Sex Differences in Aging-related Myocardial Stiffening Quantitatively Measured with MR Elastography.

Purpose To investigate the feasibility of using quantitative MR elastography (MRE) to characterize the influence of aging and sex on left ventricular (LV) shear stiffness. Materials and Methods In this prospective study, LV myocardial shear stiffness was measured in 109 healthy volunteers (age range: 18-84 years; mean age, 40 years ± 18 [SD]; 57 women, 52 men) enrolled between November 2018 and September 2019, using a 5-minute MRE acquisition added to a clinical MRI protocol. Linear regression models were used to estimate the association of cardiac MRI and MRE characteristics with age and sex; models were also fit to assess potential age-sex interaction. Results Myocardial shear stiffness significantly increased with age in female (age slope = 0.03 kPa/year ± 0.01, P = .009) but not male (age slope = 0.008 kPa/year ± 0.009, P = .38) volunteers. LV ejection fraction (LVEF) increased significantly with age in female volunteers (0.23% ± 0.08 per year, P = .005). LV end-systolic volume (LVESV) decreased with age in female volunteers (-0.20 mL/m2 ± 0.07, P = .003). MRI parameters, including T1, strain, and LV mass, did not demonstrate this interaction (P > .05). Myocardial shear stiffness was not significantly correlated with LVEF, LV stroke volume, body mass index, or any MRI strain metrics (P > .05) but showed significant correlations with LV end-diastolic volume/body surface area (BSA) (slope = -3 kPa/mL/m2 ± 1, P = .004, r2 = 0.08) and LVESV/BSA (-1.6 kPa/mL/m2 ± 0.5, P = .003, r2 = 0.08). Conclusion This study demonstrates that female, but not male, individuals experience disproportionate LV stiffening with natural aging, and these changes can be noninvasively measured with MRE. Keywords: Cardiac, Elastography, Biological Effects, Experimental Investigations, Sexual Dimorphisms, MR Elastography, Myocardial Shear Stiffness, Quantitative Stiffness Imaging, Aging Heart, Myocardial Biomechanics, Cardiac MRE Supplemental material is available for this article. Published under a CC BY 4.0 license.

Multimorbidity in Psoriasis as a Risk Factor for Psoriatic Arthritis: A Population-Based Study.

OBJECTIVES: To examine multimorbidity in psoriasis and its association with the development of PsA. METHODS: A retrospective cohort study was performed using the Rochester Epidemiology Project. Population-based incidence (2000-2009) and prevalence (Jan 1, 2010) cohorts of psoriasis were identified by manual chart review. A cohort of individuals without psoriasis (comparators) were identified (1:1 matched on age, sex, and county). Morbidities were defined using ≥2 Clinical Classification Software codes ≥30 days apart within prior five years. PsA was defined using ClASsification of Psoriatic ARthritis (CASPAR) criteria. χ2 and rank-sum tests were used to compare morbidities, and age-, sex-, and race-adjusted Cox models to examine the association of baseline morbidities in psoriasis with development of PsA. RESULTS: Among 817 incident psoriasis patients, the mean age was 45.2 years with 52.0% females, and 82.0% moderate/severe psoriasis. No multimorbidity differences were found between incident psoriasis patients and comparators. However, in the 1,088 prevalent psoriasis patients, multimorbidity was significantly more common compared with 1,086 comparators (OR : 1.35 and OR : 1.48 for ≥2 and ≥5 morbidities, respectively). Over a median 13.3-year follow-up, 23 patients (cumulative incidence: 2.9% by 15 years) developed PsA. Multimorbidity (≥2 morbidities) was associated with a 3-fold higher risk of developing PsA. CONCLUSION: Multimorbidity was more common in the prevalent but not incident cohort of psoriasis compared with the general population, suggesting patients with psoriasis may experience accelerated development of multimorbidity. Moreover, multimorbidity at psoriasis onset significantly increased the risk of developing PsA, highlighting the importance of monitoring multimorbid psoriasis patients for the development of PsA.

Multimorbidity in systemic lupus erythematosus in a population-based cohort: the lupus Midwest network.

OBJECTIVES: To assess the prevalence and incidence of multimorbidity and the association with the SLICC/ACR damage index (SDI) among patients with systemic lupus erythematosus (SLE). METHODS: Using prevalent and incident population-based cohorts of patients with SLE and their matched comparators, we assessed 57 chronic conditions. Chronic conditions were categorized as SDI-related or SDI-unrelated. Multimorbidity was defined as the presence of 2+ chronic conditions. Multimorbidity at prevalence and incidence/index was compared between cohorts using logistic regression. Cox models were used to examine development of multimorbidity after SLE incidence. RESULTS: The prevalent cohort included 449 patients with established SLE on January 1, 2015. They were three times more likely to have multimorbidity compared with non-SLE comparators (OR 2.98, 95% CI 2.18-4.11). The incident cohort included 270 patients with new-onset SLE. At SLE incidence, patients with SLE were more likely to have multimorbidity than comparators (OR 2.27, 95% CI 1.59-3.27). After incidence, the risk of developing multimorbidity was 2-fold higher among patients with SLE than comparators (hazard ratio (HR) 2.11, 95% CI 1.59-2.80). Development of multimorbidity was higher in patients with SLE based on SDI-related (HR 2.91, 95% CI 2.17-3.88) and SDI-unrelated conditions (HR 1.73, 95% CI, 1.32-2.26). CONCLUSION: Patients with SLE have a higher burden of multimorbidity, even before the onset of the disease. The risk disparity continues after SLE classification and is also seen in a prevalent SLE cohort. Multimorbidity is driven both by SDI-related and unrelated conditions.

Clinical and Imaging Outcomes of Surgically Repaired Cerebrospinal Fluid-Venous Fistulas Identified by Lateral Decubitus Digital Subtraction Myelography.

OBJECTIVE: To describe clinical and radiographic outcomes of surgical repair of cerebrospinal fluid-venous fistula (CVF), an increasingly recognized cause of spontaneous intracranial hypotension that is poorly responsive to epidural blood patch (EBP). METHODS: Retrospective review identified adult patients who had lateral decubitus digital subtraction myelography indicative of cerebrospinal fluid leak at Mayo Clinic between November 2018 and February 2020, with clearly localized CVF, followed by surgical treatment. Patients without available imaging before or after surgery were excluded. History of EBP and clinical response to EBP were evaluated along with surgical outcomes. RESULTS: Of 25 patients with CVF who met protocol criteria and were included in the data analysis, 22 (88%) received EBP, but clinical benefit lasting ≥4 weeks occurred in only 2 of 22 (9%). Headache was the most prominent preoperative feature among patients (24/25; 96%). Following surgery, 18 of 24 (75%) patients had complete headache improvement, 4 (17%) had partial improvement, and 2 (8%) had no improvement. Ten of 25 (40%) patients reported cognitive disturbance at baseline; at follow-up, 5 of 10 (50%) had complete improvement, 3 (30%) had partial improvement, and 2 (20%) had no improvement. On postoperative brain magnetic resonance imaging, 6 of 25 (24%) patients had complete resolution of findings by Bern score criteria, 18 (72%) showed partial improvement, and 1 (4%) patient showed no improvement. Adverse events were minor and included surgical site pain and paresthesias. CONCLUSIONS: Surgical repair of CVF resulted in improvements in headache and other symptoms, with few side effects.

Using Unsupervised Machine Learning Methods to Cluster Comorbidities in a Population-Based Cohort of Patients With Rheumatoid Arthritis.

OBJECTIVE: To identify clusters of comorbidities in patients with rheumatoid arthritis (RA) using 4 methods and to compare to patients without RA. METHODS: In this retrospective, population-based study, residents of 8 Minnesota counties with prevalent RA as of January 1, 2015 were identified. Age-, sex-, and county-matched non-RA comparators were selected from the same underlying population. Diagnostic codes were retrieved for 5 years before January 1, 2015. Using 2 codes ≥30 days apart, 44 previously defined morbidities and 11 nonoverlapping chronic disease categories based on Clinical Classifications Software were defined. Unsupervised machine learning methods of interest included hierarchical clustering, factor analysis, K-means clustering, and network analysis. RESULTS: Two groups of 1,643 patients with and without RA (72% female; mean age 63.1 years in both groups) were studied. Clustering of comorbidities revealed strong associations among mental/behavioral comorbidities and among cardiovascular risk factors and diseases. The clusters were associated with age and sex. Differences between the 4 clustering methods were driven by comorbidities that are rare and those that were weakly associated with other comorbidities. Common comorbidities tended to group together consistently across approaches. The instability of clusters when using different random seeds or bootstrap sampling impugns the usefulness and reliability of these methods. Clusters of common comorbidities between RA and non-RA cohorts were similar. CONCLUSION: Despite the higher comorbidity burden in patients with RA compared to the general population, clustering comorbidities did not identify substantial differences in comorbidity patterns between the RA and non-RA cohorts. The instability of clustering methods suggests caution when interpreting clustering using 1 method.

Lower Frequency of Comorbidities Prior to Onset of Giant Cell Arteritis: A Population-Based Study.

OBJECTIVE: To assess the frequency of comorbidities and metabolic risk factors at and prior to giant cell arteritis (GCA) diagnosis. METHODS: This is a retrospective case control study of patients with incident GCA between January 1, 2000, and December 31, 2019, in Olmsted County, Minnesota. Two age- and sex-matched controls were identified, and each assigned an index date corresponding to an incidence date of GCA. Medical records were manually abstracted for comorbidities and laboratory data at incidence date, 5 years, and 10 years prior to incidence date. Twenty-five chronic conditions using International Classification of Diseases, 9th revision, diagnosis codes were also studied at incidence date and 5 years prior to incidence date. RESULTS: One hundred and twenty-nine patients with GCA (74% female) and 253 controls were identified. At incidence date, the prevalence of diabetes mellitus (DM) was lower among patients with GCA (5% vs 17%; P = 0.001). At 5 years prior to incidence date, patients were less likely to have DM (2% vs 13%; P < 0.001) and hypertension (27% vs 45%; P = 0.002) and had a lower mean number (SD) of comorbidities (0.7 [1.0] vs 1.3 [1.4]; P < 0.001) compared to controls. Moreover, patients had significantly lower median fasting blood glucose (FBG; 96 mg/dL vs 104 mg/dL; P < 0.001) and BMI (25.8 vs 27.7; P = 0.02) compared to controls. Multivariable logistic regression analysis revealed negative associations for FBG with GCA at 5 and 10 years prior to diagnosis/index date. CONCLUSION: DM prevalence and median FBG and BMI were lower in patients with GCA up to 5 years prior to diagnosis, suggesting that metabolic factors influence the risk of GCA.

Utilization of preventive services in a systemic lupus erythematosus population-based cohort: a Lupus Midwest Network (LUMEN) study.

BACKGROUND: Systemic lupus erythematosus (SLE) is a disease that can lead to damage of multiple organs and, along with certain treatments, increase the risk of developing cancer, cardiovascular disease, diabetes, osteoporosis, and infections. Preventive services are particularly important in patients with SLE to mitigate the aforementioned risks. We aimed to evaluate the trends of preventive services utilization in patients with systemic lupus erythematosus, compared with non-SLE population. METHODS: All ≥19-year-old patients in the Lupus Midwest Network (LUMEN) registry, a population-based cohort, with SLE on January 1, 2015, were included and matched (1:1) by sex, age, race, and county to non-SLE comparators. Among both groups, we compared the rates of screenings for breast and cervical cancer, hypertension, hyperlipidemia, diabetes mellitus, and osteoporosis as well as immunizations. RESULTS: We included 440 SLE patients and 430 non-SLE comparators. The probability of breast cancer screening among women with SLE was similar to comparators (hazard ratio [HR] 1.09, 95% CI 0.85-1.39), while cervical cancer screening was lower (HR 0.75, 95% CI 0.58-0.96). Hypertension screening was higher among patients with SLE (HR 1.35, 95% CI 1.13-1.62); however, hyperlipidemia screening was similar to comparators (HR 1.16, 95% CI 0.96-1.41). Diabetes and osteoporosis screenings were more likely to be performed for SLE patients than for comparators (HR 2.46, 95% CI 2.11-2.87; and HR 3.19, 95% CI 2.31-4.41; respectively). Influenza and pneumococcal immunizations were higher among SLE patients (HR 1.31, 95% CI 1.12-1.54; and HR 2.06, 95% CI 1.38-3.09; respectively), while zoster vaccination was similar (HR 1.17, 95% CI 0.81-1.69). CONCLUSIONS: The trends of utilization of preventive services by SLE patients vary according to screening or vaccine compared with the general population. Considering these differences, we demonstrate an opportunity for improvement, particularly in cervical cancer, hyperlipidemia, and osteoporosis screenings and vaccinations.

COVID-19 Vaccine Uptake Among Patients With Systemic Lupus Erythematosus in the American Midwest: The Lupus Midwest Network (LUMEN).

OBJECTIVE: Patients with systemic lupus erythematosus (SLE) are at higher risk of poor outcomes from coronavirus disease 2019 (COVID-19). The vaccination rate among such patients is unknown. We aimed to assess COVID-19 vaccine uptake among patients with SLE. METHODS: We included 342 patients with SLE from the Lupus Midwest Network (LUMEN) and 350 age-, sex-, race-, and county-matched comparators. Vaccination uptake for influenza, pneumococcal, and zoster vaccines before pandemic restrictions began (up to February 29, 2020) was assessed. First-dose COVID-19 vaccine uptake was electronically retrieved and manually ascertained (December 15, 2020, to July 31, 2021). Time to COVID-19 vaccination, demographics, SLE manifestations, medications, Charlson Comorbidity Index, Area Deprivation Index, and Rural-Urban Commuting Area codes were compared. RESULTS: On July 31, 2021, 83.3% of patients with SLE and 85.5% of comparators were vaccinated against COVID-19. The COVID-19 vaccination rates were similar among SLE and comparators (hazard ratio 0.93, 95% CI 0.79-1.10). Unvaccinated patients with SLE were more likely than vaccinated patients to be men (27.3% vs 14.1%), younger (mean age 54.1 vs 58.8 yrs), have a shorter SLE duration (median 7.3 vs 10.7 yrs), and be less frequently vaccinated with influenza and pneumococcal vaccines. CONCLUSION: Patients with SLE in the Lupus Midwest Network had similar COVID-19 vaccination uptake as matched comparators, most of whom were vaccinated early when the vaccine became available. One in 6 patients with SLE remain unvaccinated.

Evaluation of hearing loss in young adults after exposure to 3.0T MRI with standard hearing protection.

Standard clinical protocols require hearing protection during magnetic resonance imaging (MRI) for patient safety. This investigation prospectively evaluated the auditory function impact of acoustic noise exposure during a 3.0T MRI in healthy adults. Twenty-nine participants with normal hearing underwent a comprehensive audiologic assessment before and immediately following a clinically indicated head MRI. Appropriate hearing protection with earplugs (and pads) was used per standard of practice. To characterize noise hazards, current sound monitoring tools were used to measure levels of pulse sequences measured. A third audiologic test was performed if a significant threshold shift (STS) was identified at the second test, within 30 days post MRI. Some sequences produced high levels (up to 114.5 dBA; 129 dB peak SPL) that required hearing protection but did not exceed 100% daily noise dose. One participant exhibited an STS in the frequency region most highly associated with noise-induced hearing loss. No participants experienced OSHA-defined STS in either ear. Overall, OAE measures did not show evidence of changes in cochlear function after MRI. In conclusion, hearing threshold shifts associated with hearing loss or OAE level shifts reflecting underlying cochlear damage were not detected in any of the 3.0T MRI study participants who used the current recommended hearing protection.

Comprehensive assessment of multimorbidity burden in a population-based cohort of patients with rheumatoid arthritis.

OBJECTIVE: To comprehensively assess multimorbidity burden in patients with rheumatoid arthritis (RA) in order to unify the multimorbidity definition for RA research and clinical practice. METHODS: In this population-based study, residents of eight Minnesota counties with prevalent RA on 1 January 2015 were identified. Age, sex and county-matched non-RA comparators were selected from the same population. Diagnostic codes were retrieved for 5 years before 1 January 2015. Using two codes ≥30 days apart, 44 previously defined morbidities and 78 non-overlapping chronic disease categories based on Clinical Classification Software were defined. Prevalence of each morbidity in the RA versus non-RA cohorts was compared using false discovery rate to adjust for multiple comparisons. Morbidities more common in RA than non-RA and those with prevalence ≥5% were retained. RESULTS: 1643 patients with RA and 1643 non-RA subjects (72% women; mean age 63.1 years) were studied. Using the 44 morbidities, multimorbidity (defined as 2+ morbidities) was present in 1411 (86%) of RA and 1164 (71%) of non-RA subjects (p<0.001) with 5+ morbidities present in 907 (55%) of RA and 619 (38%) of non-RA (p<0.001). Patients with RA had significantly higher prevalence of 24 of the 44 morbidities compared with non-RA, especially interstitial lung disease, fibromyalgia, osteoarthritis and osteoporosis. Among the additional 78 categories, 7 were significantly higher in RA than non-RA, including organic sleep disorders, vitamin D deficiency and foot ulcers. CONCLUSION: Patients with RA have a higher prevalence of multimorbidity compared with non-RA subjects. These results confirm the list of 44 morbidities and add several other morbidities of interest in RA.

Natural History of Clinical, Laboratory, and Echocardiographic Parameters of a Primary Hyperoxaluria Cohort on Long Term Hemodialysis.

Background: Primary hyperoxaluria type 1 (PH1) is a rare monogenic disorder characterized by excessive hepatic production of oxalate leading to recurrent nephrolithiasis, nephrocalcinosis, and progressive kidney damage, often requiring renal replacement therapy (RRT). Though systemic oxalate deposition is well-known, the natural history of PH1 during RRT has not been systematically described. In this study, we describe the clinical, laboratory, and echocardiographic features of a cohort of PH1 patients on RRT. Methods: Patients with PH1 enrolled in the Rare Kidney Stone Consortium PH Registry who progressed to require RRT, had ≥2 plasma oxalate (pOx) measurements 3-36 months after start of RRT, and at least one pair of pOx measurements between 6 and 18 months apart were retrospectively analyzed. Clinical, echocardiographic, and laboratory results were obtained from the Registry. Results: The 17 PH1 patients in our cohort had a mean total HD hours/week of 17.4 (SD 7.9; range 7.5-36) and a range of age of RRT start of 0.2-75.9 years. The average change in plasma oxalate (pOx) over time on RRT was -0.74 [-2.9, 1.4] µmol/L/month with the mean pOx never declining below 50 µmol/L. Over time on RRT, oxalosis progressively developed in multiple organ systems. Echocardiography performed on 13 subjects showed worsening of left ventricular global longitudinal strain correlated with pOx (p < 0.05). Conclusions: Even when a cohort of PH1 patients were treated with intensified RRT, their predialysis pOx remained above target and they developed increasing evidence of oxalosis. Echocardiographic data suggest that cardiac dysfunction could be related to elevated pOx and may worsen over time.

Multimorbidity Burden in Rheumatoid Arthritis: A Population-based Cohort Study.

OBJECTIVE: To estimate the prevalence and incidence of multimorbidity (MM) in a population-based cohort of patients with rheumatoid arthritis (RA) compared to subjects without RA. METHODS: Between 1999-2013, residents of Olmsted County, Minnesota with incident RA who met the 1987 American College of Rheumatology criteria were compared to age- and sex-matched non-RA subjects from the same population. Twenty-five chronic comorbidities from a combination of the Charlson, Elixhauser, and Rheumatic Disease Comorbidity Indices were included, excluding rheumatic comorbidities. The Aalen-Johansen method was used to estimate the cumulative incidence of MM (MM2+; ≥ 2 chronic comorbidities) or substantial MM (MM5+; ≥ 5), adjusting for the competing risk of death. RESULTS: The study included 597 patients with RA and 594 non-RA subjects (70% female, 90% White, mean age 55.5 yrs). At incidence/index date, the prevalence of MM2+ was higher in RA than non-RA subjects (38% RA vs 32% non-RA, P = 0.02), whereas prevalence of MM5+ was similar (5% RA vs. 4% non-RA, P = 0.68). During follow-up (median 11.6 yrs RA, 11.3 yrs non-RA), more patients with RA developed MM2+ (214 RA vs 188 non-RA; adjusted HR 1.39, 95% CI 1.14-1.69). By 10 years after RA incidence/index, the cumulative incidence of MM2+ was 56.5% among the patients with RA (95% CI 56.5-62.3%) compared with 47.9% among the non-RA (95% CI 42.8-53.7%). Patients with RA showed no evidence of increase in incidence of MM5+ (adjusted HR 1.17, 95% CI 0.93-1.47). CONCLUSION: Patients with RA have both a higher prevalence of MM at the time of RA incidence as well as increased incidence thereafter.

Breast cancers observed in transplant patients in a single institution.

OBJECTIVE: Document occurrence of breast cancer in females after liver, kidney, or pancreas transplantation seen at a tertiary medical center. METHODS: Medical records of adult female patients with liver, kidney, or pancreas transplants from 1/1/1995 to 4/4/2014 were retrospectively reviewed. Patients with a history of breast cancer, no mammogram post-transplant, or no research authorization were excluded. Mammogram findings and pathology results were reviewed and recorded. Cancer rates could not be measured in patients followed up outside the institution. Descriptive statistics summarized the cohort. Occurrence rates were estimated using Poisson regression. RESULTS: 1095 women were included and 33 were diagnosed with breast cancer post-transplant. Median age at diagnosis was 58 years. Average interval from transplant to cancer diagnosis was 82.6 months. Observed occurrence of invasive and in-situ breast cancer (reported as per 100,000 person-years [95% confidence interval]) was 353 [243-496]. Liver transplant patients showed the lowest rate (181 [95% CI 73-372]), vs. kidney (476 [305-708]) or pancreas (467 [57-1688]). Patients with the highest breast density showed increased occurrence despite younger age (1001 [367-2178]) compared to those with lower breast density (range 239 [109-454] to 372 [186-666]). CONCLUSIONS: Female patients after organ transplant experienced increased breast cancer occurrence in this observational study. Those who developed breast cancer also had increased breast density. The findings underscore the importance of breast cancer screening in this population.

Multimorbidity and Fatigue in Rheumatoid Arthritis: A Cross-Sectional Study of a Population-Based Cohort.

INTRODUCTION: The objective was to evaluate the relationships between multimorbidity and overall fatigue as well as fatigue subdomains in patients with rheumatoid arthritis (RA). METHODS: A cross-sectional study of a population-based cohort of patients with RA was performed. Fatigue was assessed using the Bristol Rheumatoid Arthritis Fatigue Multidimensional Questionnaire (BRAF-MDQ). Patients' medical records were reviewed for 25 chronic comorbidities prior to the BRAF-MDQ. Linear and logistic regression models were used to estimate the differences in BRAF-MDQ total and subdomain (physical, living, cognitive, and emotional) scores associated with multimorbidity, adjusting for age, sex, disease duration, obesity, smoking, C-reactive protein, and RA autoantibodies. Higher BRAF-MDQ scores indicate greater fatigue severity. RESULTS: The cohort included 192 patients, median age 62 years, and median RA duration 13 years. Multimorbidity was common with 93 (48%) having ≥ 2 comorbidities, and 27 (14%) having ≥ 4 comorbidities. The median BRAF-MDQ total score was 9 (interquartile range 3-18), with higher scores indicating greater fatigue. Patients with ≥ 4 comorbidities had higher total BRAF-MDQ scores (median 16.5, interquartile range: 6.8-24.8) than patients with < 4 comorbidities (7.5, 2.8-16.0; p = 0.014). Each additional comorbidity was associated with a 2.33 (95% confidence interval [CI] 1.10-3.56) unit increase in total BRAF-MDQ score (p < 0.001), and the presence of ≥ 4 comorbidities was associated with a 9.33 (95% CI 3.92-14.7) unit increase in total BRAF-MDQ score. Multimorbidity was significantly associated with all four fatigue subdomains in adjusted models. CONCLUSIONS: Multimorbidity is associated with increased fatigue in patients with RA. The findings suggest that interventions targeting multimorbidity could help alleviate treatment-refractory fatigue in patients with RA and other rheumatic diseases.

[89Zr]Zr-DBN labeled cardiopoietic stem cells proficient for heart failure.

INTRODUCTION: Radiolabeling of stem cells with a positron emitting radioisotope represents a major advancement in regenerative biotherapy enabling non-invasive imaging. To assess the value of such an approach in a clinically relevant scenario, the tolerability and therapeutic aptitude of [89Zr]zirconium-p-isothiocyanatobenzyl-desferrioxamine ([89Zr]Zr-DBN) labeled human cardiopoietic stem cells (CPs) were evaluated in a model of ischemic heart failure. METHODS AND RESULTS: [89Zr]Zr-DBN based radiolabeling of human CPs yielded [89Zr]Zr-DBN-CPs with radioactivity yield of 0.70 ± 0.20 MBq/106 cells and excellent label stability. Compared to unlabeled cell counterparts, [89Zr]Zr-DBN-CPs maintained morphology, viability, and proliferation capacity with characteristic expression of mesodermal and pro-cardiogenic transcription factors defining the cardiopoietic phenotype. Administered in chronically infarcted murine hearts, [89Zr]Zr-DBN-CPs salvaged cardiac pump failure, documented by improved left ventricular ejection fraction not inferior to unlabeled CPs and notably superior to infarcted hearts without cell treatment. CONCLUSION: The present study establishes that [89Zr]Zr-DBN labeling does not compromise stem cell identity or efficacy in the setting of heart failure, offering a non-invasive molecular imaging platform to monitor regenerative biotherapeutics post-transplantation.

Elastic Bandage vs Hypertonic Albumin for Diuretic-Resistant Volume-Overloaded Patients in Intensive Care Unit: A Propensity-Match Study.

OBJECTIVE: To compare elastic bandage (EB) vs hypertonic albumin solution administration to increase fluid removal by enhancing loop diuretic efficiency (DE) in patients with volume overload and diuretic resistance. PATIENTS AND METHODS: In this historic cohort study with propensity matching, we included diuretic-resistant adult (≥18 years) patients with volume overload after fluid resuscitation admitted in the intensive care unit from January 1, 2006, through June 30, 2017. Regression models and propensity matching were used to assess the associations of these interventions with changes in DE and other clinical outcomes. RESULTS: Of 1147 patients (median age, 66; interquartile range [IQR], 56-76 years; 51% [n=590] men), 384 (33%) received EB and 763 (67%) received hypertonic albumin solution. In adjusted models, EB was significantly associated with higher DE compared with hypertonic albumin solution (odds ratio, 1.37; 95% CI, 1.04 to 1.81; P=.004). After propensity matching of 345 pairs, DE remained significantly different between the 2 groups (median, 2111; IQR, 1092 to 4665 mL for EB vs median, 1829; IQR, 1032 to 3436 mL for hypertonic albumin solution; P=.02). EB, male sex, lower baseline serum urea nitrogen level, lower Charlson Comorbidity Index score, and higher baseline left ventricular ejection fraction were DE determinants. The lowest DE quartile (<1073 mL/40-mg furosemide equivalent) following adjustment for known predictors of mortality remained independently associated with higher 90-day death rate (odds ratio, 1.64; 95% CI, 1.13 to 2.36; P=.009). CONCLUSION: EB use is associated with greater DE than hypertonic albumin solution during the deescalation phase of sepsis resuscitation. Prospective clinical trials would validate the findings of this hypothesis-generating study.

Use of diuretics in shock: Temporal trends and clinical impacts in a propensity-matched cohort study.

OBJECTIVE: Fluid overload is common among critically ill patients and is associated with worse outcomes. We aimed to assess the effect of diuretics on urine output, vasopressor dose, acute kidney injury (AKI) incidence, and need for renal replacement therapies (RRT) among patients who receive vasopressors. PATIENTS AND METHODS: This is a single-center retrospective study of all adult patients admitted to the intensive care unit between January 2006 and December 2016 and received >6 hours of vasopressor therapy and at least one concomitant dose of diuretic. We excluded patients from cardiac care units. Hourly urine output and vasopressor dose for 6 hours before and after the first dose of diuretic therapy was compared. Rates of AKI development and RRT initiation were assessed with a propensity-matched cohort of patients who received vasopressors but did not receive diuretics. RESULTS: There was an increasing trend of prescribing diuretics in patients receiving vasopressors over the course of the study. We included 939 patients with median (IQR) age of 68(57, 78) years old and 400 (43%) female. The average hourly urine output during the first six hours following time zero in comparison with average hourly urine output during the six hours prior to time zero was significantly higher in diuretic group in comparison with patients who did not receive diuretics [81 (95% CI 73-89) ml/h vs. 42 (95% CI 39-45) ml/h, respectively; p<0.001]. After propensity matching, the rate of AKI within 7 days of exposure and the need for RRT were similar between the study and matched control patients (66 (15.6%) vs. 83 (19.6%), p = 0.11, and 34 (8.0%) vs. 37 (8.7%), p = 0.69, respectively). Mortality, however, was higher in the group that received diuretics. Ninety-day mortality was 191 (45.2%) in the exposed group VS 156 (36.9%) p = .009. CONCLUSIONS: While the use of diuretic therapy in critically ill patients receiving vasopressor infusions augmented urine output, it was not associated with higher vasopressor requirements, AKI incidence, and need for renal replacement therapy.

Comparison of non-contrast vessel wall imaging and 3-D time-of-flight MRA for atherosclerotic stenosis and plaque characterization within intracranial arteries.

PURPOSE: We compared the ability of intracranial high-resolution vessel wall imaging (VWI) without gadolinium and 3-D time-of-flight (3D-TOF) MRA techniques to characterize intracranial arterial stenosis and arterial wall plaque consistent with atherosclerotic plaque. METHODS: Consecutive intracranial VWI examinations performed within 2 months of a 3D-TOF exam with at least 1 noted plaque was included. Examinations assessed 17 vessel segments for plaque and diameters of stenotic and normal segments using double oblique reformatted images. Results were compared with the VWI and 3D-TOF exams considered the reference standard for plaque and luminal stenosis, respectively. RESULTS: Assessed segments totaled 286 from 17 patients. Proximal segment sensitivity and specificity for luminal stenosis detection with VWI was 92.5% and 82.1%, respectively, whereas for assessing plaque with 3D-TOF it was 59.4% and 98.3%, respectively. The mean intra-rater difference in luminal diameter measurements between VWI and 3D-TOF at normal segments and at the area of maximal stenosis was 0.02mm (SD 0.51mm) and 0.08mm (SD 0.66mm), respectively. CONCLUSIONS: Intracranial VWI demonstrated reasonably high sensitivity and specificity for luminal stenosis assessment using 3D-TOF as a reference standard, while 3D-TOF demonstrated low sensitivity for plaque detection. Our results suggest that VWI can be used for simultaneous assessment of luminal stenosis and plaque in the intracranial arteries.