Predictors of nonresponse to dupilumab in patients with atopic dermatitis: A machine learning analysis.

BACKGROUND: Many patients with atopic dermatitis (AD) have a suboptimal response to systemic therapy. OBJECTIVE: This study assessed predictors of nonresponse to dupilumab in patients with AD. METHODS: Data (April 2017 through June 2019) for patients aged 12 years and above with AD (International Classification of Diseases-9/10-Clinical Modification: 691.8/L20.x) who initiated dupilumab on or after April 1, 2017 (index date) were collected from an electronic health record and insurance claims database. Nonresponse indicators (dupilumab discontinuation, addition of another systemic therapy or phototherapy, addition of a high-potency topical corticosteroid, AD-related hospital visit, AD-related emergency department visit, incident skin infection) were predicted from available demographic and clinical variables using machine learning. RESULTS: Among 419 patients (mean age: 45 years), 145 (35%) experienced at least 1 indicator of nonresponse in the 6-month postindex period. In patients with at least 1 indicator, the most common was dupilumab discontinuation (47% [68/145]). Of note, this analysis could not capture nonmedical reasons for dupilumab discontinuation (eg, cost, access). The most common predictors of nonresponse were a claim for ibuprofen (in 69% of patients with a nonresponse indicator) and a Quan-Charlson Comorbidity Index value of 3 to 4 (59%). CONCLUSION: Systemic dupilumab therapy for AD can be associated with a relatively high prevalence of nonresponse indicators. Factors associated with these indicators-that is, predictors of nonresponse-may be used to optimize disease management.

Parkinsonian gait ameliorated with a moving handrail, not with a banister.

OBJECTIVE: To determine whether haptic (touch and proprioception) cues from touching a moving handrail while walking can ameliorate the gait symptoms of Parkinson disease (PD), such as slowness and small stride length. DESIGN: Nonrandomized, controlled before-after trial. SETTING: Physical therapy clinic. PARTICIPANTS: People with PD (n=16) and healthy age-matched control subjects (n=16) with no neurologic disorders volunteered. No participants withdrew. INTERVENTIONS: We compared gait using a moving handrail as a novel assistive aid (speed self-selected) versus a banister and unassisted walking. Participants with PD were tested on and off dopaminergic medication. MAIN OUTCOME MEASURES: Mean gait speed, stride length, stride duration, double-support duration, and medial-lateral excursion. RESULTS: With the moving handrail, participants with PD increased gait speed relative to unassisted gait by 16% (.166m/s, P=.009, d=.76; 95% confidence interval [CI], .054-.278m/s) and increased stride length by 10% (.053m, P=.022, d=.37; 95% CI, .009-.097m) without significantly changing stride or double-support duration. The banister reduced speed versus unassisted gait by 11% (-.097m/s, P=.040, d=.40; 95% CI, .002-.193m/s) and reduced stride length by 8% (.32m, P=.004, d=.26; 95% CI, .010-.054m), whereas it increased stride duration by 3% (.023s, P=.022, d=.21; 95% CI, .004-.041s) and double-support duration by 35% (.044s, P=.031, d=.58; 95% CI, .005-.083s). All medication × condition interactions were P>.05. CONCLUSIONS: Using haptic speed cues from the moving handrail, people with PD walked faster by spontaneously (ie, without specific instruction) increasing stride length without altering cadence; banisters slowed gait. Haptic cues from the moving handrail can be used by people with PD to engage biomechanical and neural mechanisms for interpreting tactile and proprioception changes related to gait speed to control gait better than static cues afforded by banisters.

Neuronal migration defect of the developing cerebellar vermis in substrains of C57BL/6 mice: cytoarchitecture and prevalence of molecular layer heterotopia.

Abnormal development of the cerebellum is often associated with disorders of movement, postural control, and motor learning. Rodent models are widely used to study normal and abnormal cerebellar development and have revealed the roles of many important genetic and environmental factors. In the present report we describe the prevalence and cytoarchitecture of molecular-layer heterotopia, a malformation of neuronal migration, in the cerebellar vermis of C57BL/6 mice and closely-related strains. In particular, we found a diverse number of cell-types affected by these malformations including Purkinje cells, granule cells, inhibitory interneurons (GABAergic and glycinergic), and glia. Heterotopia were not observed in a sample of wild-derived mice, outbred mice, or inbred mice not closely related to C57BL/6 mice. These data are relevant to the use of C57BL/6 mice as models in the study of brain and behavior relationships and provide greater understanding of human cerebellar dysplasia.

Unifying theory of carotid plaque disruption based on structural phenotypes and forces expressed at the lumen/wall interface.

OBJECTIVES: To integrate morphological, haemodynamic and mechanical analysis of carotid atheroma driving plaque disruption. MATERIALS AND METHODS: First, we analysed the phenotypes of carotid endarterectomy specimens in a photographic dataset A, and matched them with the likelihood of preoperative stroke. Second, laser angioscopy was used to further define the phenotypes in intact specimens (dataset B) and benchmark with histology. Third, representative vascular geometries for each structural phenotype were analysed with Computational Fluid Dynamics (CFD), and the mechanical strength of the complicated atheroma to resist penetrating forces was quantified (n=14). RESULTS: In dataset A (n=345), ulceration (fibrous cap disruption) was observed in 82% of all plaques, intraplaque haemorrhage in 68% (93% subjacent to an ulcer) and false luminal formation in 48%. At least one of these 'rupture' phenotypes was found in 97% of symptomatic patients (n=69) compared with 61% in asymptomatic patients. In dataset B (n=30), laser angioscopy redemonstrated the structural phenotypes with near-perfect agreement with histology. In CFD, haemodynamic stress showed a large pulse magnitude, highest upstream to the point of maximal stenosis and on ulceration the inflow stream excavates the necrotic core cranially and then recirculates into the true lumen. Based on mechanical testing (n=14), the necrotic core is mechanically weak and penetrated by the blood on fibrous cap disruption. CONCLUSIONS: Fibrous cap ulceration, plaque haemorrhage and excavation are sequential phenotypes of plaque disruption resulting from the chiselling effect of haemodynamic forces over unmatched mechanical tissue strength. This chain of events may result in thromboembolic events independently of the degree of stenosis.

Undergraduate Neuroscience Education in the U.S.: An Analysis using Data from the National Center for Education Statistics.

Despite an apparent increase in undergraduate neuroscience programs offered by colleges and universities, there has been little effort to document this growth. In the present report we describe our analysis of the expansion of undergraduate neuroscience programs of study over more than 20 years and detail a number of institutional characteristics of colleges and universities that offer undergraduate neuroscience programs. These data reveal more than 100 institutions with undergraduate neuroscience programs as well as over 2000 college graduates that majored in neuroscience in 2008-2009. Understanding the current number as well as growth trends of undergraduate neuroscience programs found in U.S. colleges and universities has implications for neuroscience educators as well as for the funding of neuroscience research and educational activities.

Thrombus Histology as It Relates to Mechanical Thrombectomy: A Meta-Analysis and Systematic Review.

BACKGROUND: Appropriate thrombus-device interaction is critical for recanalization. Histology can serve as a proxy for mechanical properties, and thus inform technique selection. OBJECTIVE: To investigate the value of histologic characterization, we conducted a systematic review and meta-analysis on the relationship between thrombus histology and recanalization, technique, etiology, procedural efficiency, and imaging findings. METHODS: In this meta-analysis, we identified studies published between March 2010 and March 2020 reporting findings related to the histologic composition of thrombi in large vessel occlusion stroke. Studies with at least 10 patients who underwent mechanical thrombectomy using stent retriever or aspiration were considered. Only studies in which retrieved thrombi were histologically processed were included. Patient-level data were requested when data could not be directly extracted. The primary outcome assessed was the relationship between thrombus histology and angiographic outcome. RESULTS: A total of 22 studies encompassing 1623 patients met inclusion criteria. Clots associated with good angiographic outcome had higher red blood cell (RBC) content (mean difference [MD] 9.60%, 95% CI 3.85-15.34, P = .008). Thrombi retrieved by aspiration had less fibrin (MD -11.39, 95% CI -22.50 to -0.27, P = .046) than stent-retrieved thrombi. Fibrin/platelet-rich clots were associated with longer procedure times (MD 13.20, 95% CI 1.30-25.10, P = .037). Hyperdense artery sign was associated with higher RBC content (MD 14.17%, 95% CI 3.07-25.27, P = .027). No relationship was found between composition and etiology. CONCLUSION: RBC-rich thrombi were associated with better recanalization outcomes and shorter procedure times, suggesting that preinterventional compositional characterization may yield important prognostic and therapeutic guidance.

Neocortical molecular layer heterotopia in substrains of C57BL/6 and C57BL/10 mice.

Abnormal development of the neocortex is often associated with cognitive deficits and epilepsy. Rodent models are widely used to study normal and abnormal cortical development and have revealed the roles of many important genetic and environmental factors. Interestingly, several inbred mouse strains commonly used in behavioral, anatomical, and/or physiological studies display neocortical malformations including C57BL/6J mice, which are among the most widely utilized mice. In the present report we describe the prevalence and cytoarchitecture of molecular-layer heterotopia in C57BL/6J mice and related strains obtained from three commercial vendors as well as mice bred in academic vivaria from founders obtained commercially. In particular, we found that the prevalence of molecular-layer heterotopia vaired according to the sex as well as the vendor-of-origin of the mouse. These data are relevant to the use of this strain as a mouse-model in the study of brain-behavior relationships.