Publications by authors named "Mimi Kim"

283 Publications

Racial/ethnic disparities in early-onset colorectal cancer: implications for a racial/ethnic-specific screening strategy.

Cancer Med 2021 Feb 28. Epub 2021 Feb 28.

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

Introduction: Early-onset colorectal cancer (EO-CRC) is a public health concern. Starting screening at 45 years has been considered, but there is discrepancy in the recommendations. Racial disparities in EO-CRC incidence and survival are reported; however, racial/ethnic differences in EO-CRC features that could inform a racial/ethnic-tailored CRC screening strategy have not been reported. We compared features and survival among Non-Hispanic White (NHW), Non-Hispanic Black (NHB), and Hispanics with EO-CRC.

Methods: CRC patients from SEER 1973-2010 database were identified, and EO-CRC was defined as CRC at <50 years. Clinical/pathological features and survival were compared between NHW, NHB, and Hispanics. Cancer-specific survival (CSS) predictors were assessed in a multivariable Cox proportional hazard model.

Results: Of 166,416 patients with CRC, 16,545 (9.9%) had EO-CRC. The EO-CRC frequencies in NHB and Hispanics were higher than NHW (12.7% vs. 16.5% vs. 8.7%, p < 0.001). EO-CRC in NHB presents more frequently in females, with well/moderately differentiated, stage IV, and is less likely to present in locations targetable by sigmoidoscopy than NHW (54.6% vs. 67.7% OR:1.7, 95% p < 0.001). 5-year CSS was lower in NHB (59.4% vs. 72.8%, HR: 1.7; 95% CI: 1.54-1.82) and Hispanics (66.4% vs. 72.8%, HR: 1.3; 95% CI: 1.16-1.39) than NHW. A regression model among patients with EO-CRC showed that being NHB or Hispanic were independent predictors for cancer-specific mortality, after adjusting for gender, grade, stage, and surgery.

Conclusion: EO-CRC is more likely in NHB and Hispanics. Racial disparities in clinical/pathological features and CSS between NHB and NHW/Hispanics were evidenced. A racial/ethnic specific screening strategy could be considered as an alternative for patients younger than 50 years.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cam4.3811DOI Listing
February 2021

First-in-human study of inhaled Azacitidine in patients with advanced non-small cell lung cancer.

Lung Cancer 2021 Feb 17;154:99-104. Epub 2021 Feb 17.

Department of Oncology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY10461, USA. Electronic address:

Background: Aerosolized Azacitidine has been shown to inhibit orthotopic lung cancer growth and induce re-expression of methylated tumor suppressor genes in murine models. We hypothesized that inhaled Azacitidine is safe and effective in reversing epigenetic changes in the bronchial epithelium secondary to chronic smoking.

Patients And Methods: We report the first in human study of inhaled Azacitidine. Azacitidine in aqueous solution was used to generate an aerosol suspension of 0.25-5 μm particle size. Main inclusion criteria: Stage IV or recurrent NSCLC with predominantly lung involvement, ≥1 prior systemic therapy, ECOG PS 0-1, and adequate pulmonary function. Patients received inhaled Azacitidine daily on days 1-5 and 15-19 of 28-day cycles, at 3 escalating doses (15, 30 and 45 mg/m daily). The primary objective was to determine the feasibility and tolerability of this new therapeutic modality. The key secondary objectives included pharmacokinetics, methylation profiles and efficacy.

Results: From 3/2015 to 2/2018, eight patients received a median number of 2 (IQR = 1) cycles of inhaled Azacitidine. No clinically significant adverse events were observed, except one patient treated at the highest dose developed an asymptomatic grade 2 decreased DLCO which resolved spontaneously. One patient receiving 12 cycles of therapy had an objective and durable partial response, and two patients had stable disease. Plasma Azacitidine was only briefly detectable in patients treated at the higher doses. Moreover, in 2 of 3 participants who agreed and underwent pre- and post-treatment bronchoscopy, the global DNA methylation in the bronchial epithelium decreased by 24 % and 79 % post-therapy, respectively. The interval between last inhaled treatment and bronchoscopy was 3 days.

Conclusions: Inhaled Azacitidine resulted in negligible plasma levels compared to the previously reported subcutaneous administration and was well-tolerated. The results justify the continued development of inhaled Azacitidine at non-cytotoxic doses for patients with lung-confined malignant and/or premalignant lesions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lungcan.2021.02.015DOI Listing
February 2021

Radiologic Definition of Sarcopenia in Chronic Liver Disease.

Life (Basel) 2021 Jan 25;11(2). Epub 2021 Jan 25.

Department of Radiology, College of Medicine, Hanyang University, Seoul 04763, Korea.

Sarcopenia is prevalent in patients with chronic liver disease, and affected patients tend to have worse clinical outcomes and higher mortality. However, relevant analyses are limited by heterogeneity in the definition of sarcopenia and in the methodological approaches in assessing it. We reviewed several radiologic methods for sarcopenia in patients with chronic liver disease. Dual energy X-ray absorptiometry (DXA) can measure muscle mass, but it is difficult to evaluate muscle quality using this technique. Computed tomography, known as the gold standard for diagnosing sarcopenia, enables the objective measurement of muscle quantity and quality. The third lumbar skeletal muscle index (L3 SMI) more accurately predicted the mortality of subjects than the psoas muscle index (PMI). Few studies have evaluated the sarcopenia of chronic liver disease using ultrasonography and magnetic resonance imaging, and more studies are needed. Unification of the measurement method and cut-off value would facilitate a more systematic and universal prognosis evaluation in patients with chronic liver disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/life11020086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910987PMC
January 2021

Clinical implications of serum Mac-2-binding protein glycan isomer as a novel biomarker of advanced hepatic fibrosis in diabetes.

Ann Transl Med 2020 Dec;8(23):1583

Department of Radiology, Hanyang University College of Medicine, Seoul, Korea.

Background: Appropriate strategy for screening, identification, and linkage to care of patients with advanced fibrosis in the general population is a current issue. The aim of this study was to find reference values and the clinical role of Mac-2 binding protein glycan isomer (M2BPGi) in a health check-up setting.

Methods: This study was designed as cross-sectional study. Adult subjects (n=1,073) who underwent a health check-up were included in the final analysis, and 952 subjects with risk factors for liver disease and insufficient data were excluded. M2BPGi quantification was based on a lectin antibody sandwich immunoassay. Fatty liver was diagnosed using abdominal sonography.

Results: The reference value of M2BPGi was 0.5-1.0 cut off index (COI) in the average risk group. Serum M2BPGi showed a positive correlation with metabolic parameters as well as age. Prevalence of abnormal M2BPGi (>1.0) was higher in low muscle mass (4.7%, 17.4%, P=0.002), metabolic syndrome (14.2% 30.4%, P=0.003), and hypertension (21.8%, 58.7%, P<0.001) compared to healthy controls. M2BPGi was positively correlated with estimated fibrosis values such as FIB-4 (R=0.293, P<0.001) and NAFLD fibrosis score (R=0.248, P<0.001). Although the prevalence of advanced fibrosis in the total population was just 1.6% (FIB-4 >2.65), the prevalence of advanced fibrosis increased to 50% in the high M2BPGi (>1.0) group with diabetes. This value was 31.25 times higher than in the total population group.

Conclusions: The results indicated a high possibility of advanced hepatic fibrosis in diabetic subjects with abnormal M2BPGi level (>1.0).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/atm-20-5216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791238PMC
December 2020

Detection of pneumoperitoneum in the abdominal radiograph images using artificial neural networks.

Eur J Radiol Open 2021 21;8:100316. Epub 2020 Dec 21.

Department of Radiology, Hanyang University Seoul Hospital, Seoul, Republic of Korea.

Background/purpose: The purpose of this study was to assess the diagnostic performance of artificial neural networks (ANNs) to detect pneumoperitoneum in abdominal radiographs for the first time.

Materials And Methods: This approach applied a novel deep-learning algorithm, a simple ANN training process without employing a convolution neural network (CNN), and also used a widely utilized deep-learning method, ResNet-50, for comparison.

Results: By applying ResNet-50 to abdominal radiographs, we obtained an area under the ROC curve (AUC) of 0.916 and an accuracy of 85.0 % with a sensitivity of 85.7 % and a predictive value of the negative tests (NPV) of 91.7 %. Compared with the most commonly applied deep-learning methods such as a CNN, our novel approach used extremely small ANN structures and a simple ANN training process. The diagnostic performance of our approach, with a sensitivity of 88.6 % and NPV of 91.3 %, was compared decently with that of ResNet-50.

Conclusions: The results of this study showed that ANN-based computer-assisted diagnostics can be used to accurately detect pneumoperitoneum in abdominal radiographs, reduce the time delay in diagnosing urgent diseases such as pneumoperitoneum, and increase the effectiveness of clinical practice and patient care.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejro.2020.100316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770533PMC
December 2020

Prefrontal Cortex and Amygdala Subregion Morphology Are Associated With Obesity and Dietary Self-control in Children and Adolescents.

Front Hum Neurosci 2020 3;14:563415. Epub 2020 Dec 3.

Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States.

A prefrontal control system that is less mature than the limbic reward system in adolescence is thought to impede self-regulatory abilities, which could contribute to poor dietary choices and obesity. We, therefore, aimed to examine whether structural morphology of the prefrontal cortex (PFC; involved in cognitive control) and the amygdala (a key brain region for reward-related processing) are associated with dietary decisions and obesity in children and adolescents. Seventy-one individuals between the ages of 8-22 years (17.35 ± 4.76 years, 51% female, 56% were overweight or obese) participated in this study; each participant completed a computer-based food choice task and a T1- and T2-weighted structural brain scans. Two indices of obesity were assessed, including age- and sex-specific body mass index (BMIz) and waist-to-height ratio (WHtR). The behavioral task included rating 60 food stimuli for tastiness, healthiness, and liking. Based on each participant's self-ratings, 100 binary food choices were then made utilizing a computer mouse. Dietary "self-control" was calculated as the proportion of trials where the individual chose the healthier food item (vs. the tastier food item) over the total number of trials. Cortical thickness and amygdala subnuclei volumes were quantified using FreeSurfer 6.0 and CIT168 atlas, respectively. We found that WHtR was negatively associated with the thickness of bilateral superior frontal, left superior temporal, right insula, and right inferior temporal regions ( < 0.05, corrected for multiple comparisons). We also found WHtR to be positively associated with the volume of the central nucleus (CEN) region of the amygdala ( = 0.006), after adjusting for the hemisphere, age, sex, and intracranial volumes. A similar data pattern was observed when BMIz was used. Moreover, we found that across all participants, thinner right superior frontal cortex and larger left CEN volumes predicted lower dietary self-control. These results suggest that differential development of the PFC and amygdala relate to obesity and dietary self-control. Further longitudinal studies are merited to determine causal relationships among altered PFC to amygdala neural circuitry, dietary self-control, and obesity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnhum.2020.563415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744283PMC
December 2020

No evidence for a difference in 2D:4D ratio between youth with elevated prenatal androgen exposure due to congenital adrenal hyperplasia and controls.

Horm Behav 2021 Feb 9;128:104908. Epub 2020 Dec 9.

Center for Endocrinology, Diabetes, and Metabolism, Children's Hospital Los Angeles, United States of America; The Saban Research Institute at Children's Hospital Los Angeles, United States of America; Keck School of Medicine of University of Southern California, United States of America.

The second-to-fourth digit ratio (2D:4D) has been associated with sexual dimorphism, with a lower 2D:4D in males. A large body of research has relied on the 2D:4D as a proxy for prenatal androgen exposure, and includes reports of relationships between 2D:4D and a wide range of human traits. Here, we examine the validity of the 2D:4D proxy by studying the association between 2D:4D and classical Congenital Adrenal Hyperplasia (CAH) due to 21-hydroxylase deficiency, a condition characterized by excessive prenatal exposure to androgens during most of the gestational period. To this end, we retrospectively examine 513 serial radiographs of the left hand obtained clinically in 90 youth with classical CAH (45 female) and 70 control youth (31 female). Replicating previous reports, we observe associations of the 2D:4D with sex (lower 2D:4D in males) and age (increase of 2D:4D through development). However, we find no evidence for differences in 2D:4D between CAH and controls (full sample: β = -0.001 (-0.008, 0.006); females: β = -0.004 [-0.015, 0.007]; males: β = 0.001, [-0.008, 0.011]). Although our findings do not rule out a small association between the 2D:4D and CAH, they cast doubt on the usefulness of the 2D:4D as a biomarker for prenatal androgen exposure in behavioral research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yhbeh.2020.104908DOI Listing
February 2021

Preoperative CT anthropometric measurements and pancreatic pathology increase risk for postoperative pancreatic fistula in patients following pancreaticoduodenectomy.

PLoS One 2020 3;15(12):e0243515. Epub 2020 Dec 3.

Department of Radiology, Hanyang University College of Medicine, Seoul, Republic of Korea.

Postoperative pancreatic fistula (POPF) is a common complication following pancreaticoduodenectomy (PD). However, risk factors for this complication remain controversial. We conducted a retrospective analysis of 107 patients who underwent PD. POPF was diagnosed in strict accordance with the definition of the 2016 update of pancreatic fistula from the International Study Group on Pancreatic Fistula (ISGPF). Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for POPF. A total of 19 (17.8%) subjects of pancreatic fistula occurred after PD, including 15 (14.1%) with grade B POPF and 4 (3.7%) with grade C POPF. There were 33 (30.8%) patients with biochemical leak. Risk factors for POPF (grade B and C) were larger area of visceral fat (odds ratio [OR], 1.40; p = 0.040) and pathology other than pancreatic adenocarcinoma or pancreatitis (OR, 12.45; p = 0.017) in the multivariate regression analysis. This result could assist the surgeon to identify patients at a high risk of developing POPF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243515PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7714124PMC
January 2021

Assessment of Facial Morphologic Features in Patients With Congenital Adrenal Hyperplasia Using Deep Learning.

JAMA Netw Open 2020 11 2;3(11):e2022199. Epub 2020 Nov 2.

Keck School of Medicine of the University of Southern California, Los Angeles.

Importance: Congenital adrenal hyperplasia (CAH) is the most common primary adrenal insufficiency in children, involving excess androgens secondary to disrupted steroidogenesis as early as the seventh gestational week of life. Although structural brain abnormalities are seen in CAH, little is known about facial morphology.

Objective: To investigate differences in facial morphologic features between patients with CAH and control individuals with use of machine learning.

Design, Setting, And Participants: This cross-sectional study was performed at a pediatric tertiary center in Southern California, from November 2017 to December 2019. Patients younger than 30 years with a biochemical diagnosis of classical CAH due to 21-hydroxylase deficiency and otherwise healthy controls were recruited from the clinic, and face images were acquired. Additional controls were selected from public face image data sets.

Main Outcomes And Measures: The main outcome was prediction of CAH, as performed by machine learning (linear discriminant analysis, random forests, deep neural networks). Handcrafted features and learned representations were studied for CAH score prediction, and deformation analysis of facial landmarks and regionwise analyses were performed. A 6-fold cross-validation strategy was used to avoid overfitting and bias.

Results: The study included 102 patients with CAH (62 [60.8%] female; mean [SD] age, 11.6 [7.1] years) and 59 controls (30 [50.8%] female; mean [SD] age, 9.0 [5.2] years) from the clinic and 85 controls (48 [60%] female; age, <29 years) from face databases. With use of deep neural networks, a mean (SD) AUC of 92% (3%) was found for accurately predicting CAH over 6 folds. With use of classical machine learning and handcrafted facial features, mean (SD) AUCs of 86% (5%) in linear discriminant analysis and 83% (3%) in random forests were obtained for predicting CAH over 6 folds. There was a deviation of facial features between groups using deformation fields generated from facial landmark templates. Regionwise analysis and class activation maps (deep learning of regions) revealed that the nose and upper face were most contributory (mean [SD] AUC: 69% [17%] and 71% [13%], respectively).

Conclusions And Relevance: The findings suggest that facial morphologic features in patients with CAH is distinct and that deep learning can discover subtle facial features to predict CAH. Longitudinal study of facial morphology as a phenotypic biomarker may help expand understanding of adverse lifespan outcomes for patients with CAH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamanetworkopen.2020.22199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675110PMC
November 2020

Severe Acute Respiratory Syndrome Coronavirus 2 Clinical Syndromes and Predictors of Disease Severity in Hospitalized Children and Youth.

J Pediatr 2021 03 14;230:23-31.e10. Epub 2020 Nov 14.

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

Objective: To characterize the demographic and clinical features of pediatric severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) syndromes and identify admission variables predictive of disease severity.

Study Design: We conducted a multicenter, retrospective, and prospective study of pediatric patients hospitalized with acute SARS-CoV-2 infections and multisystem inflammatory syndrome in children (MIS-C) at 8 sites in New York, New Jersey, and Connecticut.

Results: We identified 281 hospitalized patients with SARS-CoV-2 infections and divided them into 3 groups based on clinical features. Overall, 143 (51%) had respiratory disease, 69 (25%) had MIS-C, and 69 (25%) had other manifestations including gastrointestinal illness or fever. Patients with MIS-C were more likely to identify as non-Hispanic black compared with patients with respiratory disease (35% vs 18%, P = .02). Seven patients (2%) died and 114 (41%) were admitted to the intensive care unit. In multivariable analyses, obesity (OR 3.39, 95% CI 1.26-9.10, P = .02) and hypoxia on admission (OR 4.01; 95% CI 1.14-14.15; P = .03) were predictive of severe respiratory disease. Lower absolute lymphocyte count (OR 8.33 per unit decrease in 10 cells/L, 95% CI 2.32-33.33, P = .001) and greater C-reactive protein (OR 1.06 per unit increase in mg/dL, 95% CI 1.01-1.12, P = .017) were predictive of severe MIS-C. Race/ethnicity or socioeconomic status were not predictive of disease severity.

Conclusions: We identified variables at the time of hospitalization that may help predict the development of severe SARS-CoV-2 disease manifestations in children and youth. These variables may have implications for future prognostic tools that inform hospital admission and clinical management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpeds.2020.11.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666535PMC
March 2021

Is there a safe threshold for alcohol consumption in nonalcoholic fatty liver disease?

Hepatobiliary Surg Nutr 2020 Oct;9(5):644-646

Department of Internal Medicine, Hanyang University School of Medicine, Seoul, Korea.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/hbsn.2019.11.36DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603935PMC
October 2020

Factors related to passing the safety fast test among neonates with hypoglycemia in the neonatal intensive care unit.

J Paediatr Child Health 2020 Nov 3. Epub 2020 Nov 3.

Department of Pediatrics, Albert Einstein College of Medicine/Children's Hospital at Montefiore, Bronx, New York, United States.

Aim: To investigate the success rates and predictors of safety fast test among neonates admitted to the neonatal intensive care unit for hypoglycemia.

Methods: A retrospective review of neonates transferred from the newborn nursery unit to the neonatal intensive care unit for intravenous dextrose therapy for hypoglycemia from January 2016 to June 2019. Neonatal clinical and demographic variables were abstracted from the medical records. A successful safety fast test was defined by blood glucose >60 mg/dL (3.3 mmol/L) at 3, 4, 5 and 6 h after a feed.

Results: Of the 76 neonates who had a safety fast test, 80% passed on their first attempt. Neonates who passed the safety fast test were less likely to be premature/small for gestational age (54.1% vs. 92.9%, P = 0.03), required less maximum glucose infusion rate (median 6 vs. 7 mg/kg/min; P = 0.04), and were younger at fasting challenge (median 5 vs. 9 days; P = 0.02), required lower overall intravenous glucose load (median 12 vs. 24 g/kg; P = 0.006).

Conclusion: Safety fast test may be a useful tool evaluating discharge readiness of neonates with persistent hypoglycemia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jpc.15247DOI Listing
November 2020

Digit ratio (2D:4D) and congenital adrenal hyperplasia (CAH): Systematic literature review and meta-analysis.

Horm Behav 2020 Nov 6;126:104867. Epub 2020 Oct 6.

School of Psychology, Faculty of Medical Sciences, Newcastle University, UK; Department of Psychology of Conflict, Risk and Safety, University of Twente, Netherlands.

The ratio of length between the second and fourth fingers (2D:4D) is commonly used as an indicator of prenatal sex hormone exposure. Several approaches have been used to try to validate the measure, including examining 2D:4D in people with congenital adrenal hyperplasia (CAH), a suite of conditions characterised by elevated adrenal androgen production secondary to defective steroidogenesis. We present a systematic review and meta-analysis that examines the relationship between these two variables. Twelve articles relating to nine CAH cohorts were identified, and 2D:4D comparisons have been made between cases and controls in eight of these cohorts. Altogether, at least one 2D:4D variable has been compared between n = 251 females with CAH and n = 358 unaffected females, and between n = 108 males with CAH and n = 204 unaffected males. A previous meta-analysis (Hönekopp and Watson, 2010) reported lower right hand (R2D:4D) and left hand (L2D:4D) digit ratios in patients with CAH relative to sex-matched controls. Our meta-analysis showed the same pattern, with medium effect sizes for R2D:4D and small effect sizes for L2D:4D. Differences of small magnitude were also observed for M2D:4D, and no significant effects were observed for D. Notably, the only effects that remained statistically significant when stratified by sex were R2D:4D in males and L2D:4D in females, and the average effect size had reduced by 46.70% since the meta-analysis of Hönekopp and Watson (2010). We also found that individual comparisons in this literature were considerably underpowered, and that patterns of sexual dimorphism in 2D:4D were similar in CAH samples as in typically developing populations. Findings are discussed in relation to the prenatal androgen hypothesis as well as alternative explanations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yhbeh.2020.104867DOI Listing
November 2020

Electrocardiographic QT Intervals in Infants Exposed to Hydroxychloroquine Throughout Gestation.

Circ Arrhythm Electrophysiol 2020 10 9;13(10):e008686. Epub 2020 Sep 9.

New York University School of Medicine, New York, NY (R. Clancy, C.K.P., R. Cohen, M.M., B.J.W., A.S., P.M.I., J.P.B.).

Background: Based on inhibition of viral replication and limited reports on clinical efficacy, hydroxychloroquine is being considered as prophylaxis and treatment of coronavirus disease-19 (COVID-19). Although hydroxychloroquine is generally considered safe during pregnancy based on studies in patients with systemic lupus erythematosus and other rheumatic conditions, there may still be reluctance to institute this antimalarial during pregnancy for the sole purpose of antiviral therapy.

Methods: To provide data regarding any potential fetal/neonatal cardiotoxicity, we leveraged a unique opportunity in which neonatal ECGs and hydroxychloroquine blood levels were available in a recently completed study evaluating the efficacy of hydroxychloroquine 400 mg daily to prevent the recurrence of congenital heart block associated with anti-SSA/Ro (anti-Sjögren's Syndrome A/Ro) antibodies.

Results: Forty-five ECGs were available for corrected QT interval (QTc) measurement, and levels of hydroxychloroquine were assessed during each trimester of pregnancy and in the cord blood, providing unambiguous assurance of drug exposure. Overall, there was no correlation between cord blood levels of hydroxychloroquine and the neonatal QTc (=0.02, =0.86) or the mean of hydroxychloroquine values obtained throughout each individual pregnancy and the QTc (=0.04, =0.80). In total 5 (11% [95% CI, 4%-24%]) neonates had prolongation of the QTc >2 SD above historical healthy controls (2 markedly and 3 marginally) but ECGs were otherwise normal.

Conclusions: In aggregate, these data provide reassurances that the maternal use of hydroxychloroquine is associated with a low incidence of infant QTc prolongation. However, if included in clinical COVID-19 studies, early postnatal ECGs should be considered. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01379573.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCEP.120.008686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7668319PMC
October 2020

Discontinuation of hydroxychloroquine in older patients with systemic lupus erythematosus: a multicenter retrospective study.

Arthritis Res Ther 2020 08 17;22(1):191. Epub 2020 Aug 17.

Division of Rheumatology, Department of Medicine, New York University School of Medicine, New York, NY, USA.

Background: Although hydroxychloroquine (HCQ) is a mainstay of treatment for patients with systemic lupus erythematosus (SLE), ocular toxicity can result from accumulated exposure. As the longevity of patients with SLE improves, data are needed to balance the risk of ocular toxicity and the risk of disease flare, especially in older patients with quiescent disease. Accordingly, this study was initiated to examine the safety of HCQ withdrawal in older SLE patients.

Methods: Data were obtained by retrospective chart review at three major lupus centers in New York City. Twenty-six patients who discontinued HCQ and thirty-two patients on HCQ matched for gender, race/ethnicity, and age were included in this study. The primary outcome was the occurrence of a lupus flare classified by the revised version of the Safety of Estrogens in Lupus Erythematosus: National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) Flare composite index, within 1 year of HCQ withdrawal or matched time of continuation.

Results: Five patients (19.2%) in the HCQ withdrawal group compared to five (15.6%) in the HCQ continuation group experienced a flare of any severity (odds ratio [OR] = 1.28; 95% CI 0.31, 5.30; p = 0.73). There were no severe flares in either group. The results were similar after adjusting for length of SLE, number of American College of Rheumatology criteria, low complement levels, and SELENA-SLEDAI score, and in a propensity score analysis (OR = 1.18; 95% CI 0.23, 6.16; p = 0.84). The analysis of time to any flare revealed a non-significant earlier time to flare in the HCQ withdrawal group (log-rank p = 0.67). Most flares were in the cutaneous and musculoskeletal systems, but one patient in the continuation group developed pericarditis. The most common reason for HCQ withdrawal was retinal toxicity (42.3%), followed by patient's preference (34.6%), other confirmed or suspected adverse effects (15.4%), ophthalmologist recommendation for macular degeneration (3.8%), and rheumatologist recommendation for quiescent SLE (3.8%).

Conclusions: In this retrospective study of older stable patients with SLE on long-term HCQ, withdrawal did not significantly increase the risk of flares.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13075-020-02282-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430013PMC
August 2020

Optimism bias in understanding neonatal prognoses.

J Perinatol 2020 Aug 10. Epub 2020 Aug 10.

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

Objective: Discrepancies between physician and parent neonatal prognostic expectations are common. Optimism bias is a possible explanation.

Study Design: Parents interpreted hypothetical neonatal prognoses in an online survey.

Results: Good prognoses tended to be interpreted accurately, while poor prognoses were interpreted as less than the stated value. One-third of participants consistently overstated survival for the three lowest prognoses, compared to the sample as a whole. Three significant predictors of such optimistic interpretations were single-parent status (OR 0.39; 95% CI 0.2-0.75; p = 0.005), African-American descent (OR 3.78; 95% CI 1.63-8.98; p = 0.002) and the belief that physicians misrepresented prognoses (OR 3.11; 95% CI 1.47-6.65; p = 0.003). Participants' explanations echoed research on optimism bias in clinical and decision science studies.

Conclusion: Participants accepted positive prognoses for critically ill neonates, but reinterpreted negative ones as being unduly pessimistic demonstrating optimism bias.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41372-020-00773-1DOI Listing
August 2020

Leveraging the United States Epicenter to Provide Insights on COVID-19 in Patients With Systemic Lupus Erythematosus.

Arthritis Rheumatol 2020 12 28;72(12):1971-1980. Epub 2020 Oct 28.

New York University School of Medicine, New York, New York.

Objective: To characterize patients with systemic lupus erythematosus (SLE) affected by coronavirus disease 2019 (COVID-19) and to analyze associations of comorbidities and medications on infection outcomes.

Methods: Patients with SLE and reverse transcriptase-polymerase chain reaction-confirmed COVID-19 were identified through an established New York University lupus cohort, query of 2 hospital systems, and referrals from rheumatologists. Data were prospectively collected via a web-based questionnaire and review of medical records. Data on baseline characteristics were obtained for all patients with COVID-19 to analyze risk factors for hospitalization. Data were also collected on asymptomatic patients and those with COVID-19-like symptoms who tested negative or were not tested. Statistical analyses were limited to confirmed COVID-19-positive patients.

Results: A total of 226 SLE patients were included: 41 with confirmed COVID-19, 19 who tested negative for COVID-19, 42 with COVID-19-like symptoms who did not get tested, and 124 who remained asymptomatic without testing. Of the SLE patients with confirmed COVID-19, hospitalization was required in 24 (59%) and intensive care unit-level of care in 4, and 4 died. Hospitalized patients tended to be older, nonwhite, Hispanic, have higher body mas index (BMI), history of nephritis, and at least 1 comorbidity. An exploratory (due to limited sample size) logistic regression analysis identified race, presence of at least 1 comorbidity, and BMI as independent predictors of hospitalization.

Conclusion: In general, the variables predictive of hospitalization in our SLE patients were similar to those identified in the general population. Further studies are needed to understand additional risk factors for poor COVID-19 outcomes in patients with SLE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/art.41450DOI Listing
December 2020

Framing potential for adverse effects of repetitive subconcussive impacts in soccer in the context of athlete and non-athlete controls.

Brain Imaging Behav 2020 Jul 25. Epub 2020 Jul 25.

Albert Einstein College of Medicine, Montefiore Medical Center, 1300 Morris Park Avenue, Bronx, NY, 10461, USA.

The benefits of athletic activity may be attenuated by sport-related head impacts, including soccer-related concussion and subconcussive events. The purpose of this study is to characterize the specific effects of soccer heading on white matter microstructure and cognitive function, independent of concussion, relative to non-athlete controls and relative to active athletes who are not involved in collision sports. 246 amateur soccer players, 72 non-contact/non-collision sports athletes and 110 healthy,non-athlete controls were included in the study, and underwent cognitive testing and 3T diffusion tensor imaging (DTI). Voxelwise linear regression, comparing soccer players and non-contact/non-collision sports athletes healthy,non-athlete controls, identified regions of abnormally low and high fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD) in athlete participants. Generalized estimating equations were used to examine the effects of 2 week and 1 year heading exposure quartile on cognitive performance and on the volume of each high and each low DTI parameter. Athletes with no or lower exposure to repetitive heading exhibited greater expression of low RD, greater expression of high FA and better performance on tasks of attention, processing speed, verbal memory, and working memory compared to non-athletes. Soccer players with the highest exposure to repetitive head impacts, however, did not differ significantly from healthy, non-athletes on either micro-structural features or cognitive performance, findings not explained by concussion history or demographic factors. These results are consistent with the notion that beneficial effects of athletic conditioning or training on brain structure and function may be attenuated by exposure to repeated subconcussive head impacts.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11682-020-00297-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861653PMC
July 2020

Hydroxychloroquine to Prevent Recurrent Congenital Heart Block in Fetuses of Anti-SSA/Ro-Positive Mothers.

J Am Coll Cardiol 2020 07;76(3):292-302

New York University School of Medicine, New York, New York. Electronic address: https://twitter.com/JillBuyonMD.

Background: Experimental and clinical evidence support the role of macrophage Toll-like receptor signaling in maternal anti-SSA/Ro-mediated congenital heart block (CHB).

Objectives: Hydroxychloroquine (HCQ), an orally administered Toll-like receptor antagonist widely used in lupus including during pregnancy, was evaluated for efficacy in reducing the historical 18% recurrence rate of CHB.

Methods: This multicenter, open-label, single-arm, 2-stage clinical trial was designed using Simon's optimal approach. Anti-SSA/Ro-positive mothers with a previous pregnancy complicated by CHB were recruited (n = 19 Stage 1; n = 35 Stage 2). Patients received 400 mg daily of HCQ prior to completion of gestational week 10, which was maintained through pregnancy. The primary outcome was 2° or 3° CHB any time during pregnancy, and secondary outcomes included isolated endocardial fibroelastosis, 1° CHB at birth and skin rash.

Results: By intention-to-treat (ITT) analysis, 4 of 54 evaluable pregnancies resulted in a primary outcome (7.4%; 90% confidence interval: 3.4% to 15.9%). Because 9 mothers took potentially confounding medications (fluorinated glucocorticoids and/or intravenous immunoglobulin) after enrollment but prior to a primary outcome, to evaluate HCQ alone, 9 additional mothers were recruited and followed the identical protocol. In the per-protocol analysis restricted to pregnancies exposed to HCQ alone, 4 of 54 (7.4%) fetuses developed a primary outcome as in the ITT. Secondary outcomes included mild endocardial fibroelastosis (n = 1) and cutaneous neonatal lupus (n = 4).

Conclusions: These prospective data support that HCQ significantly reduces the recurrence of CHB below the historical rate by >50%, suggesting that this drug should be prescribed for secondary prevention of fetal cardiac disease in anti-SSA/Ro-exposed pregnancies. (Preventive Approach to Congenital Heart Block With Hydroxychloroquine [PATCH]; NCT01379573).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jacc.2020.05.045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7394202PMC
July 2020

Patient and Caregiver Attitudes toward Disorders of Sex Development Nomenclature.

J Urol 2020 10 17;204(4):835-842. Epub 2020 Apr 17.

Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois.

Purpose: The medical terminology applied to differences/disorders of sex development has been viewed negatively by some affected individuals. A clinical population of patients with differences/disorders of sex development and their caregivers were surveyed regarding current nomenclature, hypothesizing that those unaffiliated with support groups would have more favorable attitudes.

Materials And Methods: We recruited English and Spanish speaking patients 13 years old or older with differences/disorders of sex development and their caregivers at 5 national tertiary care clinics from July 2016 to December 2018. No diagnoses were excluded. Participants completed a survey rating terminology commonly applied to differences/disorders of sex development. Responses were compared between subgroups, including members vs nonmembers of a support group.

Results: Of 185 potential participants approached 133 completed the survey (72% response rate). Congenital adrenal hyperplasia (33%) was the most common diagnosis. "Variation of sex development" was the most liked term (37%) but was not liked more significantly than "disorders of sex development" (27%, p=0.16). No term was liked by a majority of respondents. "Disorders of sex development" (37%) and "intersex" (53%) were the only terms most frequently viewed unfavorably. Support group members were significantly more likely to dislike the term "intersex" (p=0.02) and to like "variation of sex development" (p=0.02).

Conclusions: A clinical population of patients and their caregivers had generally neutral attitudes toward nomenclature applied to differences/disorders of sex development. Members of a support group had clearer terminology preferences. "Variation of sex development" was the most liked term, and "disorders of sex development" and "intersex" were the most disliked. No term was liked by most respondents, and no clear alternative to the present nomenclature was identified.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/JU.0000000000001076DOI Listing
October 2020

Sequential Combination of FIB-4 Followed by M2BPGi Enhanced Diagnostic Performance for Advanced Hepatic Fibrosis in an Average Risk Population.

J Clin Med 2020 Apr 14;9(4). Epub 2020 Apr 14.

Centre for Digestive and Liver Diseases, Nara City Hospital, Nara 630-8305, Japan.

The fibrosis-4 (FIB-4) index is the most widely used estimated formula to screen for advanced hepatic fibrosis; however, it has a considerable intermediate zone. Here, we propose an algorithm to reduce the intermediate zone and improve the diagnostic performance of screening for advanced liver fibrosis by incorporating Mac-2-binding protein glycan isomer (M2BPGi) into a FIB-4 based screening strategy in an average risk group. Four-hundred eighty-eight healthy and chronic liver disease subjects were analyzed using a 1:1 propensity score matched for age and sex. Advanced liver fibrosis (≥F3) was defined by magnetic resonance elastography (MRE, ≥3.6 kPa). Classification tree analysis was employed to improve diagnostic performance using a combination of the FIB-4 index and M2BPGi. The median serum M2BPGi levels of healthy subjects, patients without advanced fibrosis, and those with the condition were 0.48, 0.94, and 2.93, respectively. The area under the receiver operating characteristic (AUROC) curve of M2BPGi (0.918) for advanced fibrosis was the highest compared to those of the FIB-4 index (0.887), APRI (0.873), and AST/ALT ratio (0.794). When M2BPGi was incorporated following the FIB-4 index, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 87.1%, 82.5%, 54.0%, and 96.4%, respectively. Moreover, 74.3% (133/179) of cases in the intermediate zone of the FIB-4 index avoided unnecessary referrals. Two-step pathway (FIB-4 followed by M2BPGi) could reduce unnecessary referrals and/or liver biopsies in an average-risk population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm9041119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230806PMC
April 2020

Low frequency of flares during pregnancy and post-partum in stable lupus patients.

Arthritis Res Ther 2020 03 19;22(1):52. Epub 2020 Mar 19.

Hospital for Special Surgery, 535 E 70th Street, New York, NY, 10021, USA.

Background: Lupus patients are at risk for pregnancy loss, and it has been generally accepted that women with SLE should have low disease activity prior to conception. However, there are conflicting results regarding the effect of pregnancy on SLE flares. This study aims to identify predictors of flares during and after pregnancy in SLE patients with inactive or stable disease activity during the first trimester and to characterize and estimate the frequency of post-partum flares in these patients.

Methods: SLE patients in the multicenter, prospective PROMISSE (Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus) study were evaluated for flares during and after pregnancy using the SELENA-SLEDAI Flare Index. Flares during pregnancy were assessed in all 384 patients and post-partum flares in 234 patients with study visits 2-6 months post-partum. Logistic regression models were fit to the data to identify independent risk factors for flare.

Results: During pregnancy, 20.8% of patients had mild/moderate flares and 6.25% had severe. Post-partum, 27.7% of patients had mild/moderate flares and 1.7% had severe. The mild flares rarely required treatment. Younger age, low C4 and higher PGA at baseline were independently associated with higher risk of having at least one mild/moderate or severe flare during pregnancy. Older patients were at decreased risk of flare, as well as those with quiescent disease at baseline. No variables evaluated at baseline or the visit most proximal to delivery was significantly associated with risk of flare post-partum. Medications were not associated with flare during or after pregnancy.

Conclusion: In patients with inactive or stable mild disease activity at the time of conception, lupus disease flares during and after pregnancy are typically mild and occur at similar rates. Flares during pregnancy are predicted by the patients' age and clinical and serological activity at baseline.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13075-020-2139-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081564PMC
March 2020

Individual vs. Group Delivery of Acupuncture Therapy for Chronic Musculoskeletal Pain in Urban Primary Care-a Randomized Trial.

J Gen Intern Med 2020 04 19;35(4):1227-1237. Epub 2020 Feb 19.

Department of Family and Social Medicine, Albert Einstein College of Medicine, New York, USA.

Background: Acupuncture has been shown to be effective for the treatment of chronic musculoskeletal back, neck, and osteoarthritis pain. However, access to acupuncture treatment has been limited in medically underserved and low-income populations.

Objective: Acupuncture therapy delivered in groups could reduce cost and expand access. We compared the effectiveness of group versus individual acupuncture for pain and function among ethnically diverse, low-income primary care patients with chronic musculoskeletal pain.

Design: This was a randomized comparative effectiveness non-inferiority trial in 6 Bronx primary care community health centers. Participants with chronic (> 3 months) back, neck, or osteoarthritis pain were randomly assigned to individual or group acupuncture therapy for 12 weeks.

Participants: Seven hundred seventy-nine participants were randomized. Mean age was 54.8 years. 35.3% of participants identified as black and 56.9% identified as Latino. Seventy-six percent were Medicaid insured, 60% reported poor/fair health, and 37% were unable to work due to disability.

Interventions: Participants received weekly acupuncture treatment in either group or individual setting for 12 weeks.

Main Measures: Primary outcome was pain interference on the Brief Pain Inventory at 12 weeks; secondary outcomes were pain severity (BPI), physical and mental well-being (PROMIS-10), and opiate use. Outcome measures were collected at baseline, 12 and 24 weeks.

Key Results: 37.5% of individual arm and 30.3% in group had > 30% improvement in pain interference (d = 7.2%, 95% CI - 0.6%, 15.1%). Non-inferiority of group acupuncture was not demonstrated for the primary outcome assuming a margin of 10%. In the responder analysis of physical well-being, 63.1% of individual participants and 59.5% of group had clinically important improvement at 12 weeks (d = 3.6%, 95% CI - 4.2%, 11.4%).

Conclusions: Both individual and group acupuncture therapy delivered in primary care settings reduced chronic pain and improved physical function at 12 weeks; non-inferiority of group was not shown.

Trial Registration: Clinicaltrials.gov # NCT02456727.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11606-019-05583-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7174252PMC
April 2020

Diagnostic Performance of Serum Asialo α-Acid Glycoprotein Levels to Predict Liver Cirrhosis.

Gut Liver 2021 Jan;15(1):109-116

Departments of Radiology, Hanyang University College of Medicine, Seoul, Korea.

Background/aims: To date, studies on various noninvasive techniques have been suggested to evaluate the degree of liver fibrosis. We aimed to investigate the diagnostic performance of serum asialo α1-acid glycoprotein (AsAGP) in the diagnosis of liver cirrhosis compared with chronic hepatitis for clinically useful result.

Methods: We conducted a case-control study of 96 patients with chronic liver disease. Chronic hepatitis was defined as the presence of chronic liver disease on ultrasonography, with a liver stiffness of less than 5.0 kPa as shown on magnetic resonance elastography (MRE). Liver cirrhosis was defined as liver stiffness of more than 5.0 kPa on MRE. The serum AsAGP concentration was compared between the two groups.

Results: Serum AsAGP levels were significantly higher in patients with cirrhosis than in those with chronic hepatitis (1.83 µg/mL vs 1.42 µg/mL, p<0.001). Additionally, when comparing patients in each cirrhotic group (Child-Pugh grades A, B, and C) to those with chronic hepatitis, AsAGP levels were significantly higher in all the cirrhotic groups (p<0.05, p<0.01, p<0.001, respectively). The sensitivity and specificity of AsAGP for detecting cirrhosis were 79.2% and 64.6%, respectively, and the area under the curve value was 0.733. The best diagnostic cutoff to predict cirrhosis was 1.4 µg/mL. AsAGP and bilirubin were found to be independent risk factors for the prediction of cirrhosis in the logistic regression analysis.

Conclusions: Serum AsAGP showed an acceptable diagnostic performance in predicting liver cirrhosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5009/gnl19282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817921PMC
January 2021

Phase I and pharmacokinetic study of veliparib, a PARP inhibitor, and pegylated liposomal doxorubicin (PLD) in recurrent gynecologic cancer and triple negative breast cancer with long-term follow-up.

Cancer Chemother Pharmacol 2020 04 13;85(4):741-751. Epub 2020 Feb 13.

NYU Langone Health, Division of Gynecologic Oncology, New York University School of Medicine, 240 East 38th street, 19th floor, New York, NY, USA.

Objective: Poly(ADP-ribosyl) polymerases (PARPs) are nuclear enzymes with roles in DNA damage recognition and repair. PARP1 inhibition enhances the effects of DNA-damaging agents like doxorubicin. We sought to determine the recommended phase two dose (RP2D) of veliparib with pegylated liposomal doxorubicin (PLD) in breast and recurrent gynecologic cancer patients.

Methods: Veliparib and PLD were administered in a standard phase 1, 3 + 3 dose-escalation design starting at 50 mg veliparib BID on days 1-14 with PLD 40 mg/mg on day 1 of a 28-day cycle. Dose escalation proceeded in two strata: A (prior PLD exposure) and B (no prior PLD exposure). Patients underwent limited pharmacokinetic (PK) sampling; an expansion PK cohort was added.

Results: 44 patients with recurrent ovarian or triple negative breast cancer were enrolled. Median age 56 years; 23 patients BRCA mutation carriers; median prior regimens four. Patients received a median of four cycles of veliparib/PLD. Grade 3/4 toxicities were observed in 10% of patients. Antitumor activity was observed in both sporadic and BRCA-deficient cancers. Two BRCA mutation carriers had complete responses. Two BRCA patients developed oral squamous cell cancers after completing this regimen. PLD exposure was observed to be higher when veliparib doses were > 200 mg BID.

Conclusions: The RP2D is 200 mg veliparib BID on days 1-14 with 40 mg/m PLD on day 1 of a 28-day cycle. Anti-tumor activity was seen in both strata. However, given development of long-term squamous cell cancers and the PK interaction observed, efforts should focus on other targeted combinations to improve efficacy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00280-020-04030-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845144PMC
April 2020

Associations of Apolipoprotein E ε4 Genotype and Ball Heading With Verbal Memory in Amateur Soccer Players.

JAMA Neurol 2020 04;77(4):419-426

Gruss Magnetic Resonance Imaging Center, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York.

Importance: Emerging evidence suggests that long-term exposure to ball heading in soccer, the most popular sport in the world, confers risk for adverse cognitive outcomes. However, the extent to which the apolipoprotein E ε4 (APOE ε4) allele, a common risk factor for neurodegeneration, and ball heading are associated with cognition in soccer players remains unknown.

Objective: To determine whether the APOE ε4 allele and 12-month ball heading exposure are associated with verbal memory in a cohort of adult amateur soccer players.

Design, Settings, And Participants: A total of 379 amateur soccer players were enrolled in the longitudinal Einstein Soccer Study from November 11, 2013, through January 23, 2018. Selection criteria included participation in soccer for more than 5 years and for more than 6 months per year. Of the 379 individuals enrolled in the study, 355 were genotyped. Three players were excluded for reporting extreme levels of heading. Generalized estimating equation linear regression models were employed to combine data across visits for a cross-sectional analysis of the data.

Exposures: At each study visit every 3 to 6 months, players completed the HeadCount 12-Month Questionnaire, a validated, computer-based questionnaire to estimate 12-month heading exposure that was categorized as low (quartiles 1 and 2), moderate (quartile 3), and high (quartile 4).

Main Outcome And Measures: Verbal memory was assessed at each study visit using the International Shopping List Delayed Recall task from CogState.

Results: A total of 352 soccer players (256 men and 96 women; median age, 23 years [interquartile range, 21-28 years]) across a total of 1204 visits were analyzed. High levels of heading were associated with worse verbal memory performance (β = -0.59; 95% CI, -0.93 to -0.25; P = .001). There was no main association of APOE ε4 with verbal memory (β = 0.09; 95% CI, -0.24 to 0.42; P = .58). However, there was a significant association of APOE ε4 and heading with performance on the ISRL task (χ2 = 7.22; P = .03 for overall interaction). In APOE ε4-positive players, poorer verbal memory associated with high vs low heading exposure was 4.1-fold greater (APOE ε4 negative, β = -0.36; 95% CI, -0.75 to 0.03; APOE ε4 positive, β = -1.49; 95% CI, -2.05 to -0.93), and poorer verbal memory associated with high vs moderate heading exposure was 8.5-fold greater (APOE ε4 negative, β = -0.13; 95% CI, -0.54 to 0.29; APOE ε4 positive, β = -1.11, 95% CI, -1.70 to -0.53) compared with that in APOE ε4-negative players.

Conclusions And Relevance: This study suggests that the APOE ε4 allele is a risk factor for worse memory performance associated with higher heading exposure in the prior year, which highlights that assessing genetic risks may ultimately play a role in promoting safer soccer play.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamaneurol.2019.4828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6990972PMC
April 2020

Brain Differences in the Prefrontal Cortex, Amygdala, and Hippocampus in Youth with Congenital Adrenal Hyperplasia.

J Clin Endocrinol Metab 2020 04;105(4)

Department of Pediatrics, Keck School of Medicine of University of Southern California, Los Angeles, California.

Context: Classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency results in hormone imbalances present both prenatally and postnatally that may impact the developing brain.

Objective: To characterize gray matter morphology in the prefrontal cortex and subregion volumes of the amygdala and hippocampus in youth with CAH as compared to controls.

Design: A cross-sectional study of 27 CAH youth (16 female; 12.6 ± 3.4 years) and 35 typically developing, healthy controls (20 female; 13.0 ± 2.8 years) with 3-T magnetic resonance imaging scans. Brain volumes of interest included bilateral prefrontal cortex and 9 amygdala and 6 hippocampal subregions. Between-subject effects of group (CAH vs. control) and sex, and their interaction (group-by-sex) on brain volumes, were studied while controlling for intracranial volume (ICV) and group differences in body mass index and bone age.

Results: Congenital adrenal hyperplasia youth had smaller ICV and increased cerebrospinal fluid volume compared to controls. In fully-adjusted models, CAH youth had smaller bilateral superior and caudal middle frontal volumes, and smaller left lateral orbitofrontal volumes compared to controls. Medial temporal lobe analyses revealed that the left hippocampus was smaller in fully-adjusted models. Congenital adrenal hyperplasia youth also had significantly smaller lateral nucleus of the amygdala and hippocampal subiculum and CA1 subregions.

Conclusions: This study replicates previous findings of smaller medial temporal lobe volumes in CAH patients and suggests that the lateral nucleus of the amygdala, as well as subiculum and subfield CA1 of the hippocampus, are particularly affected within the medial temporal lobes in CAH youth.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/clinem/dgaa023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7058446PMC
April 2020

Shifting the Lens: An Implementation Study of a Community-Based and Social Network Intervention to Gender-Based Violence.

Authors:
Mimi E Kim

Violence Against Women 2021 Feb 13;27(2):222-254. Epub 2020 Jan 13.

California State University, Long Beach, USA.

Responding to the call to "shift the lens" and expand gender-based violence remedies beyond individualized direct services and law enforcement remedies, anti-violence providers have struggled to redefine and redirect intervention approaches. This implementation study leverages the framework of implementation science to investigate an exploratory statewide initiative based on the Creative Interventions model and aimed to build organizational and regional capacity to implement community-based or social network interventions within provider organizations. Using data from nine organizations, this mixed-methods study identifies factors related to implementation of this innovative approach including organizational motivation, capacity, and perceived needs related to adoption and implementation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1077801219889176DOI Listing
February 2021

BDNF ValMet Positive Players Demonstrate Diffusion Tensor Imaging Consistent With Impaired Myelination Associated With High Levels of Soccer Heading: Indication of a Potential Gene-Environment Interaction Mechanism.

Front Neurol 2019 11;10:1297. Epub 2019 Dec 11.

The Gruss Magnetic Resonance Research Center, Albert Einstein College of Medicine and Montefiore Medical Center, The Bronx, NY, United States.

The purpose of this study was to examine the potential effect modifying role of the BDNF ValMet polymorphism on the association of soccer heading with white matter microstructure. We studied 312 players enrolled in the ongoing Einstein Soccer Study, a longitudinal study of amateur soccer player in New York City and surrounding areas. At enrollment and 2 years later, total heading in the prior 12 months (12-mo.) was estimated using an established self-report instrument and diffusion tensor imaging (DTI) was performed. Generalized Estimating Equations (GEE) logistic regression models were employed to test effect modification by the BDNF ValMet polymorphism on the association between 12-mo. heading exposure and DTI. We identified a significant interaction of 12-mo headingBDNF ValMet genotype on the presence of low Radial Diffusivity, a DTI marker associated with myelination. Only Met (+) players demonstrated significantly reduced odds of low RD [OR (95 % CI): -2.36 (-3.53, -1.19)] associated with the highest vs. lowest quartile of 12-mo heading exposure. BDNF ValMet (+) soccer players with long-term exposure to high levels of heading exhibit less low Radial Diffusivity, suggesting impaired re-myelination may be a substrate of the previously reported association between heading and poor functional outcomes in soccer players.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2019.01297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6918922PMC
December 2019

Correction to: The Society for Implementation Research Collaboration Instrument Review Project: a methodology to promote rigorous evaluation.

Implement Sci 2020 Jan 3;15(1). Epub 2020 Jan 3.

Department of Psychiatry and Behavioral Sciences, Harborview Medical Center, School of Medicine, University of Washington, Box 359911, 325 9th Ave, Seattle, WA, 98104, USA.

Following publication of the original article [1] the authors reported an important acknowledgement was mistakenly omitted from the 'Acknowledgements' section. The full acknowledgement is included in this Correction article.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13012-019-0963-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6942395PMC
January 2020