Publications

OBJECTIVE: To determine the association between novel lifestyle factors on risk of rheumatoid arthritis (RA)-associated interstitial lung disease (ILD), define the threshold at which smoking increases RA-ILD risk, and calculate the degree to which known lifestyle and clinical factors predict RA-ILD.

METHODS: This nested case-control study matched incident RA-ILD cases to RA non-ILD controls on age, sex, RA duration, rheumatoid factor, and time from exposure assessment to RA-ILD. Exposures included education, BMI, smoking, anticyclic citrullinated peptide antibodies, race, joint erosions, rheumatoid nodules, C-reactive protein (CRP), disease activity score, functional status, disease-modifying antirheumatic drug use, and glucocorticoid use. OR for each exposure on risk of RA-ILD were obtained from logistic regression models. Area under the curve (AUC) was calculated based on all lifestyle and clinical exposures.

RESULTS: We identified 84 incident RA-ILD cases and 233 matched controls. After adjustment, obesity, high-positive CRP (≥ 10 mg/L), and poor functional status (multidimensional Health Assessment Questionnaire [MDHAQ] ≥ 1) were associated with increased risk of RA-ILD (OR 2.42, 95% CI 1.11-5.24 vs normal BMI; OR 2.61, 95% CI 1.21-5.64 vs CRP < 3 mg/L; OR 3.10, 95% CI 1.32-7.26 vs MDHAQ < 0.2). Smoking 30 pack-years or more was strongly associated with risk of RA-ILD compared to never smokers (OR 6.06, 95% CI 2.72-13.5). Together, lifestyle and clinical risk factors for RA-ILD had an AUC of 0.79 (95% CI 0.73-0.85).

CONCLUSION: Obesity, CRP, functional status, and extensive smoking may be novel risk factors for RA-ILD that may be useful for RA-ILD risk assessment and prevention. The overall ability to predict RA-ILD remains modest.

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.

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.

Primary aldosteronism is an underdiagnosed cause of hypertension. Although inadequate screening is one reason for underdiagnosis, another important contributor is that clinicians may inappropriately exclude the diagnosis when screening aldosterone concentrations fall below traditionally established thresholds. We evaluated the intraindividual variability in screening aldosterone concentrations and aldosterone-to-renin ratios, and how this variability could impact case detection, among 51 patients with confirmed primary aldosteronism who had 2 or more screening measurements of renin and aldosterone on different days. There were a total of 137 screening measurements with a mean of 3 (range 2-6) per patient. The mean intraindividual variability, expressed as coefficients of variation, was 31% for aldosterone and 45% for the aldosterone-to-renin ratio. Aldosterone concentrations ranged from 4.9 to 51 ng/dL; 49% of patients had at least one aldosterone measurement below 15 ng/dL, 29% had at least 2 aldosterone measurements below 15 ng/dL, and 29% had at least one measurement below 10 ng/dL. Individual aldosterone-to-renin ratios ranged from 8.2 to 427 ng/dL per ng/mL·hour; 57% had at least one ratio below 30 ng/dL per ng/mL·hour, 27% had at least 2 ratios below 30 ng/dL per ng/mL·hour, and 24% had at least one ratio below 20 ng/dL per ng/mL·hour. Aldosterone concentrations and aldosterone-to-renin ratios are highly variable in patients with primary aldosteronism, with many screening values falling below conventionally accepted diagnostic thresholds. The diagnostic yield for primary aldosteronism may be substantially increased by recalibrating the definition of a positive screen to include more liberal thresholds for aldosterone and the aldosterone-to-renin ratio.

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.

PURPOSE: To determine the prevalence of isolated right-sided varicocele due to an obstructing malignancy in patients with no other evidence of malignancy.

METHODS: This retrospective, multi-institutional study included a text search for right-sided varicocele in consecutive reports of scrotal ultrasound studies performed between 4/22/1999 and 06/24/2018. Diagnosis was confirmed by a radiologist based on the following criteria: pampiniform plexus vein diameter of ≥ 2 mm, which has augmented flow or increases by ≥ 1 mm on Valsalva. Inclusion criteria for adequate follow-up were (1) abdominopelvic CT or MRI performed within 3 months prior to, or any time after, the ultrasound study; or (2) presence of clinical documentation more than 2 years after the ultrasound date. Exclusion criteria were existing cancer diagnosis in the abdomen or pelvis, epididymo-orchitis, intratesticular or intrascrotal mass, and prior scrotal surgery. Images of available CT or MRI studies were reviewed for presence of any explanation of right-sided varicocele.

RESULTS: 210 patients with right-sided varicocele met inclusion and exclusion criteria. 118/210 had abdominopelvic CT or MRI in the assigned timeframe. Of these, no patients had malignancy that could account for right-sided varicoceles. Of the 92/210 patients without CT or MRI but with available clinical follow-up, none had a malignancy that could have caused an isolated right-sided varicocele. There was no underlying malignancy to explain the right-sided varicocele in any of the patients, 0/210, 95% CI [0.0-1.4%].

CONCLUSION: No associated malignancy was found in patients with isolated right-sided varicoceles to support additional imaging for malignancy screening.

Testosterone therapy (TT) is administered to enhance masculinization in transgender individuals. The long-term effect of exogenous testosterone on breast tissues remains unclear. Our study evaluated the modulation of breast morphology by TT in transgender individuals with special attention to duration of TT. We reviewed 447 breast surgical specimens from gender affirming chest-contouring surgery, and compared histopathological findings including degree of lobular atrophy, and atypical and non-atypical proliferations between subjects who did (n = 367) and did not (n = 79) receive TT. TT for one patient was unknown. TT for >12 months was associated with seven histopathological features. Longer duration of TT was significantly associated with higher degrees of lobular atrophy (p < 0.001). This relationship remained significant after accounting for age at surgery, ethnicity, body mass index, and presurgical oophorectomy (adjusted p < 0.001). Four types of lesions were more likely to be absent in breast tissues exposed to longer durations of TT: cysts (median = 16.2 months; p < 0.01; adjusted p = 0.01), fibroadenoma (median = 14.8 months; p = 0.02; adjusted p = 0.07), pseudoangiomatous stromal hyperplasia (median = 17.0 months; p < 0.001; adjusted p < 0.001), and papillomas (median = 14.7 months; p = 0.04; adjusted p = 0.20). Columnar cell change and mild inflammation were also less likely to occur in subjects receiving TT (p < 0.05), but were not linked to the duration of TT. Atypia and ductal carcinoma in situ were detected in 11 subjects (2.5%) all of whom received TT ranging from 10.1 to 64.1 months. The incidental findings of high-risk lesions and carcinoma as well as the risk of cancer in residual breast tissue after chest-contouring surgery warrant the consideration of culturally sensitive routine breast cancer screening protocols for transgender men and masculine-centered gender nonconforming individuals. Long-term follow-up studies and molecular investigations are needed to understand the breast cancer risk of transgender individuals who receive TT.

OBJECTIVES: To determine the feasibility and safety of ultrasound-guided minimally invasive autopsy in COVID-19 patients.

METHODS: 60 patients who expired between 04/22/2020-05/06/2020 due to COVID-19 were considered for inclusion in the study, based on availability of study staff. Minimally invasive ultrasound-guided autopsy was performed with 14G core biopsies through a 13G coaxial needle. The protocol required 20 cores of the liver, 30 of lung, 12 of spleen, 20 of heart, 20 of kidney, 4 of breast, 4 of testis, 2 of skeletal muscle, and 4 of fat with total of 112 cores per patient. Quality of the samples was evaluated by number, size, histology, immunohistochemistry, and in situ hybridization for COVID-19 and PCR-measured viral loads for SARS-CoV-2.

RESULTS: Five (5/60, 8%) patients were included. All approached families gave their consent for the minimally invasive autopsy. All organs for biopsy were successfully targeted with ultrasound guidance obtaining all required samples, apart from 2 patients where renal samples were not obtained due to atrophic kidneys. The number, size, and weight of the tissue cores met expectation of the research group and tissue histology quality was excellent. Pathology findings were concordant with previously reported autopsy findings for COVID-19. Highest SARS-CoV-2 viral load was detected in the lung, liver, and spleen that had small to moderate amount, and low viral load in was detected in the heart in 2/5 (40%). No virus was detected in the kidney (0/3, 0%).

CONCLUSIONS: Ultrasound-guided percutaneous post-mortem core biopsies can safely provide adequate tissue. Highest SARS-CoV-2 viral load was seen in the lung, followed by liver and spleen with small amount in the myocardium.