Health-related quality of life and economic burden of prurigo nodularis.

BACKGROUND: Prurigo nodularis (PN) is an understudied, pruritic inflammatory skin disease. Little is known about the effect of PN on quality of life and its associated economic burden. OBJECTIVE: To quantify the impact of PN on quality of life and its economic implications. METHODS: A cohort study of PN patients (n = 36) was conducted using the Health Utilities Index Mark 3 questionnaire. Control data from US adults (n = 4187) were obtained from the 2002-2003 Joint Canada/United States Survey of Health. Quality-adjusted life year loss and economic costs were estimated by comparing the Health Utilities Index Mark 3 scores of the PN patients with those of the controls. RESULTS: The PN patients had lower overall health performance compared to the controls, (mean ± SE, 0.52 ± 0.06 vs 0.86 ± 0.003, respectively, P < .001). In multivariable regression, PN was found to be associated with worse health performance (coefficient -0.34, 95% CI [-0.46 to -0.23]), most prominent in the pain subdomain (coefficient -0.24, 95% CI [-0.35 to -0.13]). This correlated to an average of 6.5 lifetime quality-adjusted life years lost per patient, translating to an individual lifetime economic burden of $323,292 and a societal burden of $38.8 billion. CONCLUSION: These results demonstrate that PN is associated with significant quality-of-life impairment, similar to the level of other chronic systemic conditions. PN is also associated with a substantial individual economic burden, emphasizing the necessity of research on effective treatment options.

Real-world comorbidities of atopic dermatitis in the pediatric ambulatory population in the United States.

BACKGROUND: Increasing evidence has suggested the systemic nature of atopic dermatitis (AD), a common inflammatory skin condition in children. However, comprehensive analyses of real-world comorbidities in pediatric AD are limited. OBJECTIVE: To characterize comorbidity burden in patients with AD aged <18 years old. METHODS: The MarketScan commercial claims database was queried from January 1, 2017, to December 31, 2017. Age- and sex-matched analyses were used to compare patients with AD with general population controls. RESULTS: A total of 86,969 pediatric patients with AD and 116,564 matched controls were identified. Increased anxiety (odds ratio [OR], 1.20) and attention-deficit hyperactivity disorder (OR, 1.11) were noted in patients with AD. In addition to dermatologic/allergic diseases, AD was also associated with infections, including methicillin-resistant Staphylococcus aureus (OR, 3.76), and autoimmune conditions, including vitiligo (OR, 2.98) and alopecia areata (OR, 4.32). Pediatric patients with AD had higher likelihoods of lymphoid/hematologic malignancies (OR, 1.94), ocular disorders (OR, 1.37-2.02), metabolic syndrome (OR, 1.61), and obesity (OR, 1.81). For all the ORs mentioned above, P was <.001. LIMITATIONS: Retrospective analysis of health care claims data. CONCLUSIONS: AD in pediatric patients was associated with a wide range of psychologic and systemic comorbidities. Increased awareness can help minimize its negative effects on the quality of life and prevent long-term health consequences in young patients with AD.

Sleep disturbance in adults with chronic pruritic dermatoses is associated with increased C-reactive protein levels.

BACKGROUND: Pruritus is a common symptom that can significantly reduce quality of life through sleep disruption. OBJECTIVE: To examine features of disturbed sleep in patients with chronic pruritic dermatoses and test the hypothesis that systemic inflammation may serve as a biomarker for impaired sleep in these patients. METHODS: Cross-sectional analysis of the National Health and Nutrition Examination Survey investigating systemic inflammation using C-reactive protein (CRP) levels. Logistic regression was used to compare patients with and without sleep disturbances, adjusting for demographics (model 1) and medical comorbidities (model 2). RESULTS: Chronic pruritic dermatoses were associated with multiple sleep disturbances, including nighttime awakenings (model 1: odds ratio [OR], 1.646; 95% confidence interval [CI], 1.031-2.627; model 2: OR, 1.329; 95% CI, 0.888-1.989) and early morning awakening (model 1: OR, 1.669, 95% CI, 1.118-2.493; model 2: OR, 1.582; 95% CI, 1.008-2.481). Mean CRP levels were 52.8% higher among patients with pruritic dermatoses reporting trouble sleeping compared with those who did not (0.663 vs 0.434 mg/dL; P = .034). Trouble sleeping was also positively correlated with CRP levels (ß = 0.142, P = .025). LIMITATIONS: Potential recall bias among participants. CONCLUSIONS: In addition to confirming sleep disturbances with pruritic dermatoses, we found these disturbances are more likely to present with elevated CRP levels. Clinicians should consider the potential risk for sleep-related and cardiac comorbidities in patients diagnosed with itchy skin conditions.

Cognitive, Graphomotor, and Psychosocial Challenges in Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections (PANDAS).

OBJECTIVES: Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) is characterized by the sudden onset of obsessive-compulsive disorder (OCD) and other neurobehavioral symptoms following group A streptococcal infection. The cardinal neuropsychiatric symptoms are believed to reflect an aberrant autoimmune or inflammatory response that may selectively disrupt basal ganglia function. The investigators examined whether neuropsychological skills associated with frontostriatal networks (executive functions and motor skills) are affected in patients with PANDAS following resolution of acute symptoms and the degree to which there are persistent social, emotional, and academic difficulties. METHODS: Twenty-seven patients ages 6-14 years (mean age=9.63 years [SD=1.78]; male, N=22) completed neuropsychological testing as part of routine clinical care. Performances on measures of intellectual ability, executive function, motor skills, and academic skills are reported, as well as parent-reported emotional, behavioral, and social skills. RESULTS: On neuropsychological measures, patients exhibited average intellectual functioning with relative and mild difficulties in skills supporting cognitive efficiency, including attentional regulation, inhibitory control, and processing speed. Dexterity was normal but graphomotor skills were reduced. Core reading, math, and writing skills were within expectations, but reading and math fluency were reduced, and the majority of patients received special education services or accommodations. Parents reported high levels of concern about anxiety, depression, inattention, hyperactivity, and social skills. CONCLUSIONS: These findings indicated relative difficulties with aspects of executive and motor functions. Although evaluations were performed following the resolution of acute symptoms, ongoing and significant academic difficulties and emotional, behavioral, and social concerns were targets for clinical intervention and support.

Prurigo nodularis: Epidemiology and clinical features.

Prurigo nodularis (PN) is a chronic inflammatory skin disease characterized by intensely pruritic, hyperkeratotic nodules that favor the extensor surfaces of the extremities and the trunk. In addition to its significant impact on quality of life, many patients with PN are recalcitrant to therapy because there are currently no therapies approved by the US Food and Drug Administration. In the first article of this 2-part continuing medical education series, we describe the broader epidemiology, patient demographics, physical examination findings, and symptoms to aid in the timely recognition and diagnosis of PN. Furthermore, we quantify the burden of comorbidities in PN by discussing the broad spectrum of systemic diseases and mental health conditions that have been associated with this condition. The second article of this 2-part series focuses on the pathogenesis of PN and provides detailed algorithms for comprehensive work-up and management.

Prurigo nodularis: Pathogenesis and management.

Prurigo nodularis is a chronic skin condition characterized by severely pruritic nodules that cause a profound negative impact on quality of life. The second article in this 2-part continuing medical education series focuses on reviewing the pathogenesis of prurigo nodularis and exploring management algorithms for this condition. In addition, we discuss some emerging and novel therapies for treating prurigo nodularis. The first article in this 2-part series describes the broader epidemiology, patient demographics, physical examination findings, and symptoms to aid in the timely recognition and diagnosis of prurigo nodularis.

Diagnosing and Treating Pediatric Autoimmune Neuropsychiatric Disorder Associated With Streptococcal Infections.

The Psychiatric Consultation Service at Massachusetts General Hospital sees medical and surgical inpatients with comorbid psychiatric symptoms and conditions. During their twice weekly rounds, Dr Stern and other members of the Consultation Service discuss diagnosis and management of hospitalized patients with complex medical or surgical problems who also demonstrate psychiatric symptoms or conditions. These discussions have given rise to rounds reports that will prove useful for clinicians practicing at the interface of medicine and psychiatry.Prim Care Companion CNS Disord 2024;26(3):23f03662. Author affiliations are listed at the end of this article.

Disparities in Basal Cell Carcinoma: A Comparative Analysis of Hispanic and Non-Hispanic White Individuals.

Objective: We sought to examine possible differences in BCC characteristics and treatment patterns between two matched cohorts of Hispanic White and non-Hispanic White individuals. Methods: In this single institution, retrospective matched cohort study, data from patients with biopsy proven BCC from June 2005 to May 2022 was collected. Demographic, BCC, and treatment characteristics were compared between Hispanic White and non-Hispanic White individuals using a Wilcoxon rank-sum test, for continuous and ordinal variables, and Fisher's exact test, for categorical variables. Results: A total of 604 individuals with a diagnosis of biopsy-proven BCC were matched in a 1:1 fashion by age (± 0 years) and sex, based on self-identified ethnicity as Hispanic or non-Hispanic. Since all patients self-identified as White race, the two cohorts were labeled Hispanic White (n=302) and non-Hispanic White (n=302). The most frequent location for BCC was in the H area, 129 [42.7%] White Hispanic group vs 132 [43.7%] White non-Hispanic group (p = 0.87). In both Hispanic White and non-Hispanic White groups, the predominant subtype of BCC was the nodular (149 [50.2%] vs 164 [54.7%], p = 0.25). The median BCC pre-operative size in the Hispanic White group was 0.9 cm, whereas in the non-Hispanic White group, it was 1.0 cm (p = 0.004). Furthermore, the MMS defect size in the Hispanic White group had a median of 1.3 cm, while in the non-Hispanic White group, it was 1.6 cm (p < 0.001). Limitations: Retrospective design, single-center study, and self-reported race and ethnicity. Conclusion: Both groups had similar demographics, tumor features, treatments, and post-operative complications. Notably, preoperative lesion and MMS defect sizes were larger in non-Hispanic Whites than in Hispanic Whites, contrary to expectations. Despite assumptions of poorer skin cancer outcomes among Hispanics, our findings indicate increased sizes in non-Hispanic Whites. Given the diversity in genetics and clinical traits within ethnicities, especially Hispanics, more research is needed for precise insights into disease outcomes across diverse backgrounds.

Effect of singular value decomposition on removing injection variability in 2D quantitative angiography: An in silico and in vitro phantoms study.

BACKGROUND: Intraoperative 2D quantitative angiography (QA) for intracranial aneurysms (IAs) has accuracy challenges due to the variability of hand injections. Despite the success of singular value decomposition (SVD) algorithms in reducing biases in computed tomography perfusion (CTP), their application in 2D QA has not been extensively explored. This study seeks to bridge this gap by investigating the potential of SVD-based deconvolution methods in 2D QA, particularly in addressing the variability of injection durations. PURPOSE: Building on the identified limitations in QA, the study aims to adapt SVD-based deconvolution techniques from CTP to QA for IAs. This adaptation seeks to capitalize on the high temporal resolution of QA, despite its two-dimensional nature, to enhance the consistency and accuracy of hemodynamic parameter assessment. The goal is to develop a method that can reliably assess hemodynamic conditions in IAs, independent of injection variables, for improved neurovascular diagnostics. MATERIALS AND METHODS: The study included three internal carotid aneurysm (ICA) cases. Virtual angiograms were generated using computational fluid dynamics (CFD) for three physiologically relevant inlet velocities to simulate contrast media injection durations. Time-density curves (TDCs) were produced for both the inlet and aneurysm dome. Various SVD variants, including standard SVD (sSVD) with and without classical Tikhonov regularization, block-circulant SVD (bSVD), and oscillation index SVD (oSVD), were applied to virtual angiograms. The method was applied on virtual angiograms to recover the aneurysmal dome impulse response function (IRF) and extract flow related parameters such as Peak Height PHIRF, Area Under the Curve AUCIRF, and Mean transit time MTT. Next, correlations between QA parameters, injection duration, and inlet velocity were assessed for unconvolved and deconvolved data for all SVD methods. Additionally, we performed an in vitro study, to complement our in silico investigation. We generated a 2D DSA using a flow circuit design for a patient-specific internal carotid artery phantom. The DSA showcases factors like x-ray artifacts, noise, and patient motion. We evaluated QA parameters for the in vitro phantoms using different SVD variants and established correlations between QA parameters, injection duration, and velocity for unconvolved and deconvolved data. RESULTS: The different SVD algorithm variants showed strong correlations between flow and deconvolution-adjusted QA parameters. Furthermore, we found that SVD can effectively reduce QA parameter variability across various injection durations, enhancing the potential of QA analysis parameters in neurovascular disease diagnosis and treatment. CONCLUSION: Implementing SVD-based deconvolution techniques in QA analysis can enhance the precision and reliability of neurovascular diagnostics by effectively reducing the impact of injection duration on hemodynamic parameters.

Identification of State Markers in Anorexia Nervosa: Replication and Extension of Inflammation-Associated Biomarkers Using Multiplex Profiling.

Background: Proteomics offers potential for detecting and monitoring anorexia nervosa (AN) and its variant, atypical AN (atyp-AN). However, research has been limited by small protein panels, a focus on adult AN, and lack of replication. Methods: In this study, we performed Olink multiplex profiling of 92 inflammation-related proteins in females with AN/atyp-AN (n = 64), all of whom were ≤90% of expected body weight, and age-matched healthy control individuals (n = 44). Results: Five proteins differed significantly between the primary AN/atyp-AN group and the healthy control group (lower levels: HGF, IL-18R1, TRANCE; higher levels: CCL23, LIF-R). The expression levels of 3 proteins (lower IL-18R1, TRANCE; higher LIF-R) were uniquely disrupted in participants with AN in our primary model. No unique expression levels emerged for atyp-AN. In the total sample, 12 proteins (ADA, CD5, CD6, CXCL1, FGF-21, HGF, IL-12B, IL18, IL-18R1, SIRT2, TNFSF14, TRANCE) were positively correlated with body mass index and 5 proteins (CCL11, FGF-19, IL8, LIF-R, OPG) were negatively correlated with body mass index in our primary models. Conclusions: Our results replicate the results of a previous study that demonstrated a dysregulated inflammatory status in AN and extend those results to atyp-AN. Of the 17 proteins correlated with body mass index, 11 were replicated from a previous study that used similar methods, highlighting the promise of inflammatory protein expression levels as biomarkers of AN disease monitoring. Our findings underscore the complexity of AN and atyp-AN by highlighting the inability of the identified proteins to differentiate between these 2 subtypes, thereby emphasizing the heterogeneous nature of these disorders.

We examined 73 inflammation proteins in adolescent girls with anorexia nervosa (AN) and atypical AN and compared them with age-matched healthy control girls. Significant differences were found, driven by 5 key proteins (lower: HGF, IL-18R1, TRANCE; higher: CCL23, LIF-R). Three proteins (TRANCE, LIF-R, IL-18R1) uniquely distinguished low-weight participants with AN from control participants. Our study reveals distinct inflammation patterns in AN and atypical AN and sheds light on potential state-specific factors that underlie these disorders.

Skin of color in dermatopathology: does color matter?

Skin of color (SoC) remains an understudied and under taught area of dermatology despite its rising importance. Race and ethnicity play a particularly important role in dermatology as skin pigmentation can affect the manifestation and presentation of many common dermatoses. With this review, we seek to review pertinent differences in SoC histology, as well as highlight the histopathology of conditions more common in SoC and address inherent bias that may affect accurate dermatopathology sign out.

Use of high-speed angiography HSA-derived boundary conditions and Physics Informed Neural Networks (PINNs) for comprehensive estimation of neurovascular hemodynamics.

Purpose: Physics-informed neural networks (PINNs) and computational fluid dynamics (CFD) have both demonstrated an ability to derive accurate hemodynamics if boundary conditions (BCs) are known. Unfortunately, patient-specific BCs are often unknown, and assumptions based upon previous investigations are used instead. High speed angiography (HSA) may allow extraction of these BCs due to the high temporal fidelity of the modality. We propose to investigate whether PINNs using convection and Navier-Stokes equations with BCs derived from HSA data may allow for extraction of accurate hemodynamics in the vasculature. Materials and Methods: Imaging data generated from in vitro 1000 fps HSA, as well as simulated 1000 fps angiograms generated using CFD were utilized for this study. Calculations were performed on a 3D lattice comprised of 2D projections temporally stacked over the angiographic sequence. A PINN based on an objective function comprised of the Navier-Stokes equation, the convection equation, and angiography-based BCs was used for estimation of velocity, pressure and contrast flow at every point in the lattice. Results: Imaging-based PINNs show an ability to capture such hemodynamic phenomena as vortices in aneurysms and regions of rapid transience, such as outlet vessel blood flow within a carotid artery bifurcation phantom. These networks work best with small solution spaces and high temporal resolution of the input angiographic data, meaning HSA image sequences represent an ideal medium for such solution spaces. Conclusions: The study shows the feasibility of obtaining patient-specific velocity and pressure fields using an assumption-free data driven approach based purely on governing physical equations and imaging data.

Geometrically independent contrast dilution gradient (CDG) velocimetry using photon-counting 1000 fps High Speed Angiography (HSA) for 2D velocity distribution estimation.

Purpose: Previous studies have demonstrated the efficacy of contrast dilution gradient (CDG) analysis in determining large vessel velocity distributions from 1000 fps high-speed angiography (HSA). However, the method required vessel centerline extraction, which made it applicable only to non-tortuous geometries using a highly specific contrast injection technique. This study seeks to remove the need for a priori knowledge regarding the direction of flow and modify the vessel sampling method to make the algorithm more robust to non-linear geometries. Materials and Methods: 1000 fps HSA acquisitions were obtained in vitro with a benchtop flow loop using the XC-Actaeon (Varex Inc.) photon-counting detector, and in silico using a passive-scalar transport model within a computational fluid dynamics (CFD) simulation. CDG analyses were obtained using gridline sampling across the vessel, and subsequent 1D velocity measurement in both the x- and y-directions. The velocity magnitudes derived from the component CDG velocity vectors were aligned with CFD results via co-registration of the resulting velocity maps and compared using mean absolute percent error (MAPE) between pixels values in each method after temporal averaging of the 1-ms velocity distributions. Results: Regions well-saturated with contrast throughout the acquisition showed agreement when compared to CFD (MAPE of 18% for the carotid bifurcation inlet and MAPE of 27% for the internal carotid aneurysm), with respective completion times of 137 seconds and 5.8 seconds. Conclusions: CDG may be used to obtain velocity distributions in and surrounding vascular pathologies provided the contrast injection is sufficient to provide a gradient, and diffusion of contrast through the system is negligible.

Angiographic velocimetry analysis using contrast dilution gradient method with a 1000 frames per second photon-counting detector.

Purpose: Contrast dilution gradient (CDG) analysis is a quantitative method allowing blood velocity estimation using angiographic acquisitions. Currently, CDG is restricted to peripheral vasculature due to the suboptimal temporal resolution of current imaging systems. We investigate extension of CDG methods to the flow conditions of proximal vasculature using 1000 frames per second (fps) high-speed angiographic (HSA) imaging. Approach: We performed in-vitro HSA acquisitions using the XC-Actaeon detector and 3D-printed patient-specific phantoms. The CDG approach was used for blood velocity estimation expressed as the ratio of temporal and spatial contrast gradients. The gradients were extracted from 2D contrast intensity maps synthesized by plotting intensity profiles along the arterial centerline at each frame. In-vitro results obtained at various frame rates via temporal binning of 1000 fps data were retrospectively compared to computational fluid dynamics (CFD) velocimetry. Full-vessel velocity distributions were estimated at 1000 fps via parallel line expansion of the arterial centerline analysis. Results: Using HSA, the CDG method displayed agreement with CFD at or above 250 fps [mean-absolute error (MAE): 2.6±6.3 cm/s, p=0.05]. Relative velocity distributions correlated well with CFD at 1000 fps with universal underapproximation due to effects of pulsatile contrast injection (MAE: 4.3 cm/s). Conclusions: Using 1000 fps HSA, CDG-based extraction of velocities across large arteries is possible. The method is sensitive to noise; however, image processing techniques and a contrast injection, which adequately fills the vessel assist algorithm accuracy. The CDG method provides high resolution quantitative information for rapidly transient flow patterns observed in arterial circulation.

Identification of State Markers in Anorexia Nervosa: Replication and Extension of Inflammation Associated Biomarkers Using Multiplex Profiling in Anorexia Nervosa and Atypical Anorexia Nervosa.

Proteomics provides an opportunity for detection and monitoring of anorexia nervosa (AN) and its related variant, atypical-AN (atyp-AN). However, research to date has been limited by the small number of proteins explored, exclusive focus on adults with AN, and lack of replication across studies. This study performed Olink Proseek Multiplex profiling of 92 proteins involved in inflammation among females with AN and atyp-AN (N = 64), all < 90% of expected body weight, and age-matched healthy controls (HC; N=44). After correction for multiple testing, nine proteins differed significantly in the AN/atyp-AN group relative to HC group ( lower levels: CXCL1, HGF, IL-18R1, TNFSF14, TRANCE; higher levels: CCL23, Flt3L, LIF-R, MMP-1). The expression levels of three proteins ( lower IL-18R1, TRANCE; higher LIF-R) were uniquely disrupted in females with AN. No unique expression levels emerged for atyp-AN. Across the whole sample, twenty-one proteins correlated positively with BMI (ADA, AXIN1, CD5, CD244, CD40, CD6, CXCL1, FGF-21, HGF, IL-10RB, IL-12B, IL18, IL-18R1, IL6, LAP TGF-beta-1, SIRT2, STAMBP, TNFRSF9, TNFSF14, TRAIL, TRANCE) and six (CCL11, CCL23, FGF-19, IL8, LIF-R, OPG) were negatively correlated with BMI. Overall, our results replicate the prior study demonstrating a dysregulated inflammatory status in AN, and extend these results to atyp-AN (AN/atyp-AN all < 90% of expected body weight). Of the 27 proteins correlated with BMI, 18 were replicated from a prior study using similar methods, highlighting the promise of inflammatory protein expression levels as biomarkers of disease monitoring. Additional studies of individuals across the entire weight spectrum are needed to understand the role of inflammation in atyp-AN.

2D vessel contrast dilution gradient (CDG) analysis using 1000 fps high speed angiography (HSA) for velocity distribution estimation.

Purpose: Contrast dilution gradient (CDG) analysis is a technique used to extract velocimetric 2D information from digitally subtracted angiographic (DSA) acquisitions. This information may then be used by clinicians to quantitatively assess the effects of endovascular treatment on flow conditions surrounding pathologies of interest. The method assumes negligible diffusion conditions, making 1000 fps high speed angiography (HSA), in which diffusion between 1 ms frames may be neglected, a strong candidate for velocimetric analysis using CDG. Previous studies have demonstrated the success of CDG analysis in obtaining velocimetric one-dimensional data at the arterial centerline of simple vasculature. This study seeks to resolve velocity distributions across the entire vessel using 2D-CDG analysis with HSA acquisitions. Materials and Methods: HSA acquisitions for this study were obtained in vitro with a benchtop flow loop at 1000 fps using the XC-Actaeon (Direct Conversion Inc.) photon counting detector. 2D-CDG analyses were compared with computational fluid dynamics (CFD) via automatic co-registration of the results from each velocimetry method. This comparison was performed using mean absolute error between pixel values in each method (after temporal averaging). Results: CDG velocity magnitudes were slightly under approximated relative to CFD results (mean velocity: 27 cm/s, mean absolute error: 4.3 cm/s) as a result of incomplete contrast filling. Relative 2D spatial velocity distributions in CDG analysis agreed well with CFD distributions qualitatively. Conclusions: CDG may be used to obtain velocity distributions in and surrounding vascular pathologies provided diffusion is negligible relative to convection in the flow, given a continuous gradient of contrast.