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Background An escape room is a cooperative game that has been adapted into medical education and major academic conferences. Methods We describe the design, development, and implementation of an educational ID-themed escape room activity entitled "Out-BREAK!" at an international conference, IDWeek 2023. An anonymous survey was conducted to collect demographic data, assess participant satisfaction with the escape room puzzles, and gauge participant interest in game-based learning. Results Thirty escape room sessions were held over 3 days and included 201 participants. Escape room survey respondents (n = 132) were younger and more likely to be trainees compared with in-person IDWeek attendants. Among 131 responses, all respondents enjoyed the experience and would recommend the escape room activity to friends. Survey respondents enjoyed the puzzle solving (93%), medical content (92%), and team building (79%) components. Only 35% of the respondents had ever previously participated in game-based learning; 95% thought the escape room was a valuable teaching method. Among the 72 survey respondents involved in medical education, almost all (90%) said they were interested in incorporating escape rooms into medical education. Conclusions The Out-BREAK! escape room at IDWeek 2023 was successfully implemented and well received. Despite only a third of participants having prior experience with game-based learning, almost all respondents perceived the escape room to be an effective teaching method. [ABSTRACT FROM AUTHOR]

Background Valganciclovir is the only approved antiviral for cytomegalovirus (CMV) prevention in pediatric solid organ transplantation (SOT). Additional approaches may be needed to improve outcomes. Methods A multicenter retrospective study from 2016 to 2019 was conducted of pediatric SOT recipients in whom at least 3 months of valganciclovir prophylaxis was planned. Episodes of CMV DNA in blood (DNAemia), CMV disease, drug-related toxicities, as well as other infections in the first year posttransplant and demographic and clinical data were collected. CMV DNAemia in the first year after prophylaxis or during prophylaxis (breakthrough) was analyzed by multivariate hazard models. Results Among the 749 patients enrolled, 131 (17.5%) had CMV DNAemia at any time in the first year; 85 (11.4%) had breakthrough DNAemia, and 46 (6.1%) had DNAemia after prophylaxis. CMV disease occurred in 30 (4%). In a multivariate model, liver transplantation compared to kidney or heart, intermediate or high risk based on donor/recipient serologies, neutropenia, and valganciclovir dose modifications attributed to toxicity were associated with increased risk of total and/or breakthrough DNAemia. Bacteremia was also associated with increased hazard ratio for CMV DNAemia. In a separate multivariate analysis, rejection occurred more often in those with breakthrough CMV DNAemia (P =.002); liver transplants, specifically, had increased rejection if CMV DNAemia occurred in the first year (P =.004). These associations may be bidirectional as rejection may contribute to infection risk. Conclusions CMV DNAemia in the first year posttransplantation occurs despite valganciclovir prophylaxis and is associated with medication toxicity, bacteremia, and rejection. Pediatric studies of newer antivirals, especially in higher-risk subpopulations, appear to be warranted. [ABSTRACT FROM AUTHOR]

Background Since November 2019, the SARS-CoV-2 pandemic has created challenges for preventing and managing COVID-19 in children and adolescents. Most research to develop new therapeutic interventions or to repurpose existing ones has been undertaken in adults, and although most cases of infection in pediatric populations are mild, there have been many cases of critical and fatal infection. Understanding the risk factors for severe illness and the evidence for safety, efficacy, and effectiveness of therapies for COVID-19 in children is necessary to optimize therapy. Methods A panel of experts in pediatric infectious diseases, pediatric infectious diseases pharmacology, and pediatric intensive care medicine from 21 geographically diverse North American institutions was re-convened. Through a series of teleconferences and web-based surveys and a systematic review with meta-analysis of data for risk factors, a guidance statement comprising a series of recommendations for risk stratification, treatment, and prevention of COVID-19 was developed and refined based on expert consensus. Results There are identifiable clinical characteristics that enable risk stratification for patients at risk for severe COVID-19. These risk factors can be used to guide the treatment of hospitalized and non-hospitalized children and adolescents with COVID-19 and to guide preventative therapy where options remain available. [ABSTRACT FROM AUTHOR]

Introduction/Background Atopic dermatitis (AD) has different clinical presentations, pathophysiology, comorbidity frequencies, and genetic profiles in adult-onset vs childhood-onset disease. Based on these differences, it is plausible that treatment response would also be different between adult- and childhood-onset AD. Lebrikizumab, a novel, high affinity monoclonal antibody, selectively targeting IL-13 with high affinity and slow dissociation rate, has been approved in the EU, UK, and Japan and is under investigation in the US and elsewhere for the treatment of moderate-to-severe AD. Objectives To evaluate the Week-16 efficacy of lebrikizumab monotherapy by age of AD onset in adults and adolescents with moderate-to-severe AD from ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967), identically-designed, randomized, double-blind, placebo-controlled phase 3 trials. Methods In ADvocate1 and ADvocate2, eligible patients were randomly allocated 2:1 to receive lebrikizumab 250 mg or placebo every 2 weeks. The date of AD onset was collected, and age of onset was calculated accordingly. Patients were stratified by age of AD-onset as ≤2, >2-to-<18, and ≥18 years. Efficacy was assessed at Week 16 with the proportion of patients with Investigator's Global Assessment score of 0 or 1 with ≥2-point improvement (IGA 0,1; the trials' primary endpoint); ≥75% (EASI 75) and ≥90% (EASI 90) improvement in the Eczema Area and Severity Index from baseline; ≥4-point Pruritus Numeric Rating Scale (NRS) improvement from baseline (with baseline score ≥4), and percentage change in total EASI from baseline. Data from patients who received topical or systemic rescue medication or discontinued treatment due to lack of efficacy were imputed as nonresponders or set to baseline values. Data from patients who discontinued treatment for other reasons were set to missing and analyzed by multiple imputation. This was a post-hoc analysis conducted on the modified, pooled intent-to-treat population. Treatment-by-age subgroup interaction was assessed with logistic regression. Binary outcomes were analyzed by the Cochran-Mantel-Haenszel method, and continuous outcomes were analyzed with ANCOVA. Results At baseline, the numbers of patients treated with lebrikizumab and placebo, respectively, were 215 and 117 in the ≤2 years AD-onset subgroup, 178 and 103 in the >2-to-<18 years subgroup, and 171 and 67 in the ≥18 years subgroup. At baseline, the percentages of patients with ≥1 atopic comorbidity were 81% in the ≤2 years subgroup, 74% in the >2-to-<18 years subgroup, and 58% in the ≥18 years subgroup. At Week 16, treatment-by-age subgroup interactions were not significant at the 0.10 level for IGA 0,1; EASI 75; EASI 90; and Pruritus NRS 4-pt improvement. Within each subgroup, a higher proportion of lebrikizumab-treated compared with placebo-treated patients (p<0.001) achieved IGA 0,1 responses (≤2 years: 41% vs. 12%; >2-to-<18 years: 35% vs. 12%; ≥18 years: 38% vs. 12%), EASI 75 responses (≤2 years: 57% vs. 17%; >2-to-<18 years: 51% vs. 16%; ≥18 years: 58% vs. 20%), and EASI 90 responses (≤2 years: 38% vs. 10%; >2-to-<18 years: 32% vs. 9%; ≥18 years: 33% vs. 8%). Additionally, the least-squares mean percentage change from baseline in total EASI score for lebrikizumab and placebo, respectively, was -65% and -26% in the ≤2 years subgroup, -60% and -26% in the >2-to-<18 years subgroup, and -63% and -30% in the ≥18 years subgroup (p<0.001 for lebrikizumab vs. placebo in all subgroups). The proportion of lebrikizumab-treated patients who reported ≥4-point improvement in Pruritus NRS from baseline (baseline ≥4) was greater compared with placebo-treated patients ([N]; ≤2 years: 43% [201] vs. 11% [108]; >2-to-<18 years: 41% [161] vs. 14% [96]; ≥18 years: 45% [154] vs. 12% [60]; p<0.001). Conclusions Regardless of age of AD onset, lebrikizumab was associated with significant improvements in AD signs and symptoms compared with placebo over 16 weeks of treatment. [ABSTRACT FROM AUTHOR]

There are limited resources for guidance on the transition from fellowship into a new faculty role in pediatric infectious diseases. This review aims to address this gap and provides a framework for a successful transition that is composed of four essential pillars—(1) stepping into your role, (2) finding your niche, (3) building your network, and (4) self-care—all of which are supported by strong mentorship/sponsorship and continual realignment with one's personal mission statement. In addition to providing general principles and guidance, this review also outlines specific steps that a junior faculty member can take to expand their influence and build a successful, fulfilling career in pediatric infectious diseases. [ABSTRACT FROM AUTHOR]

Background Antibiotics are prescribed to most pediatric intensive care unit (PICU) patients, but data describing indications and appropriateness of antibiotic orders in this population are lacking. Methods We performed a multicenter point prevalence study that included children admitted to 10 geographically diverse PICUs over 4 study days in 2019. Antibiotic orders were reviewed for indication, and appropriateness was assessed using a standardized rubric. Results Of 1462 patients admitted to participating PICUs, 843 (58%) had at least 1 antibiotic order. A total of 1277 antibiotic orders were reviewed. Common indications were empiric therapy for suspected bacterial infections without sepsis or septic shock (260 orders, 21%), nonoperative prophylaxis (164 orders, 13%), empiric therapy for sepsis or septic shock (155 orders, 12%), community-acquired pneumonia (CAP; 118 orders, 9%), and post-operative prophylaxis (94 orders, 8%). Appropriateness was assessed for 985 orders for which an evidence-based rubric for appropriateness could be created. Of these, 331 (34%) were classified as inappropriate. Indications with the most orders classified as inappropriate were empiric therapy for suspected bacterial infection without sepsis or septic shock (78 orders, 24%), sepsis or septic shock (55 orders, 17%), CAP (51 orders, 15%), ventilator-associated infections (47 orders, 14%), and post-operative prophylaxis (44 orders, 14%). The proportion of antibiotics classified as inappropriate varied across institutions (range, 19%–43%). Conclusions Most PICU patients receive antibiotics. Based on our study, we estimate that one-third of antibiotic orders are inappropriate. Improved antibiotic stewardship and research focused on strategies to optimize antibiotic use in critically ill children are needed. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic, inflammatory skin disease characterized by intense itch and eczematous skin lesions that can impact individuals at any age across any area of the body. There is a need for safe treatments for AD that provide rapid itch relief and skin clearance and that are suitable for long-term use. Upadacitinib is a selective, reversible oral Janus kinase 1 (JAK1) inhibitor, which is approved in multiple countries for the treatment of adolescents and adults with moderate-to-severe AD. The current analysis assessed the long-term safety for up to 4 years of upadacitinib 15 and 30 mg in adolescents and adults with moderate-to-severe AD, using integrated data from three ongoing global pivotal phase 3 studies. The Measure Up 1, Measure Up 2, and AD Up studies are ongoing pivotal phase 3, randomized, placebo-controlled, multicenter studies evaluating the safety and efficacy of upadacitinib 15 mg and upadacitinib 30 mg in adolescents and adults with moderate-to-severe AD. Patients were randomized 1 : 1 : 1 to receive oral upadacitinib 15 mg, upadacitinib 30 mg or placebo once daily alone (Measure Up 1 and Measure Up 2) or with concomitant topical corticosteroids (AD Up). At Week 16, patients receiving upadacitinib 15 or 30 mg during the double-blinded period continued their assigned treatment in the blinded extension (BE) period, whereas patients receiving placebo were re-randomized 1 : 1 to receive either upadacitinib 15 or 30 mg in the BE period (upadacitinib treatment for up to 260 weeks). A total of 2693 adults and adolescents (upadacitinib 15 mg, 1340; upadacitinib 30 mg, 1353) who received at least one dose of upadacitinib were included in the integrated analysis. Treatment-emergent adverse events of special interest (AESI) were analysed as exposure-adjusted rates per 100 patient-years (PY) for the entire treatment period to adjust for potentially different durations of follow-up. Upadacitinib was well tolerated by both adults and adolescents. For all patients, rates of AESIs were similar at the 1-year analysis and up to 4-year analysis for upadacitinib (15 mg/30 mg) for: serious infections, 2.3 and 2.2/2.8 and 2.8; opportunistic infections, 1.6 and 1.8/1.9 and 2.4; active tuberculosis, <0.1/<0.1 at both time points; herpes zoster, 3.5 and 3.1/5.2 and 5.8; nonmelanoma skin cancer (NMSC), 0.3 and 0.4/0.4 and 0.3; malignancy excluding NMSC, 0.1 and 0.4/0.5 and 0.3; and adverse events leading to death, 0 and 0/<0.1 and <0.1. Rates of adjudicated major adverse cardiovascular events (MACE) were 0.1 and <0.1/<0.1 and <0.1, and for venous thromboembolic events (VTE) were <0.1 for both doses at the 1-year analysis and up to 4-year analysis. Rates of gastrointestinal perforations were 0 for both doses at both timepoint analyses. Rates of serious infections remain low (<3.0 E/100 PY). Based on the integrated analysis of long-term safety data for up to 4 years, rates of AESIs remained low throughout a longer duration of treatment with upadacitinib 15 or 30 mg among adults and adolescents with moderate-to-severe AD. No new safety risks were observed. Findings of the current safety analysis continue to support a favorable benefit-risk profile of upadacitinib in the treatment of adults and adolescents with moderate-to-severe AD for up to 4 years of treatment. [ABSTRACT FROM AUTHOR]

Summary: Background: Tralokinumab, a fully human IgG4 monoclonal antibody that specifically binds with high affinity to interleukin‐13, effectively reduces moderate‐to‐severe atopic dermatitis (AD) when given every 2 weeks. The incidence of conjunctivitis is elevated vs. placebo, but severity and aetiology have not been examined. Objective: To analyse conjunctivitis data recorded in five randomized, placebo‐controlled trials of tralokinumab in adult patients with moderate‐to‐severe AD. Methods: Overall, 2285 adults with AD were studied up to 16 weeks. Cochran–Mantel–Haenszel weights were applied to calculate the adjusted incidence of adverse events. Results: The incidence of conjunctivitis was higher (7·5%) with tralokinumab than with placebo (3·2%). Most events were mild or moderate in severity, and 78·6% and 73·9% of events resolved during the trial in the tralokinumab and placebo groups, respectively. Two (1·4%) events led to the permanent discontinuation of tralokinumab. An increased incidence of conjunctivitis, regardless of treatment group, was associated with more severe baseline AD, and history of allergic conjunctivitis/atopic keratoconjunctivitis, as well as the number of atopic comorbidities. Limitations: This analysis reports events up to week 16 only, with limited confirmation of conjunctivitis and its aetiology by an ophthalmologist, and insufficient reporting of ophthalmic treatments. Conclusions: Treatment with tralokinumab was associated with an increased incidence of conjunctivitis vs. placebo, but these cases were mostly mild and transient. Whatis already known about this topic? Ocular disorders, including conjunctivitis, occur more frequently in patients with atopic dermatitis (AD).When using the interleukin (IL)‐4 and IL‐13 receptor blocking biologic dupilumab, patients with AD in clinical trials and real‐world practice experience higher rates of conjunctivitis, which increases with baseline AD severity.Tralokinumab, a fully human monoclonal antibody, binds specifically to IL‐13 with high affinity.Various rates of conjunctivitis have been observed in different clinical trials of tralokinumab. Whatdoes this study add? This is the first investigation of conjunctivitis in phase III studies of a biological drug specifically targeting IL‐13, in contrast to dupilumab, which targets the IL‐4 and IL‐13 receptorsThe incidence of conjunctivitis was higher with tralokinumab (7·5%) vs. placebo (3·2%); most cases were mild and resolved, or were resolving during study treatment.Risk factors included high AD severity, history of conjunctivitis, disease biomarker levels, and number and type of atopic comorbiditiesThis is the first study to show that some atopic comorbidities have a greater influence on the risk of conjunctivitis than others. Linked Comment: R. Nguyen. Br J Dermatol 2022; 186:391–392. [ABSTRACT FROM AUTHOR]

Introduction Roflumilast is a selective, highly potent phosphodiesterase 4 inhibitor under investigation as a nonsteroidal, once-daily cream for treatment of atopic dermatitis (AD). Methods We present pooled results from two identical phase 3 randomized controlled trials (INTEGUMENT-1: NCT04773587; INTEGUMENT-2: NCT04773600) of roflumilast cream 0.15%. Patients aged ≥6 years with mild to moderate AD were randomized 2:1 to apply roflumilast (n=884) or vehicle (n=453) cream once-daily for 4 weeks. The primary endpoint was validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) Success (Clear/Almost Clear vIGA-AD plus ≥2-grade improvement from baseline) at Week 4. Patient-reported outcomes (PROs) were evaluated using the Worst Itch-Numeric Rating Scale (WI-NRS), SCORing AD (SCORAD), Patient-Oriented Eczema Measure, Dermatology Life Quality Index/Children's Dermatology Life Quality Index, and the Dermatitis Family Impact questionnaire. Safety and tolerability were also evaluated. Results At Week 4, more roflumilast- than vehicle-treated patients achieved vIGA-AD Success (31.3% vs. 14.1%, P<0.0001), WI-NRS Success (≥4-point improvement on WI-NRS in patients aged ≥12 years with baseline WI-NRS ≥4; 31.9% vs. 16.6%, P<0.0001); and WI-NRS of 0/1 (in patients with baseline WI-NRS ≥2; 28.8% vs 18.5%, P=0.0087). At Week 4, roflumilast-treated patients improved more than vehicle-treated on the pruritus and sleep components of SCORAD (least squares mean percentage change −48.2% vs. −27.8%; [P<0.0001] and −47.9% vs. −22.9% [P<0.05], respectively). Differences favoring roflumilast were also seen for other secondary endpoints, including quality of life of the patient and family. Safety and local tolerability were favorable. Conclusion Once-daily, nonsteroidal roflumilast cream 0.15% improved PROs in patients with AD. [ABSTRACT FROM AUTHOR]

Introduction Roflumilast cream 0.15% is a selective, highly potent phosphodiesterase 4 inhibitor under investigation as a non-steroidal, once-daily treatment for atopic dermatitis (AD). Objectives: Here, pooled results from two identical Phase 3 randomized controlled trials (INTEGUMENT-1: NCT04773587 and INTEGUMENT-2: NCT04773600) are presented. Methods: Patients with AD aged ≥6 years with baseline Eczema Area and Severity Index (EASI) score ≥5 and Validated Investigator Global Assessment-AD (vIGA-AD) score of Mild or Moderate were randomized 2:1 to apply roflumilast (n=884) or vehicle (n=453) once daily for 4 weeks. Results: A significantly greater percentage of roflumilast-versus vehicle-treated patients achieved the primary endpoint, vIGA-AD Success (Clear or Almost Clear vIGA-AD plus ≥2-grade improvement from baseline) at Week 4 (31.3% vs. 14.1%; P<0.0001). Significant differences favoring roflumilast were observed for multiple secondary endpoints at Week 4: percentage of patients achieving vIGA-AD of Clear or Almost Clear (41.1% vs. 21.4%; P<0.0001), percentage achieving 75% reduction in EASI (42.7% vs. 20.6%; P<0.0001), and percentage with baseline Worst Itch-Numeric Rating Scale ≥4 achieving a 4-point reduction (31.9% vs. 16.6%; P<0.0001). Improvement in itch was reported as early as 24 hours. Both groups had low incidences of treatment-emergent adverse events (TEAE), serious adverse events, and TEAEs leading to discontinuation. Local tolerability was favorable, with >90% of patients reporting no or mild sensation across both treatment groups at all timepoints. Conclusions: Once-daily roflumilast cream 0.15% provided improvement across multiple efficacy endpoints by Week 4 with favorable safety and tolerability in patients aged ≥6 years with AD in two Phase 3 trials. [ABSTRACT FROM AUTHOR]

Introduction/Background Type 2 inflammatory cytokines interleukin 4 (IL-4) and IL-13 play an important role in skin barrier disruption in atopic dermatitis (AD). Filaggrin and ceramides play a crucial role in skin barrier integrity. Loss of function mutations in the FLG gene are associated with the impaired skin barrier function and more severe AD.1,2 FLG mutations only affect a minority of AD patients; however, increased IL-4 and IL-13 cytokines are a common cause of reduced filaggrin expression in patients with AD, independent of FLG genotype. Objectives: To explore whether dupilumab treatment improves skin barrier function in patients with or without FLG mutations. Methods: In the BArrier function and LIpidomics STudy in Atopic Dermatitis (BALISTAD; NCT04447417), a 16-week study in patients with AD aged 12 to 65 years, adult patients with AD received dupilumab 300 mg every 2 weeks; adolescent patients with AD received dupilumab 200 mg every 2 weeks if their baseline weight was <60 kg and 300 mg if =60 kg. FLG mutations were evaluated in DNA from blood samples of consenting patients with AD and healthy volunteers. Transepidermal water loss (TEWL) was assessed longitudinally after 5 skin tape strippings (STS) from AD lesions (n = 26) and from the skin of healthy participants (n =26) (age: 12 to 63 years) over a 16-week course of dupilumab treatment. Quantitative N(C18) S-ceramide analysis of STS samples collected on Days 1, 15, 29, 57, and 85, and at Week 16 from AD lesions and from the skin of healthy participants was performed using liquid chromatography tandem mass spectrometry. Results: At baseline, mean TEWL after 5 STS (TEWL5) was significantly higher in AD lesional skin than healthy skin (p<0.0001). The mean TEWL5 in AD lesions in subjects with FLG mutations (n = 6/19) was significantly higher at baseline than in AD subjects without mutations (P < 0.0001). Dupilumab treatment significantly reduced TEWL5 in AD lesional skin as early as Week 2 with a progressive decrease through Week 16 (P < 0.0001). Reduction in mean TEWL5 was similar from Week 2 to Week 16 in AD patients with and without FLG mutations. At Week 16, TEWL5 was comparable to healthy skin in the lesional skin of AD patients with and without FLG mutations (P > 0.05). AD skin lesions had increased levels of N(C18)S-ceramides at baseline (P < 0.0001); but no differences were noted in subjects with or without FLG mutations (P > 0.05). Dupilumab treatment significantly reduced levels of N(C18)S-ceramides in AD lesional skin as early as Week 2 with a progressive decrease through Week 16 (P < 0.0001). Dupilumab treatment decreased levels of N(C18)S-ceramides in STS samples similarly in subjects with and without FLG mutations from Week 2 to Week 16. Conclusions: Dupilumab treatment normalizes TEWL5 and decreases levels of N(C18)S-ceramides in AD lesional skin of subjects with and without FLG mutations. [ABSTRACT FROM AUTHOR]

Introduction/Background As symptoms of atopic dermatitis (AD) can wax and wane over time, disease control is better represented by consistency of response over a long treatment duration rather than at a single time point. Objective To evaluate the proportion of pediatric patients achieving and maintaining mild or no itch (defined by a SCORing Atopic Dermatitis (SCORAD) itch visual analog scale (VAS; 0-10 over last 3 days) score of lower than 4) across 5 visits during a 52-week open label extension trial of dupilumab. Methods: Patients who previously participated in 16-week trials and were aged 0.5-5 years (LIBERTY AD PRESCHOOL; NCT03346434), 6-11 years (LIBERTY AD PEDs; NCT03345914), and 12-17 years (LIBERTY AD ADOL; NCT03054428), were subsequently enrolled in the phase 3, open-label extension trial, LIBERTY AD PED-OLE (NCT02612454). Patients were treated with 300 mg q4w or 200/300 mg q2w (body weight <60 or ≥60 kg, respectively). In this analysis, patients with a SCORAD itch VAS score of greater than 4 at OLE baseline, were assessed for the maintenance of SCORAD itch VAS lower than 4, at 5 timepoints: Weeks 4, 16, 28, 40, and 52. Results: In 763 patients, 400 patients with a SCORAD itch VAS score of greater than 4 were assessed. Mild or no itch was achieved in at least 4 of 5 timepoints in most patients aged 0.5-5 years (55/110; 50%), 6-11 years (76/148; 51%), and 12-17 years (73/142; 51%). Across these age groups, over 65% maintained this response for at least 3 of 5 timepoints. Safety was consistent with the known dupilumab safety profile in patients with atopic dermatitis. Conclusions: Most pediatric patients achieved improvement in itch, maintained during 1 year of treatment with dupilumab. Results were consistent for infants/preschoolers, children, and adolescents. [ABSTRACT FROM AUTHOR]

Introduction/Background Atopic dermatitis (AD) is an inflammatory skin disease associated with atopic comorbidities, including asthma, food allergy, hay fever, and allergic conjunctivitis. Tralokinumab, a high-affinity monoclonal antibody that specifically targets IL-13, is indicated for the treatment of moderate-to-severe AD. Objectives: To assess the impact of atopic comorbidities on the efficacy and safety of tralokinumab vs. placebo for moderateto-severe AD in patients age ≥12 years. Methods: This post-hoc analysis presents data from the adult trials ECZTRA 1 and 2 (NCT03131648 and NCT03160885 pooled; 300 mg tralokinumab every 2 weeks [Q2W] vs. placebo) and ECZTRA 3 (NCT03363854; 300 mg tralokinumab Q2W vs. placebo, both plus TCS as needed), and the ECZTRA 6 adolescent trial (NCT03526861; pooled 150 mg and 300 mg tralokinumab Q2W vs. placebo). Tralokinumab-treated patients received a loading dose. Proportion of patients achieving IGA 0/1 and EASI-75 at Week 16 according to patient-reported current or past atopic comorbidity are presented as observed regardless of rescue medication use; missing data were imputed as non-responders. Results: In total 2,223 patients were included across four trials. Among patients in ECZTRA 1 and 2, 50.5% reported history of asthma, 38.5% food allergy, 53.8% hay fever, and 33.5% allergic conjunctivitis, while 19.8% reported no atopic comorbidities and 79.3% reported ≥1 atopic comorbidity. Proportions of patients in ECZTRA 3 and 6 reporting history of atopic comorbidities were largely similar, although more adolescent patients reported food allergy. In all subgroups at Week 16, higher proportions of patients receiving tralokinumab vs. placebo achieved EASI-75. In ECZTRA 1 and 2, response rates among patients in each subgroup were asthma: 35.3% vs. 12.8%, food allergy: 33.2% vs. 14.7%, hay fever: 36.8% vs. 16.5%, allergic conjunctivitis: 34.8% vs. 12.7%, none: 34.6% vs. 20.5%; and ≥1 atopic comorbidity: 35.5% vs. 15.2% (P<0.05 for all). A similar pattern of response was observed in ECZTRA 3 and 6, and for IGA 0/1 across trials. EASI-75 response rates for tralokinumab-treated patients were consistent across patients with different numbers of atopic comorbidities. Safety across subgroups was consistent with the safety profile of tralokinumab observed overall in adults and adolescents. Conclusions: 16 weeks of tralokinumab treatment improved AD signs and symptoms in adult and adolescent patients with and without atopic comorbidities, regardless of type or number of atopic comorbidities. The safety profile of tralokinumab was consistent between patients with and without atopic comorbidities. [ABSTRACT FROM AUTHOR]

Introduction/Background Atopic dermatitis (AD) is a chronic, relapsing, inflammatory skin disease characterized by intense itch and eczematous skin lesions, impacting individuals at any age. There is a need for AD treatments that provide rapid itch relief and skin clearance that are safe for long-term use. Upadacitinib is a selective, reversible oral Janus kinase 1 (JAK1) inhibitor approved in multiple countries for the treatment of moderate-to-severe AD in adults and adolescents. Objectives: We evaluated the long-term safety for up to 5 years of upadacitinib 15 mg and 30 mg use in adolescents and adults with moderate-to-severe AD, based on the results of integrated data from three ongoing global pivotal Phase 3 studies. Materials & Methods: The Measure Up 1, Measure Up 2, and AD Up studies are ongoing pivotal Phase 3, randomized, placebo-controlled, multicenter studies evaluating the safety and efficacy of upadacitinib 15 mg and upadacitinib 30 mg in adolescents and adults with moderate-to-severe AD. Patients were randomized 1:1:1 to receive oral upadacitinib 15 mg, upadacitinib 30 mg, or placebo once daily alone (Measure Up 1 and 2) or with concomitant topical corticosteroids (AD Up). At Week 16, patients receiving upadacitinib 15 mg or 30 mg during the double-blinded period continued their assigned treatment in the blinded extension (BE) period, whereas patients receiving placebo were re-randomized 1:1 to receive either upadacitinib 15 mg or 30 mg in the BE period (upadacitinib treatment for up to 260 weeks). Results: A total of 2683 patients (2154 adults, 529 adolescents) who received at least 1 dose of upadacitinib (15 mg, 1337; 30 mg, 1346) were included in the integrated analysis. Treatmentemergent adverse events of special interest (AESI) were analyzed as exposure-adjusted rates per 100 patient-years (PY) for the entire treatment period to adjust for potentially different durations of follow-up. Rates of AESIs were similar at the 1-year analysis and up to 5-year analysis for upadacitinib for: serious infections, 15 mg, 2.3 (1 yr) and 2.2 (5 yrs)/30 mg, 2.8 (1 yr) and 2.6 (5 yrs); opportunistic infections, 15 mg, 1.6 (1 yr) and 1.7 (5 yrs)/30 mg, 1.9 (1 yr) and 2.2 (5 yrs); active tuberculosis, <0.1 at both timepoints for both doses; herpes zoster, 15 mg, 3.5 (1 yr) and 3.1 (5 yrs)/30 mg, 5.2 (1 yr) and 5.5 (5 yrs); non-melanoma skin cancer (NMSC), 15 mg, 0.3 (1 yr) and 0.4 (5 yrs)/30 mg, 0.4 (1 yr) and 0.3 (5 yrs); malignancy excluding NMSC, 15 mg, 0.1 (1 yr) and 0.3 (5 yrs)/30 mg, 0.5 (1 yr) and 0.4 (5 yrs); gastrointestinal perforations, 15 mg, 0 at both time points/30 mg, 0 (1 yr) and <0.1 (5 yrs); adjudicated major adverse cardiovascular events (MACE), 15 mg, 0.1 (1 yr) and 0.2 (5 yrs)/30 mg, <0.1 at both timepoints; adjudicated venous thromboembolic events (VTE), <0.1 for both doses at 1 year and 0.1 for both doses at 5 years. Rates of adverse events leading to death were: 15 mg, 0 (1 yr) and <0.1 (5 yrs)/30 mg, <0.1 at both timepoints. Rates of serious infection at both timepoints and doses remained low (<3.0 E/100PYs). Upadacitinib was well-tolerated by both adults and adolescents. Conclusions: The integrated analysis of long-term safety data for up to 5 years indicates that rates of AESIs remained low throughout treatment with upadacitinib 15 mg or 30 mg among adults and adolescents with moderate-to-severe AD. There were no new safety risks. The current safety analysis continues to support a favorable benefit-risk profile of upadacitinib in the treatment of adults and adolescents with moderate-to-severe AD for up to 5 years of treatment, including over 7000 years of patient exposure. [ABSTRACT FROM AUTHOR]

Systemic treatments often require laboratory monitoring. Here we report 52-week laboratory safety data for dupilumab-treated children aged 6 months to 5 years with moderate-to-severe AD. LIBERTY AD PED-OLE (NCT02612454) is an open-label extension study of children aged 6 months to <18 years with moderate-to-severe AD. This analysis includes hematologic and chemistry laboratory parameters in children aged 6 months to 5 years treated with dupilumab every 4 weeks (q4w; 200 mg: ≥5 to <15 kg; 300 mg: ≥15 to <30 kg). Of the 180 patients enrolled, 122 (67.8%) completed up to 16 weeks and 30 (16.7%) completed up to 52 weeks. Mean (SD) eosinophil counts increased slightly from baseline [1.15 × 109/L (1.18) ] to Week 16 [1.5 × 109/L (1.91)], but then decreased below baseline by Week 52 [0.80 × 109/L (0.64)]. Mean (SD) platelet counts were relatively stable with a modest decrease from baseline [388.7 × 109/L (102.51)] to Week 52 [356.1 × 109/L (107.48)]. Chemistry parameters remained within the normal reference ranges. One patient (0.6%) reported a mild case of anemia, and one patient (0.6%) reported a mild case of thrombocytopenia, which were resolving and resolved at the time of this interim analysis, respectively. Overall safety was consistent with the known dupilumab safety profile. No clinically meaningful changes in hematologic and chemistry parameters were observed during 52 weeks of dupilumab treatment. As with adults, adolescents and older children, routine laboratory monitoring is unnecessary in children aged 6 months to 5 years with moderate-to-severe AD. [ABSTRACT FROM AUTHOR]

Summary: Background: Structured patient‐reported outcomes of atopic dermatitis (AD) severity are not standardized in clinical practice. Objectives: To determine the construct validity, internal consistency, cross‐cultural validity and floor or ceiling effects of multiple AD severity assessments. Methods: This is a cross‐sectional, population‐based study of 2893 adults, including 602 adults who met a modified set of U.K. diagnostic criteria for AD. AD severity was assessed using self‐reported global AD severity, Patient‐Oriented Eczema Measure (POEM), Patient‐Oriented Scoring Atopic Dermatitis (PO‐SCORAD) and its objective and subjective components, and numerical rating scale (NRS)‐itch. Quality of life was assessed using Short‐Form (SF)‐12 mental and physical health scores, Short‐Form Six Dimensions (SF‐6D) health utility scores and Dermatology Life Quality Index (DLQI). Mental health was assessed with the Hospital Anxiety and Depression Scale (HADS). Results: PO‐SCORAD, PO‐SCORAD objective and subjective subscores, NRS‐itch and POEM all had moderate‐to‐strong correlations with each other and DLQI, fair‐to‐moderate correlations with HADS‐anxiety and HADS‐depression, and inverse correlations with SF‐12 mental component score and SF‐6D (Pearson correlations, P < 0·001). All scores showed good criterion validity as judged by anova and receiver operator characteristics. PO‐SCORAD, PO‐SCORAD objective subscore and POEM had similarly good internal consistency (Cronbach's alpha = 0·84, 0·82 and 0·86); the PO‐SCORAD subjective subscore was less internally consistent (alpha = 0·57). All scores showed potentially poor cross‐cultural validity as demonstrated by uniform and nonuniform differential item functioning by age, sex and/or race/ethnicity for multiple items. There were floor effects for POEM, but not for the other assessments. Conclusions: PO‐SCORAD, PO‐SCORAD objective and subjective subscores, NRS‐itch and POEM appear to be valid for assessing AD severity in clinical practice. What's already known about this topic? Few studies have demonstrated the validity of the atopic dermatitis severity assessments Patient‐Oriented Scoring Atopic Dermatitis (PO‐SCORAD), PO‐SCORAD subscores, numerical rating scale (NRS)‐itch and Patient‐Oriented Eczema Measure (POEM). What does this study add? This study demonstrates that PO‐SCORAD, PO‐SCORAD subscores, NRS‐itch and POEM all had good construct validity in the assessment of atopic dermatitis severity in adults.Only POEM demonstrated floor effects. What are the clinical implications of this work? PO‐SCORAD, PO‐SCORAD subscores, NRS‐itch and POEM all appear to have sufficient validity to be used as assessments of atopic dermatitis severity in clinical practice. Plain language summary available online Respond to this article [ABSTRACT FROM AUTHOR]

Summary: Background: The relationship between atopic dermatitis (AD), anxiety and depression in the U.S. adult population is not well established. Objectives: To determine the relationship of AD and its severity with symptoms and diagnosis of anxiety and depression in U.S. adults. Methods: A cross‐sectional, population‐based study of 2893 adults was performed. AD was determined using modified U.K. Diagnostic Criteria. Results: Adults with AD vs. those without AD had higher mean Hospital Anxiety and Depression Scale anxiety (HADS‐A) (7·7 vs. 5·6) and depression (HADS‐D) (6·0 vs. 4·3) scores and higher prevalences of abnormal (≥ 11) HADS‐A (28·6% vs. 15·5%) and HADS‐D (13·5% vs. 9·0%) scores. In multivariable linear and logistic regression models controlling for sociodemographics, AD was associated with significantly higher mean HADS‐A and HADS‐D scores (7·7 and 6·0) and higher odds of abnormal HADS‐A [odds ratio (OR) 2·19, 95% confidence interval (CI) 1·65–2·91] and HADS‐D scores (OR 1·50, 95% CI 1·04–2·17) (P ≤ 0·03 for all). Mean and abnormal HADS‐A and HADS‐D scores were increased in moderate and severe/very severe self‐reported global AD severity, Patient‐Oriented Eczema Measure (POEM), Patient‐Oriented Scoring AD (PO‐SCORAD), PO‐SCORAD itch and sleep (P < 0·0001 for all). All respondents with severe PO‐SCORAD, POEM and PO‐SCORAD itch had borderline or abnormal HADS‐A and HADS‐D scores. Adults with AD vs. those without AD had higher prevalence of self‐reported healthcare‐diagnosed anxiety or depression in the past year (40·0% vs. 17·5%). Many adults with AD who had borderline and/or abnormal HADS‐A or HADS‐D scores reported no diagnosis of anxiety or depression. Conclusions: AD is associated with significantly increased anxiety and depression, which may go undiagnosed. What's already known about this topic? Previous studies found higher rates of anxiety and depression in clinical cohorts of patients with atopic dermatitis. What does this study add? This study found dramatically higher rates of anxiety and depression among adults with atopic dermatitis in the U.S. population, which was primarily driven by atopic dermatitis severity.Anxiety and depression often go undiagnosed in adults with atopic dermatitis. Linked Comment: Nicholas and Drucker. Br J Dermatol 2019; 181:442–443. Plain language summary available online Respond to this article [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a type 2 inflammatory disease characterized by elevations in several biomarkers including serum IgE—a key downstream mediator in the type 2 adaptive immune response. Patients with moderate-to-severe AD were enrolled for 16 weeks in any of six randomized, placebo-controlled, phase 3 studies: in LIBERTY AD PRESCHOOL, (NCT03346434 part B) patients aged 6 months to 5 years were treated with dupilumab 200/300 mg every 4 weeks (q4w) + topical corticosteroids (TCS; n = 83) or placebo + TCS (n = 79); in LIBERTY AD PEDS (NCT03345914), patients aged 6–11 years were treated with dupilumab + TCS [100/200 mg q2w (n = 122), 300 mg q4w (n = 122)] or placebo + TCS (n = 123); in LIBERTY AD ADOL (NCT03054428), patients aged 12–17 years were treated with dupilumab [200/300 mg q2w (n = 82), 300 mg q4w (n = 83)] or placebo (n = 85); and in LIBERTY AD CHRONOS/SOLO1/SOLO2 (NCT02260986/NCT02277743/NCT02277769, pooled), patients aged ≥18 years were treated with dupilumab [300 mg q2w (n = 563),300 mg qw (n = 781) ] or placebo (n = 775). The TCS were allowed in CHRONOS only. At Week 16, dupilumab treatment significantly (P < 0.0001) reduced median total serum IgE levels [kU/L (IQR)] compared with placebo in patients aged 6 months to 5 years [843 (207–3300) vs. 3625 (540.5–8585)], 6–11 years [1519 (532–3808) vs. 3862 (1166–9999)], 12–17 years [1391 (436–2842) vs. 4569 (800.5–10000)] and ≥18 years [1340 (229–4360) vs. 3722 (555–10000)]. Dupilumab treatment reduced total serum IgE levels in patients aged 6 months and older with moderate-to-severe AD. Overall safety was consistent with the known dupilumab safety profile. [ABSTRACT FROM AUTHOR]

Background The increased susceptibility of patients with atopic dermatitis ( AD) to disseminated viral skin infections such as eczema herpeticum ( ADEH+) is poorly understood. Objectives The primary goal of the current study was to determine whether ADEH+ subjects have identifiable defects in cell-mediated immunity that reduce their ability to control viral infections. Materials and methods In this study, we evaluated cytokine expression by various subsets of peripheral blood mononuclear cells from ADEH+ ( n = 24) compared with AD without a history of viral infections ( ADEH-) ( n = 20) before and after treatment with herpes simplex virus ( HSV). Results We found that interferon ( IFN)-γ expression after HSV treatment was lower in the CD8+ T cells and monocytes from patients with ADEH+ compared with patients who are ADEH- or nonatopic. Given the induction of CD8+ T cells as the result of antigen presentation by human leucocyte antigen ( HLA) class I, consistent with the findings described above we also found that the HLA B7 allele was significantly associated with risk of the ADEH+ phenotype (odds ratio = 1·91, P = 0·02, 125 ADEH+ and 161 ADEH- subjects). Conclusions These data suggest that defects in viral-induced IFN-γ from CD8+ T cells contribute to the ADEH+ phenotype. [ABSTRACT FROM AUTHOR]

Background Combination therapy with pimecrolimus cream 1%, a topical calcineurin inhibitor (TCI), and fluticasone propionate cream 0·05% (FP), a mid-potency topical corticosteroid, may have a synergistic effect for treatment of atopic dermatitis (AD) because their mechanism of action differs. Objectives To assess the efficacy of concomitant pimecrolimus twice daily/FP once daily vs. vehicle twice daily/FP once daily in patients with severe AD. Methods An exploratory, 2-week, double-blind, randomized, within-patient study was conducted ( n = 45). Two target areas of similar severity, size and location were assessed. Assessments included the modified Eczema Area and Severity Index (0–12 scale) (primary variable), localized investigator global assessment (0–4 scale) and Patients’ Self-Assessment of Disease Severity (0–4 scale). Results Data for all variables were similar for the TCI/FP and vehicle/FP treatments. Conclusions The efficacy observed for treatment of severe AD flares with this TCI/FP combination regimen was equivalent to that of vehicle/FP. [ABSTRACT FROM AUTHOR]

Background Antibiotics are prescribed in up to 80% of pediatric intensive care unit (PICU) patients, but multicenter studies systematically evaluating antibiotic indications and appropriateness in this high-utilizing population are lacking. Methods A multicenter point prevalence study was conducted at 10 geographically diverse tertiary care US children's hospitals. All PICU patients < 21 years of age who were receiving systemic antibiotics at 8:00 AM on each study day were included. Study days occurred in February and March 2019. Data were abstracted by critical care and/or infectious diseases trained clinicians using standardized data collection forms and definitions of antibiotic appropriateness. Results 408 of 732 PICU patients (56%) received 618 antibiotics on the two study days. Empiric therapy for suspected bacterial infections without sepsis was the most common indication for antibiotics (22%), followed by treatment of community-acquired pneumonia and empiric therapy for septic shock (12% each, Figure 1). Overall, 194 antibiotic orders (32%) were classified as inappropriate and 158 patients (39%) received at least one inappropriate antibiotic. Vancomycin, cefepime, and ceftriaxone were the antibiotics most often inappropriately prescribed (Figure 2). Antibiotics prescribed inappropriately for the top 5 indications shown in Figure 1 accounted for 77% of all inappropriate antibiotic use. Prolonged (>4 days) empiric therapy and prolonged (>24 hours) post-operative prophylaxis were the most common reasons antibiotics prescribed for these indications were classified as inappropriate. Pneumonia and ventilator-associated infections were the most common infections for which antibiotics were prescribed inappropriately (46%). Reasons for inappropriate antibiotic use included lack of evidence supporting a bacterial infection (no radiographic infiltrate or significant increase in respiratory support) and use of unnecessarily broad antibiotics (Table 1). Conclusion Inappropriate antibiotic use is common in the PICU, particularly for pneumonia. Studies focused on defining optimal treatment strategies, as well as improved diagnostic approaches to curtail prolonged courses of empiric therapy, should be prioritized. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding the history of eczema herpeticum (ADEH) in atopic dermatitis (AD) patients who are incapable of increasing antimicrobial peptides (AMPs), cathelicidin, human β-defensin (HBD)-2 and HBD-3 against inflammation.

Summary: 特应性皮炎 (AD) 也称为特应性湿疹, 是一种常见的皮肤疾病, 尤其在儿童中。 AD 可能导致多种可影响不同身体部位的皮肤病灶(湿疹斑块)以及不同程度的瘙痒和睡眠障碍。这些是 AD 严重程度的重要部分。 已经创建了许多不同的系统或"工具"来询问患者 AD 严重程度的这些方面的信息。这些工具可用于临床实践(即供医生和护士使用), 以确保患者获得正确的治疗。尚未明确其中一些工具的有效性(准确性)以及如何相互比较它们。 作者使用美国研究中的 AD 数据, 比较了 602 例美国成人 AD 患者对 6 个测量他们疾病严重程度的不同调查问卷的回答。 以患者为导向的湿疹测量 (POEM)、以患者为导向的 AD 评分 (PO‐SCORAD) 总分与客观和主观子评分, 以及数字评定量表 (NRS)‐瘙痒均可充分表明 AD 的严重程度。PO‐SCORAD 可很好地显示 AD 的严重程度以及对生活质量和心理健康的影响。 虽然这些工具存在一些有效性问题, 但作者认为它们足以评估 AD 在临床实践中的严重程度。 This summary relates to the study: 成人特应性皮炎严重程度的五种患者报告结果的验证 Linked Article: Silverberg et al. Br J Dermatol 2020; 182:104–111 [ABSTRACT FROM AUTHOR]

Summary: Atopic dermatitis (AD), also known as atopic eczema, is a common skin disease, especially in childhood. AD can cause several types of skin lesions (patches of eczema) that can affect different parts of the body, and varying levels of itch and sleep disturbance. These are important parts of AD severity. Many different systems, or 'tools', have been created that ask patients about these aspects of AD severity. These tools could be used in clinical practice (i.e. by doctors and nurses) to make sure patients get the right treatment. It was unknown how valid (accurate) some of these tools are and how they compare to each other. Using data from the AD in America study, the authors compared how a group of 602 U.S. adults with AD answered 6 different surveys to measure their disease severity. The Patient‐Oriented Eczema Measure (POEM), Patient‐Oriented Scoring AD (PO‐SCORAD) total score and objective and subjective sub‐scores, and Numeric Rating Scale (NRS)‐itch all did a good job of showing how severe the AD was. PO‐SCORAD did the best job of telling how severe the AD was, and how much AD harmed quality of life and mental health. While there were some problems with the validity of these tools, the authors think they are valid enough to assess how severe AD is in clinical practice. This summary relates to the study: Validation of five patient‐reported outcomes for atopic dermatitis severity in adults Linked Article: Silverberg et al. Br J Dermatol 2020; 182:104–111 [ABSTRACT FROM AUTHOR]

Summary: 特应性皮炎(AD)也简称为湿疹,是一种导致瘙痒性皮疹的长期皮肤病。搔抓可导致皮肤渗液,结痂,感染和增厚。美国有 1650 万人患有特应性皮炎,660 万人报告中重度症状。发现病情越严重,生活质量越差,抑郁和焦虑的风险越高。 这项基于美国的研究调查了 2,893 名成人,以了解患有特应性皮炎和其严重程度是否影响同时存在焦虑或抑郁的可能性。通过发送一份调查收集了信息。使用改良英国诊断标准筛查特应性皮炎患者。由患者使用例如患者来源湿疹测量和皮肤病学生活质量指数等工具来自行报告疾病严重程度。使用医院焦虑和抑郁量表 (HADS) 测量焦虑和抑郁。 602 名成人患有特应性皮炎。他们的 HADS 评分高于(意味着焦虑和抑郁水平更高) 2291 名无特应性皮炎的成人。在特应性皮炎成人中,同时有焦虑或抑郁正式诊断的人数多于在无特应性皮炎的成人中。但是,很多 HADS 评分高的特应性皮炎患者并没有焦虑或抑郁的正式诊断。此外,特应性皮炎较严重患者的 HADS 评分较病情较轻患者更高。 结论是,特应性皮炎增加焦虑和抑郁的可能性,尤其当病情严重时。这可能被漏诊。 Linked Article: Silverberg et al. Br J Dermatol 2019; 181:554–565 [ABSTRACT FROM AUTHOR]

Summary: Atopic dermatitis, also known simply as eczema, is a long‐term skin condition that causes an itchy rash. Scratching can cause skin to weep, crust, become infected and become thicker. 16.5 million adults in the USA suffer from atopic dermatitis, with 6.6 million reporting moderate to severe symptoms. Those with more severe disease have been found to have worse quality of life and increased risk of depression and anxiety. This US‐based study looked at 2893 adults to see if having atopic dermatitis, and how severe it is, affects the likelihood of also having anxiety or depression. Information was collected by sending out a survey. Modified UK diagnostic criteria were used to screen for patients with atopic dermatitis. Disease severity was self‐reported by patients using tools such as the Patient‐Orientated Eczema Measure and Dermatology Life Quality Index. The Hospital Anxiety and Depression Scale (HADS) was used for measuring anxiety and depression. 602 adults had atopic dermatitis. They had higher HADS scores (meaning higher levels of anxiety and depression) than the 2291 adults without atopic dermatitis. There were more adults with atopic dermatitis who also had a formal diagnosis of anxiety or depression than those without atopic dermatitis. However, many atopic dermatitis patients with high HADS scores had no formal diagnosis of anxiety or depression. Furthermore, patients with more severe atopic dermatitis had higher HADS scores than those with milder disease. The conclusion is that atopic dermatitis increases the likelihood of having anxiety and depression, especially if one has severe disease. This may go undiagnosed. Linked Article: Silverberg et al. Br J Dermatol 2019; 181:554–565 [ABSTRACT FROM AUTHOR]

Introduction: Gastric lipomatosis (GL) is an extremely rare entity where gastric submucosa is diffusely expanded by accumulation of fat, but without well-defined histological criteria. GL presenting as multiple polyps is not reported in the literature. We encountered such a case in a bariatric partial gastrectomy specimen, which prompted the current study to assess extent of fat in gastric submucosa in morbidly obese patients. Methods: H&E slides of 128 bariatric partial gastrectomy specimens including the index case were examined. The amount of submucosal fat was categorized as 0 (no fat), 1 (up to 70% fat), and 2 (> 70% fat). The maximum submucosal thickness was measured with the interval cutoff of 5 mm (radiologic upper normal thickness) and 10 mm. Results: The index case was of a 46-year-old morbidly obese man, who underwent preoperative endoscopy followed by bariatric partial gastrectomy. Multiple gastric polyps were noted endoscopically as well as grossly upon pathologic examination. Histological evaluation revealed GL with polypoid thickening of the submucosa up to 12 mm by fat. Of the 128 cases, seven (5.4%) fell in category 0, 90 (70.3%) in category 1, and 31 (24.2%) in category 3. Maximum submucosal thickness was <5 mm in 104 (81.3%) and ≥5 mm in 24 (18.8%) cases, in which three (2.3%) cases, including the index case, showed ≥10 mm of submucosal fat. Conclusions: We report a first case of GL presenting as gastric polyposis. Gastric submucosa is significantly thickened by fat and/or shows diffuse fat accumulation in 18.8% and 24.2% of morbidly obese patients, respectively. Based on our findings, we propose a submucosal thickness of a minimum of 10 mm and diffuse (>70%) fat accumulation as diagnostic criteria for GL. Using these criteria, the prevalence of GL in the morbidly obese population is 2.3%. A subset of these may present as polyps and gastric polyps secondary to GL may be under-recognized. [ABSTRACT FROM AUTHOR]