Cardiovascular Follow-up of Patients Treated for MIS-C.

OBJECTIVES: To assess the prevalence of residual cardiovascular pathology by cardiac MRI (CMR), ambulatory rhythm monitoring, and cardiopulmonary exercise testing (CPET) in patients ∼6 months after multisystem inflammatory disease in children (MIS-C). METHODS: Patients seen for MIS-C follow-up were referred for CMR, ambulatory rhythm monitoring, and CPET ∼6 months after illness. Patients were included if they had ≥1 follow-up study performed by the time of data collection. MIS-C was diagnosed on the basis of the Centers for Disease Control and Prevention criteria. Myocardial injury during acute illness was defined as serum Troponin-I level >0.05 ng/mL or diminished left ventricular systolic function on echocardiogram. RESULTS: Sixty-nine of 153 patients seen for MIS-C follow-up had ≥1 follow-up cardiac study between October 2020-June 2022. Thirty-seven (54%) had evidence of myocardial injury during acute illness. Of these, 12 of 26 (46%) had ≥1 abnormality on CMR, 4 of 33 (12%) had abnormal ambulatory rhythm monitor results, and 18 of 22 (82%) had reduced functional capacity on CPET. Of the 37 patients without apparent myocardial injury, 11 of 21 (52%) had ≥1 abnormality on CMR, 1 of 24 (4%) had an abnormal ambulatory rhythm monitor result, and 11 of 15 (73%) had reduced functional capacity on CPET. The prevalence of abnormal findings was not statistically significantly different between groups. CONCLUSIONS: The high prevalence of abnormal findings on follow-up cardiac studies and lack of significant difference between patients with and without apparent myocardial injury during hospitalization suggests that all patients treated for MIS-C warrant cardiology follow-up.

Therapy-associated remodeling of pancreatic cancer revealed by single-cell spatial transcriptomics and optimal transport analysis.

In combination with cell intrinsic properties, interactions in the tumor microenvironment modulate therapeutic response. We leveraged high-plex single-cell spatial transcriptomics to dissect the remodeling of multicellular neighborhoods and cell-cell interactions in human pancreatic cancer associated with specific malignant subtypes and neoadjuvant chemotherapy/radiotherapy. We developed Spatially Constrained Optimal Transport Interaction Analysis (SCOTIA), an optimal transport model with a cost function that includes both spatial distance and ligand-receptor gene expression. Our results uncovered a marked change in ligand-receptor interactions between cancer-associated fibroblasts and malignant cells in response to treatment, which was supported by orthogonal datasets, including an ex vivo tumoroid co-culture system. Overall, this study demonstrates that characterization of the tumor microenvironment using high-plex single-cell spatial transcriptomics allows for identification of molecular interactions that may play a role in the emergence of chemoresistance and establishes a translational spatial biology paradigm that can be broadly applied to other malignancies, diseases, and treatments.

Left Ventricle Size Correlates with Peak Exercise Capacity in Pediatric Cancer Survivors Exposed to Anthracycline Chemotherapy.

Cancer survivors exposed to anthracycline chemotherapy are at risk for developing cardiomyopathy, which may have delayed clinical manifestation. In a retrospective cross-sectional study, we evaluated the utility of cardiopulmonary exercise testing (CPET) for detecting early cardiac disease in 35 pediatric cancer survivors by examining the associations between peak exercise capacity (measured via percent predicted peak VO2) and resting left ventricular (LV) function on echocardiography and cardiac magnetic resonance imaging (cMRI). We additionally assessed the relationships between LV size on resting echocardiography or cMRI and percent predicted peak VO2 since LV growth arrest can occur in anthracycline-exposed patients prior to changes in LV systolic function. We found reduced exercise capacity in this cohort, with low percent predicted peak VO2 (62%, IQR: 53-75%). While most patients in our pediatric cohort had normal LV systolic function, we observed associations between percent predicted peak VO2 and echocardiographic and cMRI measures of LV size. These findings indicate that CPET may be more sensitive in manifesting early anthracycline-induced cardiomyopathy than echocardiography in pediatric cancer survivors. Our study also highlights the importance of assessing LV size in addition to function in pediatric cancer survivors exposed to anthracyclines.

A Pilot of Digital Whiteboards for Improving Patient Satisfaction in the Emergency Department: Nonrandomized Controlled Trial.

BACKGROUND: Electronic paper (E-paper) screens use electrophoretic ink to provide paper-like low-power displays with advanced networking capabilities that may potentially serve as an alternative to traditional whiteboards and television display screens in hospital settings. E-paper may be leveraged in the emergency department (ED) to facilitate communication. Providing ED patient status updates on E-paper screens could improve patient satisfaction and overall experience and provide more equitable access to their health information. OBJECTIVE: We aimed to pilot a patient-facing digital whiteboard using E-paper to display relevant orienting and clinical information in real time to ED patients. We also sought to assess patients' satisfaction after our intervention and understand our patients' overall perception of the impact of the digital whiteboards on their stay. METHODS: We deployed a 41-inch E-paper digital whiteboard in 4 rooms in an urban, tertiary care, and academic ED and enrolled 110 patients to understand and evaluate their experience. Participants completed a modified Hospital Consumer Assessment of Health Care Provider and Systems satisfaction questionnaire about their ED stay. We compared responses to a matched control group of patients triaged to ED rooms without digital whiteboards. We designed the digital whiteboard based on iterative feedback from various departmental stakeholders. After establishing IT infrastructure to support the project, we enrolled patients on a convenience basis into a control and an intervention (digital whiteboard) group. Enrollees were given a baseline survey to evaluate their comfort with technology and an exit survey to evaluate their opinions of the digital whiteboard and overall ED satisfaction. Statistical analysis was performed to compare baseline characteristics as well as satisfaction. RESULTS: After the successful prototyping and implementation of 4 digital whiteboards, we screened 471 patients for inclusion. We enrolled 110 patients, and 50 patients in each group (control and intervention) completed the study protocol. Age, gender, and racial and ethnic composition were similar between groups. We saw significant increases in satisfaction on postvisit surveys when patients were asked about communication regarding delays (P=.03) and what to do after discharge (P=.02). We found that patients in the intervention group were more likely to recommend the facility to family and friends (P=.04). Additionally, 96% (48/50) stated that they preferred a room with a digital whiteboard, and 70% (35/50) found the intervention "quite a bit" or "extremely" helpful in understanding their ED stay. CONCLUSIONS: Digital whiteboards are a feasible and acceptable method of displaying patient-facing data in the ED. Our pilot suggested that E-paper screens coupled with relevant, real-time clinical data and packaged together as a digital whiteboard may positively impact patient satisfaction and the perception of the facility during ED visits. Further study is needed to fully understand the impact on patient satisfaction and experience. TRIAL REGISTRATION: ClinicalTrials.gov NCT04497922; https://clinicaltrials.gov/ct2/show/NCT04497922.

Examination of Adverse Reactions After COVID-19 Vaccination Among Patients With a History of Multisystem Inflammatory Syndrome in Children.

Importance: Data are limited regarding adverse reactions after COVID-19 vaccination in patients with a history of multisystem inflammatory syndrome in children (MIS-C). The lack of vaccine safety data in this unique population may cause hesitancy and concern for many families and health care professionals. Objective: To describe adverse reactions following COVID-19 vaccination in patients with a history of MIS-C. Design, Setting, and Participants: In this multicenter cross-sectional study including 22 North American centers participating in a National Heart, Lung, and Blood Institute, National Institutes of Health-sponsored study, Long-Term Outcomes After the Multisystem Inflammatory Syndrome in Children (MUSIC), patients with a prior diagnosis of MIS-C who were eligible for COVID-19 vaccination (age ≥5 years; ≥90 days after MIS-C diagnosis) were surveyed between December 13, 2021, and February 18, 2022, regarding COVID-19 vaccination status and adverse reactions. Exposures: COVID-19 vaccination after MIS-C diagnosis. Main Outcomes and Measures: The main outcome was adverse reactions following COVID-19 vaccination. Comparisons were made using the Wilcoxon rank sum test for continuous variables and the χ2 or Fisher exact test for categorical variables. Results: Of 385 vaccine-eligible patients who were surveyed, 185 (48.1%) received at least 1 vaccine dose; 136 of the vaccinated patients (73.5%) were male, and the median age was 12.2 years (IQR, 9.5-14.7 years). Among vaccinated patients, 1 (0.5%) identified as American Indian/Alaska Native, non-Hispanic; 9 (4.9%) as Asian, non-Hispanic; 45 (24.3%) as Black, non-Hispanic; 59 (31.9%) as Hispanic or Latino; 53 (28.6%) as White, non-Hispanic; 2 (1.1%) as multiracial, non-Hispanic; and 2 (1.1%) as other, non-Hispanic; 14 (7.6%) had unknown or undeclared race and ethnicity. The median time from MIS-C diagnosis to first vaccine dose was 9.0 months (IQR, 5.1-11.9 months); 31 patients (16.8%) received 1 dose, 142 (76.8%) received 2 doses, and 12 (6.5%) received 3 doses. Almost all patients received the BNT162b2 vaccine (347 of 351 vaccine doses [98.9%]). Minor adverse reactions were observed in 90 patients (48.6%) and were most often arm soreness (62 patients [33.5%]) and/or fatigue (32 [17.3%]). In 32 patients (17.3%), adverse reactions were treated with medications, most commonly acetaminophen (21 patients [11.4%]) or ibuprofen (11 [5.9%]). Four patients (2.2%) sought medical evaluation, but none required testing or hospitalization. There were no patients with any serious adverse events, including myocarditis or recurrence of MIS-C. Conclusions and Relevance: In this cross-sectional study of patients with a history of MIS-C, no serious adverse events were reported after COVID-19 vaccination. These findings suggest that the safety profile of COVID-19 vaccination administered at least 90 days following MIS-C diagnosis appears to be similar to that in the general population.

Early-Onset Late Gadolinium Enhancement is a Prognostic Factor for Duchenne Cardiomyopathy.

Dilated cardiomyopathy (DCM) is an inevitable complication of Duchenne muscular dystrophy (DMD). Late gadolinium enhancement (LGE) demonstrated by cardiac MRI occurs in DMD-related DCM, indicating myocyte death and remodeling. We conducted a retrospective chart review identifying DMD patients in our center between January 2009 and July 2013. Subjects were cohorted by presence of LGE before age 14. We excluded patients in whom we could not determine LGE status prior to age 14. We reviewed comprehensive clinical data. Of the 41 subjects with complete data, 15 demonstrated LGE before age 14 ("early LGE") and 26 had no LGE by age 14 ("controls"). Those with early LGE exhibited a more rapid decline in LV fractional shortening (p = 0.028). Patients with early LGE were younger at age of initiation of ACE inhibition (p = 0.025), mineralocorticoid receptor antagonism (p = 0.0024), and beta-blockade (p = 0.0017), suggesting aggressive clinical management in response to abnormal MRI findings. There were no significant differences in LV dilation between the two groups (p = 0.1547). Early LGE was not associated with obesity (p = 0.32), age at loss of ambulation (p = 0.31), or heart rate (p-value > 0.8). Early onset of myocardial fibrosis as indicated by LGE on cardiac MRI is associated with earlier progression of cardiomyopathic changes despite earlier medication therapy. Identifying this risk factor, observed in 34% of our cohort during preadolescence, may guide medical therapy and early counseling about cardiomyopathy progression. We advocate for obtaining at least one MRI in patients with DMD prior to age 14 to risk stratify patients.

Treatment-associated remodeling of the pancreatic cancer endothelium at single-cell resolution.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most treatment refractory and lethal malignancies. The diversity of endothelial cell (EC) lineages in the tumor microenvironment (TME) impacts the efficacy of antineoplastic therapies, which in turn remodel EC states and distributions. Here, we present a single-cell resolution framework of diverse EC lineages in the PDAC TME in the context of neoadjuvant chemotherapy, radiotherapy, and losartan. We analyzed a custom single-nucleus RNA-seq dataset derived from 37 primary PDAC specimens (18 untreated, 14 neoadjuvant FOLFIRINOX + chemoradiotherapy, 5 neoadjuvant FOLFIRINOX + chemoradiotherapy + losartan). A single-nucleus transcriptome analysis of 15,185 EC profiles revealed two state programs (ribosomal, cycling), four lineage programs (capillary, arterial, venous, lymphatic), and one program that did not overlap significantly with prior signatures but was enriched in pathways involved in vasculogenesis, stem-like state, response to wounding and hypoxia, and endothelial-to-mesenchymal transition (reactive EndMT). A bulk transcriptome analysis of two independent cohorts (n = 269 patients) revealed that the lymphatic and reactive EndMT lineage programs were significantly associated with poor clinical outcomes. While losartan and proton therapy were associated with reduced lymphatic ECs, these therapies also correlated with an increase in reactive EndMT. Thus, the development and inclusion of EndMT-inhibiting drugs (e.g., nintedanib) to a neoadjuvant chemoradiotherapy regimen featuring losartan and/or proton therapy may be most effective in depleting both lymphatic and reactive EndMT populations and potentially improving patient outcomes.

Early prediction of failure to progress in single ventricle palliation: A step toward personalizing care for severe congenital heart disease.

BACKGROUND: Advances in surgical technique and medical surveillance have improved outcomes of single ventricle (SV) palliation, particularly during the first interstage period. However, there remains a considerable mortality risk beyond this period. METHODS: Patients born between January 2004 and December 2011 who required SV palliation were retrospectively identified. Patients who survived stage 1 palliation, were discharged home, and then were evaluated for Glenn candidacy, and continued care at our institution were included. Perioperative echocardiographic, hemodynamic, and operative data were analyzed at each surgical stage. The primary outcome was death or need for transplant. Univariate and multivariate analysis was completed using Cox proportional-hazards modeling. RESULTS: A total of 175 patients were included. Three patients died after pre-operative evaluation before Glenn. Glenn was completed in 168 patients, 16 died before Fontan. Fontan was completed in 149 patients; 117 were alive without need for transplant, 17 died post-Fontan, and 1 required transplantation. Twenty-one patients were lost to follow-up throughout the study period and were censored at time of last follow-up. Pre-Glenn moderate or severe atrioventricular valve regurgitation (AVVR) was an independent risk factor for death/transplant (HR 2.41; p-value .026). Pre-Glenn moderate ventricular dysfunction was also an independent risk factor (HR 5.29; p-value .012). Other risk factors included right ventricular (RV) dominant morphology and perinatal acidosis. CONCLUSIONS: Despite advances in SV palliation, a subset of these children remains at increased risk for poor outcomes. Early risk factors include RV dominant morphology and perinatal acidosis. Patients with substantial AVVR or ventricular dysfunction before Glenn palliation are also at significantly higher risk for death or requirement of transplantation later in childhood.

Single-nucleus and spatial transcriptome profiling of pancreatic cancer identifies multicellular dynamics associated with neoadjuvant treatment.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal and treatment-refractory cancer. Molecular stratification in pancreatic cancer remains rudimentary and does not yet inform clinical management or therapeutic development. Here, we construct a high-resolution molecular landscape of the cellular subtypes and spatial communities that compose PDAC using single-nucleus RNA sequencing and whole-transcriptome digital spatial profiling (DSP) of 43 primary PDAC tumor specimens that either received neoadjuvant therapy or were treatment naive. We uncovered recurrent expression programs across malignant cells and fibroblasts, including a newly identified neural-like progenitor malignant cell program that was enriched after chemotherapy and radiotherapy and associated with poor prognosis in independent cohorts. Integrating spatial and cellular profiles revealed three multicellular communities with distinct contributions from malignant, fibroblast and immune subtypes: classical, squamoid-basaloid and treatment enriched. Our refined molecular and cellular taxonomy can provide a framework for stratification in clinical trials and serve as a roadmap for therapeutic targeting of specific cellular phenotypes and multicellular interactions.

DNA repair and immune checkpoint blockade response.

Immune checkpoint blockade (ICB) has shown immense promise for treating patients with various cancer types, but its effectiveness relies on our ability to identify likely responders. Here, we examined the association between mutations in 25 core DNA repair genes and ICB outcomes in 6619 patients across 9 cancer types with advanced disease and MSK-IMPACT tumor sequencing. Notably, we observed that mutations in 7 of the DNA repair genes (ATM, ATR, POLE, ERCC4, NBN, RAD50, PARP1) were significantly associated with improved overall survival in ICB-treated patients (p < 0.05 for all) and had significant interaction with treatment (pinteraction <0.05 for all). Similarly, DNA repair mutations were enriched in other cancer types not previously assessed and primary tumors of unknown origins, suggesting that mutations could serve as a biomarker independent of cancer type. Although our cohort was enriched in certain cancer types, such as melanoma and non-small cell lung cancer, and clinically matched samples were not assessed, our study provides a robust approach in characterizing clinically-adoptable biomarkers that can select for potential ICB responders.

Cardiac Function in Children and Young Adults Treated with MEK Inhibitors: A Retrospective Cohort Study.

MEK inhibitors (MEKi) have shown efficacy in pediatric low-grade glioma as well as plexiform neurofibroma. MEKi have been associated with acute cardiac dysfunction in adults. Cardiac consequences in children are unknown. We performed a single center retrospective cohort study evaluating cardiac function by echocardiography (echo) in children and young adults < 21 years receiving MEKi between October 2013 and May 2018. Blinded assessment of left ventricular function by fractional shortening (FS) and ejection fraction (EF) was performed on all available echocardiograms performed before, during, and following therapy, as well as after re-initiation of therapy. Twenty-six patients underwent MEKi therapy with echo follow-up during the study period. Twenty-four of these had complete echo data. Median follow-up was 12 months. Borderline EF (EF 53-57.9%) occurred in 12 (50%) patients; and 3 (12.5%) progressed to abnormal EF (EF < 53%). Cardiac dysfunction, when it occurred, was mild (lowest documented EF was 45%, and lowest FS was 24.4%). EF abnormalities typically fluctuated during therapy, resolved off therapy, and recurred with MEKi re-initiation. No clinical or demographic differences were detected between those who maintained normal cardiac function and those who developed borderline or overt cardiac dysfunction. Symptomatic heart failure did not occur. In this cohort of children and young adults, MEKi use was associated with a high (50%) incidence of borderline or mildly decreased left ventricular function. There was no evidence of permanent cardiac dysfunction. Further evaluation in larger prospective trials is needed.

Prevalence of pulmonary hypertension on echocardiogram in children with severe obstructive sleep apnea.

STUDY OBJECTIVES: Pulmonary hypertension (PH) is a rare yet serious complication of obstructive sleep apnea (OSA). Echocardiographic screening for PH is recommended in children with severe OSA, but the health care burden of universal screening is high. We sought to determine the prevalence of PH on echocardiogram among children with severe OSA and identify variables associated with a positive PH screen. METHODS: Retrospective study of 318 children with severe OSA (obstructive apnea-hypopnea index ≥ 10 events/h) and echocardiogram within 1 year of polysomnogram. PH-positive echocardiogram was defined by peak tricuspid regurgitation velocity ≥ 2.5 m/s and/or 2 or more right-heart abnormalities suggestive of elevated pulmonary artery pressure. Patient characteristics and polysomnogram data were compared to identify factors associated with PH. RESULTS: Twenty-six children (8.2%; 95% confidence interval [CI] 5.4-11.8%) had echocardiographic evidence of PH. There was no difference in age, sex, body mass index, obstructive apnea-hypopnea index, or oxygenation indices between patients with and without PH. Sleep-related hypoventilation (end-tidal CO2 > 50 mmHg for > 25% of total sleep time) was present in 25% of children with PH compared with 6.3% of children without PH (adjusted prevalence ratio = 2.73; 95% CI 1.18-6.35). Forty-six percent of children (12/26) with PH had Down syndrome vs 14% (41/292) without PH (adjusted prevalence ratio = 3.11; 95% CI 1.46-6.65). CONCLUSIONS: There was a relatively high prevalence of PH on echocardiogram in our cohort of children with severe OSA. The findings of increased PH prevalence among children with sleep-related hypoventilation or Down syndrome may help inform the development of targeted screening recommendations for specific pediatric OSA populations. CITATION: Maloney MA, Davidson Ward SL, Su JA, et al. Prevalence of pulmonary hypertension on echocardiogram in children with severe obstructive sleep apnea. J Clin Sleep Med. 2022;18(6):1629-1637.

Therapeutic avenues for cancer neuroscience: translational frontiers and clinical opportunities.

With increasing attention on the essential roles of the tumour microenvironment in recent years, the nervous system has emerged as a novel and crucial facilitator of cancer growth. In this Review, we describe the foundational, translational, and clinical advances illustrating how nerves contribute to tumour proliferation, stress adaptation, immunomodulation, metastasis, electrical hyperactivity and seizures, and neuropathic pain. Collectively, this expanding knowledge base reveals multiple therapeutic avenues for cancer neuroscience that warrant further exploration in clinical studies. We discuss the available clinical data, including ongoing trials investigating novel agents targeting the tumour-nerve axis, and the therapeutic potential for repurposing existing neuroactive drugs as an anti-cancer approach, particularly in combination with established treatment regimens. Lastly, we discuss the clinical challenges of these treatment strategies and highlight unanswered questions and future directions in the burgeoning field of cancer neuroscience.

Drug Treatment of Heart Failure in Children: Gaps and Opportunities.

Medical therapy for pediatric heart failure is based on a detailed mechanistic understanding of the underlying causes, which are diverse and unlike those encountered in most adult patients. Diuresis and improved perfusion are the immediate goals of care in the child with acute decompensated heart failure. Conversion to maintenance oral therapy for heart failure is based on the results of landmark studies in adults, as well as recent pediatric clinical trials and heart failure guidelines. There will continue to be an important role for newer drugs, some of which are in active trials in adults, and some of which are already approved for use in children. The need to plan for clinical trials in children during drug development for heart failure is emphasized.

mRNA Coronavirus Disease 2019 Vaccine-Associated Myopericarditis in Adolescents: A Survey Study.

In this survey study of institutions across the US, marked variability in evaluation, treatment, and follow-up of adolescents 12 through 18 years of age with mRNA coronavirus disease 2019 (COVID-19) vaccine-associated myopericarditis was noted. Only one adolescent with life-threatening complications was reported, with no deaths at any of the participating institutions.

Electronic Paper Displays in Hospital Operations: Proposal for Deployment and Implementation.

BACKGROUND: Display signage is ubiquitous and essential in hospitals to serve several clerical, operational, and clinical functions, including displaying notices, providing directions, and presenting clinical information. These functions improve efficiency and patient engagement, reduce errors, and enhance the continuity of care. Over time, signage has evolved from analog approaches such as whiteboards and handwritten notices to digital displays such as liquid crystal displays, light emitting diodes, and, now, electronic ink displays. Electronic ink displays are paper-like displays that are not backlit and show content by aligning microencapsulated color beads in response to an applied electric current. Power is only required to generate content and not to retain it. These displays are very readable, with low eye strain; minimize the emission of blue light; require minimal power; and can be driven by several data sources, ranging from virtual servers to electronic health record systems. These attributes make adapting electronic ink displays to hospitals an ideal use case. OBJECTIVE: In this paper, we aimed to outline the use of signage and displays in hospitals with a focus on electronic ink displays. We aimed to assess the advantages and limitations of using these displays in hospitals and outline the various public-facing and patient-facing applications of electronic ink displays. Finally, we aimed to discuss the technological considerations and an implementation framework that must be followed when adopting and deploying electronic ink displays. METHODS: The public-facing applications of electronic ink displays include signage and way-finders, timetables for shared workspaces, and noticeboards and bulletin boards. The clinical display applications may be smaller form factors such as door signs or bedside cards. The larger, ≥40-inch form factors may be used within patient rooms or at clinical command centers as a digital whiteboard to display general information, patient and clinician information, and care plans. In all these applications, such displays could replace analog whiteboards, noticeboards, and even other digital screens. RESULTS: We are conducting pilot research projects to delineate best use cases and practices in adopting electronic ink displays in clinical settings. This will entail liaising with key stakeholders, gathering objective logistical and feasibility data, and, ultimately, quantifying and describing the effect on clinical care and patient satisfaction. CONCLUSIONS: There are several use cases in a clinical setting that may lend themselves perfectly to electronic ink display use. The main considerations to be studied in this adoption are network connectivity, content management, privacy and security robustness, and detailed comparison with existing modalities. Electronic ink displays offer a superior opportunity to future-proof existing practices. There is a need for theoretical considerations and real-world testing to determine if the advantages outweigh the limitations of electronic ink displays.

Clinical Utility of Guselkumab in the Treatment of Moderate-to-Severe Plaque Psoriasis.

Psoriasis is a chronic immune-mediated disease involving complex interaction of T cells and keratinocytes. The comprehensive pathogenesis of psoriasis is not fully understood but the IL-23/Th17 axis is a central pathway in driving disease development. Guselkumab is the first treatment of moderate-to-severe psoriasis that specifically targets the p19 subunit of IL-23. The benefit of guselkumab has been established by a number of clinical trials including demonstration of greater long-term efficacy in recent comparator trials. This review addresses the results of head-to-head trials (ECLIPSE, IXORA-R, and POLARIS) that compared guselkumab to secukinumab, ixekizumab, and fumaric acid esters. The previously demonstrated long-term efficacy of guselkumab has been corroborated by many recently published studies. The effective and safe profile, convenient dosing, and improved quality of life in patients make gulselkumab a viable first-line treatment option for moderate-to-severe psoriasis.

Frequency of Allergenic Ingredients in Antifungal Creams.

BACKGROUND: Allergic contact dermatitis (ACD) may occur secondary to topical antifungals containing potential allergens in their vehicles. Variation of allergenic ingredients among commonly used antifungal creams (AFCs) has not been well characterized. OBJECTIVE: The study goal was to assess the frequency of allergenic ingredients in 4 commonly used topical AFCs. METHODS: Topical AFCs (clotrimazole, ketoconazole, miconazole, and terbinafine) were selected, and the ingredient lists for these products were obtained from the US Food and Drug Administration's Online Label Repository via a proprietary name search. A systematic literature review was performed using the ingredient name on MEDLINE (PubMed) database to identify reports of ACD confirmed by patch testing. RESULTS: Of the 20 ingredients analyzed, 6 had frequent allergenic potential. Propylene glycol was the most common cause of ACD identified in the literature and is an ingredient in ketoconazole 2% and miconazole nitrate 2%. Ketoconazole 2% and miconazole nitrate 2% creams contained the highest number of potential allergens (n = 3) among the 4 creams analyzed. CONCLUSIONS: Of the 4 creams, terbinafine hydrochloride 1% and clotrimazole 1% contained the least number of potential allergenic ingredients. Awareness of the allergenic potential of commonly used AFCs may help health care providers when evaluating patients with ACD.