say: Susceptibility in Deployment of Clinical Decision-Aids.”. NPJ Digital Medicine 4 (1): 31. https://doi.org/10.1038/s41746-021-00385-9.

Artificial intelligence (AI) models for decision support have been developed for clinical settings such as radiology, but little work evaluates the potential impact of such systems. In this study, physicians received chest X-rays and diagnostic advice, some of which was inaccurate, and were asked to evaluate advice quality and make diagnoses. All advice was generated by human experts, but some was labeled as coming from an AI system. As a group, radiologists rated advice as lower quality when it appeared to come from an AI system; physicians with less task-expertise did not. Diagnostic accuracy was significantly worse when participants received inaccurate advice, regardless of the purported source. This work raises important considerations for how advice, AI and non-AI, should be deployed in clinical environments.

Satyam, Abhigyan, Maria G Tsokos, Olga R Brook, Jonathan L Hecht, Vaishali R Moulton, and George C Tsokos. (2021) 2021. “Activation of Classical and Alternative Complement Pathways in the Pathogenesis of Lung Injury in COVID-19.”. Clinical Immunology (Orlando, Fla.) 226: 108716. https://doi.org/10.1016/j.clim.2021.108716.

Lung inflammation and damage is prominent in people infected with SARS-Cov-2 and a major determinant of morbidity and mortality. We report the deposition of complement components in the lungs of people who succumbed to COVID-19 consistent with the activation of the classical and the alternative pathways. Our study provides strong rationale for the expansion of trials involving the use of complement inhibitors to treat patients with COVID-19.

Alkalay, Ron N, Robert Adamson, Alexander Miropolsky, Roger B Davis, Mike L Groff, and David B Hackney. (2021) 2021. “Large Lytic Defects Produce Kinematic Instability and Loss of Compressive Strength in Human Spines: An in Vitro Study.”. The Journal of Bone and Joint Surgery. American Volume 103 (10): 887-99. https://doi.org/10.2106/JBJS.19.00419.

BACKGROUND: In patients with spinal metastases, kinematic instability is postulated to be a predictor of pathologic vertebral fractures. However, the relationship between this kinematic instability and the loss of spinal strength remains unknown.

METHODS: Twenty-four 3-level thoracic and lumbar segments from 8 cadaver spines from female donors aged 47 to 69 years were kinematically assessed in axial compression (180 N) and axial compression with a flexion or extension moment (7.5 Nm). Two patterns of lytic defects were mechanically simulated: (1) a vertebral body defect, corresponding to Taneichi model C (n = 13); and (2) the model-C defect plus destruction of the ipsilateral pedicle and facet joint, corresponding to Taneichi model E (n = 11). The kinematic response was retested, and compression strength was measured. Two-way repeated-measures analysis of variance was used to test the effect of each model on the kinematic response of the segment. Multivariable linear regression was used to test the association between the kinematic parameters and compressive strength of the segment.

RESULTS: Under a flexion moment, and for both models C and E, the lesioned spines exhibited greater flexion range of motion (ROM) and axial translation than the control spines. Both models C and E caused lower extension ROM and greater axial, sagittal, and transverse translation under an extension moment compared with the control spines. Two-way repeated-measures analysis revealed that model E, compared with model C, caused significantly greater changes in extension and torsional ROM under an extension moment, and greater sagittal translation under a flexion moment. For both models C and E, greater differences in flexion ROM and sagittal translation under a flexion moment, and greater differences in extension ROM and in axial and transverse translation under an extension moment, were associated with lower compressive strength of the lesioned spines.

CONCLUSIONS: Critical spinal lytic defects result in kinematic abnormalities and lower the compressive strength of the spine.

CLINICAL RELEVANCE: This experimental study demonstrates that lytic foci degrade the kinematic stability and compressive strength of the spine. Understanding the mechanisms for this degradation will help to guide treatment decisions that address inferred instability and fracture risk in patients with metastatic spinal disease.

Larocque, Natasha, Anuradha Shenoy-Bhangle, Alexander Brook, Ronald Eisenberg, Yu-Ming Chang, and Pritesh Mehta. (2021) 2021. “Resident Experiences With Virtual Radiology Learning During the COVID-19 Pandemic.”. Academic Radiology 28 (5): 704-10. https://doi.org/10.1016/j.acra.2021.02.006.

RATIONALE AND OBJECTIVES: COVID-19 has disrupted radiology education and forced a transition from traditional in-person learning to a virtual platform. As a result of hospital and state mandates, our radiology residency program quickly transitioned to a virtual learning platform to continue dissemination of knowledge, maintain resident engagement, and ensure professional development. The goal of this study is to assess the strengths and weaknesses of the virtual learning platform at our institution using resident ratings.

MATERIALS AND METHODS: This institutional IRB-exempt study involved a survey of 17 questions which was electronically distributed to 45 radiology residents using SurveyMonkey. Questions encompassed resident satisfaction with teaching and professional development, scheduling changes, and engagement with the virtual platform. Answers to most questions were submitted on a Likert scale.

RESULTS: A total of 31 of 45 respondents completed the survey (response rate = 69%). Most residents were satisfied with the virtual platform with teaching activities identified as a strength and the incorporation of professional development as a weakness. The most frequent barriers to attending the virtual curriculum were technical difficulties (43%) and childcare (36%). Residents who reported experiencing barriers were less likely to adhere to the virtual curriculum (p = 0.004). Most respondents (81%) reported a desire to maintain elements of the virtual learning practice postpandemic.

CONCLUSION: The majority of residents reported high satisfaction with virtual learning during the COVID-19 pandemic. Teaching activities are a curricular strength. Weaknesses identified include the incorporation of professional development and extrinsic barriers, such as technical difficulties and family obligations, which require further support for trainees.

Thavikulwat, Amalie C, Jim S Wu, Xiaohe Chen, Megan E Anderson, Ashley Ward, and Justin Kung. (2021) 2021. “Image-Guided Core Needle Biopsy of Adipocytic Tumors: Diagnostic Accuracy and Concordance With Final Surgical Pathology.”. AJR. American Journal of Roentgenology 216 (4): 997-1002. https://doi.org/10.2214/AJR.20.23080.

OBJECTIVE. Diagnostic accuracy of core needle biopsy (CNB) for adipocytic tumors can be low because of sampling error from these often large, heterogeneous lesions. The purpose of this study was to evaluate the diagnostic accuracy of image-guided CNB for various adipocytic tumors in comparison with excisional pathology. MATERIALS AND METHODS. Adipocytic tumors (n = 77) of all adult patients undergoing image-guided CNB and subsequent surgical excision of an adipocytic tumor at a tertiary referral center between 2005 and 2019 were studied. To determine concordance, we compared pathologic diagnoses based on CNB to the reference standard of pathologic diagnoses after surgical excision. Tumors were divided into three categories (benign lipomatous tumors [lipoma, lipoma variants, hibernomas], atypical lipomatous tumors [ALTs] or well-differentiated liposarcomas [WDLs], and higher grade liposarcomas [myxoid, dedifferentiated, pleomorphic]), and diagnostic accuracy was calculated for each category. RESULTS. In 73 of 77 adipocytic tumors (95%), diagnosis at CNB and diagnosis after excision were concordant. Accuracy of diagnosis was poorer for ALTs and WDLs than for the other two categories, and the difference was statistically significant (p < .002). For the 29 benign lipomatous tumors and the 27 higher-grade liposarcomas, diagnoses at CNB and after excision were concordant in all cases (100%). Seventeen of the 21 tumors (81%) diagnosed as ALTs or WDLs at CNB had a concordant diagnosis after excision; four of the 21 were upgraded (dedifferentiated liposarcoma, n = 3; myxoid liposarcoma, n = 1). CONCLUSION. CNB provides high diagnostic accuracy for adipocytic tumors, particularly for benign lipomatous tumors and higher grade liposarcomas. However, though still high at 81%, diagnostic accuracy of CNB is not as high for tumors diagnosed as ALTs or WDLs. Awareness of this limitation is important when determining management, particularly of cases of ALT or WDL for which surgery is not planned.

Yozamp, Nicholas, Gregory L Hundemer, Marwan Moussa, Johnathan Underhill, Tali Fudim, Barry Sacks, and Anand Vaidya. (2021) 2021. “Variability of Aldosterone Measurements During Adrenal Venous Sampling for Primary Aldosteronism.”. American Journal of Hypertension 34 (1): 34-45. https://doi.org/10.1093/ajh/hpaa151.

BACKGROUND: Variability of aldosterone concentrations has been described in patients with primary aldosteronism.

METHODS: We performed a retrospective cohort study of 340 patients with primary aldosteronism who underwent adrenal venous sampling (AVS) at a tertiary referral center, 116 of whom also had a peripheral venous aldosterone measured hours before the procedure. AVS was performed by the same interventional radiologist using bilateral, simultaneous sampling, under unstimulated and then stimulated conditions, and each sample was obtained in triplicate. Main outcome measures were: (i) change in day of AVS venous aldosterone from pre-AVS to intra-AVS and (ii) variability of triplicate adrenal venous aldosterone concentrations during AVS.

RESULTS: Within an average duration of 131 minutes, 81% of patients had a decline in circulating aldosterone concentrations (relative decrease of 51% and median decrease of 7.0 ng/dl). More than a quarter (26%) of all patients had an inferior vena cava aldosterone of ≤5 ng/dl at AVS initiation. The mean coefficient of variation of triplicate adrenal aldosterone concentrations was 30% and 39%, in the left and right veins, respectively (corresponding to a percentage difference of 57% and 73%), resulting in lateralization discordance in up to 17% of patients if the lateralization index were calculated using only one unstimulated aldosterone-to-cortisol ratio rather than the average of triplicate measures.

CONCLUSIONS: Circulating aldosterone levels can reach nadirs conventionally considered incompatible with the primary aldosteronism diagnosis, and adrenal venous aldosterone concentrations exhibit acute variability that can confound AVS interpretation. A single venous aldosterone measurement lacks precision and reproducibility in primary aldosteronism.

Dolan, Daniel P, Abby White, Emanuele Mazzola, Daniel N Lee, Ritu Gill, Suden Kucukak, Raphael Bueno, Michael T Jaklitsch, Steven J Mentzer, and Scott J Swanson. (2021) 2021. “Outcomes of Superior Segmentectomy Versus lower Lobectomy for Superior Segment Stage I Non-Small-Cell Lung Cancer Are Equivalent: An Analysis of 196 Patients at a Single, High Volume Institution.”. Journal of Surgical Oncology 123 (2): 570-78. https://doi.org/10.1002/jso.26304.

OBJECTIVES: To determine if superior segmentectomy has equivalent overall (OS), disease-free (DFS), and locoregional-recurrence-free survival (LRFS) to lower lobectomy for early-stage non-small-cell lung cancer (NSCLC) in the superior segment.

METHODS: We retrospectively reviewed all Stage 1 lower lobectomies for superior segment lesions and superior segmentectomies at our hospital from 2000 to 2018. Comparison statistics and Cox hazard modeling were performed to determine differences between groups and attempt to identify risk factors for OS, DFS, and LRFS.

RESULTS: Superior segmentectomy patients, compared with lower lobectomy patients, had more current smokers, worse forced expiratory volume in 1 s percentage, radiologic emphysema scores, clinically and pathologically smaller tumors, and more occurrences of 0 lymph nodes examined. Outcomes for superior segmentectomy compared with lower lobectomy were equivalent for 5-year OS (67.0% vs. 75.1%, p = 0.70), DFS (56.9% vs. 60.4%, p = 0.59), and LRFS (87.9% vs. 91.3%, p = 0.46). Multivariable Cox modeling lacked utility due to no outcome differences.

CONCLUSIONS: In well-selected patients, superior segmentectomies can have equivalent OS, DFS, and LRFS compared with lower lobectomies of superior segment tumors for early stage lung cancer. Further data are needed to provide better risk estimates.

Cruz-Romero, Cinthia, Abra Guo, William F Bradley, Joao R T Vicentini, Vijay Yajnik, and Michael S Gee. (2021) 2021. “Novel Associations Between Genome-Wide Single Nucleotide Polymorphisms and MR Enterography Features in Crohn’s Disease Patients.”. Journal of Magnetic Resonance Imaging : JMRI 53 (1): 132-38. https://doi.org/10.1002/jmri.27250.

BACKGROUND: Patient genetic polymorphism is associated with Crohn's clinical behavior; however, its association with magnetic resonance enterography (MRE) imaging appearance is not known.

PURPOSE: To analyze a set of known Crohn's disease (CD)-related single nucleotide polymorphisms for associations with MRE imaging phenotype and frequency of imaging.

STUDY TYPE: Retrospective.

POPULATION: 54 patients (mean age 40 years; 32 females and 22 males) with established CD from 2009 to 2016 who underwent baseline MRE and genetic testing for the presence of 168 single nucleotide polymorphisms (SNPs) potentially associated with inflammatory bowel disease.

FIELD STRENGTH/SEQUENCE: 1.5T or 3T clinical scanners, standard MRE clinical pulse sequences, including T2 -weighted single-shot fast spin echo, balanced steady-state free precession, T2 -weighted fast spin echo fat-suppressed, and T1 -weighted fat-suppressed pre- and postcontrast imaging.

ASSESSMENT: Three readers (all body imaging fellowship-trained radiologists) independently evaluated all imaging for the presence or absence of active disease and penetrating complications. Date of onset and frequency of endoscopies and cross-sectional imaging (CSI) were recorded. Disease behavior and distribution were categorized according to the Vienna and Montreal classifications, respectively.

STATISTICAL TESTS: Student's t-test and Fisher's exact test were used to assess significance of continuous and categorical variables, respectively. A hidden Markov model statistical knockoff approach was also applied for the analysis of genetic-imaging associations, with corrected P < 0.05 considered significant.

RESULTS: MRE demonstrated active bowel inflammation in 42 (78%) patients, strictures in 13 (28%), and fistulae in 13 (28%). The SNP rs1292053 (RBS6KB1) was highly associated with small bowel inflammation and luminal narrowing, with observed frequencies of association 0.66 and 0.39, respectively (P = 0.001). rs6062504 (Decoy receptor 3) was associated with lower age of onset (P = 0.012), higher proportion of early disease onset patients (P = 0.012), and higher average number of CSI/year (P = 0.014).

DATA CONCLUSION: This study demonstrated significant associations between CD genotype and MRE phenotype and frequency of cross-sectional imaging.

LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.