Total cortical interstitial inflammation predicts chronic kidney disease progression in patients with lupus nephritis.

BACKGROUND: End-stage kidney disease (ESKD) from lupus nephritis (LN) is a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Kidney biopsy is the gold standard for diagnosis and prognostication of LN. While interstitial fibrosis and tubular atrophy (IFTA) predict progression to ESKD, the National Institutes of Health (NIH) classification of interstitial inflammation in unscarred cortical parenchyma is not predictive of chronic kidney disease (CKD) progression. The objective of this study was to determine whether total cortical interstitial inflammation that accounts for inflammation in the entire cortical parenchyma could predict CKD progression in patients with LN. Early identification of at-risk patients may improve outcomes. METHODS: This retrospective cohort study included 125 SLE patients with LN class III, IV, V or mixed (III/V, IV/V) on the index biopsy (2005-2018). Kidney biopsies were reviewed and assigned based on the 2018 NIH Activity Index (AI) and tubulointerstitial lesion categories. Total interstitial inflammation in the entire cortical parenchyma was graded as 0, 1, 2 or 3, corresponding to <10%, 10-25%, 26-50% and >50%, respectively, of the total cortical parenchyma containing an inflammatory infiltrate (similar to the definition used in the Banff total inflammation score). CKD progression was defined as an estimated glomerular filtration rate decrease of ≥30% within 5 years after the index biopsy. Kaplan-Meier survival curves and Cox proportional hazards models were performed to compare the two scoring systems, the total cortical intestinal inflammation score and the NIH interstitial inflammation score as predictors of CKD progression. RESULTS: Of 125 patients, 46 experienced CKD progression; 21 of 46 subsequently developed ESKD, 28 (22.4%) had moderate-severe total cortical interstitial inflammation and 8 (6.4%) had moderate-severe NIH interstitial inflammation. There were no differences in baseline characteristics between progressors and nonprogressors. Total cortical interstitial inflammation was associated with CKD progression in time-dependent analyses [hazard ratio 2.45 (95% confidence interval 1.2-4.97)] adjusted for age at biopsy, race, sex, LN class and hypertensive vascular change on kidney biopsy. The NIH interstitial inflammation was not associated with CKD progression. CONCLUSIONS: In contrast to the current NIH interstitial inflammation classification, accounting for interstitial inflammation in the entire cortical parenchyma allows identification of patients at risk for CKD progression in LN.

Screening Electrocardiograms Have Low Utility in Medical Clearance Before Pediatric Inpatient Psychiatric Admission.

OBJECTIVES: Children presenting to the emergency department (ED) requiring psychiatric admission often undergo screening electrocardiograms (ECG) as part of the medical clearance process. The diagnostic yield of screening ECGs for this purpose has not been reported. The purpose of this study was to determine the clinical utility of screening ECGs in children and adolescents requiring acute inpatient psychiatric admission. METHODS: A single-center retrospective study of patients aged 5 to 18 years who did not have documented indications for ECG and underwent screening ECG before psychiatric inpatient admission over a 2-year period was conducted. Abnormal ECGs were identified via chart review and were reinterpreted by a pediatric cardiologist to determine potential significance to psychiatric care. Impact on treatment and disposition was examined. RESULTS: From January 2018 through December 2019, 252 eligible pediatric patients had a screening ECG in the ED before psychiatric admission. Twenty-one (8.3%) of these ECGs were interpreted as abnormal, and 6 (2.4%) were determined to be potentially relevant to psychiatric care in the setting of specific medication use. The abnormal ECG interpretations resulted in additional workup and/or cardiology consultation for 7 (2.7%) patients but had no impact on psychiatric admission. CONCLUSIONS: In the absence of concerning individual or family history or cardiac symptoms, routine screening ECGs as part of medical clearance for psychiatric admission are not warranted given the low yield of meaningful findings. The decision to obtain an ECG should be made with careful consideration of medical history and in the presence of specific indications.

Antiepileptogenic effects of rapamycin in a model of infantile spasms due to structural lesions.

OBJECTIVE: Infantile spasms may evolve into persistent epilepsies including Lennox-Gastaut syndrome. We compared adult epilepsy outcomes in models of infantile spasms due to structural etiology (multiple-hit model) or focal cortical inflammation and determined the anti-epileptogenic effects of pulse-rapamycin, previously shown to stop spasms in multiple-hit rats. METHODS: Spasms were induced in 3-day-old male rats via right intracerebral doxorubicin/lipopolysaccharide (multiple-hit model) infusions. Controls and sham rats were used. Separate multiple-hit rats received pulse-rapamycin or vehicle intraperitoneally between postnatal days 4 and 6. In adult mice, video-EEG (electroencephalography) scoring for seizures and sleep and histology were done blinded to treatment. RESULTS: Motor-type seizures developed in 66.7% of multiple-hit rats, usually from sleep, but were reduced in the pulse-rapamycin-treated group (20%, p = .043 vs multiple-hit) and rare in other groups (0-9.1%, p < .05 vs multiple-hit). Spike-and-wave bursts had a slower frequency in multiple-hit rats (5.4-5.8Hz) than in the other groups (7.6-8.3Hz) (p < .05); pulse rapamycin had no effect on the hourly spike-and-wave burst rates in adulthood. Rapamycin, however, reduced the time spent in slow-wave-sleep (17.2%), which was increased in multiple-hit rats (71.6%, p = .003). Sham rats spent more time in wakefulness (43.7%) compared to controls (30.6%, p = .043). Multiple-hit rats, with or without rapamycin treatment, had right more than left corticohippocampal, basal ganglia lesions. There was no macroscopic pathology in the other groups. SIGNIFICANCE: Structural corticohippocampal/basal ganglia lesions increase the risk for post-infantile spasms epilepsy, Lennox-Gastaut syndrome features, and sleep dysregulation. Pulse rapamycin treatment for infantile spasms has anti-epileptogenic effects, despite the structural lesions, and decreases the time spent in slow wave sleep.

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.

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 χ2 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.

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

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.

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

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.

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

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.

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

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.

Scalp EEG Ictal gamma and beta activity during infantile spasms: Evidence of focality.

OBJECTIVE: We investigated temporal and spatial characteristics of ictal gamma and beta activity on scalp EEG during spasms in patients with West syndrome (WS) to evaluate potential focal cortical onset. METHODS: A total of 1,033 spasms from 34 patients with WS of various etiologies were analyzed on video-electroencephalography (EEG) using time-frequency analysis. Ictal gamma (35-90 Hz) and beta (15-30 Hz) activities were correlated with visual symmetry of spasms, objective EMG (electromyography) analysis, and etiology of WS. RESULTS: Prior to the ictal motor manifestation, focal ictal gamma activity emerged from one hemisphere (71%, 24/34) or from midline (26%, 9/34), and was rarely simultaneously bilateral (3%, 1/34). Focal ictal beta activity emerged from either one hemisphere (68%, 23/34) or from midline (32%, 11/34). Onsets of focal ictal gamma and beta activity were most commonly observed around the parietal areas. Focal ictal gamma activity propagated faster than ictal beta activity to adjacent electrodes (median: 65 vs. 170 msec, p < 0.01), and to contralateral hemisphere (median: 100 vs. 170 msec, p = 0.01). Asymmetric peak amplitude of ictal gamma activity in the centroparietal areas (C3-P3 vs. C4-P4) correlated with asymmetric semiology. On the other hand, most of the visually symmetric spasms showed asymmetry in peak amplitude and interhemispheric onset latency difference in both ictal gamma and beta activity. SIGNIFICANCE: Spasms may be a seizure with focal electrographic onset regardless of visual symmetry. Asymmetric involvement of ictal gamma activity to the centroparietal areas may determine the motor manifestations in WS. Scalp EEG ictal gamma and beta activity may be useful to demonstrate localized seizure onset in infants with WS.

Preclinical Screening for Treatments for Infantile Spasms in the Multiple Hit Rat Model of Infantile Spasms: An Update.

Infantile spasms are the typical seizures of West syndrome, an infantile epileptic encephalopathy with poor outcomes. There is an increasing need to identify more effective and better tolerated treatments for infantile spasms. We have optimized the rat model of infantile spasms due to structural etiology, the multiple-hit rat model, for therapy discovery. Here, we test three compounds administered after spasms induction in the multiple hit model for efficacy and tolerability. Specifically, postnatal day 3 (PN3) male Sprague-Dawley rats were induced by right intracerebral injections of doxorubicin and lipopolysaccharide. On PN5 p-chlorophenylalanine was given intraperitoneally (i.p.). Daily monitoring of weights and developmental milestones was done and rats were intermittently video monitored. A blinded, randomized, vehicle-controlled study design was followed. The caspase 1 inhibitor VX-765 (50-200 mg/kg i.p.) and the GABAB receptor inhibitor CGP35348 (12.5-100 mg/kg i.p.) each was administered in different cohorts as single intraperitoneal injections on PN4, using a dose- and time-response design with intermittent monitoring till PN5. 17ß-estradiol (40 ng/g/day subcutaneously) was given daily between PN3-10 and intermittent monitoring was done till PN12. None of the treatments demonstrated acute or delayed effects on spasms, yet all were well tolerated. We discuss the implications for therapy discovery and challenges of replication trials.

Association between antiphospholipid antibodies and all-cause mortality among end-stage renal disease patients with and without SLE: a retrospective cohort study.

OBJECTIVE: To investigate the association between the presence of aPL and/or LA and all-cause mortality among end-stage renal disease (ESRD) patients with and without SLE. METHODS: We included ESRD patients >18 years old followed at an urban tertiary care centre between 1 January 2006 and 31 January 2014 who had aPL measured at least once after initiating haemodialysis. All SLE patients met ACR/SLICC criteria. APL/LA+ was defined as aCL IgG or IgM >40 IU, anti-ß2glycoprotein1 IgG or IgM >40 IU or LA+. Deaths as at 31 January 2014 were captured in the linked National Death Index data. Time to death was defined from the first aPL measurement. RESULTS: We included 34 SLE ESRD and 64 non-SLE ESRD patients; 30 patients died during the study period. SLE ESRD patients were younger [40.4 (12.5) vs 51.9 (18.1) years, P = 0.001] and more were women (88.2% vs 54.7%, P < 0.001) vs non-SLE ESRD patients. The frequency of aPL/LA+ was 24% in SLE and 13% in non-SLE ESRD (P = 0.16). Median (inter-quartile range) follow-up time was 1.6 (0.3-3.5) years in SLE and 1.4 (0.4-3.2) years in non-SLE, P = 0.74. The adjusted hazard ratio (HR) for all-cause mortality for SLE patients who were aPL/LA+ vs aPL/LA- was 9.93 (95% CI 1.33, 74.19); the adjusted HR for non-SLE aPL/LA+ vs aPL/LA- was 0.77 (95% CI 0.14, 4.29). CONCLUSION: SLE ESRD patients with aPL/LA+ had higher all-cause mortality risk than SLE ESRD patients without these antibodies, while the effects of aPL/LA on mortality were comparable among non-SLE ESRD patients.

Risky business: Considerations of emotion regulation and high-risk behaviors in anxious adolescents.

A growing body of empirical literature connects anxiety symptoms and high-risk suicidal and self-harming behaviors in youth. Emotion regulation (ER) processes and deficits have been identified as important factors in the etiology, maintenance, and treatment of both youth anxiety and high-risk behaviors. The present study assessed the association between these variables using an acute, socio-demographically diverse clinical sample of youth presenting to an outpatient mental health clinic. Ninety-nine youth aged 12-20 years old completed measures of anxiety symptoms, ER difficulties, and lifetime history of high-risk behaviors including non-suicidal self-injury (NSSI) and suicide attempts. Unadjusted analyses show that more severe anxiety symptoms were associated with more ER difficulties and history of risk behavior. Multivariate linear regression models considering age, sex, race/ethnicity, and risk history show that more severe anxiety symptoms remained significantly associated with more ER difficulties (p < 0.0001) and positive suicide attempt history (p < 0.01). Findings highlight the importance of integrating considerations of ER into the case conceptualization and treatment planning of high-risk, anxious youth to inform evidenced-based care with this population. The need for targeted, ongoing risk assessment with anxious youth to identify and mitigate risk is also demonstrated.

Association of Hydroxychloroquine Dose With Adverse Cardiac Events in Patients With Systemic Lupus Erythematosus.

OBJECTIVE: To determine whether hydroxychloroquine (HCQ) dose is associated with adverse cardiac outcomes in patients with systemic lupus erythematosus (SLE). METHODS: Patients with SLE taking HCQ and with ≥1 echocardiogram followed at a tertiary care center in the Bronx, New York between 2005 and 2021 were included. The HCQ weight-based dose at the HCQ start date was the main exposure of interest. The outcome was incident all-cause heart failure with reduced ejection fraction (HFrEF), life-threatening arrhythmia, or cardiac death. We used Fine-Gray regression models with death as a competing event to study the association of HCQ dose with the outcome. Due to a significant interaction between smoking and HCQ exposure, models were stratified by smoking status. Propensity score analysis was performed as a secondary analysis. RESULTS: Of 294 patients, 37 (13%) developed the outcome over a median follow-up time of 7.9 years (interquartile range [IQR] 4.2-12.3 years). In nonsmokers (n = 226), multivariable analysis adjusted for age, body mass index, hypertension, chronic kidney disease, diabetes mellitus, and thromboembolism showed that higher HCQ weight-based doses were not associated with an increased risk of the outcome (subdistribution hazard ratio [HR] 0.62 [IQR 0.41-0.92], P = 0.02). Similarly, higher baseline HCQ doses were not associated with a higher risk of the outcome among smokers (n = 68) (subdistribution HR 0.85 [IQR 0.53-1.34] per mg/kg, P = 0.48). Propensity score analysis showed comparable results. CONCLUSION: Higher HCQ doses were not associated with an increased risk of HFrEF, life-threatening arrhythmia, or cardiac death among patients with SLE and may decrease the risk among nonsmokers.

Early preclinical plasma protein biomarkers of brain trauma are influenced by early seizures and levetiracetam.

OBJECTIVE: We used the lateral fluid percussion injury (LFPI) model of moderate-to-severe traumatic brain injury (TBI) to identify early plasma biomarkers predicting injury, early post-traumatic seizures or neuromotor functional recovery (neuroscores), considering the effect of levetiracetam, which is commonly given after severe TBI. METHODS: Adult male Sprague-Dawley rats underwent left parietal LFPI, received levetiracetam (200 mg/kg bolus, 200 mg/kg/day subcutaneously for 7 days [7d]) or vehicle post-LFPI, and were continuously video-EEG recorded (n = 14/group). Sham (craniotomy only, n = 6), and naïve controls (n = 10) were also used. Neuroscores and plasma collection were done at 2d or 7d post-LFPI or equivalent timepoints in sham/naïve. Plasma protein biomarker levels were determined by reverse phase protein microarray and classified according to injury severity (LFPI vs. sham/control), levetiracetam treatment, early seizures, and 2d-to-7d neuroscore recovery, using machine learning. RESULTS: Low 2d plasma levels of Thr231 -phosphorylated tau protein (pTAU-Thr231 ) and S100B combined (ROC AUC = 0.7790) predicted prior craniotomy surgery (diagnostic biomarker). Levetiracetam-treated LFPI rats were differentiated from vehicle treated by the 2d-HMGB1, 2d-pTAU-Thr231 , and 2d-UCHL1 plasma levels combined (ROC AUC = 0.9394) (pharmacodynamic biomarker). Levetiracetam prevented the seizure effects on two biomarkers that predicted early seizures only among vehicle-treated LFPI rats: pTAU-Thr231 (ROC AUC = 1) and UCHL1 (ROC AUC = 0.8333) (prognostic biomarker of early seizures among vehicle-treated LFPI rats). Levetiracetam-resistant early seizures were predicted by high 2d-IFNγ plasma levels (ROC AUC = 0.8750) (response biomarker). 2d-to-7d neuroscore recovery was best predicted by higher 2d-S100B, lower 2d-HMGB1, and 2d-to-7d increase in HMGB1 or decrease in TNF (P < 0.05) (prognostic biomarkers). SIGNIFICANCE: Antiseizure medications and early seizures need to be considered in the interpretation of early post-traumatic biomarkers.

Prescribing Patterns of Hydroxychloroquine and Glucocorticoids Among Lupus Patients After New-Onset End-Stage Renal Disease.

OBJECTIVE: Optimal strategies for managing lupus medications after end-stage renal disease (ESRD) have not been addressed. The objective was to identify the current US-wide prescribing patterns of hydroxychloroquine (HCQ) and oral glucocorticoids (GS) among systemic lupus erythematosus (SLE) patients with incident ESRD enrolled in the US Renal Data System (USRDS) registry. METHODS: We identified incident ESRD patients age ≥18 years with SLE as a primary cause of ESRD between January 2006 and June 2013. Patients who were started on dialysis at ESRD onset and enrolled in Medicare Part D within 93 days as required by Medicare were included. RESULTS: Among the 2,654 new-onset ESRD patients with Part D, the median duration of follow-up was 761 days (interquartile range [IQR] 374-1,375). At baseline, 1,076 patients (41%) were not receiving HCQ or GS, 220 (8%) were prescribed HCQ alone, 509 (19%) were prescribed both HCQ and GS, and 849 (32%) were prescribed GS alone. Of the 1,983 patients who either never received or discontinued HCQ after ESRD onset, 667 (34%) continued GS to the end of the follow-up period. The median GS dose was lower for patients taking HCQ (14 mg [IQR 9-21]) compared to patients who were never prescribed HCQ (15 mg [IQR 9-27]) or patients who discontinued HCQ after ESRD (17 mg [IQR 10-27]; P = 0.001). CONCLUSION: Approximately one-third of patients with lupus nephritis and new-onset ESRD received GS monotherapy at high doses. As GS-related complications contribute to hospitalizations and deaths in SLE ESRD, changing these prescribing practices may improve morbidity and mortality outcomes.

Corrected cerebral blood flow and reduced cerebral inflammation in berk sickle mice with higher fetal hemoglobin.

Fetal hemoglobin (HbF) is known to lessen the severity of sickle cell disease (SCD), through reductions in peripheral vaso-occlusive disease and reduced risk for cerebrovascular events. However, the influence of HbF on oxygen delivery to high metabolism tissues like the brain, or its influence on cerebral perfusion, metabolism, inflammation or function have not been widely studied. We employed a Berkley mouse model (BERK) of SCD with gamma transgenes q3 expressing exclusively human α- and ßS-globins with varying levels of γ globin expression to investigate the effect of HbF expression on the brain using magnetic resonance imaging (MRI), MRI diffusion tensor imaging (DTI) and spectroscopy (MRS) and hematological parameters. Hematological parameters improved with increasing γ level expression, as did markers for brain metabolism, perfusion and inflammation. Brain microstructure assessed by DTI fractional anisotropy improved, while myo-inositol levels increased, suggesting improved microstructural integrity and reduced cell loss. Our results suggest that increasing γ levels not only improves sickle peripheral disease, but also improves brain perfusion and oxygen delivery while reducing brain inflammation while protecting brain microstructural integrity.

The Effect of a Multidisciplinary Spine Clinic on Time to Care in Patients with Chronic Back and/or Leg Pain: A Propensity Score-Matched Analysis.

Chronic back and leg pain are leading causes of disability worldwide. The purpose of this study was to compare the care in a unidisciplinary (USC) versus multidisciplinary (MSC) spine clinic, where patients are evaluated by different specialists during the same office visit. Adult patients presenting with a chief complaint of back and/or leg pain between June 2018 and July 2019 were assessed for eligibility. The main outcome measures included the first treatment recommendations, the time to treatment order, and the time to treatment occurrence. A 1:1 propensity score-matched analysis was performed on 874 patients (437 in each group). For all patients, the most common recommendation was physical therapy (41.4%), followed by injection (14.6%), and surgery (9.7%). Patients seen in the MSC were more likely to be recommended injection (p < 0.001) and less likely to be recommended surgery as first treatment (p = 0.001). They also had significantly shorter times to the injection order (log-rank test, p = 0.004) and the injection occurrence (log-rank test, p < 0.001). In this study, more efficient care for patients with back and/or leg pain was delivered in the MSC setting, which was evidenced by the shorter times to the injection order and occurrence. The impact of the MSC approach on patient satisfaction and health-related quality-of-life outcome measures warrants further investigation.

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

STUDY DESIGN: Retrospective single-institution study. OBJECTIVE: The aim of this study was 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. CONCLUSION: 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.

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

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.

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

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