Publications

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.

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.

OBJECTIVE. The purpose of this study was to determine clinical outcomes of patients undergoing TIPS reduction. MATERIALS AND METHODS. In this institutional review board-approved, HIPAA-compliant study, all TIPS reductions performed at two institutions from January 1, 2008 to January 31, 2016, were retrospectively identified. Patients were divided into two groups according to pre-TIPS symptoms: volume overload due to ascites or hydrothorax (VO; n = 14) or variceal bleeding (VB; n = 12). Patient demographics, pre-TIPS model for end-stage liver disease score, pre- and post-TIPS portosystemic gradients, and clinical parameters were recorded. The primary endpoint was change in symptoms of hepatic encephalopathy (HE; West Haven criteria), right heart failure, or liver dysfunction. Secondary endpoints included paracentesis rate for the VO group and rebleeding for the VB group. RESULTS. The degree of HE increased in 24 of 26 patients (92%) after TIPS placement and decreased in 24 of 26 patients (92%) after TIPS reduction. Mean West Haven scores for the VO group decreased after TIPS reduction (from 2.57 ± 0.97 [SD] to 1.07 ± 0.70; p < .001). Mean West Haven scores for the VB group also decreased after TIPS reduction (from 2.45 ± 0.89 to 1.27 ± 0.86; p = .007). Right heart failure improved in two of three patients (67%), and total bilirubin improved in one of three patients (33%). Follow-up data were available up to median of 134 days (interquartile range, 44-286). TIPS reduction led to an increased paracentesis rate compared with before TIPS placement in four of 14 patients with VO (29%). One patient had a stable paracentesis rate after TIPS reduction compared with before TIPS placement. Variceal rebleeding did not occur in any patients with VB after TIPS reduction. At 54 days after TIPS reduction, one of the 12 patients with VB (9%) experienced hematemesis due to an endoscopically proven band-related ulcer. CONCLUSION. TIPS reduction successfully resolved HE and refractory right heart failure in most patients. In patients with VB, TIPS reduction with variceal embolization results in a low risk of short-term recurrent VB. However, in patients with VO, ascites may return or worsen after TIPS reduction despite improvement in HE.

Background Tumor perfusion may inform therapeutic response and resistance in metastatic renal cell carcinoma (RCC) treated with antiangiogenic therapy. Purpose To determine if arterial spin labeled (ASL) MRI perfusion changes are associated with tumor response and disease progression in metastatic RCC treated with vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs). Materials and Methods In this prospective study (ClinicalTrials.gov identifier: NCT00749320), metastatic RCC perfusion was measured with ASL MRI before and during sunitinib or pazopanib therapy between October 2008 and March 2014. Objective response rate (ORR) and progression-free survival (PFS) were calculated. Perfusion was compared between responders and nonresponders at baseline, at week 2, after cycle 2 (12 weeks), after cycle 4 (24 weeks), and at disease progression and compared with the ORR by using the Wilcoxon rank sum test and with PFS by using the log-rank test. Results Seventeen participants received sunitinib (mean age, 59 years ± 7.0 [standard deviation]; 11 men); 11 participants received pazopanib (mean age, 63 years ± 6.6; eight men). Responders had higher baseline tumor perfusion than nonresponders (mean, 404 mL/100 g/min ± 213 vs 199 mL/100 g/min ± 136; P = .02). Perfusion decreased from baseline to week 2 (-53 mL/100 g/min ± 31; P < .001), after cycle 2 (-65 mL/100 g/min ± 25; P < .001), and after cycle 4 (-79 mL/100 g/min ± 15; P = .008). Interval reduction in perfusion at those three time points was not associated with ORR (P = .63, .29, and .27, respectively) or PFS (P = .28, .27, and .32). Perfusion increased from cycle 4 to disease progression (51% ± 11; P < .001). Conclusion Arterial spin labeled perfusion MRI may assist in identifying responders to vascular endothelial growth factor receptor tyrosine kinase inhibitors and may help detect early evidence of disease progression in patients with metastatic renal cell carcinoma. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Goh and De Vita in this issue.

PURPOSE: To prospectively validate electromagnetic hand motion tracking in interventional radiology to detect differences in operator experience using simulation.

METHODS: Sheath task: Six attending interventional radiologists (experts) and 6 radiology trainees (trainees) placed a wire through a sheath and performed a "pin-pull" maneuver, while an electromagnetic motion detection system recorded the hand motion. Radial task: Eight experts and 12 trainees performed palpatory radial artery access task on a radial access simulator. The trainees repeated the task with the nondominant hand. The experts were classified by their most frequent radial artery access technique as having either palpatory, ultrasound, or overall limited experience. The time, path length, and number of movements were calculated. Mann-Whitney U tests were used to compare the groups, and P < .05 was considered significant.

RESULTS: Sheath task: The experts took less time, had shorter path lengths, and used fewer movements than the trainees (11.7 seconds ± 3.3 vs 19.7 seconds ± 6.5, P < .01; 1.1 m ± 0.3 vs 1.4 m ± 0.4, P < .01; and 19.5 movements ± 8.5 vs 31.0 movements ± 8.0, P < .01, respectively). Radial task: The experts took less time, had shorter path lengths, and used fewer movements than the trainees (24.2 seconds ± 10.6 vs 33.1 seconds ± 16.9, P < .01; 2.0 m ± 0.5 vs 3.0 m ± 1.9, P < .001; and 36.5 movements ± 15.0 vs 54.5 movements ± 28.0, P < .001, respectively). The trainees had a shorter path length for their dominant hand than their nondominant hand (3.0 m ± 1.9 vs 3.5 m ± 1.9, P < .05). The expert palpatory group had a shorter path length than the ultrasound and limited experience groups (1.8 m ± 0.4 vs 2.0 m ± 0.4 and 2.3 m ± 1.2, respectively, P < .05).

CONCLUSIONS: Electromagnetic hand motion tracking can differentiate between the expert and trainee operators for simulated interventional tasks.

IMPORTANCE: Despite approximately 40% of patients having Eastern Cooperative Oncology Group (ECOG) performance status (PS) scores of at least 2 in the real world, most landmark clinical trials that led to the use of pembrolizumab as standard of care in advanced non-small cell lung cancer (NSCLC) excluded this group.

OBJECTIVE: To evaluate whether an ECOG PS score of at least 2 at the start of therapy is associated with progression-free survival (PFS) and overall survival (OS) in advanced NSCLC treated with pembrolizumab monotherapy.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included all consecutive patients with advanced NSCLC who underwent treatment with palliative pembrolizumab monotherapy from February 2016 to October 2019 at a single academic cancer center, with data censoring on January 15, 2020.

EXPOSURES: ECOG PS score at start of therapy, with 0 and 1 indicating fully active or restricted in strenuous activity and scores of 2 and higher indicating increasing disability.

MAIN OUTCOMES AND MEASURES: PFS and OS, measured from initiation of pembrolizumab monotherapy.

RESULTS: Of 74 patients (median [range] age, 68.5 [33-87] years; 36 [48.7%] women; 53 [71.6%] White individuals) with median follow-up of 19.5 (95% CI, 13.4-27.8) months, 45 (60.8%) had an ECOG PS of 0 or 1, while 29 (39.2%) had an ECOG PS of at least 2. There were no significant differences in the baseline characteristics, except in age. Compared with patients with PS scores of 0 or 1, those with PS scores of at least 2 had significantly lower disease control rates (38 [88.4%] vs 15 [53.6%]; P = .002), shorter median PFS (7.9 [95% CI, 4.6-15.4] months vs 2.3 [95% CI, 1.8-4.8] months; P = .004), and shorter median OS (23.2 [14.0 vs 35.7] months vs 4.1 [95% CI, 2.1-6.9] months; P < .001). Among those potentially eligible for subsequent cancer-directed therapy beyond pembrolizumab monotherapy, patients in the group with PS scores of at least 2 were less likely to receive it than those with PS scores of 0 or 1 (2 [8.3%] vs 14 [45.2%]; P = .003). Multivariable adjustment for baseline characteristics confirmed ECOG PS of at least 2 as an independent risk factor for worse PFS (HR, 2.02; 95% CI, 1.09-3.74; P = .03) and worse OS (HR, 2.87; 95% CI, 1.40-5.89; P = .004).

CONCLUSIONS AND RELEVANCE: In this cohort study, having an ECOG PS score of at least 2 was associated with poorer prognosis for treatment of advanced NSCLC with palliative pembrolizumab monotherapy. Further prospective studies are needed to evaluate more objective and consistent measures of functional status to facilitate identification of patients with borderline performance status who may achieve durable clinical benefit from treatment with pembrolizumab monotherapy.

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.

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.