Publications by authors named "W Mowrey"

59 Publications

MR Elastography demonstrates reduced white matter shear stiffness in early-onset hydrocephalus.

Neuroimage Clin 2021 Feb 2;30:102579. Epub 2021 Feb 2.

Montefiore Medical Center, Department of Neurosurgery, Bronx, NY, USA.

Introduction: Hydrocephalus that develops early in life is often accompanied by developmental delays, headaches and other neurological deficits, which may be associated with changes in brain shear stiffness. However, noninvasive approaches to measuring stiffness are limited. Magnetic Resonance Elastography (MRE) of the brain is a relatively new noninvasive imaging method that provides quantitative measures of brain tissue stiffness. Herein, we aimed to use MRE to assess brain stiffness in hydrocephalus patients compared to healthy controls, and to assess its associations with ventricular size, as well as demographic, shunt-related and clinical outcome measures.

Methods: MRE was collected at two imaging sites in 39 hydrocephalus patients and 33 healthy controls, along with demographic, shunt-related, and clinical outcome measures including headache and quality of life indices. Brain stiffness was quantified for whole brain, global white matter (WM), and lobar WM stiffness. Group differences in brain stiffness between patients and controls were compared using two-sample t-tests and multivariable linear regression to adjust for age, sex, and ventricular volume. Among patients, multivariable linear or logistic regression was used to assess which factors (age, sex, ventricular volume, age at first shunt, number of shunt revisions) were associated with brain stiffness and whether brain stiffness predicts clinical outcomes (quality of life, headache and depression).

Results: Brain stiffness was significantly reduced in patients compared to controls, both unadjusted (p ≤ 0.002) and adjusted (p ≤ 0.03) for covariates. Among hydrocephalic patients, lower stiffness was associated with older age in temporal and parietal WM and whole brain (WB) (beta (SE): -7.6 (2.5), p = 0.004; -9.5 (2.2), p = 0.0002; -3.7 (1.8), p = 0.046), being female in global and frontal WM and WB (beta (SE): -75.6 (25.5), p = 0.01; -66.0 (32.4), p = 0.05; -73.2 (25.3), p = 0.01), larger ventricular volume in global, and occipital WM (beta (SE): -11.5 (3.4), p = 0.002; -18.9 (5.4), p = 0.0014). Lower brain stiffness also predicted worse quality of life and a higher likelihood of depression, controlling for all other factors.

Conclusions: Brain stiffness is reduced in hydrocephalus patients compared to healthy controls, and is associated with clinically-relevant functional outcome measures. MRE may emerge as a clinically-relevant biomarker to assess the neuropathological effects of hydrocephalus and shunting, and may be useful in evaluating the effects of therapeutic alternatives, or as a supplement, of shunting.
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http://dx.doi.org/10.1016/j.nicl.2021.102579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905205PMC
February 2021

Impact of Technology-Based Interventions on Patient-Reported Outcomes in Asthma: A Systematic Review.

J Allergy Clin Immunol Pract 2021 Feb 4. Epub 2021 Feb 4.

Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY. Electronic address:

Background: Technology-based interventions (TBIs) can improve asthma management by facilitating patient education, symptom monitoring, environmental trigger control, comorbid condition management, and medication adherence. Collecting patient-reported outcomes (PROs) can identify effective interventions and ensure patient-centered care, but it is unclear which TBIs have been formally evaluated using PROs.

Objectives: We aim to: (1) identify the TBIs that have been evaluated in clinical trials using PROs; (2) identify the most commonly used PROs in these trials; and (3) determine the impact of TBIs on PROs in the management of chronic asthma.

Methods: We searched the PubMed and Clinicaltrials.gov databases for studies published in English between January 2000 and February 2020 using the following search criteria: "asthma," "IT-based interventions," "information technology," "technology," "dyspnea," "patient reported outcomes," "PROs," "telehealth," "telemedicine," and "mobile devices." Two independent reviewers screened the studies and determined study inclusion. Studies were examined for the types of interventions used, the types of PROs collected, and outcomes.

Results: The final analysis included 14 clinical trials with either 1, 2, or 3 arms. Five different types of TBIs were identified, most commonly involving multimedia education. Four different categories of PROs were identified, most commonly involving treatment self-efficacy. Positive outcomes in at least 1 PRO domain were reported in 12 of 14 studies. Pooled meta-analysis was not possible due to the heterogeneity of PRO instruments across studies.

Conclusion: TBIs improve PROs overall in patients with asthma. Future trials investigating TBIs should include standardized PROs as endpoints to better clarify this relationship.
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http://dx.doi.org/10.1016/j.jaip.2021.01.027DOI Listing
February 2021

Association of Medicare and Medicaid Insurance Status with Increased Spine Surgery Utilization Rates.

Spine (Phila Pa 1976) 2021 01 25. Epub 2021 Jan 25.

Center for Surgical Optimization, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY, USA Spinal Disorders Study Group, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY, USA Department of Neurosurgery, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY, USA Department of Epidemiology and Public Health, Albert Einstein College of Medicine, Bronx, New York, USA Section of Pediatric Hematology/Oncology, Department of Pediatrics, Yale School of Medicine and Yale-New Haven Hospital, New Haven, Connecticut, USA.

Study Design: Retrospective single-institution study.

Objective: To determine the relationship between patients' insurance status and the likelihood for them to be recommended various spine interventions upon evaluation in our neurosurgical clinics.

Summary Of Background Data: Socioeconomically disadvantaged populations have worse outcomes after spine surgery. No studies have looked at the differential rates of recommendation for surgery for patients presenting to spine surgeons based on socioeconomic status.

Methods: We studied patients initially seeking spine care from spine-fellowship trained neurosurgeons at our institution from July 1, 2018 to June 30, 2019. Multivariable logistic regression was used to assess the association between insurance status and the recommended patient treatment.

Results: Overall, 663 consecutive outpatients met inclusion criteria. Univariate analysis revealed a statistically significant association between insurance status and treatment recommendations for surgery (p < 0.001). Multivariate logistic regression demonstrated that compared with private insurance, Medicare (odds ratio [OR] 3.54, 95% confidence interval [CI] 1.21 - 7.53, p = 0.001) and Medicaid patients (OR 2.46, 95% CI 1.21 - 5.17, p = 0.014) were more likely to be recommended for surgery. Uninsured patients did not receive recommendations for surgery at significantly different rates than patients with private insurance.

Conclusions: Medicare and Medicaid patients are more likely to be recommended for spine surgery when initially seeking spine care from a neurosurgeon. These findings may stem from a number of factors, including differential severity of the patient's condition at presentation, disparities in access to care, and differences in shared decision making between surgeons and patients.Level of Evidence: 3.
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http://dx.doi.org/10.1097/BRS.0000000000003968DOI Listing
January 2021

FGFR Regulation of Dendrite Elaboration in Adult-born Granule Cells Depends on Intracellular Mediator and Proximity to the Soma.

Neuroscience 2021 01 24;453:148-167. Epub 2020 Nov 24.

Departments of Neuroscience and Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA. Electronic address:

Fibroblast Growth Factor Receptors (FGFRs) play crucial roles in promoting dendrite growth and branching during development. In mice, three FGFR genes, Fgfr1, Fgfr2, and Fgfr3, remain expressed in the adult neurogenic niche of the hippocampal dentate gyrus. However, the function of FGFRs in the dendritic maturation of adult-born neurons remains largely unexplored. Here, using conditional alleles of Fgfr1, Fgfr2, and Fgfr3 as well as Fgfr1 alleles lacking binding sites for Phospholipase-Cγ (PLCγ) and FGF Receptor Substrate (FRS) proteins, we test the requirement for FGFRs in dendritogenesis of adult-born granule cells. We find that deleting all three receptors results in a small decrease in proximal dendrite elaboration. In contrast, specifically mutating Tyr766 in FGFR1 (a PLCγ binding site) in an Fgfr2;Fgfr3 deficient background results in a dramatic increase of overall dendrite elaboration, while blocking FGFR1-FRS signaling causes proximal dendrite deficits and, to a lesser extent than Tyr766 mutants, increases distal dendrite elaboration. These findings reveal unexpectedly complex roles for FGFRs and their intracellular mediators in regulating proximal and distal dendrite elaboration, with the most notable role in suppressing distal elaboration through the PLCγbinding site.
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http://dx.doi.org/10.1016/j.neuroscience.2020.10.024DOI Listing
January 2021

Systemic lupus Erythematosus activity and Hydroxychloroquine use before and after end-stage renal disease.

BMC Nephrol 2020 10 28;21(1):450. Epub 2020 Oct 28.

Division of Rheumatology, Department of Medicine, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New York, USA.

Background: SLE manifestations after ESRD may be underdiagnosed and undertreated, contributing to increased morbidity and mortality. Whether specific symptoms persist after ESRD or a shift towards new manifestations occurs has not been extensively studied, especially in the non-Caucasian patients in the United States. In addition, hydroxychloroquine (HCQ) prescribing patterns post-ESRD have not been described. The objective of this study was to assess lupus activity and HCQ prescribing before and after ESRD development. Knowledge gained from this study may aid in the identification of SLE manifestations and improve medication management post-ESRD.

Methods: We performed a retrospective cohort study of SLE patients with incident ESRD between 2010 and 2017. SLE-related symptoms, serologic markers of disease activity, and medication use were collected from medical records before and after ESRD development.

Results: Fifty-nine patients were included in the study. Twenty-five (43%) patients had at least one clinical (non-renal) SLE manifestation documented within 12 months before ESRD. Of them, 11/25 (44%) continued to experience lupus symptoms post-ESRD; 9 patients without clinical or serological activity pre-ESRD developed new symptoms of active SLE. At the last documented visit post-ESRD, 42/59 (71%) patients had one or more clinical or serological markers of lupus activity; only 17/59 (29%) patients achieved clinical and serological remission. Thirty-three of 59 (56%) patients had an active HCQ prescription at the time of ESRD. Twenty-six of the 42 (62%) patients with active SLE manifestations post-ESRD were on HCQ. Patients who continued HCQ post-ESRD were more likely to be followed by a rheumatologist (26 [87%] vs 17 [61%], p = 0.024), had a higher frequency of documented arthritis (10 [32%] vs 1 [4%], p = 0.005), CNS manifestations (6 [20%] vs 1 [4%], p = 0.055), and concurrent immunosuppressive medication use (22 [71%] vs 12 [43%], p = 0.029).

Conclusions: Lupus activity may persist after the development of ESRD. New onset arthritis, lupus-related rash, CNS manifestations, low complement and elevated anti-dsDNA may develop. HCQ may be underutilized in patients with evidence of active disease pre- and post ESRD. Careful clinical and serological monitoring for signs of active disease and frequent rheumatology follow up is advised in SLE patients both, pre and post-ESRD.
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http://dx.doi.org/10.1186/s12882-020-02083-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592532PMC
October 2020

A Multidisciplinary Spine Surgical Indications Conference Leads to Alterations in Surgical Plans in a Significant Number of Cases: A Case Series.

Spine (Phila Pa 1976) 2021 01;46(1):E48-E55

Center for Surgical Optimization, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, NY.

Study Design: Case series.

Objective: To evaluate the impact of a multidisciplinary spine surgery indications conference (MSSIC) on surgical planning for elective spine surgeries.

Summary Of Background Data: Identifying methods for pairing the proper patient with the optimal intervention is of the utmost importance for improving spine care and patient outcomes. Prior studies have evaluated the utility of multidisciplinary spine conferences for patient management, but none have evaluated the impact of a MSSIC on surgical planning and decision making.

Methods: We implemented a mandatory weekly MSSIC with all spine surgeons at our institution. Each elective spine surgery in the upcoming week is presented. Subsequently, a group consensus decision is achieved regarding the best treatment option based on the expertise and opinions of the participating surgeons. We reviewed cases presented at the MSSIC from September 2019 to December 2019. We compared the surgeon's initial proposed surgery for a patient with the conference attendees' consensus decision on the best treatment and measured compliance rates with the group's recommended treatment.

Results: The conference reviewed 100 patients scheduled for elective spine surgery at our indications conference during the study period. Surgical plans were recommended for alteration in 19 cases (19%) with the proportion statistically significant from zero indicated by a binomial test (P < 0.001). The median absolute change in the invasiveness index of the altered procedures was 3 (interquartile range [IQR] 1-4). Participating surgeons complied with the group's recommendation in 96.5% of cases.

Conclusion: In conjunction with other multidisciplinary methods, MSSICs can lead to surgical planning alterations in a significant number of cases. This could potentially result in better selection of surgical candidates and procedures for particular patients. Although long-term patient outcomes remain to be evaluated, this care model will likely play an integral role in optimizing the care spine surgeons provide patients.

Level Of Evidence: 4.
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http://dx.doi.org/10.1097/BRS.0000000000003715DOI Listing
January 2021

Surgical Outcomes for Upper Lumbar Disc Herniations: A Systematic Review and Meta-analysis.

Global Spine J 2020 Aug 3:2192568220941815. Epub 2020 Aug 3.

Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA.

Study Design: Systematic review and meta-analysis.

Objective: To conduct a literature review on outcomes of discectomy for upper lumbar disc herniations (ULDH), estimate pooled rates of satisfactory outcomes, compare open laminectomy/microdiscectomy (OLM) versus minimally invasive surgical (MIS) techniques, and compare results of disc herniations at L1-3 versus L3-4.

Methods: A systematic review of articles reporting outcomes of nonfusion surgical treatment of L1-2, L2-3, and/or L3-4 disc herniations was performed. The inclusion and exclusion of studies was performed according to the latest version of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.

Results: A total of 20 articles were included in the quantitative meta-analysis. Pooled proportion of satisfactory outcome (95% CI) was 0.77 (0.70, 0.83) for MIS and 0.82 (0.78, 0.84) for OLM. There was no significant improvement with MIS techniques compared with standard OLM, odds ratio (OR) = 0.86, 95% CI (0.42, 1.74), = .66. Separating results by levels revealed a trend of higher satisfaction with L3-4 versus L1-3 with OLM surgery, OR = 0.46, 95% CI (0.19, 1.12), = .08.

Conclusion: Our analysis reveals that discectomy for ULDH has an overall success rate of approximately 80% and has not improved with MIS. Discectomy for herniations at L3-4 trends toward better outcomes compared with L1-2 and L2-3, but was not significant.
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http://dx.doi.org/10.1177/2192568220941815DOI Listing
August 2020

Developing and evaluating ASTHMAXcel adventures: A novel gamified mobile application for pediatric patients with asthma.

Ann Allergy Asthma Immunol 2020 11 22;125(5):581-588. Epub 2020 Jul 22.

Division of Allergy and Immunology, Department of Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York. Electronic address:

Background: The ASTHMAXcel mobile application has been linked to favorable outcomes among adult patients with asthma.

Objective: To assess the impact of ASTHMAXcel Adventures, a gamified, guideline-based, pediatric version on asthma control, knowledge, health care utilization, and patient satisfaction.

Methods: Pediatric patients with asthma received the ASTHMAXcel Adventures mobile intervention on-site only at baseline (visit 1), 4 months (visit 2), and 6 months (visit 3). The asthma control test, asthma illness representation scale-self-administered, pediatric asthma impact survey, and Client Satisfaction Questionnaire-8 were used to assess asthma control, knowledge, and patient satisfaction. Patients reported the number of asthma-related emergency department (ED) visits, hospitalizations, and oral prednisone use.

Results: A total of 39 patients completed the study. The proportion of controlled asthma increased from visit 1 to visits 2 and 3 (30.8% vs 53.9%, P = .04; 30.8% vs 59.0%, P = .02), and largely seen in boys. The mean asthma illness representation scale-self-administered scores increased from baseline pre- to postintervention, with sustained improvements at visits 2 and 3 (3.55 vs 3.76, P < .001; 3.55 vs 3.80, P = .001; 3.55 vs 3.99, P < .001). The pediatric asthma impact survey scores improved from baseline to visits 2 and 3 (43.33 vs 34.08, P < .001; 43.33 vs 31.74, P < .001). ED visits and prednisone use significantly decreased from baseline to visits 2 and 3 (ED: 0.46 vs 0.13, P = .03; 0.46 vs 0.02, P = .02; prednisone use, 0.49 vs 0.13, P = .02; 0.49 vs 0.03, P = .003. Satisfaction was high with mean client satisfaction questionnaire score of approximately 30 (out of 32) at all visits.

Conclusion: ASTHMAXcel Adventures improved asthma control, knowledge, and quality of life, and reduced ED visits and prednisone use with high satisfaction scores.
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http://dx.doi.org/10.1016/j.anai.2020.07.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375272PMC
November 2020

Adverse Childhood Experiences Are Associated with Childhood-Onset Arthritis in a National Sample of US Youth: An Analysis of the 2016 National Survey of Children's Health.

J Pediatr 2020 Jun 15. Epub 2020 Jun 15.

Division of Developmental Medicine, Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY; Division of Developmental Medicine, Children's Hospital at Montefiore, Bronx, NY.

Objectives: To determine whether there is an association between adverse childhood experiences (ACEs) and childhood-onset arthritis, comparing youth with arthritis to both healthy youth and youth with other acquired chronic physical diseases (OCPD); and to examine whether ACEs are associated with disease-related characteristics among children with arthritis.

Study Design: In a cross-sectional analysis of data from the 2016 National Survey of Children's Health we examined whether ACEs were associated with having arthritis vs either being healthy or having a nonrheumatologic OCPD. ACE scores were categorized as 0, 1, 2-3, ≥4 ACEs. Multinomial logistic regression models examined associations between ACEs and health status while adjusting for age, sex, race/ethnicity, and poverty status. Among children with arthritis, associations between ACEs and disease-related characteristics were assessed by Pearson χ analyses.

Results: Compared with children with no ACEs, children with 1, 2-3, and ≥4 ACEs had an increased odds of having arthritis vs being healthy (adjusted OR for ≥4 ACEs, 9.4; 95% CI, 4.0-22.1) and vs OCPD (adjusted OR for ≥4 ACEs, 3.7; 95% CI-1.7, 8.1). Among children with arthritis, ACEs were associated with worse physical impairment.

Conclusions: Children with higher numbers of ACEs are more likely to have arthritis, when arthritis status is compared either with being healthy or with having OCPD. Further studies are needed to determine the direction of the association between ACEs and childhood arthritis, its impact on disease course, and potential intervention targets that might mitigate these effects.
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http://dx.doi.org/10.1016/j.jpeds.2020.06.046DOI Listing
June 2020

Evaluating the ASTHMAXcel Mobile Application Regarding Asthma Knowledge and Clinical Outcomes.

Respir Care 2020 Aug 2;65(8):1112-1119. Epub 2020 Jun 2.

Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York.

Background: We sought to longitudinally assess the efficacy of the patient-facing ASTHMAXcel mobile application in improving asthma knowledge and outcomes in adults with asthma.

Methods: ASTHMAXcel is a novel smartphone application consistent with the National Asthma Education and Prevention Program, Global Initiative for Asthma, and British Thoracic Society/Scottish Intercollegiate Guidelines Network guidelines. The intervention was provided for 1-time use at baseline only. The Asthma Knowledge Questionnaire (AKQ), the Asthma Control Test (ACT), and the mini-Asthma Quality of Life Questionnaire (mini-AQLQ) were administered at baseline and at 2, 4, and 6 months thereafter. Rates of asthma-related emergency department visits, hospitalizations, and prednisone use were also evaluated.

Results: ACT scores increased significantly at 2, 4, and 6 months (mean scores: 15.1 vs 16.9, = .038; 15.1 vs 17.2, = .02; 15.1 vs 17.9, = .003) after baseline. There were significant increases in AKQ scores at 4 and 6 months (11.7 vs 12.6, = .02; 11.7 vs 13.1, = .005) and in mini-AQLQ scores at 6 months (55.5 vs 64.2, = .02). There were significant decreases in asthma-related emergency department visits at 6 months (0.6 vs 0, < .001) and in hospitalizations at 4 and 6 months (0.3 vs 0.1, = .02; 0.3 vs 0, = .002). Prednisone use decreased at 4 and 6 months (1.2 vs 0.6, = .01; 1.2 vs 0.3, < .001).

Conclusions: ASTHMAXcel contributes to improved asthma knowledge and outcomes and to decreased health care utilization. ASTHMAXcel is an inexpensive, scalable aid for out-patient asthma management.
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http://dx.doi.org/10.4187/respcare.07550DOI Listing
August 2020

Glycemic management and clinical outcomes in underserved minority kidney transplant recipients with type 2 and posttransplantation diabetes: A single-center retrospective study.

Diabetes Res Clin Pract 2020 Jul 20;165:108221. Epub 2020 May 20.

Department of Medicine, Division of Endocrinology, Albert Einstein College of Medicine, Bronx, NY, United States.

Aims: Little is known about glycemic management, particularly with novel cardio-nephroprotecive agents, in underserved minority kidney transplant recipients with pre-transplant type 2 (T2DM) and posttransplantation diabetes mellitus (PTDM). We assessed glycemic management and outcomes in this high-risk population.

Methods: We reviewed records of patients who received kidney transplants between June 2012 and December 2014 at a single center. Hemoglobin A1c (HbA1c) and prescribed glucose-lowering medications were examined, and mortality was compared between T2DM, PTDM, and no diabetes (NoDM) patients.

Results: We followed 302 patient records (41.1% Hispanic, 41.1% non-Hispanic black) for a median (IQR) of 45.5 (37.0, 53.0) months post-transplant. Pre-transplant T2DM was present in 152 (50.3%), while 58 (19.2%) developed PTDM and 92 (30.4%) remained NoDM. At 1-year post-transplant, the average HbA1c was 8.1 ± 1.8% in T2DM and 6.6 ± 1.3% in PTDM. No glucose-lowering agents were prescribed in 3.4% of T2DM and 44.8% of PTDM. When treated, both received mostly insulin and metformin. Diabetes, HbA1c and insulin therapy were not independently associated with risk of mortality.

Conclusions: Glycemic management was suboptimal and relied on older medications. Further studies are needed to assess longer-term outcomes of more rigorous glycemic management, and the value of novel cardio-nephroprotective agents in kidney transplant recipients.
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http://dx.doi.org/10.1016/j.diabres.2020.108221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415727PMC
July 2020

Mobile Brain/Body Imaging of cognitive-motor impairment in multiple sclerosis: Deriving EEG-based neuro-markers during a dual-task walking study.

Clin Neurophysiol 2020 05 21;131(5):1119-1128. Epub 2020 Feb 21.

The Cognitive Neurophysiology Laboratory, Children's Evaluation and Rehabilitation Center (CERC), Department of Pediatrics, Albert Einstein College of Medicine, Van Etten Building - Wing 1C, 1225 Morris Park Avenue, Bronx, NY 10461, USA; The Dominick P. Purpura Department of Neuroscience, Rose F. Kennedy Intellectual and Developmental Disabilities Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA; The Cognitive Neurophysiology Laboratory, The Ernest J. Del Monte Institute for Neuroscience, Department of Neuroscience, University of Rochester Medical Center, 601 Elmwood Ave, Rochester, NY 14642, USA.

Objective: Individuals with a diagnosis of multiple sclerosis (MS) often present with cognitive and motor deficits, and thus the ability to perform tasks that rely on both domains may be particularly impaired. Yet, dual-task walking studies yield mixed results. Individual variance in the ability to cope with brain insult and mobilize additional brain resources may contribute to mixed findings.

Methods: To test this hypothesis, we acquired event-related potentials (ERP) in individuals with MS and healthy controls (HCs) performing a Go/NoGo task while sitting (i.e., single task) or walking (i.e., dual-task) and looked at the relationship between task related modulation of the brain response and performance.

Results: On the Go/NoGo task the MS group showed dual-task costs when walking, whereas HCs showed a dual-task benefit. Further, whereas the HC group showed modulation of the brain response as a function of task load, this was not the case in the MS group. Analysis for the pooled sample revealed a positive correlation between load-related ERP effects and dual-task performance.

Conclusions: These data suggest a neurophysiological marker of cognitive-motor dysfunction in MS.

Significance: Understanding neural processes underlying dual-task walking will help identify objective brain measurements of real-world issues and may improve assessment of MS.
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http://dx.doi.org/10.1016/j.clinph.2020.01.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196176PMC
May 2020

Developing and pilot testing ASTHMAXcel, a mobile app for adults with asthma.

J Asthma 2020 Feb 19:1-14. Epub 2020 Feb 19.

Division of Allergy/Immunology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA.

We sought to compare the impact of ASTHMAXcel, a novel, guideline-based, patient-facing mobile app to human-delivered asthma education. We conducted a focus group with asthma patients in the Bronx to identify desired mobile app features. ASTHMAXcel was designed based on patient feedback and consistent with NAEPP, BTS/SIGN, and GINA guidelines. The app was reviewed by internists, allergist/immunologists, and pulmonologists specializing in asthma treatment, asthma educators, and a behavioral scientist, and iteratively refined. The refined version of ASTHMAXcel was administered once via tablet at our outpatient Montefiore Asthma Center (MAC). Asthma knowledge was measured through the Asthma Knowledge Questionnaire (AKQ) pre and post-intervention. We also recorded process outcomes including completion time and patient satisfaction. In parallel, human-delivered education was delivered once at MAC. These outcomes were similarly collected. 60 patients were enrolled with 30 in the ASTHMAXcel and 30 in the human-educator group. Mean AKQ in the ASTHMAXcel group vs human-educator group pre-intervention was 9.9 vs 10.5,  = 0.27. Mean AKQ post-intervention in the ASTHMAXcel group vs human-educator group was 12.3 vs 14.4,  = 0.0002. The mean AKQ improvement for both groups were 2.4 vs 3.9,  = 0.007. Patients were highly satisfied in the ASTHMAXcel group scoring on average 27.9 out of 30 maximum points on the satisfaction survey. There was no difference in satisfaction scores or completion times (minutes) of either intervention. ASTHMAXcel was associated with an increase in AKQ, but the human-educator group experienced a greater improvement. ASTHMAXcel demonstrated no differences in process outcomes vs human-delivered education.
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http://dx.doi.org/10.1080/02770903.2020.1728770DOI Listing
February 2020

Child and Adolescent Psychiatry Trainees' Attitudes Toward Prescribing and Managing Psychotropic Medications.

Acad Psychiatry 2020 Jun 6;44(3):277-282. Epub 2020 Jan 6.

Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.

Objective: There has been a recent concern about the overuse of psychotropic medications in children. This study was designed to assess the attitudes held by child and adolescent psychiatry trainees toward the prescription and management of medications in the pediatric population.

Methods: An online survey was sent to all Accreditation Council for Graduate Medical Education (ACGME)-accredited child and adolescent psychiatry training programs across the USA with the goal of assessing trainee comfort and confidence with prescribing skills and concepts.

Results: About 63 trainees (7.2% of the targeted population) were included in the analyses. While most participants reported confidence in basic prescribing skills, areas of lower confidence included cross-tapering medications, managing side effects, knowledge of the evidence base, drug-drug interactions, and de-prescribing. Advanced year in training was associated with higher confidence overall but failed to reach significance with some complex concepts such as polypharmacy (p = 0.27) and de-prescribing (p = 0.10). In contrast, increased supervision had a significant impact on confidence regarding complex concepts (p = 0.04) but not basic skills (p = 0.51). Supervision was also associated with higher training satisfaction (p = 0.001).

Conclusions: Though the study was limited by a low response rate, these preliminary findings suggest potential areas for targeted psychopharmacology training. The findings also support how the important role supervision plays in the development of more complex skills. Further studies are needed to better understand these potential areas of curricula development and to explore the most effective training modalities.
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http://dx.doi.org/10.1007/s40596-019-01177-wDOI Listing
June 2020

Early Infectious Disease Consultation Is Associated With Lower Mortality in Patients With Severe Sepsis or Septic Shock Who Complete the 3-Hour Sepsis Treatment Bundle.

Open Forum Infect Dis 2019 Oct 31;6(10):ofz408. Epub 2019 Oct 31.

Division of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York, USA.

Objective: Severe sepsis and septic shock (SS/SS) treatment bundles reduce mortality, and early infectious diseases (ID) consultation also improves patient outcomes. We retrospectively examined whether early ID consultation further improves outcomes in Emergency Department (ED) patients with SS/SS who complete the sepsis bundle.

Method: We included 248 adult ED patients with SS/SS who completed the 3-hour bundle. Patients with ID consultation within 12 hours of ED triage (n = 111; early ID) were compared with patients who received standard care (n = 137) for in-hospital mortality, 30-day readmission, length of hospital stay (LOS), and antibiotic management. A competing risk survival analysis model compared risks of in-hospital mortality and discharge alive between groups.

Results: In-hospital mortality was lower in the early ID group unadjusted (24.3% vs 38.0%, = .02) and adjusted for covariates (odds ratio, 0.47; 95% confidence interval (CI), 0.25-0.89; = .02). There was no significant difference in 30-day readmission (22.6% vs 23.5%, = .89) or median LOS (10.2 vs 12.1 days, = .15) among patients who survived. A trend toward shorter time to antibiotic de-escalation in the early ID group (log-rank test = .07) was observed. Early ID consultation was protective of in-hospital mortality (adjusted subdistribution hazard ratio (asHR), 0.60; 95% CI 0.36-1.00, = .0497) and predictive of discharge alive (asHR 1.58, 95% CI, 1.11-2.23; -value .01) after adjustment.

Conclusions: Among patients receiving the SS/SS bundle, early ID consultation was associated with a 40% risk reduction for in-hospital mortality. The impact of team-based care and de-escalation on SS/SS outcomes warrants further study.
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http://dx.doi.org/10.1093/ofid/ofz408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821928PMC
October 2019

Association between dietary zinc intake and abdominal aortic calcification in US adults.

Nephrol Dial Transplant 2020 07;35(7):1171-1178

Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA.

Background: In animal studies, zinc supplementation inhibited phosphate-induced arterial calcification. We tested the hypothesis that higher intake of dietary zinc was associated with lower abdominal aortic calcification (AAC) among adults in the USA. We also explored the associations of AAC with supplemental zinc intake, total zinc intake and serum zinc level.

Methods: We performed cross-sectional analyses of 2535 participants from the National Health and Nutrition Examination Survey 2013-14. Dietary and supplemental zinc intakes were obtained from two 24-h dietary recall interviews. Total zinc intake was the sum of dietary and supplemental zinc. AAC was measured using dual-energy X-ray absorptiometry in adults ≥40 years of age and quantified using the Kauppila score system. AAC scores were categorized into three groups: no AAC (AAC = 0, reference group), mild-moderate (AAC >0-≤6) and severe AAC (AAC >6).

Results: Dietary zinc intake (mean ± SE) was 10.5 ± 0.1 mg/day; 28% had AAC (20% mild-moderate and 8% severe), 17% had diabetes mellitus and 51% had hypertension. Higher intake of dietary zinc was associated with lower odds of having severe AAC. Per 1 mg/day higher intake of dietary zinc, the odds of having severe AAC were 8% lower [adjusted odds ratio 0.92 (95% confidence interval 0.86-0.98), P = 0.01] compared with those without AAC, after adjusting for demographics, comorbidities and laboratory measurements. Supplemental zinc intake, total zinc intake and serum zinc level were not associated with AAC.

Conclusions: Higher intake of dietary zinc was independently associated with lower odds of having severe AAC among noninstitutionalized US adults.
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http://dx.doi.org/10.1093/ndt/gfz134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7417001PMC
July 2020

Efficacy and safety of direct oral factor Xa inhibitors compared with warfarin in patients with morbid obesity: a single-centre, retrospective analysis of chart data.

Lancet Haematol 2019 Jul 24;6(7):e359-e365. Epub 2019 May 24.

Division of Hematology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY, USA.

Background: Because studies of direct oral anticoagulants in patients with venous thromboembolism and non-valvular atrial fibrillation have had minimal representation of morbidly obese patients (ie, body-mass index [BMI] ≥40 kg/m), their efficacy and safety in this population are unclear. We investigated whether apixaban and rivaroxaban are as effective and safe as warfarin in morbidly obese patients.

Methods: We did a single-centre, retrospective analysis of chart data for all adult patients aged at least 18 years at Montefiore Medical Center (Bronx, NY, USA) with a BMI of at least 40 kg/m who were prescribed apixaban, rivaroxaban, or warfarin for either venous thromboembolism or atrial fibrillation between March 1, 2013, and March 1, 2017. Patients who had both venous thromboembolism and atrial fibrillation were excluded, as were patients with indications other than atrial fibrillation and venous thromboembolism. Outcomes of recurrent venous thromboembolism, stroke, and bleeding were measured from the first prescription date to the earliest of a thrombotic event, medication discontinuation, death, or end of study on June 30, 2017. Analyses were stratified by anticoagulation indication and adjusted for comorbidities, CHADS-VASc score, and age where appropriate. Outcome rates were compared using Pearson's χ or Fisher's exact test. Time-to-event analyses accounting for length of follow-up were used to compare risks of outcomes.

Findings: We obtained data for 795 patients: 150 prescribed apixaban, 326 rivaroxaban, and 319 warfarin. In 366 patients prescribed an anticoagulant for venous thromboembolism, the incidence of recurrent venous thromboembolism was similar between the apixaban, rivaroxaban, and warfarin cohorts (1/47 [2·1%, 95% CI 0·0-6·3], 3/152 [2·0%, 0·0-4·2], and 2/167 [1·2%, 0·0-2·9], respectively; p=0·74). Incidence of major bleeding in this patient group was also similar between the treatment cohorts (1/47 patients on apixaban [2·1%, 95% CI 0·0-6·3], 2/152 on rivaroxaban [1·3%, 0·0-3·1], and 4/167 on warfarin [2·4%, 0·1-4·7]; p=0·77). In 429 patients prescribed an anticoagulant for atrial fibrillation, incidence of stroke was similar between the treatment cohorts (1/103 patients on apixaban [1·0%, 95% CI 0·0-2·9], 4/174 on rivaroxaban [2·3%, 0·1-4·5], and 2/152 on warfarin [1·3%, 0·0-3·1], p=0·71). In this patient group, major bleeding occurred in 3/103 patients on apixaban (2·9%, 95% CI 0·0-6·2), 5/174 on rivaroxaban (2·9%, 0·4-5·4), and 12/152 on warfarin (7·9%, 3·6-12·2); p=0·063. Time-to-event analyses showed that risk of all outcomes in patients with venous thromboembolism, and stroke and composite bleeding in patients with atrial fibrillation, were similar between the anticoagulant cohorts.

Interpretation: Our retrospective study provides further evidence of similar efficacy and safety between the direct oral anticoagulants apixaban and rivaroxaban, and warfarin in morbidly obese patients with atrial fibrillation and venous thromboembolism. These data, if confirmed in prospective studies, might enable patients with a BMI of at least 40 kg/m to benefit from more convenient, and possibly safer, anticoagulants.

Funding: None.
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http://dx.doi.org/10.1016/S2352-3026(19)30086-9DOI Listing
July 2019

Current Mechanistic and Pharmacodynamic Understanding of Melanocortin-4 Receptor Activation.

Molecules 2019 May 16;24(10). Epub 2019 May 16.

Rhythm Pharmaceuticals, Boston, MA 02116, USA.

In this work we summarize our understanding of melanocortin 4 receptor (MC4R) pathway activation, aiming to define a safe and effective therapeutic targeting strategy for the MC4R. Delineation of cellular MC4R pathways has provided evidence for distinct MC4R signaling events characterized by unique receptor activation kinetics. While these studies remain narrow in scope, and have largely been explored with peptidic agonists, the results provide a possible correlation between distinct ligand groups and differential MC4R activation kinetics. In addition, when a set of small-molecule and peptide MC4R agonists are compared, evidence of biased signaling has been reported. The results of such mechanistic studies are discussed.
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http://dx.doi.org/10.3390/molecules24101892DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572030PMC
May 2019

Validation of concurrent preimplantation genetic testing for polygenic and monogenic disorders, structural rearrangements, and whole and segmental chromosome aneuploidy with a single universal platform.

Eur J Med Genet 2019 Aug 23;62(8):103647. Epub 2019 Apr 23.

Genomic Prediction Inc., 675 US Highway One, North Brunswick, NJ, 08902, USA.

Preimplantation genetic testing (PGT) has been successfully applied to reduce the risk of miscarriage, improve IVF success rates, and prevent inheritance of monogenic disease and unbalanced translocations. The present study provides the first method capable of simultaneous testing of aneuploidy (PGT-A), structural rearrangements (PGT-SR), and monogenic (PGT-M) disorders using a single platform. Using positive controls to establish performance characteristics, accuracies of 97 to >99% for each type of testing were observed. In addition, this study expands PGT to include predicting the risk of polygenic disorders (PGT-P) for the first time. Performance was established for two common diseases, hypothyroidism and type 1 diabetes, based upon availability of positive control samples from commercially available repositories. Data from the UK Biobank, eMERGE, and T1DBASE were used to establish and validate SNP-based predictors of each disease (7,311 SNPs for hypothyroidism and 82 for type 1 diabetes). Area under the curve of disease status prediction from genotypes alone were 0.71 for hypothyroidism and 0.68 for type 1 diabetes. The availability of expanded PGT to evaluate the risk of polygenic disorders in the preimplantation embryo has the potential to lower the prevalence of common genetic disease in humans.
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http://dx.doi.org/10.1016/j.ejmg.2019.04.004DOI Listing
August 2019

Using clinical decision support through the electronic medical record to increase prescribing of high-dose parenteral thiamine in hospitalized patients with alcohol use disorder.

J Subst Abuse Treat 2019 04 23;99:117-123. Epub 2019 Jan 23.

Department of Psychiatry and Behavioral Sciences, Montefiore Medical Center, 111 East 210th Street, Bronx, NY 10467, USA.

Background: Patients with alcohol use disorder (AUD) are at an increased risk of developing Wernicke's encephalopathy (WE), a devastating and difficult diagnosis caused by thiamine deficiency. Even as AUD is present in up to 25% of hospitalized patients on medical floors, appropriate thiamine supplementation in the hospital setting remains inadequate. These patients are particularly susceptible to thiamine deficiency and subsequent WE due to both their alcohol use and active medical illnesses. The electronic medical record (EMR) has become ubiquitous in health care systems and can be used as a tool to improve the care of hospitalized patients.

Methods: As a quality improvement initiative, we implemented a medication order panel in the EMR with autopopulated orders for thiamine dosing to increase the appropriate use of high-dose parenteral thiamine (HPT) for hospitalized patients with AUD. We conducted a retrospective cohort study of all inpatients with AUD who received an Addiction Psychiatry Consult Service consult three months before and after the EMR change. We compared the proportion of patients receiving HPT prior to consultation (primary outcome) and the length of stay (secondary outcome) between the historical control group and the EMR intervention group.

Results: Patients in the EMR intervention group were significantly more likely to receive HPT than the historical control group (20.2% vs. 2.7%, p < 0.0001). This difference remained statistically significant when adjusted for potential confounders (OR: 9.89, 95% CI: [2.77, 35.34], p = 0.0004). There was a trend towards statistical significance that the intervention group had a higher likelihood of being prescribed any thiamine (76.6% vs. 64.6%, p = 0.06) and had a shorter length of stay (median (IQR): 3.8 (2.4, 7.0) vs. 4.6 (2.9, 7.8) days, p = 0.06).

Conclusion: These results indicate that providing autopopulated thiamine order panels for patients with AUD can be an effective method for specialty services to increase appropriate care practices without additional education or training for providers. Further research should consider the clinical outcomes of increasing HPT for patients with AUD.
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http://dx.doi.org/10.1016/j.jsat.2019.01.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6541495PMC
April 2019

Validation of the Attention, Memory, and Frontal Abilities Screening Test (AMFAST).

Assessment 2020 10 9;27(7):1502-1514. Epub 2019 Jan 9.

Albert Einstein College of Medicine, Bronx, NY, USA.

The aim of this study is to validate the Attention, Memory, and Frontal Abilities Screening Test (AMFAST), a novel, 10-minute, paper-and-pencil measure developed to identify attention, processing speed, memory, and executive functioning deficits in children and adults with various conditions characterized by frontal-subcortical dysfunction. We administered the AMFAST to 186 English-speaking healthy control participants (aged 8-88 years) without reported cognitive impairment. The AMFAST was also administered to a mixed clinical sample that included 114 English-speaking individuals (aged 8-84 years) who also received comprehensive neuropsychological testing. Results indicated that total AMFAST scores in the healthy control sample were not significantly affected by education or gender. There was, however, a significant effect of age, as the 8- to 10-year-old group scored significantly lower than other age groups. Thus, only participants 11+ years were included in further analyses. The AMFAST demonstrated high test-retest and interrater reliabilities, good construct validity, and the identified optimal cutoff score of 70 had excellent sensitivity and specificity for differentiating between cognitively intact and cognitively impaired individuals. These findings demonstrate that the AMFAST is a highly effective screening test that can be used to identify attention, memory, processing speed, and executive functioning deficits in individuals from middle childhood through older adulthood.
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http://dx.doi.org/10.1177/1073191118822734DOI Listing
October 2020

The association between pollutant levels and asthma-related emergency department visits in the Bronx after the World Trade Center attacks.

J Asthma 2019 10 25;56(10):1049-1055. Epub 2018 Oct 25.

Division of Allergy/Immunology, Albert Einstein College of Medicine, Bronx, NY, USA.

: To examine the potential impact of the World Trade Center (WTC) attacks on asthma-related emergency department visits (AREDV) in the New York City borough of the Bronx. We obtained daily nitrogen dioxide (NO), sulfur dioxide (SO) and ozone (O) values from the National Climatic Data Center's collection station in the Bronx from 1999 and 2002, a year before and after the WTC attacks. We compared daily AREDV and pollutant levels between 1999 and 2002 using the Wilcoxon signed rank sum test. We considered each season separately due to seasonal variations of AREDV and pollutants. We then used multiple linear regression models to assess the relationships between the changes in AREDV and the changes in pollutants from 1999 to 2002 in each season. : There were statistically significant increases from 1999 to 2002 in the daily NO in the summer. Significant increases for daily SO and O values from 1999 to 2002 occurred in all seasons. Significant increases occurred in daily AREDV values in the spring and fall. Multiple linear regression analyses showed that increases in the daily O values were significantly associated with increases in AREDV from 1999 to 2002 in the summer season. : We observed a possible association between the WTC attacks and significant increases in O and SO for all seasons, and NO for the summer. AREDV significantly increased following the WTC attacks. Increases in daily O values were significantly associated with increases in AREDV in the summer season.
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http://dx.doi.org/10.1080/02770903.2018.1531989DOI Listing
October 2019

Methodological considerations in comparing access to Pre-emptive renal transplantation between SLE and other ESRD causes in the USRDS.

Semin Arthritis Rheum 2019 02 12;48(4):678-685. Epub 2018 Jun 12.

Division of Biostatistics, Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, United States. Electronic address:

Background: We compared pre-emptive transplant rates between SLE and non-SLE end-stage renal disease (ESRD) from the U.S. Renal Data System (USRDS) and investigated the potential influence of frequency matching and primary ESRD causes in the non-SLE group.

Methods: 4830 adult SLE patients with incident ESRD from USRDS 2005-2009 were frequency matched by age, sex and race to 4830 patients with incident non-SLE ESRD. Multivariable logistic regression models were used to estimate the odds of pre-emptive transplantation in SLE and non-SLE, and with the non-SLE subgroups by primary ESRD cause.

Results: The odds ratios (OR) of receiving a pre-emptive transplant were similar among non-SLE and SLE (referent group): OR = 1.18 (95% CI: 0.92, 1.50; p = 0.20). However, the ORs for receiving a pre-emptive transplant were 0.19 (95% CI: 0.08, 0.42) in type 2 diabetes ESRD, 0.42 (95% CI: 0.23, 0.75) for hypertension-associated ESRD, 1.67 (95% CI: 1.10, 2.54) in type 1 diabetes ESRD, and 2.06 (95% CI: 1.55, 2.73) for "other" ESRD. In contrast to non-SLE, younger SLE patients were less likely to receive a pre-emptive transplant than older SLE patients.

Conclusion: The results of this study provide compelling evidence that major improvements need to be made in optimizing access to pre-emptive transplantation in SLE by addressing sociodemographic disparities and the unique challenges faced by SLE patients. Applying careful matching and selecting appropriate comparison groups in future studies may facilitate the development of effective strategies to address these barriers and to increase the number of pre-emptive renal transplants among SLE patients.
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http://dx.doi.org/10.1016/j.semarthrit.2018.05.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6291358PMC
February 2019

Brief Report: Tubulointerstitial Damage in Lupus Nephritis: A Comparison of the Factors Associated With Tubulointerstitial Inflammation and Renal Scarring.

Arthritis Rheumatol 2018 11 24;70(11):1801-1806. Epub 2018 Sep 24.

Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York.

Objective: To characterize and compare the factors associated with tubulointerstitial inflammation (TII) and tubulointerstitial scarring, defined as interstitial fibrosis and/or tubular atrophy (IF/TA), in patients with lupus nephritis (LN).

Methods: We identified systemic lupus erythematosus patients who had renal biopsy results consistent with LN between 2005 and 2017. Clinical data were collected from medical records. Multivariable logistic regression models were fitted to assess factors associated with TII and with IF/TA (moderate-to-severe versus none/mild).

Results: Of 203 LN patients included, 41 (20%) had moderate-to-severe TII, 45 (22%) had moderate-to-severe IF/TA, and 21 (10%) had both. Multivariable logistic regression models showed that moderate-to-severe TII was associated with a shorter disease duration, African American race, proliferative LN, and an estimated glomerular filtration rate (eGFR) of <60 ml/minute/1.73 m at the time of biopsy. Hydroxychloroquine use was associated with significantly lower odds of moderate-to-severe TII (odds ratio 0.27 [95% confidence interval 0.10-0.70], P = 0.008). Similar to TII, factors associated with moderate-to-severe IF/TA included proliferative LN and eGFR <60 ml/minute/1.73 m at the time of biopsy. In addition, the presence of moderate-to-severe TII and older age was associated with moderate-to-severe IF/TA. None of the routinely available serologic markers-including anti-double-stranded DNA antibodies, anti-Ro/La antibodies, and low complement-were associated with tubulointerstitial damage.

Conclusion: The use of hydroxychloroquine was strongly associated with less inflammation, while the presence of TII, proliferative LN, and low eGFR were major determinants of tubulointerstitial scarring. Identifying modifiable factors is critical for the development of better preventive and therapeutic strategies with the goal of improving survival in patients with lupus-related kidney disease.
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http://dx.doi.org/10.1002/art.40575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6203636PMC
November 2018

Convalescent Plasmodium falciparum-specific seroreactivity does not correlate with paediatric malaria severity or Plasmodium antigen exposure.

Malar J 2018 Apr 25;17(1):178. Epub 2018 Apr 25.

Albert Einstein College of Medicine, Bronx, NY, USA.

Background: Antibody immunity is thought to be essential to prevent severe Plasmodium falciparum infection, but the exact correlates of protection are unknown. Over time, children in endemic areas acquire non-sterile immunity to malaria that correlates with development of antibodies to merozoite invasion proteins and parasite proteins expressed on the surface of infected erythrocytes.

Results: A 1000 feature P. falciparum 3D7 protein microarray was used to compare P. falciparum-specific seroreactivity during acute infection and 30 days after infection in 23 children with uncomplicated malaria (UM) and 25 children with retinopathy-positive cerebral malaria (CM). All children had broad P. falciparum antibody reactivity during acute disease. IgM reactivity decreased and IgG reactivity increased in convalescence. Antibody reactivity to CIDR domains of "virulent" PfEMP1 proteins was low with robust reactivity to the highly conserved, intracellular ATS domain of PfEMP1 in both groups. Although children with UM and CM differed markedly in parasite burden and PfEMP1 exposure during acute disease, neither acute nor convalescent PfEMP1 seroreactivity differed between groups. Greater seroprevalence to a conserved Group A-associated ICAM binding extracellular domain was observed relative to linked extracellular CIDRα1 domains in both case groups. Pooled immune IgG from Malawian adults revealed greater reactivity to PfEMP1 than observed in children.

Conclusions: Children with uncomplicated and cerebral malaria have similar breadth and magnitude of P. falciparum antibody reactivity. The utility of protein microarrays to measure serological recognition of polymorphic PfEMP1 antigens needs to be studied further, but the study findings support the hypothesis that conserved domains of PfEMP1 are more prominent targets of cross reactive antibodies than variable domains in children with symptomatic malaria. Protein microarrays represent an additional tool to identify cross-reactive Plasmodium antigens including PfEMP1 domains that can be investigated as strain-transcendent vaccine candidates.
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http://dx.doi.org/10.1186/s12936-018-2323-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5918990PMC
April 2018

Memory Binding Test Predicts Incident Dementia: Results from the Einstein Aging Study.

J Alzheimers Dis 2018 ;62(1):293-304

Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA.

Background: The Memory Binding Test (MBT) demonstrated good cross-sectional discriminative validity and predicted incident aMCI.

Objective: To assess whether the MBT predicts incident dementia better than a conventional list learning test in a longitudinal community-based study.

Methods: As a sub-study in the Einstein Aging Study, 309 participants age≥70 initially free of dementia were administered the MBT and followed annually for incident dementia for up to 13 years. Based on previous work, poor memory binding was defined using an optimal empirical cut-score of≤17 on the binding measure of the MBT, Total Items in the Paired condition (TIP). Cox proportional hazards models were used to assess predictive validity adjusting for covariates. We compared the predictive validity of MBT TIP to that of the free and cued selective reminding test free recall score (FCSRT-FR; cut-score:≤24) and the single list recall measure of the MBT, Cued Recalled from List 1 (CR-L1; cut-score:≤12).

Results: Thirty-five of 309 participants developed incident dementia. When assessing each test alone, the hazard ratio (HR) for dementia was significant for MBT TIP (HR = 8.58, 95% CI: (3.58, 20.58), p < 0.0001), FCSRT-FR (HR = 4.19, 95% CI: (1.94, 9.04), p = 0.0003) and MBT CR-L1 (HR = 2.91, 95% CI: (1.37, 6.18), p = 0.006). MBT TIP remained a significant predictor of dementia (p = 0.0002) when adjusting for FCSRT-FR or CR-L1.

Conclusions: Older adults with poor memory binding as measured by the MBT TIP were at increased risk for incident dementia. This measure outperforms conventional episodic memory measures of free and cued recall, supporting the memory binding hypothesis.
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http://dx.doi.org/10.3233/JAD-170714DOI Listing
March 2019

Diffusion tensor imaging and ventricle volume quantification in patients with chronic shunt-treated hydrocephalus: a matched case-control study.

J Neurosurg 2018 12;129(6):1611-1622

1Department of Radiology, Gruss Magnetic Resonance Research Center, and.

OBJECTIVEThe object of this study was to use diffusion tensor imaging (DTI) and tract-based spatial statistics (TBSS) to characterize the long-term effects of hydrocephalus and shunting on white matter integrity and to investigate the relationship of ventricular size and alterations in white matter integrity with headache and quality-of-life outcome measures.METHODSPatients with shunt-treated hydrocephalus and age- and sex-matched healthy controls were recruited into the study and underwent anatomical and DTI imaging on a 3-T MRI scanner. All patients were clinically stable, had undergone CSF shunt placement before 2 years of age, and had a documented history of complaints of headaches. Outcome was scored based on the Headache Disability Inventory and the Hydrocephalus Outcome Questionnaire. Fractional anisotropy (FA) and other DTI-based measures (axial, radial, and mean diffusivity; AD, RD, and MD, respectively) were extracted in the corpus callosum and internal capsule with manual region-of-interest delineation and in other regions with TBSS. Paired t-tests, corrected with a 5% false discovery rate, were used to identify regions with significant differences between patients and controls. Within the patient group, linear regression models were used to investigate the relationship between FA or ventricular volume and outcome, as well as the effect of shunt-related covariates.RESULTSTwenty-one hydrocephalus patients and 21 matched controls completed the study, and their data were used in the final analysis. The authors found significantly lower FA for patients than for controls in 20 of the 48 regions, mostly posterior white matter structures, in periventricular as well as more distal tracts. Of these 20 regions, 17 demonstrated increased RD, while only 5 showed increased MD and 3 showed decreased AD. No areas of increased FA were observed. Higher FA in specific periventricular white matter tracts, tending toward FA in controls, was associated with increased ventricular size, as well as improved clinical outcome.CONCLUSIONSThe study shows that TBSS-based DTI is a sensitive technique for elucidating changes in white matter structures due to hydrocephalus and chronic CSF shunting and provides preliminary evidence that DTI may be a valuable tool for tailoring shunt procedures to monitor ventricular size following shunting and achieve optimal outcome, as well as for guiding the development of alternate therapies for hydrocephalus.
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http://dx.doi.org/10.3171/2017.6.JNS162784DOI Listing
December 2018

Rapid Diagnostic Testing of Hospitalized Malawian Children Reveals Opportunities for Improved HIV Diagnosis and Treatment.

Am J Trop Med Hyg 2017 Dec 12;97(6):1929-1935. Epub 2017 Oct 12.

Departments of Pathology and Microbiology and Immunology, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, New York.

Recent World Health Organization (WHO) guidelines recommend antiretroviral therapy (ART) for all HIV-infected people; previously CD4+ T lymphocyte quantification (CD4 count) or clinical staging determined eligibility for children ≥ 5 years old in low- and middle-income countries. We examined positive predictive value (PPV) of a rapid diagnostic test (RDT) algorithm and ART eligibility for hospitalized children with newly diagnosed HIV infection. We enrolled 363 hospitalized Malawian children age 2 months to 16 years with two serial positive HIV RDT from 2013 to 2015. Children aged ≤ 18 months whose nucleic acid testing was negative or unavailable were later excluded from the analysis ( = 16). If RNA PCR was undetectable, human immunodeficiency virus (HIV) enzyme immunoassay (EIA) and western blot (WB) were performed. Those with negative or discordant EIA and WB were considered HIV negative and excluded from further analysis ( = 6). ART eligibility was assessed using age, CD4 count, and clinical HIV stage. Among 150 patients with HIV RNA PCR results, 15 had undetectable HIV RNA. Of those, EIA and WB were positive in nine patients and negative or discordant in six patients. PPV of serial RDT was 90% versus RNA PCR alone and 96% versus combined RNA PCR, EIA, and WB. Of all patients aged ≥ 5 years, 8.9% were ineligible for ART under previous WHO guidelines. Improved HIV testing algorithms are needed for accurate diagnosis of HIV infection in children as prevalence of pediatric HIV declines. Universal treatment will significantly increase the numbers of older children who qualify for ART.
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http://dx.doi.org/10.4269/ajtmh.17-0067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5805032PMC
December 2017

Linking EPCR-Binding PfEMP1 to Brain Swelling in Pediatric Cerebral Malaria.

Cell Host Microbe 2017 Nov 26;22(5):601-614.e5. Epub 2017 Oct 26.

Department of Medicine, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY 10461, USA. Electronic address:

Brain swelling is a major predictor of mortality in pediatric cerebral malaria (CM). However, the mechanisms leading to swelling remain poorly defined. Here, we combined neuroimaging, parasite transcript profiling, and laboratory blood profiles to develop machine-learning models of malarial retinopathy and brain swelling. We found that parasite var transcripts encoding endothelial protein C receptor (EPCR)-binding domains, in combination with high parasite biomass and low platelet levels, are strong indicators of CM cases with malarial retinopathy. Swelling cases presented low platelet levels and increased transcript abundance of parasite PfEMP1 DC8 and group A EPCR-binding domains. Remarkably, the dominant transcript in 50% of swelling cases encoded PfEMP1 group A CIDRα1.7 domains. Furthermore, a recombinant CIDRα1.7 domain from a pediatric CM brain autopsy inhibited the barrier-protective properties of EPCR in human brain endothelial cells in vitro. Together, these findings suggest a detrimental role for EPCR-binding CIDRα1 domains in brain swelling.
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http://dx.doi.org/10.1016/j.chom.2017.09.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5783720PMC
November 2017