Publications by authors named "Amber Salter"

127 Publications

Diagnostic Performance of LI-RADS Version 2018 for Evaluation of Pediatric Hepatocellular Carcinoma.

Radiology 2021 Feb 23:203559. Epub 2021 Feb 23.

From the Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 S Kingshighway Blvd, Campus Box 8131-MIR, St Louis, MO 63110 (G.K., T.J.F.); Department of Diagnostic Imaging, The Hospital for Sick Children and Department of Medical Imaging, University of Toronto, Toronto, Canada (G.B.C.); Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Tex (G.R.S.); Department of Radiology, Emory University and Children's Healthcare of Atlanta, Atlanta, Ga (A.L.A.); Department of Radiology, University of Pittsburgh Medical Center Children's Hospital of Pittsburgh, Pittsburgh, Pa (J.H.S.); Division of Biostatistics, Washington University School of Medicine, St Louis, Mo (A.S.); Nemours Children's Hospital, Nemours Children's Health System, University of Central Florida College of Medicine, Orlando, Fla (D.J.P.); and Department of Radiology, Cincinnati Children's Hospital, and Department of Radiology, University of Cincinnati College of Medicine, Cincinnati, Ohio (A.J.T.).

Background The Liver Imaging Reporting and Data System (LI-RADS) has standardized the evaluation of adult but not pediatric hepatocellular carcinoma (HCC). Purpose To evaluate the performance of LI-RADS version 2018 for diagnosis of pediatric HCC. Materials and Methods This multi-institution retrospective study evaluated all available dynamic CT and/or MRI scans of pediatric (≤18 years) HCC from five institutions between July 2009 and April 2019. The control group included an equal number of other enhancing hepatic lesions. Blinded to final diagnosis, three radiologists independently applied LI-RADS version 2018 criteria. The reference standard was pathologic examination or more than 1 year follow-up. Sensitivity and specificity of LI-RADS were computed using a dichotomous classification of LR-1, LR-2, or LR-3 versus LR-4, LR-5, LR-TIV (tumor in vein), or LR-M (probably or definitely malignant but not HCC-specific) for predicting hepatic malignancy in the entire cohort and in patients at risk for HCC. Results The cohort consisted of 116 children: 58 with HCC (mean age, 12 years ± 5; 31 girls) and 58 with other enhancing hepatic masses (mean age, 12 years ± 5; 42 girls). Frequencies of major criteria in classic HCC for the three readers were as follows: nonrim arterial phase hyperenhancement, 49%-62% (19-24 of 39 patients); nonperipheral "washout," 36%-59% (14-23 of 39 patients); and enhancing "capsule," 28%-38% (11-15 of 39 patients). For the full cohort, the sensitivity of LR-4, LR-5, LR-TIV, or LR-M for malignancy among the three readers ranged from 85% (95% CI: 76, 94) to 88% (95% CI: 80, 96); specificity of LR-1, LR-2, or LR-3 for benignity ranged from 54% (95% CI: 40, 68) to 70% (95% CI: 57, 83). In the at-risk subgroup, sensitivity ranged from 58% (95% CI: 36, 80) to 68% (95% CI: 48, 89); specificity ranged from 56% (95% CI: 37, 74) to 63% (95% CI: 45, 81). All lesions categorized as LR-TIV ( = 10-13) were HCCs. Conclusion Liver Imaging Reporting and Data System version 2018 had moderate sensitivity but low specificity for the diagnosis of pediatric hepatocellular carcinoma (HCC), which had low frequencies of the major criteria used for adult HCC diagnosis. © RSNA, 2021 See also the editorial by Paltiel in this issue.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1148/radiol.2021203559DOI Listing
February 2021

Mendelian randomization provides no evidence for a causal role in the bidirectional relationship between depression and multiple sclerosis.

Mult Scler 2021 Feb 16:1352458521993075. Epub 2021 Feb 16.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden/College of Pharmacy, University of Manitoba, Winnipeg, MB, Canada.

Background: Major depressive disorder (MDD) is common in multiple sclerosis (MS) and its incidence rises before MS diagnosis. However, the causality and direction of this association remain unclear.

Objective: The objective is to investigate the bidirectional relationship between MS and MDD using Mendelian randomization (MR).

Methods: We selected genetic instruments associated with risk of MDD ( = 660,937 cases; 1,453,489 controls) and MS ( = 47,429 cases; 68,374 controls). Using two-sample MR, we examined putative causal effects in either direction, with sensitivity analyses to assess pleiotropy. Also, we adjusted for body mass index (BMI) in multivariable MR.

Results: We found no effect of genetic liability to MDD on the odds of MS (OR = 1.07/doubling in odds, 95% CI = 0.90-1.28). Similarly, our findings did not support a causal effect of genetic liability to MS on MDD (OR = 1.00/doubling in odds, 95% CI = 0.99-1.01). Despite heterogeneity, sensitivity analyses indicated that bias from pleiotropy was unlikely. Conversely, genetic predisposition toward higher BMI increased the odds of MS (OR = 1.34/SD increase, 95% CI = 1.09-1.65) and MDD (OR = 1.08, 95% CI = 1.01-1.15).

Conclusion: This study does not support a causal association between MDD genetic liability and MS susceptibility, and vice versa. Genetic evidence suggesting commonality of obesity to both conditions may partly explain the increased incidence of depression pre-MS diagnosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1352458521993075DOI Listing
February 2021

Aging and efficacy of disease-modifying therapies in multiple sclerosis: a meta-analysis of clinical trials.

Ther Adv Neurol Disord 2020 28;13:1756286420969016. Epub 2020 Oct 28.

Neurology Section, VA North Texas Health Care System, Medical Service, 4500 South Lancaster Rd., Dallas, TX 75216, USA.

Background: Disease-modifying therapies (DMTs) for multiple sclerosis (MS) are approved for the treatment of disease activity and are effective in reducing relapses and new magnetic resonance imaging (MRI) lesions. However, disease activity generally subsides with time, and age-dependent changes in DMT efficacy are not well-established. We aimed to investigate whether age impacts the efficacy of DMTs in treating disease activity in patients with relapsing-remitting MS (RRMS).

Methods: DMT efficacy related to age was assessed through a meta-analysis of clinical trials that evaluated the efficacy of DMTs in RRMS patients as measured by reductions in the annualized relapse rate (ARR), new T2 lesions, and gadolinium-enhanced lesions on MRI. Using the mean baseline patient age from each trial, a weighted linear regression was fitted to determine whether age was associated with treatment efficacy on a group level.

Results: Group-level data from a total of 28,082 patients from 26 trials of 14 different DMTs were included in the meta-analysis. There were no statistically significant associations between age and reductions in ARR, new T2 lesions, and gadolinium-enhanced lesions of the treatment group compared with placebo.

Conclusion: DMTs for RRMS show efficacy in treating disease activity independent of age as demonstrated by group-level data from DMT clinical trials. Nevertheless, clinical trials select for patients with baseline disease activity regardless of age, thereby not representing real-world patients with RRMS, where disease activity declines with age.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1756286420969016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838219PMC
October 2020

Increased Utilization of Total Joint Arthroplasty After Medicaid Expansion.

J Bone Joint Surg Am 2021 Jan 20. Epub 2021 Jan 20.

Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri.

Background: The expansion of state Medicaid programs under the U.S. Affordable Care Act has led to a dramatic increase in the number of Americans with health insurance coverage. Prior analyses of a limited number of states have suggested that greater utilization of total hip arthroplasty (THA) and total knee arthroplasty (TKA) should be expected after Medicaid expansion. The purpose of our study was to examine whether increased utilization of THA and TKA occurred across a broader range of states after Medicaid expansion.

Methods: We analyzed administrative data from the Healthcare Cost and Utilization Project from 9 states (Arkansas, Arizona, Colorado, Iowa, Massachusetts, Maryland, Nevada, New York, and Vermont) that expanded Medicaid in 2014 and 2 states that did not expand Medicaid (Florida and Missouri). We included patients who were 18 to 64 years of age and had a primary THA or TKA from 2012 to 2015 with Medicaid as the primary payer. Other payers (including dual-eligible Medicaid and Medicare beneficiaries) were excluded. We performed multivariable regression modeling with the number of Medicaid-insured THAs or TKAs as the dependent variable and the interaction between the state Medicaid expansion status and year as the main policy independent variable, with adjustment for community characteristics.

Results: Among all 11 states, there were 39,452 total joint arthroplasties (42% THA and 58% TKA) funded by Medicaid from 2012 to 2015. After adjusting for community characteristics, within expansion states, compared with 2013, THA and TKA increased 15% in 2014 (p < 0.0001) and 23% in 2015 (p < 0.0001) within expansion states. Within non-expansion states, compared with 2013, there were significant utilization decreases of 18% in 2014 (p < 0.0001) and 11% in 2015 (p = 0.0002).

Conclusions: Medicaid expansion was associated with significant increases in Medicaid-funded THA and TKA utilization in 9 states. As additional states consider expanding Medicaid programs and as alternative health reforms that increase insurance eligibility are debated, surgeons, administrators, and policymakers should prepare for a surge in the utilization of THA and TKA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2106/JBJS.20.00303DOI Listing
January 2021

Defining phenotypic and functional heterogeneity of glioblastoma stem cells by mass cytometry.

JCI Insight 2021 Feb 22;6(4). Epub 2021 Feb 22.

Department of Medicine.

Most patients with glioblastoma (GBM) die within 2 years. A major therapeutic goal is to target GBM stem cells (GSCs), a subpopulation of cells that contribute to treatment resistance and recurrence. Since their discovery in 2003, GSCs have been isolated using single-surface markers, such as CD15, CD44, CD133, and α6 integrin. It remains unknown how these single-surface marker-defined GSC populations compare with each other in terms of signaling and function and whether expression of different combinations of these markers is associated with different functional capacity. Using mass cytometry and fresh operating room specimens, we found 15 distinct GSC subpopulations in patients, and they differed in their MEK/ERK, WNT, and AKT pathway activation status. Once in culture, some subpopulations were lost and previously undetectable ones materialized. GSCs that highly expressed all 4 surface markers had the greatest self-renewal capacity, WNT inhibitor sensitivity, and in vivo tumorigenicity. This work highlights the potential signaling and phenotypic diversity of GSCs. Larger patient sample sizes and antibody panels are required to confirm these findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1172/jci.insight.128456DOI Listing
February 2021

Comparative responsiveness of the health utilities index and the RAND-12 for multiple sclerosis.

Mult Scler 2021 Jan 5:1352458520981370. Epub 2021 Jan 5.

Department of Biostatistics, Washington University in St. Louis, St. Louis, MO, USA.

Background: Outcome measures need to be valid and have good test-retest reliability and responsiveness. We compared the responsiveness of the RAND-12 and the Health Utilities Index-mark III (HUI3) in persons with multiple sclerosis (MS).

Methods: In Spring 2018 and 2019, North American Research Committee on Multiple Sclerosis (NARCOMS) registry participants completed the HUI3, the RAND-12, and reported disability (Patient Determined Disease Steps (PDDS)) and employment status (full-time, part-time, and no). We used changes in PDDS and employment status as anchors. We assessed responsiveness using effect size, standardized response mean, and the responsiveness index. We used relative efficiency (RE) to compare the responsiveness of the health-related quality of life (HRQOL) scores, adjusting for sociodemographic factors.

Results: We included 4769 participants in the analysis. They had a mean (standard deviation (SD)) age of 60.9 (10.1) years, and 3826 participants (80.2%) were women. RE was highest for the HUI3 for changes in in disability status (HUI3: 1.0, Physical Component Score-12 (PCS-12): 0.80, and Mental Component Score-12 (MCS-12): 0.41) and for changes in employment status (HUI3: 1.0, PCS-12: 0.70, and MCS-12: 0.17).

Conclusion: The HUI3 was more responsive to changes in disability and employment status than the PCS-12 or MCS-12. Given the HUI3's other strong psychometric properties, it may be the preferred generic measure of HRQOL in MS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1352458520981370DOI Listing
January 2021

Dynamic F-FDOPA-PET/MRI for the preoperative evaluation of gliomas: correlation with stereotactic histopathology.

Neurooncol Pract 2020 Dec 7;7(6):656-667. Epub 2020 Aug 7.

Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, Missouri.

Background: MRI alone has limited accuracy for delineating tumor margins and poorly predicts the aggressiveness of gliomas, especially when tumors do not enhance. This study evaluated simultaneous 3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine (FDOPA)-PET/MRI to define tumor volumes compared to MRI alone more accurately, assessed its role in patient management, and correlated PET findings with histopathology.

Methods: Ten patients with known or suspected gliomas underwent standard of care surgical resection and/or stereotactic biopsy. FDOPA-PET/MRI was performed prior to surgery, allowing for precise co-registration of PET, MR, and biopsies. The biopsy sites were modeled as 5-mm spheres, and the local FDOPA uptake at each site was determined. Correlations were performed between measures of tumor histopathology, and static and dynamic PET values: standardized uptake values (SUVs), tumor to brain ratios, metabolic tumor volumes, and tracer kinetics at volumes of interest (VOIs) and biopsy sites.

Results: Tumor FDOPA-PET uptake was visualized in 8 patients. In 2 patients, tracer uptake was similar to normal brain reference with no histological findings of malignancy. Eight biopsy sites confirmed for glioma had FDOPA uptake without T1 contrast enhancement. The PET parameters were highly correlated only with the cell proliferation marker, Ki-67 (SUV: r = 0.985,  = .002). In this study, no statistically significant difference between high-grade and low-grade tumors was demonstrated. The dynamic PET analysis of VOIs and biopsy sites showed decreasing time-activity curves patterns. FDOPA-PET imaging directly influenced patient management.

Conclusions: Simultaneous FDOPA-PET/MRI allowed for more accurate visualization and delineation of gliomas, enabling more appropriate patient management and simplified validation of PET findings with histopathology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/nop/npaa044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716181PMC
December 2020

The impact of adjunctive tomosynthesis on screening mammography outcomes in two widely diverse radiology practices.

Breast J 2021 Jan 3;27(1):13-20. Epub 2020 Dec 3.

Department of Diagnostic Radiology, University of Kansas School of Medicine-Wichita, Kansas City, KS, USA.

To determine the effect of adjunctive digital breast tomosynthesis screening on dissimilar mammography practices. We compared the outcomes of breast cancer screening with digital mammography versus digital mammography combined with tomosynthesis in two independent breast imaging practices from June 1, 2015, to May 31, 2016. Institution one was a hospital-based academic practice of breast imaging specialists and institution two was a community-based practice with academic affiliation served by general radiologists. Screening mammography was linked to subsequent diagnostic imaging and pathology. Subject characteristics and performance metrics were compared via t test for continuous variables and the chi-square test for categorical variables. A two-sided z test was performed to test modality differences for assessment and pathology subtype. Of the 54 638 women, 54% (n = 29 295) were from institution one and 55% (n = 30 013) underwent digital mammography alone. Women undergoing mammography with tomosynthesis were older (60.8 years vs 56.9 years, P < .001) and had slightly less dense breast composition (P = .001). Performance metrics varied substantially between institutions. At both institutions the biopsy rate, positive predictive value of screening (PPV ), and invasive cancer detection rate increased significantly with adjunctive tomosynthesis. At institution one, the biopsy rate increased from 1.4% to 1.9%, the PPV from 6.0% to 8.2%, and the invasive cancer detection rate from 3.4 to 4.9/1000 women screened. At institution two, the respective increases were from 0.7% to 1.0%, 5.5% to 11.0%, and 2.3% to 4.1/1000. Tomosynthesis recalled asymmetry less and mass more and resulted in fewer BI-RADS 1 and 2 assessments than screening with mammography alone. Adjunctive tomosynthesis appears to have a consistent impact on breast cancer screening performance metrics despite marked variation in breast imaging practice. Combined tomosynthesis screening has a significantly higher PPV , leads to a greater number of biopsies, and detects more invasive cancer than screening with digital mammography.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/tbj.14121DOI Listing
January 2021

Correlation between Post-Procedure Residual Thrombus and Clinical Outcome in Deep Vein Thrombosis Patients Receiving Pharmacomechanical Thrombolysis in a Multicenter Randomized Trial.

J Vasc Interv Radiol 2020 Oct 15;31(10):1517-1528.e2. Epub 2020 Sep 15.

Mallinckrodt Institute of Radiology, Washington University in St. Louis, 510 S. Kingshighway Blvd., Box 8131, St. Louis, MO, 63110. Electronic address:

Purpose: To evaluate relationships between immediate venographic results and clinical outcomes of pharmacomechanical catheter-directed thrombolysis (PCDT).

Materials And Methods: Venograms from 317 patients with acute proximal deep vein thrombosis (DVT) who received PCDT in a multicenter randomized trial were reviewed. Quantitative thrombus resolution was assessed by independent readers using a modified Marder scale. The physician operators recorded their visual assessments of thrombus regression and venous flow. These immediate post-procedure results were correlated with patient outcomes at 1, 12, and 24 months.

Results: PCDT produced substantial thrombus removal (P < .001 for pre-PCDT vs. post-PCDT thrombus scores in all segments). At procedure end, spontaneous venous flow was present in 99% of iliofemoral venous segments and in 89% of femoral-popliteal venous segments. For the overall proximal DVT population, and for the femoral-popliteal DVT subgroup, post-PCDT thrombus volume did not correlate with 1-month or 24-month outcomes. For the iliofemoral DVT subgroup, over 1 and 24 months, symptom severity scores were higher (worse), and venous disease-specific quality of life (QOL) scores were lower (worse) in patients with greater post-PCDT thrombus volume, with the difference reaching statistical significance for the 24-month Villalta post-thrombotic syndrome (PTS) severity score (P = .0098). Post-PCDT thrombus volume did not correlate with 12-month valvular reflux.

Conclusions: PCDT successfully removes thrombus in acute proximal DVT. However, the residual thrombus burden at procedure end does not correlate with the occurrence of PTS during the subsequent 24 months. In iliofemoral DVT, lower residual thrombus burden correlates with reduced PTS severity and possibly also with improved venous QOL and fewer early symptoms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jvir.2020.07.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541749PMC
October 2020

Optimal co-clinical radiomics: Sensitivity of radiomic features to tumour volume, image noise and resolution in co-clinical T1-weighted and T2-weighted magnetic resonance imaging.

EBioMedicine 2020 Sep 2;59:102963. Epub 2020 Sep 2.

Department of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Biomedical Engineering, Washington University School of Medicine, St. Louis, MO USA. Electronic address:

Background: Radiomics analyses has been proposed to interrogate the biology of tumour as well as to predict/assess response to therapy in vivo. The objective of this work was to assess the sensitivity of radiomics features to noise, resolution, and tumour volume in the context of a co-clinical trial.

Methods: Triple negative breast cancer (TNBC) patients were recruited into an ongoing co-clinical imaging trial. Sub-typed matched TNBC patient-derived tumour xenografts (PDX) were generated to investigate optimal co-clinical MR radiomic features. The MR imaging protocol included T1-weighed and T2-weighted imaging. To test the sensitivity of radiomics to resolution, PDX were imaged at three different resolutions. Multiple sets of images with varying signal-to-noise ratio (SNR) were generated, and an image independent patch-based method was implemented to measure the noise levels. Forty-eight radiomic features were extracted from manually segmented 2D and 3D segmented tumours and normal tissues of T1- and T2- weighted co-clinical MR images.

Findings: Sixteen radiomics features were identified as volume dependent and corrected for volume-dependency following normalization. Features from grey-level run-length matrix (GLRLM), grey-level size zone matrix (GLSZM) were identified as most sensitive to noise. Radiomic features Kurtosis and Run-length variance (RLV) from GLSZM were most sensitive to changes in resolution in both T1w and T2w MRI. In general, 3D radiomic features were more robust compared to 2D (single slice) measures, although the former exhibited higher variability between subjects.

Interpretation: Tumour volume, noise characteristics, and image resolution significantly impact radiomic analysis in co-clinical studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ebiom.2020.102963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479492PMC
September 2020

Adverse event profile differences between rituximab and ocrelizumab: Findings from the FDA Adverse Event Reporting Database.

Mult Scler 2020 Aug 21:1352458520949986. Epub 2020 Aug 21.

Department of Neurology & Neurotherapeutics, Immunology Graduate Program, University of Texas Southwestern Medical Center, Dallas, TX, USA/Neurology Section, VA North Texas Health Care System, Dallas, TX, USA.

Background: Rituximab and ocrelizumab are anti-CD20 monoclonal antibodies that have shown a marked reduction in multiple sclerosis (MS) inflammatory activity. However, their real-world safety profile has not been adequately compared.

Objective: To investigate the adverse event (AE) profile of rituximab and ocrelizumab reported to the Food and Drug Administration Adverse Event Reporting System (FAERS) database.

Methods: The FAERS database was filtered by indication (MS) and drug (rituximab or ocrelizumab). Disproportionality analyses including but not limited to reporting odds ratio (ROR) were conducted to identify drug-AE associations. A signal was detected if the lower limit of the 95% confidence interval of ROR (ROR) exceeded 1.

Results: There were 623 and 7948 reports for rituximab and ocrelizumab, respectively. The most frequent AEs with rituximab and ocrelizumab were infusion-related reaction (4.82%) and urinary tract infection (10.52%), respectively. The strongest drug-AE association for rituximab and ocrelizumab were ear pruritus (ROR: 47.53) and oral herpes (ROR: 38.99), respectively. Ocrelizumab was associated with an almost two times higher frequency of infections than rituximab (21.93% vs 11.05%, respectively).

Conclusion: This study revealed differences in reporting AEs between rituximab and ocrelizumab. Infections were reported more frequently with ocrelizumab. Although speculative, a potentially different or more extensive B-cell depletion by ocrelizumab might explain these findings. Additional pharmacovigilance studies need to be performed to better characterize differences in the AE profile in B-cell-depleting therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1352458520949986DOI Listing
August 2020

The emotional impact of the COVID-19 pandemic on individuals with progressive multiple sclerosis.

J Neurol 2020 Aug 19. Epub 2020 Aug 19.

Department of Psychiatry, University of Toronto and Sunnybrook Health Sciences Centre, Toronto, ON, M5R 3B6, Canada.

Objective: Individuals with pre-existing chronic illness have shown increased anxiety and depression due to COVID-19. Here, we examine the impact of the COVID-19 pandemic on emotional symptomatology and quality of life in individuals with Progressive Multiple Sclerosis (PMS).

Methods: Data were obtained during a randomized clinical trial on rehabilitation taking place at 11 centers in North America and Europe. Participants included 131 individuals with PMS. Study procedures were interrupted in accordance with governmental restrictions as COVID-19 spread. During study closure, a COVID Impact Survey was administered via telephone or email to all participants, along with measures of depressive symptoms, anxiety symptoms, quality of life, and MS symptomatology that were previously administered pre-pandemic.

Results: 4% of respondents reported COVID-19 infection. No significant changes were noted in anxiety, quality of life, or the impact of MS symptomatology on daily life from baseline to lockdown. While total HADS-depression scores increased significantly at follow-up, this did not translate into more participants scoring above the HADS threshold for clinically significant depression. No significant relationships were noted between disease duration, processing speed ability or EDSS, and changes in symptoms of depression or anxiety. Most participants reported the impact of the virus on their psychological well-being, with a little impact on financial well-being. The perceived impact of the pandemic on physical and psychological well-being was correlated with the impact of MS symptomatology on daily life, as well as changes in depression.

Conclusions: Overall, little change was noted in symptoms of depression or anxiety or overall quality of life.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00415-020-10160-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7436067PMC
August 2020

Differences in Self-Reported Physical and Behavioral Health in Musculoskeletal Patients Based on Physician Gender.

PM R 2020 Aug 9. Epub 2020 Aug 9.

Division of Physical Medicine and Rehabilitation, Department of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, MO.

Background: Differences in patient-physician interactions based on physician gender have been demonstrated. However, the association between patients' self-perceived health and their decision to see a female versus male physician is still unclear.

Objective: To determine if self-reported physical or behavioral health is different in musculoskeletal patients who present to female vs male physicians. We hypothesized that patients who present to female physicians report worse physical and behavioral health.

Design: Cross-sectional study.

Setting: Tertiary academic medical center.

Patients: Consecutive 21 980 adult patients who presented to a musculoskeletal medicine specialist for initial evaluation of a musculoskeletal condition between April 1, 2016 and November 1, 2017.

Main Outcome Measures: Physical Function, Pain Interference, Anxiety, and Depression Computer Adaptive Test domains of the Patient-Reported Outcomes Measurement Information System (PROMIS). The primary study outcome was the mean difference (MD) in PROMIS scores by physician gender.

Results: Patients who presented to female physicians self-reported slightly worse health in all domains: Physical Function (female physicians 40.2, male physicians 42.4, MD -2.1; 95% confidence interval [CI] -2.5 to -1.8), Pain Interference (female physicians 61.6, male physicians 60.4, MD 1.3 [1.0-1.5]), Anxiety (female physicians 52.5, male physicians 51.4, MD 1.1 [0.8-1.5]), and Depression (female physicians 47.5, male physicians 46.2, MD 1.3 [0.9-1.6]) (all P < .001). Patients who presented to female physicians were also slightly younger (51.9 vs 52.4 years, P = .034) and more likely to be female (63% vs 56%, P < .001).

Conclusions: Patients who presented to female physicians self-reported slightly worse physical and behavioral health compared to those patients who presented to male physicians. Further investigation into this finding may provide insight into drivers of patients' preferences, which may enable physicians of both genders to optimize patient care.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pmrj.12468DOI Listing
August 2020

Chemokine Receptor 2-targeted Molecular Imaging in Pulmonary Fibrosis. A Clinical Trial.

Am J Respir Crit Care Med 2021 01;203(1):78-89

Department of Radiology.

Idiopathic pulmonary fibrosis (IPF) is a progressive inflammatory lung disease without effective molecular markers of disease activity or treatment responses. Monocyte and interstitial macrophages that express the C-C motif CCR2 (chemokine receptor 2) are active in IPF and central to fibrosis. To phenotype patients with IPF for potential targeted therapy, we developed Cu-DOTA-ECL1i, a radiotracer to noninvasively track CCR2 monocytes and macrophages using positron emission tomography (PET). CCR2 cells were investigated in mice with bleomycin- or radiation-induced fibrosis and in human subjects with IPF. The CCR2 cell populations were localized relative to fibrotic regions in lung tissue and characterized using immunolocalization, single-cell mass cytometry, and RNA hybridization and then correlated with parallel quantitation of lung uptake by Cu-DOTA-ECL1i PET. Mouse models established that increased Cu-DOTA-ECL1i PET uptake in the lung correlates with CCR2 cell infiltration associated with fibrosis ( = 72). As therapeutic models, the inhibition of fibrosis by IL-1β blockade ( = 19) or antifibrotic pirfenidone ( = 18) reduced CCR2 macrophage accumulation and uptake of the radiotracer in mouse lungs. In lung tissues from patients with IPF, CCR2 cells concentrated in perifibrotic regions and correlated with radiotracer localization ( = 21). Human imaging revealed little lung uptake in healthy volunteers ( = 7), whereas subjects with IPF ( = 4) exhibited intensive signals in fibrotic zones. These findings support a role for imaging CCR2 cells within the fibrogenic niche in IPF to provide a molecular target for personalized therapy and monitoring.Clinical trial registered with www.clinicaltrials.gov (NCT03492762).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1164/rccm.202004-1132OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781144PMC
January 2021

COVID-19 in people with multiple sclerosis: A global data sharing initiative.

Mult Scler 2020 09 14;26(10):1157-1162. Epub 2020 Jul 14.

MS International Federation, London, UK.

Background: We need high-quality data to assess the determinants for COVID-19 severity in people with MS (PwMS). Several studies have recently emerged but there is great benefit in aligning data collection efforts at a global scale.

Objectives: Our mission is to scale-up COVID-19 data collection efforts and provide the MS community with data-driven insights as soon as possible.

Methods: Numerous stakeholders were brought together. Small dedicated interdisciplinary task forces were created to speed-up the formulation of the study design and work plan. First step was to agree upon a COVID-19 MS core data set. Second, we worked on providing a user-friendly and rapid pipeline to share COVID-19 data at a global scale.

Results: The COVID-19 MS core data set was agreed within 48 hours. To date, 23 data collection partners are involved and the first data imports have been performed successfully. Data processing and analysis is an on-going process.

Conclusions: We reached a consensus on a core data set and established data sharing processes with multiple partners to address an urgent need for information to guide clinical practice. First results show that partners are motivated to share data to attain the ultimate joint goal: better understand the effect of COVID-19 in PwMS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1352458520941485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361123PMC
September 2020

Comorbidity is associated with disease activity in MS: Findings from the CombiRx trial.

Neurology 2020 08 17;95(5):e446-e456. Epub 2020 Jun 17.

From the Department of Biostatistics (A.S.), Washington University in St. Louis, MO; College of Pharmacy (K.K.), and Departments of Internal Medicine and Community Health Sciences (R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada; Department of Medical Epidemiology and Biostatistics (K.K.), Karolinska Institutet, Solna, Sweden; Department of Neurology (K.C.F.), Johns Hopkins School of Medicine, Baltimore, MD; and Department of Biostatistics (G.C.), University of Alabama in Birmingham School of Public Health.

Objective: To determine whether comorbidity is associated with clinical (relapses, disability worsening) and MRI outcomes in multiple sclerosis (MS) by conducting a secondary analysis of the CombiRx clinical trial.

Methods: CombiRx compared interferon beta-1a, glatiramer acetate, and the combination of these agents. For participants eligible for evaluation of 6-month confirmed disability worsening, we used medical history, concomitant medications, and adverse events to ascertain comorbidity status. Comorbid conditions evaluated included hypertension, dyslipidemia, diabetes mellitus, depression, anxiety disorders, and migraine. Clinical outcomes included disease activity consisting of protocol-defined relapses, disability worsening, and MRI activity. We summarized the prevalence of these comorbid conditions and their association with disease activity and its components using multivariable Cox regression.

Results: Of the 1,008 participants randomized, 959 (95.1%) were eligible for assessment of 6-month disability worsening; for this subgroup, the median length of follow-up was 3.4 years (range 0.5-6.9 years). Overall, 55.1% of participants had ≥1 comorbidity at enrollment. After adjustment, anxiety (hazard ratio [HR] 1.25, 95% confidence interval [CI] 1.01-1.55) and dyslipidemia (HR 1.32, 95% CI 1.01-1.72) were associated with an increased hazard of any disease activity, while migraine (HR 0.80, 95% CI 0.67-0.97) was associated with a decreased hazard.

Conclusions: In this large trial population with rigorously obtained outcomes, comorbid conditions were common among participants and influenced disease outcomes, including relapses. The comorbidity burden of clinical trial participants with MS may be an important factor in the outcome of clinical trials. Additional investigations of the impact of comorbidity on clinical trial outcomes and response to disease-modifying therapies are warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000010024DOI Listing
August 2020

Results of the 2019 Survey of the American Alliance of Academic Chief Residents in Radiology.

Acad Radiol 2020 Jun 13. Epub 2020 Jun 13.

Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 S. Kingshighway Blvd, Campus Box 8131, St. Louis, MO, 63110.

Rationale And Objectives: An annual survey of chief residents in accredited North American radiology programs is conducted by the American Alliance of Academic Chief Residents in Radiology (ACR). The purpose of this study is to summarize the 2019 ACR chief resident survey.

Materials And Methods: An online survey was distributed to chief residents from 194 Accreditation Council on Graduate Medical Education-accredited radiology residencies. Questions were designed to gather information about residency program details, call and weekend coverage, interventional radiology training, fellowship, social media use, healthcare reform, artificial intelligence, and job market status.

Results: One hundred and forty-two unique responses from 99 programs were provided, yielding a 51% program response rate. There was a mean of 7.3 women per residency with a mean program size of 28 residents (26% women). Only 3 of the 99 (3%) programs had a proportion of women that was 50% or higher. The proportion of women in radiology residencies is unchanged since 2014 (p= 0.93) and is significantly lower than 2019 graduating women medical students (49.3%; p < 0.001). Thirty-five percent of programs had 24/7 attending coverage and 40% of programs had extended hours attending shifts. Of programs without 24/7 attending coverage, the proportion of programs without face-to-face readout has increased from 34% in 2014 to 55% in 2019 (p = 0.015). The majority (67%) of respondents had no concerns about the radiology job market; compared to 2014, where only 4% had no concerns (p < 0.001).

Conclusion: Women remain underrepresented in radiology, face-to-face readout is decreasing, and there has been a shift towards a positive job market outlook.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.acra.2020.04.042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736213PMC
June 2020

Study protocol: improving cognition in people with progressive multiple sclerosis: a multi-arm, randomized, blinded, sham-controlled trial of cognitive rehabilitation and aerobic exercise (COGEx).

BMC Neurol 2020 May 22;20(1):204. Epub 2020 May 22.

Department of Biostatistics, University of Alabama at Birmingham, Birmingham, USA.

Background: Cognitive dysfunction affects up to 70% of people with progressive MS (PMS). It can exert a deleterious effect on activities of daily living, employment and relationships. Preliminary evidence suggests that performance can improve with cognitive rehabilitation (CR) and aerobic exercise (EX), but existing data are predominantly from people with relapsing-remitting MS without cognitive impairment. There is therefore a need to investigate whether this is also the case in people with progressive forms of the disease who have objectively identified cognitive impairment. It is hypothesized that CR and EX are effective treatments for people with PMS who have cognitive impairment, in particular processing speed (PS) deficits, and that a combination of these two treatments is more effective than each individual treatment given alone. We further hypothesize that improvements in PS will be associated with modifications of functional and/or structural plasticity within specific brain networks/regions involved in PS measured with advanced MRI techniques.

Methods: This study is a multisite, randomized, double-blinded, sham controlled clinical trial of CR and aerobic exercise. Three hundred and sixty subjects from 11 sites will be randomly assigned into one of four groups: CR plus aerobic exercise; CR plus sham exercise; CR sham plus aerobic exercise and CR sham plus sham exercise. Subjects will participate in the assigned treatments for 12 weeks, twice a week. All subjects will have a cognitive and physical assessment at baseline, 12 weeks and 24 weeks. In an embedded sub-study, approximately 30% of subjects will undergo structural and functional MRI to investigate the neural mechanisms underlying the behavioral response. The primary outcome is the Symbol Digit Modalities Test (SDMT) measuring PS. Secondary outcome measures include: indices of verbal and non-verbal memory, depression, walking speed and a dual cognitive-motor task and MRI.

Discussion: The study is being undertaken in 6 countries (11 centres) in multiple languages (English, Italian, Danish, Dutch); with testing material validated and standardized in these languages. The rationale for this approach is to obtain a robustly powered sample size and to demonstrate that these two interventions can be given effectively in multiple countries and in different languages.

Trial Registration: The trial was registered on September 20th 2018 at www.clinicaltrials.gov having identifier NCT03679468. Registration was performed before recruitment was initiated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12883-020-01772-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7245035PMC
May 2020

Fractures in the prodromal period of Parkinson disease.

Neurology 2020 06 28;94(23):e2448-e2456. Epub 2020 Apr 28.

From the Departments of Neurology (A.C.-S., A.G., S.S.N., M.N.W., B.A.R.) and Orthopedic Surgery (A.N.M.) and Division of Biostatistics (A.S.), Washington University School of Medicine, St. Louis, MO; and School of Public Health, Faculty of Health Sciences (B.A.R.), University of the Witwatersrand, Johannesburg, South Africa.

Objective: To examine the association between fractures and Parkinson disease (PD) during the 5-year prodromal phase as compared to controls.

Methods: We performed a population-based case-control study of Medicare beneficiaries in the United States from 2004 to 2009. We identified 89,632 incident PD cases and 117,760 comparable controls 66-90 years of age in 2009. PD case status was the outcome, and noncranial fracture the independent variable. We used logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for association between fracture and PD in yearly time intervals prior to PD diagnosis/control reference date, after adjusting for covariates.

Results: There were 39,606 total fractures (25.4% cases, 14.3% controls) over the 5 years prior to the PD diagnosis/control reference date. PD was positively associated with fractures even after adjusting for age, sex, race/ethnicity, Charlson comorbidity index, alcohol use, tobacco use, and osteoporosis. The association between PD and fracture was evident at yearly time windows prior to PD diagnosis/control reference date. The association between PD and each type of fracture strengthened as the PD diagnosis/control reference date approached (all time interaction values ≤0.02). Among beneficiaries with a mechanism of injury, the majority were attributed to falls (74.6% cases, 72.8% controls).

Conclusion: Fractures occur more commonly during the prodromal period of PD compared to controls, especially as diagnosis date approached, suggesting that patients with PD may experience unrecognized motor and nonmotor symptoms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000009452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455361PMC
June 2020

Select Atrophied Regions in Alzheimer disease (SARA): An improved volumetric model for identifying Alzheimer disease dementia.

Neuroimage Clin 2020 16;26:102248. Epub 2020 Mar 16.

Washington University in St. Louis School of Medicine, 660 S Euclid Ave, St. Louis, MO 63110, USA; Knight Alzheimer Disease Research Center, 4488 Forest Park Pkwy, St. Louis, MO 63108, USA. Electronic address:

Introduction: Volumetric biomarkers for Alzheimer disease (AD) are attractive due to their wide availability and ease of administration, but have traditionally shown lower diagnostic accuracy than measures of neuropathological contributors to AD. Our purpose was to optimize the diagnostic specificity of structural MRIs for AD using quantitative, data-driven techniques.

Methods: This retrospective study assembled several non-overlapping cohorts (total n = 1287) with publicly available data and clinical patients from Barnes-Jewish Hospital (data gathered 1990-2018). The Normal Aging Cohort (n = 383) contained amyloid biomarker negative, cognitively normal (CN) participants, and provided a basis for determining age-related atrophy in other cohorts. The Training (n = 216) and Test (n = 109) Cohorts contained participants with symptomatic AD and CN controls. Classification models were developed in the Training Cohort and compared in the Test Cohort using the receiver operating characteristics areas under curve (AUCs). Additional model comparisons were done in the Clinical Cohort (n = 579), which contained patients who were diagnosed with dementia due to various etiologies in a tertiary care outpatient memory clinic.

Results: While the Normal Aging Cohort showed regional age-related atrophy, classification models were not improved by including age as a predictor or by using volumetrics adjusted for age-related atrophy. The optimal model used multiple regions (hippocampal volume, inferior lateral ventricle volume, amygdala volume, entorhinal thickness, and inferior parietal thickness) and was able to separate AD and CN controls in the Test Cohort with an AUC of 0.961. In the Clinical Cohort, this model separated AD from non-AD diagnoses with an AUC 0.820, an incrementally greater separation of the cohort than by hippocampal volume alone (AUC of 0.801, p = 0.06). Greatest separation was seen for AD vs. frontotemporal dementia and for AD vs. non-neurodegenerative diagnoses.

Conclusions: Volumetric biomarkers distinguished individuals with symptomatic AD from CN controls and other dementia types but were not improved by controlling for normal aging.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nicl.2020.102248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7182765PMC
February 2021

Gender identity and sexual orientation affect health care satisfaction, but not utilization, in persons with Multiple Sclerosis.

Mult Scler Relat Disord 2020 Jan 12;37:101440. Epub 2019 Oct 12.

Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada; Department of Community Health Sciences, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada. Electronic address:

Objective: We aimed to determine the association between gender identity and sexual orientation on health care utilization in persons with multiple sclerosis (MS), as well as satisfaction with their doctor and comfort discussing sexual health with their doctor.

Methods: We surveyed participants from the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry regarding their gender identity and sexual orientation in 2017. Participants also reported their sociodemographic characteristics, disability status, health behaviors and health care utilization, including whether any hospitalizations or emergency room (ER) visits occurred or any disease-modifying therapy (DMT) was used within the last six months. We compared the likelihood of hospitalizations, ER visits and DMT use between (i) cisgender and transgender participants; and (ii) heterosexual, homosexual, and "other sexual orientation" participants using multivariable logistic regression models adjusting for potential confounding factors.

Results: Of the 5,604 eligible responders, 1168 (20.8%) reported their sex at birth as male and 4436 reported their sex at birth as female (79.2%). Twenty-five (0.45%) participants identified as transgender and 260 (4.6%) as non-heterosexual individuals. As compared to participants who reported their sexual orientation as heterosexual, non-heterosexual participants were younger, with an earlier age at MS symptom onset, more likely to have a post-secondary education, and more likely to be single. The frequency of any ER visits, any hospital admissions, and DMT use did not differ according to gender identity did not differ according to gender identity or sexual orientation. As compared to cisgender participants, transgender participants reported less comfort (p < 0.042) discussing sexual health with their doctor; findings were similar for non-heterosexual participants as compared to heterosexual participants. Participants reporting other sexual orientation also reported lower satisfaction (p < 0.039) with their doctor than other participants.

Conclusion: Gender identity and sexual orientation were not associated with differences in healthcare utilization in persons with MS. However, health care experiences and satisfaction with care may be altered by gender identity and sexual orientation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.msard.2019.101440DOI Listing
January 2020

Infectious disease consultation for candidaemia - Authors' reply.

Lancet Infect Dis 2020 02;20(2):165-166

Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1473-3099(20)30005-0DOI Listing
February 2020

Outcome of Lesser Metatarsophalangeal Joint Interpositional Arthroplasty With Tendon Allograft.

Foot Ankle Int 2020 03 31;41(3):313-319. Epub 2020 Jan 31.

Washington University in St. Louis, Barnes-Jewish Hospital, St. Louis, MO, USA.

Background: Lesser toe metatarsal head degeneration and collapse can cause significant pain and disability. In the setting of global metatarsal head collapse, there are limited operative options. The purpose of our study was to evaluate clinical and radiographic outcomes after lesser toe metatarsophalangeal (MTP) joint interpositional arthroplasty with a tendon allograft and to describe the operative technique.

Methods: We retrospectively reviewed a consecutive series of patients treated by 3 fellowship-trained foot and ankle surgeons at one institution. We created a phone survey to evaluate satisfaction, pain, and likelihood to repeat the surgery. Foot and Ankle Ability Measure (FAAM) scores were reviewed before and after surgery. Preoperative and postoperative radiographs were evaluated for preservation of metatarsal length. The procedure was performed through a dorsal midline approach. The metatarsal head was reamed to a concave shape. A tendon allograft was fashioned into a ball and secured to the metatarsal with an anchor. Fifteen feet in 14 patients underwent lesser MTP joint interposition arthroplasty, with the average age of 49 years (range, 24-69), and an average follow-up of 4.2 years.

Results: Eighty percent (12/15) reported they would have the procedure again. Visual analog scale pain scores showed a decrease in pain from 7 to 1. FAAM sports subscale improved from 56% to 85%. Radiographically, the ratio of the affected metatarsal length to the adjacent metatarsal remained constant before and after surgery, suggesting preservation of the metatarsal cascade.

Conclusion: Interpositional arthroplasty of the lesser MTP joints with a rolled tendon allograft provided a unique solution, as it allows the surgeon to fill a large void without harvesting an autograft. This study showed improved patient-reported outcomes, high patient satisfaction, and good radiographic outcomes. Lesser metatarsophalangeal joint allograft interposition arthroplasty was a viable solution as a salvage procedure in the setting of global metatarsal head collapse.

Level Of Evidence: Level IV, retrospective case series.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1071100720904033DOI Listing
March 2020

A Color Flow Tract in Ultrasound-Guided Random Renal Core Biopsy Predicts Complications.

J Ultrasound Med 2020 Jul 29;39(7):1335-1342. Epub 2020 Jan 29.

Mallinckrodt Institute of Radiology.

Objectives: To determine patient and procedural risk factors for major complications in ultrasound (US)-guided random renal core biopsy.

Methods: Random renal biopsies performed by radiologists in the US department at a single institution between 2014 and 2018 were retrospectively reviewed. The patient's age, sex, race, and estimated glomerular filtration rate (eGFR) were recorded. The biopsy approach, needle gauge, length of cores, number of throws, and presence of a color flow tract were recorded. Outcome data included minor and major complications. Associations between variables were tested with χ analyses and univariable/multivariable logistic regression models.

Results: A total of 231 biopsies (167 native and 64 allografts) were reviewed. There was no significant difference in the sex, age, race, or eGFR between native and allograft groups. The overall rate for any complication was 18.2%, with a 4.3% rate of major complications, which was significantly greater in native compared to allograft biopsies (6% versus 0%; P = .045). A risk analysis in native biopsies only showed that major complications were significantly associated with a low eGFR such that patients with stage 4 or 5 kidney disease had higher odds of complications (odds ratio [95% confidence interval]: stage 4, 9.405 [1.995-44.338]; P = .0393; stage 5, 10.749 [2.218-52.080]; P = .0203) than patients with normal function (eGFR >60 mL/min). The presence of a color flow tract portended a 10.7 times greater risk of having any complication (95% confidence interval, 4.595-24.994; P < .001). Other procedural factors were not significantly associated with complications.

Conclusions: There is an increased risk of major complications in US-guided random native kidney biopsy in patients with a low eGFR (<30 mL/min) and a patent color flow tract in the immediate postbiopsy setting.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jum.15227DOI Listing
July 2020

Dual antiplatelets in IV thrombolysis: How much is too much?

Neurology 2020 02 20;94(7):289-290. Epub 2020 Jan 20.

From the Beth Israel Deaconess Medical Center (V.-A.L.), Harvard Medical School, Boston, MA; and Division of Biostatistics (A.S.), Washington University School of Medicine, St. Louis, MO.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000008955DOI Listing
February 2020

New applications for independent activities of daily living in measuring disability in multiple sclerosis.

Mult Scler 2021 01 14;27(1):97-106. Epub 2020 Jan 14.

Departments of Internal Medicine and Community Health Sciences, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.

Background: Disability outcome measures in multiple sclerosis (MS) focus heavily on ambulation; however, limitations in performing everyday activities encompass another type of disability.

Objectives: The aim of this study was to examine the ability of instrumental activities of daily living (IADL) scale to discriminate between different levels of disability and to predict disability progression.

Methods: The North American Research Committee on Multiple Sclerosis (NARCOMS) registry fall 2006 semi-annual survey asked participants to complete the RAND-12, Performance Scales, Patient Determined Disease Steps (PDDS), and IADL questionnaires. We modeled the trajectory of disability change, using the PDDS, over 12 years. Analyses used linear and repeated measures regression methods.

Results: Of respondents ( = 9931), 9559 (96%) completed the PDDS and IADL scale. Respondents were mostly female (76%), Caucasian (92%), and 52.3 (10.5) years old with moderate disability (median PDDS 4 (early cane)). Mean (SD) IADL total score was 20.5 (3.7). Discriminant ability of the IADL scale was higher than other measures considered at higher levels of disability. Adjusted longitudinal models showed that needing greater assistance on IADLs was independently predictive of trajectories of greater disability change.

Conclusion: IADL scale had a greater ability to discriminate between higher disability levels than RAND-12 domains. The IADL scale may provide a useful and clinically relevant tool to measure disability in progressive MS populations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1352458519898591DOI Listing
January 2021

Clinical instrument to retrospectively capture levels of EDSS.

Mult Scler Relat Disord 2019 Dec 3;39:101884. Epub 2019 Dec 3.

Department of Neurology, Washington University in St. Louis; St. Louis, MO, USA. Electronic address:

Background: The Expanded Disability Status Scale (EDSS), a common outcome measure in Multiple Sclerosis (MS), is obtained prospectively through a direct standardized evaluation. The objective of this study is to develop and validate an algorithm to derive EDSS scores from previous neurological clinical documentation.

Methods: The algorithm utilizes data from the history, review of systems, and physical exam. EDSS scores formally obtained from research patients were compared to captured EDSS (c-EDSS) scores. To test inter-rater reliability, a second investigator captured scores from a subset of patients. Agreement between formal and c-EDSS scores was assessed using a weighted kappa. Clinical concordance was defined as a difference of one-step in EDSS (0.5) and functional system (1.0) scores.

Results: Clinical documentation from 92 patients (EDSS range 0.0-8.5) was assessed. Substantial agreement between the c-EDSS and formal EDSS (kappa 0.80; 95% CI 0.74-0.86) was observed. The mean difference between scores was 0.16. The clinical concordance was 78%. Near-perfect agreement was found between the two raters (kappa 0.89; 95% CI 0.84-0.95). The mean inter-rater difference in c-EDSS was 0.23.

Conclusions: This algorithm reliably captures EDSS scores retrospectively with substantial correlation with formal EDSS and high inter-rater agreement. This algorithm may have practical implications in clinic, MS research and clinical trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.msard.2019.101884DOI Listing
December 2019

Functional gastrointestinal disorders negatively affect health-related quality of life in MS.

Neurol Clin Pract 2019 Oct;9(5):381-390

Department of Internal Medicine (RAM), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba; Department of Community Health Sciences (RAM, SL), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada; Dignity Health (TT), St. Joseph's Hospital and Medical Center, Phoenix, AZ; Department of Biostatistics (GRC), University of Alabama at Birmingham, AL; Mellen Center for Multiple Sclerosis (RF), Neurological Institute, Cleveland Clinic, OH; and Department of Biostatistics (AS), Washington University in St. Louis, MO.

Objective: To determine the prevalence of functional gastrointestinal disorders, the demographic and clinical characteristics associated with the presence of functional gastrointestinal disorders, and the effects of these disorders with health-related quality of life (HRQOL) in a large, diverse population of persons with MS.

Methods: In 2014, we surveyed participants in the North American Research Committee on Multiple Sclerosis registry regarding functional gastrointestinal disorders using the Rome III questionnaire. Participants also reported their sociodemographic characteristics, disability status using Patient Determined Disease Steps, the presence of comorbid depression and anxiety, health behaviors, and HRQOL using the RAND-12. We determined the prevalence of each gastrointestinal disorder using the Rome III criteria. Using multivariable logistic regression models, we assessed the factors associated with the presence of each bowel disorder. Using linear regression, we evaluated the association between functional gastrointestinal disorders and HRQOL.

Results: Of 6,312 eligible respondents, 76.5% were female, with a mean (SD) age of 58.3 (10.2) years. Forty-two percent of respondents (n = 2,647) had a functional gastrointestinal disorder, most often irritable bowel syndrome (IBS), which affected 28.2% of participants. The prevalence of all functional gastrointestinal disorders increased with greater disability, and the prevalence of IBS increased with longer disease duration. After adjusting for sociodemographic and clinical characteristics, functional gastrointestinal disorders were associated with lower physical and mental HRQOL (both < 0.0001).

Conclusions: Functional gastrointestinal disorders are common in MS and are associated with reduced HRQOL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/CPJ.0000000000000668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814419PMC
October 2019

Heterogeneity Diffusion Imaging of gliomas: Initial experience and validation.

PLoS One 2019 14;14(11):e0225093. Epub 2019 Nov 14.

Department of Radiology, Washington University in St. Louis, St. Louis, Missouri, United States of America.

Objectives: Primary brain tumors are composed of tumor cells, neural/glial tissues, edema, and vasculature tissue. Conventional MRI has a limited ability to evaluate heterogeneous tumor pathologies. We developed a novel diffusion MRI-based method-Heterogeneity Diffusion Imaging (HDI)-to simultaneously detect and characterize multiple tumor pathologies and capillary blood perfusion using a single diffusion MRI scan.

Methods: Seven adult patients with primary brain tumors underwent standard-of-care MRI protocols and HDI protocol before planned surgical resection and/or stereotactic biopsy. Twelve tumor sampling sites were identified using a neuronavigational system and recorded for imaging data quantification. Metrics from both protocols were compared between World Health Organization (WHO) II and III tumor groups. Cerebral blood volume (CBV) derived from dynamic susceptibility contrast (DSC) perfusion imaging was also compared with the HDI-derived perfusion fraction.

Results: The conventional apparent diffusion coefficient did not identify differences between WHO II and III tumor groups. HDI-derived slow hindered diffusion fraction was significantly elevated in the WHO III group as compared with the WHO II group. There was a non-significantly increasing trend of HDI-derived tumor cellularity fraction in the WHO III group, and both HDI-derived perfusion fraction and DSC-derived CBV were found to be significantly higher in the WHO III group. Both HDI-derived perfusion fraction and slow hindered diffusion fraction strongly correlated with DSC-derived CBV. Neither HDI-derived cellularity fraction nor HDI-derived fast hindered diffusion fraction correlated with DSC-derived CBV.

Conclusions: Conventional apparent diffusion coefficient, which measures averaged pathology properties of brain tumors, has compromised accuracy and specificity. HDI holds great promise to accurately separate and quantify the tumor cell fraction, the tumor cell packing density, edema, and capillary blood perfusion, thereby leading to an improved microenvironment characterization of primary brain tumors. Larger studies will further establish HDI's clinical value and use for facilitating biopsy planning, treatment evaluation, and noninvasive tumor grading.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0225093PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6855653PMC
March 2020

Assessment of primary liver carcinomas other than hepatocellular carcinoma (HCC) with LI-RADS v2018: comparison of the LI-RADS target population to patients without LI-RADS-defined HCC risk factors.

Eur Radiol 2020 Feb 25;30(2):996-1007. Epub 2019 Oct 25.

Department of Radiology, University of California San Diego, 200 W Arbor Dr., San Diego, CA, 92103, USA.

Objectives: To determine whether the LI-RADS imaging features of primary liver carcinomas (PLCs) other than hepatocellular carcinoma (non-HCC PLCs) differ between patients considered high risk (RF+) versus not high risk (RF-) for HCC and to compare rates of miscategorization as probable or definite HCC between the RF+ and RF- populations.

Methods: This retrospective study included all pathology-proven non-HCC PLCs imaged with liver-protocol CT or MRI from 2007 to 2017 at two liver transplant centers. Patients were defined per LI-RADS v2018 criteria as RF+ or RF-. Two independent, blinded readers (R1, R2) categorized 265 lesions using LI-RADS v2018. Logistic regression was utilized to assess for differences in imaging feature frequencies between RF+ and RF- patients. Fisher's exact test was used to assess for differences in miscategorization rates.

Results: Non-HCC PLCs were significantly more likely to exhibit nonrim arterial phase hyperenhancement (R1: OR = 2.94; R2: OR = 7.09) and nonperipheral "washout" (R1: OR = 3.65; R2: OR = 7.69) but significantly less likely to exhibit peripheral "washout" (R1: OR = 0.30; R2: OR = 0.10) and delayed central enhancement (R1: OR = 0.18; R2: OR = 0.25) in RF+ patients relative to RF- patients. Consequently, non-HCC PLCs were more often miscategorized as probable or definite HCC in RF+ versus RF- patients (R1: 23.3% vs. 3.6%, p < 0.001; R2: 11.0% vs. 2.6%, p = 0.009).

Conclusions: Non-HCC PLCs are more likely to mimic HCCs on CT and MRI in the LI-RADS target population than in patients without LI-RADS-defined HCC risk factors.

Key Points: • The presence of LI-RADS-defined risk factors for HCC tends to alter the imaging appearances of non-HCC PLCs, resulting in higher frequencies of major features and lower frequencies of LR-M features. • Non-HCC PLCs are more likely to be miscategorized as probable or definite HCC in the LI-RADS target population than in patients without LI-RADS-defined HCC risk factors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00330-019-06448-6DOI Listing
February 2020